Medications Archives - MelioGuide

Hormone Therapy and Exercise Can Increase Bone Density

Margaret Martin — Tue, 19 Aug 2025 16:22:01 +0000

August 19, 2025

A recent comprehensive research review published in May 2025 (1) examined how combining exercise and hormone therapy improves bone health. In today’s post we will review that study and also cover what was said regarding hormone replacement therapy at the April 2025 World Congress on Osteoporosis.

If you’re concerned about osteoporosis or have been wondering whether hormone therapy might benefit your bones, this post is for you.

Hormones, Estrogen and Bone Remodeling

Let me start by explaining what happens to your bones during menopause. Throughout your life, your bones are constantly going through a process called bone remodeling — breaking down old bone tissue and building new bone. This process is carefully balanced by two types of cells: osteoblasts that build bone, and osteoclasts that break it down.

Estrogen plays a crucial role in this process. It enhances the activity of bone-building osteoblasts while suppressing the bone-breaking osteoclasts. When estrogen levels decline during menopause, this delicate balance shifts dramatically. The result? More bone is being broken down than built up, leading to decreased bone mineral density and increased fracture risk.

The research shows that postmenopausal women can lose bone at an alarming rate — with bone resorption significantly outpacing bone formation. This is why osteoporosis affects one in three women over 50 worldwide.

Now, let’s talk about menopause hormone replacement therapy, or HRT. This treatment involves supplementing the hormones your body is no longer producing in adequate amounts.

Two Types of Hormone Replacement Therapy

There are two main types of hormone replacement therapy for menopause:

Combined HRT includes both estrogen and a progestogen (like progesterone). This is recommended for women who still have their uterus, as the progestogen protects the lining of the uterus from the effects of estrogen alone.
Estrogen-only HRT is suitable for women who have had a hysterectomy, since there’s no uterus to protect.

The research shows that HRT works by reducing excessive bone resorption – essentially putting the brakes on the bone-breaking osteoclasts that go into overdrive after menopause.

Exercise and Bone Health

Exercise is another powerful tool for bone health. When you exercise, especially with weight-bearing and strength training activities, you create mechanical stress on your bones.

This stress triggers your bone cells — specifically the osteocytes — to respond by stimulating new bone formation.

The research review analyzed multiple studies and found that specific types of exercise are most effective for menopausal women:

Strength training at 70-85% of your one-repetition maximum, performed 2-3 times per week
Weight bearing exercise activities like jumping, running, or hopping, done at least 3 times per week
Combined programs that include both strength and weight bearing exercises such as Exercise for Better Bones

The key finding? Exercise alone can significantly improve bone mineral density in the lumbar spine, femoral neck, and total hip.

Hormone Therapy and Exercise

Here’s where it gets really interesting. The research found something remarkable: when hormone therapy and exercise are combined, they work better together than either intervention alone.

Specifically, the studies showed that hormone therapy and exercise generated significantly greater effects on both femoral neck bone density and lumbar spine bone density compared to exercise-only interventions. This suggests what researchers call “a positive estrogenic response to mechanical loading during exercise.”

In simpler terms, estrogen appears to amplify your bones’ response to the mechanical stress of exercise. Think of it as estrogen making your bones more receptive to the bone-building signals that exercise provides.

The research noted that mixed loading exercise programs — those combining different types of activities — were particularly sensitive to this hormone therapy enhancement, especially for spine bone density.

Hormone Therapy: Are There Risks?

While these findings are encouraging, I want to be completely transparent about the risks associated with hormone therapy. The research acknowledges several important safety considerations:

The most commonly studied form of hormone therapy in these studies was conjugated equine estrogens (CEE) with medroxyprogesterone acetate (MPA), taken orally. However, studies have linked this combination to increased risks of:

Breast cancer
Blood clots (thromboembolism)
Stroke
Cardiovascular disease

It’s important to note that current prescribing practices have evolved significantly. Many healthcare providers now prefer:

Transdermal estrogen (patches, gels, or sprays) which may have lower risks of blood clots and stroke
Bioidentical progesterone rather than synthetic progestins

The research emphasizes that most current guidelines recommend hormone therapy primarily for women under 60 or within 10 years of menopause, and only when other treatments aren’t suitable.

When the brakes were put on the use of hormone therapy for women in North America, following the Women’s Health Initiative Study in 2000 the same was not the case in Europe and South America.

At the world congress this past April, gynecologist from Brazil and Italy spoke of the youthfulness that went beyond bones in their 80 and 90 year old patients who had been using hormone replacement therapy for decades.

HRT and Exercise Recommendations

Based on this research, here are my five evidence-based recommendations:

Prioritize Exercise as Your Foundation Regardless of whether you choose hormone therapy, exercise should be central to your bone health strategy. The research consistently shows that structured exercise programs can significantly improve bone density.
Consider the Timing If you’re considering hormone therapy for bone health, the research suggests it may be most effective during perimenopause and early postmenopause — ideally within the first 10 years after menopause.
Focus on Combined Exercise Programs Aim for a program that includes:
- Strength training 2 to 3 times per week at moderate to high intensity
- Weight bearing exercise activities at least 3 times per week
- Duration of at least 6 months, with longer programs showing better results
Discuss Modern Hormone Replacement Therapy Options with Your Doctor If you’re considering hormone therapy, talk with your healthcare provider about:
- Transdermal estrogen delivery methods
- Bioidentical hormone options
- Your individual risk profile
- The timing of initiation
Take a Personalized Approach The research emphasizes that osteoporosis management requires a personalized, multifaceted approach. Your treatment plan should consider your individual risk factors, medical history, and preferences.

Conclusion

Remember, while exercise is universally beneficial and recommended for bone health, hormone therapy isn’t appropriate for everyone. The research noted that many guidelines prioritize other medications like bisphosphonates as first-line treatments for osteoporosis, with hormone therapy considered when these aren’t suitable.

The key takeaway from this research is that if you are a candidate for both interventions, combining exercise with appropriate hormone therapy may provide synergistic benefits for your bone health that neither approach can achieve alone.

This research gives us valuable insights into how we can optimize bone health during and after menopause. The combination of exercise and hormone therapy shows promise, but it’s crucial to work with knowledgeable healthcare providers who can help you weigh the benefits and risks based on your individual situation.

Remember, building and maintaining bone health is a marathon, not a sprint.

Consistency with exercise, whether combined with hormone therapy or not, remains your most powerful tool for strong bones and reduced fracture risk.

Margaret Martin

Margaret Martin is a Physical Therapist with 40 years of clinical experience. Her expertise is in the treatment and prevention of osteoporosis through exercise, safe movement and fall prevention. For the last 20 years, she has concentrated on bone health and has treated thousands of patients for their osteoporosis, osteopenia and low bone density.

Reference

Platt Olivia , Bateman James , Bakour Shagaf, Impact of menopause hormone therapy, exercise, and their combination on bone mineral density and mental wellbeing in menopausal women: a scoping review, Frontiers in Reproductive Health, Volume 7 – 2025, DOI=10.3389/frph.2025.1542746

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Aromatase Inhibitors and Bone Loss During Breast Cancer Treatment

Margaret Martin — Wed, 30 Jul 2025 15:25:03 +0000

Breast cancer patients now experience significantly higher survival rates thanks to early diagnosis and more effective treatments. Aromatase inhibitors, a class of hormone therapy medications, stand out as one of the most effective protocols for preventing hormone receptor-positive breast cancer recurrence. While highly effective, these medications can cause bone loss as a side effect. This article explores the connection between aromatase inhibitors and bone loss, their potential to cause osteoporosis or osteopenia, and strategies to protect your bone density while using these medications.

Dr. Theresa Guise, a world-renowned expert on cancer and bone health, shares her insights throughout this article. As a professor, clinician, and chief of the Bone and Mineral Disorder section at the University of Texas MD Anderson Cancer Center, Dr. Guise has dedicated her career to understanding how cancer and its treatments affect the musculoskeletal system.

How Cancer Treatment Impacts Bone Remodeling

Cancer treatments often affect bone health more significantly than cancer itself. While we typically associate cancer’s impact on bones with metastasis (cancer spreading to bone), many cancer treatments can affect bone health even when cancer hasn’t spread to the bones.

Common cancer treatments that can affect bone mineral density include:

Chemotherapy radiation used across many cancer types
Anti-estrogen therapy for breast cancer
Anti-androgen therapy for prostate cancer
Glucocorticoids (steroid hormones like prednisone or dexamethasone)

These treatments disrupt the bone remodeling process and can lead to bone loss, fractures, muscle weakness, and potentially osteoporosis.

Breast Cancer Treatment and Osteoclasts

Cancer treatments can stimulate osteoclastic bone resorption, accelerating the bone remodeling process. In this situation, osteoclasts destroy bone faster than osteoblasts can rebuild it, resulting in net bone loss.

Breast Cancer Treatment and Osteoblasts

Some treatments, particularly glucocorticoids, directly inhibit osteoblast activity. The effects can be dramatic — radiation therapy, for example, can cause significant bone loss within a short timeframe. This makes it crucial to identify these potential effects before treatment begins and implement preventive measures, such as medications or low intensity vibration therapy.

Aromatase Inhibitors and Bone Loss During Breast Cancer Treatment

As both a researcher and patient, Dr. Guise brings unique insight into aromatase inhibitors, which have become the standard first-line treatment for estrogen receptor-positive breast cancers. These drugs have proven more effective than their predecessor, Tamoxifen, by blocking the aromatase enzyme that converts androgens to estrogens.

While effective at treating breast cancer, aromatase inhibitors reduce estrogen levels below those typically seen in menopausal women, leading to various musculoskeletal problems.

Exercise and Osteoporosis

Exercise is an essential ingredient to bone health. If you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.

But what exercises should you do and which ones should you avoid? What exercises build bone and which ones reduce your chance of a fracture? Is Yoga good for your bones? Who should you trust when it comes to exercises for osteoporosis?

A great resource on exercise and osteoporosis is my free, seven day email course called Exercise Recommendations for Osteoporosis. After you provide your email address, you will receive seven consecutive online educational videos on bone health — one lesson each day. You can look at the videos at anytime and as often as you like.

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

Enter your email address and I will start you on this free course. I do not SPAM or share your email address (or any information) with third parties. You can unsubscribe from my mail list at any time.

Do Aromatase Inhibitors Cause Osteoporosis?

Bone loss affects most women taking aromatase inhibitors. Those starting treatment with osteopenia may develop osteoporosis without preventive measures. This occurs because estrogen naturally inhibits bone-resorbing osteoclasts. When aromatase inhibitors deplete estrogen, bone loss accelerates as osteoblasts struggle to keep pace with increased resorption.

Beyond bone loss from aromatase inhibitors, many postmenopausal women with breast cancer experience muscle weakness and generalized aches in their muscles, bones, and joints. These side effects are associated with aromatase inhibitors and sometimes lead to treatment discontinuation.

Aromatase Inhibitors and Bone Loss: How to Counter Bone Loss

Several strategies can help counter bone loss during aromatase inhibitor therapy:

Medications like Prolia (denosumab) or bisphosphonates like zoledronate
Low intensity vibration therapy, particularly helpful for patients experiencing muscle weakness
Mechanical loading exercises, when tolerated

Research in Dr. Guise’s laboratory shows that low intensity vibration can prevent bone loss, improve muscle strength, and reduce fat in mouse models. A clinical trial at Indiana University is currently evaluating these effects in women taking aromatase inhibitors.

Aromatase Inhibitors and Osteoporosis: Dr. Guise's Personal Journey

Dr. Guise shares her personal experience as a breast cancer patient taking aromatase inhibitors. By combining a low intensity vibration platform (used twice daily) with zoledronate treatment, she achieved a 3% increase in bone density — a marked improvement over the bone loss typically seen with aromatase inhibitors alone.

Aromatase Inhibitor Therapy and Bone Loss: Updated Guidelines for 2025

A group of clinicians and researchers (including Dr. Guise) recently published a joint position statement for a number of leading osteoporosis organizations in the August 2025 edition of the Journal of Bone Oncology. (1) The statement provides updated guidelines for the management of aromatase inhibitor associated bone loss in women with hormone sensitive breast cancer.

The key message for you is that women taking aromatase inhibitors for breast cancer face a 2 to 4 times higher risk of bone loss and fractures compared to normal menopause, making early bone-protective treatment essential rather than optional. The good news is that effective treatments like denosumab (Prolia) and bisphosphonates not only prevent fractures but may also improve breast cancer survival outcomes.

We review this joint statement in this section.

Elevated Risk of Vertebral and Hip Fractures

Women with hormone-responsive breast cancer who receive adjuvant endocrine treatment with aromatase inhibitors are known to be at higher fracture risk due to a marked increase in bone resorption.

Studies have shown that aromatase inhibitor associated bone loss in postmenopausal women with hormone-sensitive breast cancer, where estrogen is already naturally depleted, can lead to a 2 to 4 fold increase in bone loss compared to the usual postmenopausal decrease in BMD, leaving them at high risk of fragility fractures.

The relative risk (RR) for hip fractures and non-vertebral fractures was 1.18 versus controls, while the RR for vertebral fractures was much higher, at 1.84. This means women on aromatase inhibitor therapy face nearly double the risk of spine fractures compared to those not on this treatment.

Extended Aromatase Inhibitor Treatment Increases Bone Loss Risk

A systematic review and meta-analysis of seven trials of 16,349 breast cancer patients treated with either extended-duration aromatase inhibitors, placebo or no treatment found that longer treatmen

Aromatase Inhibitors and Bone Loss Risk Factors

The updated guidelines identify several key risk factors that increase your fracture risk beyond Aromatase inhibitors therapy itself. These include:

Age over 65 years
T-score below -1.5 on bone density testing
Current or history of smoking
Body mass index (BMI) less than 24
Family history of hip fracture
Personal history of fragility fracture after age 50
Previous vertebral fracture
Use of oral corticosteroids for more than 6 months

Advanced Assessment Techniques

Modern fracture risk assessment goes beyond traditional bone density (DXA) scans. The FRAX® tool was developed for use in the general population and was not specifically designed for use in patients with breast cancer undergoing aromatase inhibitor treatment.

However, newer techniques are showing promise. Trabecular bone score (TBS) utilizes grey-level texture measurements on lumbar spine DXA images to capture information relating to trabecular microarchitecture and has been shown to be an independent indicator of increased fracture risk.

A study of 100 patients with early-stage ER-positive breast cancer treated with aromatase inhibitors assessed elevated fracture risk using BMD alone, BMD plus FRAX® and a combination of BMD, FRAX® and TBS. The use of multiple assessment techniques incrementally improved the identification of patients at increased fracture risk with the combination of all three procedures maximizing the number detected.

Treatment Options: What Works Best

The good news is that effective treatments are available. The updated guidelines provide clear evidence-based recommendations:

Denosumab (Prolia) emerges as a first-line therapy. Denosumab is recommended as a first-line therapy for aromatase inhibitor associated bone loss prevention by the European Society for Medical Oncology (ESMO) and in the 2021 updated guidance on management of cancer treatment-induced bone loss (CTIBL).
Intravenous bisphosphonates have been upgraded to Level I evidence. Adjuvant zoledronate was found to significantly reduce the incidence of fractures in this patient cohort, with a 5-year fracture rate of 3.8 % compared to 5.9 % in the control arm.
Oral bisphosphonates have also shown efficacy, though with some limitations regarding absorption and compliance.

Treatment Guidelines and Monitoring

The updated algorithm is straightforward: All women receiving aromatase inhibitor treatment should be informed of this significantly increased risk and its consequences and have their individual fracture risk evaluated to determine an appropriate management strategy.

For women with T-scores below -2.0 or those with T-scores between -1.5 and -2.0 plus additional risk factors, bone-protective therapy should be initiated alongside aromatase inhibitor treatment. BMD should then be monitored every two years.

Discussion

If you’re receiving aromatase inhibitor therapy, don’t wait to address bone health. The evidence overwhelmingly supports early intervention. Work with your healthcare team to assess your individual risk, consider the most appropriate bone-protective therapy, and establish a monitoring plan. Remember, protecting your bones isn’t just about preventing fractures—it may also improve your overall cancer outcomes.

Aromatase Inhibitors and Bone Loss: Conclusion and Summary

Aromatase inhibitors are an effective treatment for breast cancer. However, they have side effects that patients and clinicians need to address.

There is a relationship between aromatase inhibitors and bone loss, osteoporosis and bone density. Aromatase inhibitors disrupt the bone remodeling process and can lead to a reduction in bone density and cause osteoporosis. In summary:

Aromatase inhibitors effectively treat estrogen receptor-positive breast cancer but can cause significant bone loss
Cancer treatments often affect bone health more than cancer itself through various mechanisms
Without preventive measures, aromatase inhibitors may lead to osteoporosis, especially in patients who already have osteopenia
Multiple treatment options exist to counter bone loss, including medications and low intensity vibration therapy
A combined approach using both medication and mechanical stimulation, specifically low intensity vibration, appears most effective at maintaining bone density during treatment

Margaret Martin

Reference

Peyman Hadji, Matty Aapro, Nasser Al-Dagri, Majed Alokail, Emmanuel Biver, Jean-Jacques Body, Maria Luisa Brandi, Janet Brown, Cyrille Confavreux, Bernard Cortet, Matthew Drake, Peter Ebeling, Erik Fink Eriksen, Ghada El-Hajj Fuleihan, Theresa A. Guise, Nick C. Harvey, Andreas Kurth, Bente Langdahl, Willem Lems, Radmila Matijevic, Eugene McCloskey, Rossella Nappi, Santiago Palacios, Georg Pfeiler, Jean-Yves Reginster, René Rizzoli, Daniele Santini, Sansin Tuzun, Catherine Van Poznak, Tobias De Villiers, M. Carola Zillikens, Robert Coleman, Management of aromatase inhibitor-associated bone loss (AIBL) in women with hormone-sensitive breast cancer: An updated joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG, Journal of Bone Oncology, Volume 53, 2025, 100694, ISSN 2212-1374, https://doi.org/10.1016/j.jbo.2025.100694.

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PTH and Osteoporosis Exercise

Margaret Martin — Sun, 25 May 2025 13:18:43 +0000

May 25, 2025

A number of clients have asked me what is the relationship between PTH and osteoporosis. The parathyroid hormone (PTH) is one of a number of factors that play an important role in keeping our skeleton healthy.

PTH is naturally produced by our parathyroid glands. These tiny, rice-size glands, located in the neck, are responsible for keeping our blood calcium levels under check.

Parathyroid hormone (PTH) can also be produced synthetically. It is a powerful osteoporosis medication clinicians can use to help rebuild bone in patients with osteoporosis.

This post will look at a two key questions related to PTH and osteoporosis:

Are parathyroid hormones an effective treatment for osteoporosis?
Are there benefits to doing osteoporosis exercise while you are taking PTH?

Let’s start with an overview of the PTH hormone and osteoporosis.

PTH for Osteoporosis: Bone Remodeling and Bone Heath

Parathyroid hormone (PTH) stands out as one of the few FDA-approved treatments that actually builds new bone in individuals with severe osteoporosis. This makes it a valuable option for many postmenopausal women and men with osteoporosis looking to strengthen their bones.

The most well known parathyroid hormones (PTH) for the treatment of osteoporosis are Tymlos and Forteo. Tymlos is the brand name for Abaloparatide and Forteo is the brand name for Teriparatide.

These medications are self administered through a daily injection. They work by binding to the parathyroid hormone receptor. The parathyroid hormones affect the bone remodelling process by stimulating the osteoblasts to make more bone and increase bone density.

When given intermittently, PTH promotes the development of new osteoblasts and extends their lifespan, stimulating bone formation, increasing bone mineral density, slowing bone loss, and reducing the risk of a fracture.

However, PTH treatment has a limitation: its bone-building benefits plateau after about 24 months. This occurs because although PTH initially increases bone formation, a gradual increase in bone resorption (breakdown) follows, creating what researchers call an “anabolic window” – a limited timeframe during which therapeutic benefits must be maximized.

PTH and Osteoporosis Exercise

Research over the years has shown that mechanical loading through weight bearing and strength training exercise has bone-building effects. Researchers wondered if exercise was combined with PTH treatment, could the two approaches work together and potentially stimulate new bone formation better than only parathyroid hormone therapy?

A new study (1) published in the journal Bone (2025) looked specifically at this question. They explored whether “priming” the skeleton with PTH treatment before starting an exercise program might enhance the overall effect. The researchers, led by Tyler J. McNeill and colleagues at Cornell University, conducted experiments with female mice to test this hypothesis.

Bone Health Research Into PTH and Osteoporosis Exercise

The study pre-treated mice with either PTH or a saline solution (as a control) for six weeks. Then, the researchers applied cyclic compression to the shin bone (a controlled form of mechanical loading similar to brisk walking or running) for either two or six weeks while continuing the PTH or saline treatment.

They analyzed bone in both the cortical (dense outer) and cancellous (spongy inner) parts of the shin bone), measuring changes in the bone structure, the presence of bone cells, and the speed at which new bone was developing.

Exercise Recommendations for Osteoporosis

Exercise is an essential ingredient to bone health. If you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

PTH and Osteoporosis Exercise: Key Research Findings

The results of this study revealed several important findings:

PTH pre-treatment for six weeks significantly increased cortical bone mass before any mechanical loading began.
When mechanical loading was applied at the same time as PTH, it enhanced load-induced increases in cortical bone mass. The bones of the mice who had six weeks of PTH before starting the mechanical loading or weight bearing, had even greater increases in their cortical bone mass.
Interestingly, concurrent PTH and loading had mixed effects in cancellous bone – PTH treatment actually blunted the effects of loading in this bone type. However, pre-treatment with PTH rescued these effects, returning the response values to those of saline-treated animals.
The study found that osteoclast populations (cells that break down bone) decreased with loading, regardless of PTH treatment. Meanwhile, active osteoblast populations (bone-building cells) increased with PTH pre-treatment but didn’t change with loading.
Bone formation rate increased with PTH pre-treatment in the group that underwent loading for 2 weeks. However, after 6 weeks there was no difference between treatment groups.

What This Means for You

This research suggests that the timing of combining PTH hormone treatment with exercise matters. Pre-treating with PTH before starting an exercise regimen appears to “prime” the skeletal tissue, enhancing the anabolic (bone-building) response when the two treatments are used together.

For men and post-menopausal women considering or currently using PTH therapy, these findings highlight the potential benefit of adding a weight-bearing exercise program to your treatment plan. The synergistic effects could help maximize bone growth during the limited “anabolic window” of PTH treatment.

Important Considerations: The PTH Hormone and Osteoporosis

While these research results are promising, there are some important points to keep in mind:

This is Preclinical Research: The study was conducted in mice, and while mouse models are valuable for understanding bone biology, human responses may differ.
Cortical vs. Cancellous Bone: The effects of combined PTH and exercise appear to differ between cortical and cancellous bone. This is relevant because many osteoporotic fractures occur at sites that contain both bone types.
The “Anabolic Window”: Since PTH treatment benefits plateau after about 24 months, timing your exercise program to coincide with PTH therapy could be important for maximizing results.
Exercise Type Matters: The mechanical loading in this study was carefully controlled. In humans, weight-bearing exercises like walking, jogging, stair climbing, would provide similar mechanical stimulation.

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Conclusion

If you’re currently using or considering PTH treatment for osteoporosis, this research on the relationship between PTH and osteoporosis exercise suggests several potential strategies for treating your osteoporosis:

Talk to Your Doctor: Discuss the possibility of combining PTH treatment with a structured osteoporosis exercise program, particularly one that includes weight-bearing activities.
Focus on Weight-Bearing Exercise: Activities that put mechanical load on your bones – like brisk walking, stair climbing, and jogging – seem to work synergistically with PTH treatment.
Be Consistent: The research suggests that continuing both PTH treatment and exercise together provides the greatest benefit.

Remember that the 24-month “anabolic window” of PTH treatment is limited, so finding ways to maximize bone building during this period is crucial. This new research suggests that pre-treatment with PTH followed by combining PTH with regular weight-bearing exercise might be one effective strategy for enhancing bone health, increasing bone mineral density in men and postmenopausal women, and reducing fracture risk.

A Comprehensive Osteoporosis Exercise Program

I encourage clients to follow an osteoporosis exercise program that is “all inclusive” for building bone in both your upper body and lower body. Weight bearing exercises primarily stimulate the bones of your lower body.

Be sure to include daily upper body weight bearing such as wall or counter top push-ups. Try to spend time on your hands and knees: consider crawling (with knee pads) to stimulate lower body bone building.

As with any medical treatment or exercise program, be sure to consult with your healthcare provider to develop a plan that’s appropriate for your specific health needs and circumstances.

Margaret Martin

Reference

McNeill TJ, Rooney AM, Ross FP, Bostrom MPG, van der Meulen MCH. PTH pre-treatment prior to tibial mechanical loading improves their synergistic anabolic effects in mice. Bone. 2025 Jul;196:117474. doi: 10.1016/j.bone.2025.117474. Epub 2025 Mar 29. PMID: 40164271.

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How to Discontinue Prolia

Margaret Martin — Mon, 24 Jun 2024 00:55:10 +0000

This post tackles a critical topic for many readers: when and how to discontinue Prolia (Denosumab). With insights from Dr. Janet Rubin, a distinguished endocrinologist and bone biology researcher at the University of North Carolina Medical School, we’ll guide you through the complexities of Prolia discontinuation.

I will use the terms Prolia and Denosumab interchangeably in this post. They both refer to the same medication. One is the commercial name (Prolia) and the other is the clinical name (Denosumab). Although I do not use the term in this post, you will also find references to the generic version of Prolia elsewhere on the internet. The generic name is Xgeva.

Before we get into when and how to discontinue Prolia, we need to discuss how the medication works. Let’s start with that topic first.

What is Prolia?

Prolia, or Denosumab, is a powerful antiresorptive medication for osteoporosis. It works by inhibiting a molecule called RANK LIGAND, which is essential for the formation and activity of osteoclasts—the cells responsible for bone resorption. By reducing osteoclast activity, Prolia helps maintain and potentially increase bone density. It can reduce fracture risk with limited side effects. (1)

How Prolia Works at the Cellular Level

Prolia effectively halts the activity of the osteoclasts that resorb old and damaged bone, while allowing osteoblasts to continue their work. During postmenopause, osteoclast activity increases and bone formation occurs more slowly due to a drop in estrogen levels. Prolia can rebalance this process by stopping the breakdown of bone, thus maintaining denser bones over time.

A single 60 mg injection of Denosumab is administered every six months by a healthcare provider.

Prolia and Blood Turnover Markers

The chart below (2) illustrates how Prolia affects Serum CTx levels over one year. Serum CTx is a bone turnover marker (BTM) that measures osteoclast activity. When the CTx levels decline, as shown in the chart, this indicates a decrease in osteoclast activity. The reduced osteoclast activity, coupled with the regular osteoblast activity, increases bone density.

The chart illustrates several vital events during the Prolia treatment:

Notice how the CTx level drops dramatically after the injection.
As the Prolia levels in your body drop over the six months, CTx levels start to increase, indicating that osteoclast activity has resumed.
The Prolia has largely left your body by the sixth month.
Your physician administers a new 60 mg injection of Denosumab or Prolia, and the cycle begins again.

Your CTx level should follow a similar pattern. Suppose you have your baseline CTx level before starting Prolia. In that case, your physician can track its behavior and changes over the six months to see the effects of Prolia on your osteoclast activity.

I have had clients who have been told after two years, and a repeat bone density test, that they need to switch to another drug because they did not respond to Denusomab. They could have found this out sooner if their bone markers were monitored.

Source: Prolia website [https://www.proliahcp.com/dosing-and-administration/prolia-injection-dosing]

Bone Loss After Denosumab Discontinuation

Significant cellular changes occur when you stop Prolia. When you discontinue Prolia, osteoclasts—those bone-resorbing cells—quickly become active again. An increase in osteoclast activity can lead to an accelerated rate of bone loss, often faster than before starting Prolia, resulting in “rebound fractures.”

A 2011 study (3) examined the effects of a sudden discontinuation of Prolia with no follow-on treatment. The research found that shortly after discontinuing Prolia (and assuming no follow-on treatment), the CTX levels of the participants rapidly increased well beyond the original CTx baseline recorded before the Prolia intervention. The rapid increase in CTx levels indicated that the osteoclast activity increased and caused rapid loss in bone density in both the lumbar spine and the hip.

The study also found that within twelve to twenty-four months after the sudden stop of Prolia, the participants lost all the gains in bone density that they had made while being on Prolia treatment for two years.

The risk of spontaneous vertebral compression fracture increased in the twelve to twenty-four months after suddenly stopping the two year long Prolia treatment phase.

What causes this sudden increase in osteoclasts when you stop Prolia and do not have a follow-on treatment? We will discuss this in the next section.

Discontinuation of Denosumab: Sudden Increase in Osteoclasts

Several leading clinicians and researchers hypothesize (4) why osteoclasts rapidly increase with a sudden discontinuation of Prolia. One theory, in particular, is seen as the possible explanation.

A 2021 groundbreaking study (5) by Dr. Michelle McDonald, published in the journal Cell, revealed that osteoclasts don’t just disappear during Prolia treatment. Instead, they break into smaller pieces called osteomorphs and hide. Once a patient stops Prolia, these pieces reassemble quickly, increasing both bone resorption and fracture risk. Notably, rebound fractures occur more frequently in the spine than in the hip area.

What To Do Before You Start Prolia

There are several issues to consider before beginning Prolia. The following are some guidelines to help you decide whether to move forward with Prolia or not. Before you start Prolia:

Book an appointment with your dentist/oral surgeon and let them know that you will soon be on Denusomab. Tell them it is a drug that you cannot get off of for several years and that the drug interferes with healing from dental extractions or implants. Do not assume they know about the complications.
Complete any major dental work, such as implants.
Discuss and evaluate alternative osteoporosis medications with your physician.
Establish a baseline bone mineral density (BMD) and a serum CTX to measure osteoclast levels.

In addition, ask your physician:

Why do they recommend intervention with Prolia, and what are their goals? Are they recommending Prolia because you have an elevated risk of fracture? Is it because they think they can get you into a lower fracture-risk zone within a reasonable time?
How long do they think you need to be on Prolia, and what are their targets so that you can stop using the medication? Is the objective to increase bone density to offset your fracture risk? If this is your case, ask them to estimate when you will achieve that target.
How to discontinue Prolia and transition you off of Denusomab if needed?

Bone Density, Bone Turnover and Discontinuation of Denosumab

Prolia is a very effective medication that increases bone density and reduces fracture risk. However, it is essential that you have a healthcare provider who knows how to discontinue Prolia since the discontinuation of Denosumab can present challenges that require attention and care. Health professionals, institutions, clinicians, and leading researchers have been investigating the best way to manage the use of Prolia.

For example, a working group of the European Calcified Tissue Society performed an updated systematic review (6) of existing literature on changes in bone turnover, bone mineral density (BMD), and fracture risk after Denosumab discontinuation. It provided advice on Prolia management based on expert opinion. Here is their guidance on starting Prolia treatment:

Taking into consideration that a longer duration of treatment also involves a risk of unplanned discontinuation, a very careful assessment of the indications to start Denosumab treatment in the first place should be performed, especially in younger patients, who may be at higher risk of fractures or bone loss following discontinuation. (6)

Exercise Recommendations for Osteoporosis

Exercise is an essential ingredient to bone health. I know you want to know how to discontinue Prolia, but if you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

Can I Stop Prolia After One Injection?

If you’ve only had one Prolia injection, you might wonder about the risks of a rebound fracture. The longer you’ve been on Prolia, the higher the rebound fracture risk upon stopping (7). Even after a single injection, you must consult your doctor about the safest action.

According to the position paper of a working group of the European Calcified Tissue Society,

Discontinuation of Denosumab following at least two Denosumab injections carries a significant risk of a rebound effect, manifesting as considerable loss of bone mass gained during the period of Denosumab treatment and an augmented risk for (multiple) VFx (vertebral compression fracture). (6)

Dr. Elena Gonzalez Rodriguez is Deputy Chief of the Clinic in the Department of Endocrinology, Diabetes, and Metabolism at the University Hospital of Vaud (CHUV). She has investigated the effects of stopping Prolia and published several studies on that topic.

I asked Dr. Gonzalez-Rodriguez if a patient could stop Prolia after one injection. She stated that if a patient discontinues Prolia treatment after a single injection, all scientific evidence suggests no risk for biological, densitometric, or clinical (vertebral fracture risk) rebound. In a recent publication, she points out that after the second denosumab dose, there is a rebound effect with an increased risk of multiple vertebral fractures. (8)

However, if your physician recommended Prolia because of elevated fracture risk and you stop using the medication, you need to consider alternative pharmaceutical intervention to offset that risk.

Prolia Dental Work

Many aging clients frequently require dental work, including dental implants, extractions, and crowns. There is an elevated risk of dental problems, including osteonecrosis of the jaw, when people are on Prolia and have dental work. The management of Prolia during dental work demands special attention and care.

Here is some guidance from the working group of the European Calcified Tissue Society position paper on Prolia and dental work:

Regarding elective dental procedures for which treatment discontinuation is demanded by the dentist, it seems prudent to perform the procedure preferably approximately five months after the last Denosumab injection and resume treatment as soon as the lesion is healed, although this is based on expert opinion only. (6)

Vertebral Fracture Risk and Prolia

There is a greater vertebral fracture risk from stopping Prolia than in a hip fracture. According to the position paper of a working group of the European Calcified Tissue Society:

Discontinuation of Denosumab following at least two Denosumab injections carries … an augmented risk for multiple vertebral fractures. (6)

Stop Denosumab Safely

Discontinuing the use of Prolia should be done thoughtfully and under the guidance of a healthcare professional. When a patient stops using Prolia, the bone resorption process, which was previously inhibited by the drug, starts again. Bone loss may occur after stopping Prolia, and it may even happen faster than if the person had never taken the drug.

Work with your primary care provider and develop a sound plan to transition off Prolia. In many cases, patients are transitioned to bisphosphonates, which are another type of osteoporosis drug that can be taken for several years. The specific bisphosphonate used may vary depending on individual circumstances and preferences. It is essential to have regular follow-up appointments and not delay or skip doses of Prolia, as rebound fractures can occur within a couple of months of discontinuation.

Ultimately, the decision to discontinue Prolia and the choice of alternative treatment should be made on an individual basis, taking into account factors such as age, overall health, bone mineral density, and the risk of fractures. It is recommended to communicate openly and ongoing with a healthcare professional to determine the best course of action.

European Calcified Tissue Society Guidance

Here is some guidance from the working group of the European Calcified Tissue Society position paper (6) on how to discontinue Prolia:

To limit this risk (rebound fractures), it is currently recommended either to continue Denosumab therapy or to prescribe a potent bisphosphonate when Denosumab is stopped.
A shorter duration of Denosumab treatment (i.e., up to 2.5 years) in patients with otherwise low fracture risk could justify treatment with an oral bisphosphonate for 1 to 2 years.
In case of previous intolerance to oral bisphosphonates, expected poor adherence, or polypharmacy, Zolendronate can be administered. Zoledronate is also known as Zoledronic acid or its trade name Zometa is a bisphosphonate that is administered by infusion. It can be given once and repeated if bone turnover is still inappropriately high.
Patients who have been treated with Denosumab for a longer period (i.e., > 2.5 years) or who are at persistently high risk for fracture should receive Zoledronate.
Pending results of ongoing randomized control trials on the optimal bisphosphonate regimen, bone turnover markers can provide clinical guidance on the timing and duration of zoledronate treatment.

Dr. Rubin's Insights

Endocrinologist, Dr. Janet Rubin provides valuable insight on how to discontinue Prolia. She emphasizes the need for personalized treatment plans. For younger patients, Dr. Rubin aims to transition them off Prolia after achieving significant bone density gains. For older patients, particularly those in their late eighties, she might continue Prolia without interruption due to its safety and effectiveness.

What to Take After Stopping Prolia

Transitioning off Prolia typically involves switching to a bisphosphonate, such as Zoledronic acid. This strategy helps maintain the gains in bone density and prevent rebound fractures. However, this approach can have challenges, including patient reluctance to take bisphosphonates or specific health conditions that preclude their use.

In a study on vertebral fractures and bone loss, after denosumab discontinuation (7) published in the journal Bone in 2021, Swiss researcher Dr. Judith Everts-Graber and colleagues made the following conclusions:

We conclude that the fracture rate after denosumab discontinuation remained low in patients with subsequent antiresorptive treatment. Multiple vertebral fractures were only observed in patients without subsequent therapy.
Zoledronate (a bisphosphonate) was associated with a lower incidence of vertebral fractures within 24 months after denosumab discontinuation.

Recent Circumstances Impacting Prolia Discontinuation

Two recent events have highlighted the importance of careful Prolia management. In Europe, some breast cancer patients who used Prolia during treatment, experienced rebound fractures upon remission and discontinuation. Similarly, during the COVID-19 pandemic, many patients missed their Prolia doses, leading to increased fracture rates and much unnecessary suffering.

Timing for Denosumab Discontinuation

The timing of the transition to bisphosphonates is critical. Rebound fractures can occur within a few months of stopping Prolia. To mitigate this risk, Dr. Rubin advises starting a bisphosphonate shortly after the last Prolia injection.

Criteria for Denosumab Discontinuation

When can you safely stop Prolia? Dr. Rubin suggests considering discontinuation once you have achieved significant bone density improvements. However, each patient’s situation is unique. Make your decisions in close consultation with your healthcare provider.

How to Discontiue Prolia: Alternative Treatments

If bisphosphonates aren’t an option after stopping Denusomab, Dr. Rubin may consider alternatives like Raloxifene (Evista) or other estrogen-like treatments. These alternatives can also help maintain bone density and reduce fracture risk.

Stopping Prolia After 5 to 10 Years

How long should you stay on Prolia if you’ve been on it for five to ten years and seen positive results? Dr. Rubin advises discussing long-term use with your doctor. The conversation should consider your overall health and fracture risk. For some patients, particularly those with specific health conditions, staying on Prolia might be necessary.

In a 2021 study (7), Swiss researcher Dr. Judith Everts-Graber and colleagues made the following conclusions:

Younger age and longer duration of Denosumab therapy were significantly associated with higher bone mineral density (BMD) loss after Denosumab discontinuation. Thus, if Denosumab is to be discontinued, special attention should be paid to early postmenopausal patients and those who have been treated with Denosumab for long periods (>3 years). These patients require more intensive monitoring and treatment than older patients with shorter treatment durations.
Also, patients with prevalent fractures should be treated and monitored more intensively because they are at particular risk for new vertebral fractures after denosumab discontinuation.

Exercise Recommendations for Osteoporosis

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

Management of Prolia Case Study

When Jane was diagnosed with osteoporosis, her physician recommended she take Prolia (Denosumab). Unfortunately, the management of her Prolia was not as good as it should have been and Jane experienced a number of problems. Here is her Prolia management story.

There are two major lessons from her experience:

You should not assume that exercises you find online labelled for “osteoporosis” or for “seniors” are safe for you to do. This applies to all social media sources, even those presented by Physical Therapists. Individuals with osteoporosis need an exercise program targeted at their fracture risk; this is particularly true for individuals with compression fractures.
If you are receiving Prolia injections, it is due to the fact that you are at an elevated risk of fracture. I have many clients who need to be on Prolia because their bone density and bone quality is so poor that a fall could lead to a catastrophic fracture. The problem is not the medication. Prolia is very effective. Problems occur when the administration of the drug is not managed as well as it should be. This is particularly true when it comes to the termination of the use of Prolia.

Here is Jane’s story.

Conclusion to How to Discontinue Prolia

The rebound effect of Denosumab on bone health has brought attention to the importance of carefully managing the discontinuation of this medication. Healthcare providers should assess an individual’s risk and work together with their patients to develop a personalized treatment plan. Regular follow-up appointments and adherence to prescribed treatments are crucial for maintaining optimal bone health and reducing the risk of fractures.

Stopping Prolia is a complex process that requires careful planning and individualized care. The insights from Dr. Janet Rubin highlight the importance of understanding how Prolia works and the risks associated with stopping it. Remember, your healthcare provider is your best resource for navigating these decisions.

Bone health is complex and highly individualized. Strengthen your relationship with your doctor to guide you through maintaining strong and healthy bones. Continue to exercise intelligently, choose foods that support healthy bones, and trust MelioGuide to help you navigate through your journey with osteopenia or osteoporosis.

References

Bone, HG, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. The Lancet. Volume 5, Issue 7. P513-523, JULY 2017
Source: Prolia website [https://www.proliahcp.com/dosing-and-administration/prolia-injection-dosing]
Bone, HG, et al., Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. Journal of Clinical Endocrinology and Metabolism. 2011 Apr;96(4):972-80. doi: 10.1210/jc.2010-1502. Epub 2011 Feb 2.
Ferrari, S., Langdahl, B. Mechanisms underlying the long-term and withdrawal effects of denosumab therapy on bone. Nat Rev Rheumatol 19, 307–317 (2023). https://doi.org/10.1038/s41584-023-00935-3
McDonald M. et al. Osteoclasts recycle via osteomorphs during RANKL stimulated bone resorption. Cell. 184, 1330–1347 March 4, 2021
E Tsourdi, M.C. Zillikens, C Meier, JJ Body, EG Rodriguez, AD Anastasilakis, B Abrahamsen, E McCloskey, LC Hofbauer, N Guanabens, B Obermayer-Pietsch, SH Ralston, R Eastell, J Pepe, A Palermo, B Langdahl. Fracture Risk and Management of Discontinuation of Denosumab Therapy: A Systematic Review and Position Statement by ECTS. The Journal of clinical endocrinology and metabolism. Vol 106. Issue 1. pp. 264-281. Published – Jan 2021
Everts-Graber. J, et al. Risk factors for vertebral fractures and bone loss after denosumab discontinuation: A real-world observational study. Bone. Volume 144, March 2021, 115830
Lamy O., Gonzalez-Rodriguez E., et al. Stopping Denosumab. Current Osteoporosis Reports. 2019 Feb;17(1):8-15. doi: 10.1007/s11914-019-00502-4.

The post How to Discontinue Prolia appeared first on MelioGuide.

EVENITY: A Physician’s Perspective

Margaret Martin — Fri, 16 Jun 2023 11:25:02 +0000

EVENITY is a medication, developed by biotechnology company Amgen. It treats post-menopausal women with osteoporosis and at a high risk of fracture. Your physician may refer to it by its product name, Romosozumab. EVENITY is its trade or marketing name.

It is one of the newest treatments available for osteoporosis. The Food and Drug Administration approved EVENITY in 2019.

For a better understanding of EVENITY, I reached out to Dr. Janet Rubin — a practicing endocrinologist, the Sarah Graham Kenan Distinguished Professor, and Vice Chair for Research at the Department of Medicine of the University of North Carolina.

Dr. Rubin kindly gave me time to speak with her and she generously shared her experience treating patients with EVENITY.

Dr. Rubin has a busy clinical practice treating patients with osteoporosis. She has been investigating bone remodelling for decades. Her particular focus has been on how exercise and mechanical force affects the cell cytoskeleton.

Conflict of Interest Disclosure

Dr. Rubin has no commercial relationship with Amgen (the manufacturer of EVENITY) or any of the other companies that make osteoporosis medications.

How EVENITY is Given (Administered)

Your physician administers EVENITY at their office. You will receive two injections each month over a one year period. The injection site is either the abdomen, thigh, or upper arm.

Dr. Rubin has not had a patient experience any problems with the double injection.

How EVENITY Works

EVENITY is a monoclonal antibody. It works by inhibiting a protein molecule called sclerostin. According to the U.S. National Library of Medicine on MedlinePlus, sclerostin “is produced in osteocytes, which are a type of bone cell. The main function of sclerostin is to stop (inhibit) bone formation. The maintenance of bone over time requires a balance between the formation of new bone tissue and the breakdown and removal (resorption) of old bone tissue. Inhibition of bone formation is necessary to ensure that bones are of the correct shape, size, and density.” (1)

Researchers found that if you block sclerostin, bone formation occurs. Scientists in the pharmaceutical industry repurposed the inhibition of this molecule in order to treat diseases of low bone density.

This finding lead to the development of Romosozumab (EVENITY) — an anti-sclerostin antibody.

Dr. Rubin points out that EVENITY has considerable potential for women with very low bone mineral density who need to move their bone density up into more target ranges. Her experience so far is that the drug “seems to work very well.”

Remember: by inhibiting sclerostin (an agent produced by your body to stop bone formation), you encourage the formation of bone — which is good.

However, EVENITY does more than stimulate bone formation by suppressing sclerostin. Dr. Rubin discusses this secondary activity in the next section.

How Long Can You be On EVENITY?

In our interview Dr. Rubin states that EVENITY is given for a one year period.

After that, it is discontinued and replaced by a different osteoporosis pharmaceutical to preserve the gains made by EVENITY. (This duration may change in the future as more studies are done on the drug.)

At that point, the bone formation has become more antiresorptive — meaning that the resorption of bone (the process by which osteoclasts break down the tissue in bones) is reduced.

In other words, inhibiting sclerostin with EVENITY also leads to decreased bone turnover or bone resorption.

At the end of the one year application of EVENITY (like all anabolic agents such as the parathyroid hormone-like drugs and this new drug), if you don’t follow EVENITY with an intervention, you will lose what you gained.

Studies have used either Prolia (Denosumab) or traditional bisphosphonates to follow EVENITY.

Exercise Recommendations for Osteoporosis

Exercise is an essential ingredient to bone health. If you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

EVENITY Side Effects

Dr. Rubin states that there is one potential adverse effect of the drug. The side effect was identified during two separate studies of Romosozumab.

One is called the ARCH study (2) and the other is called the FRAME study (3). They were slightly different in the way that they were set up.

ARCH Study: Romosozumab

The ARCH study included slightly older women than the FRAME study with potentially a little more hypertension than the FRAME participants.

Over 4,000 individuals participated in the ARCH study. The participants were evenly spilt between those receiving romosozumab for one year and those receiving a weekly oral alendronate (bisphosphonate).

The group that received the bisphosphonate had slightly less cardiovascular events than the group who were treated with Romosozumab.

Keep in mind that the difference in number of cardiovascular events between the two groups in the ARCH study is a very small amount. In addition this was a long-term study and the incidence of cardiovascular disease a regular feature of this age group.

Dr. Rubin states that there were 38 cardiovascular events in the bisphosphonate group (Dr. Rubin uses the term “arm” to describe a study group in the interview) and 50 events in the Romosozumab group.

While the difference was small, it was enough to catch the attention of the FDA and cause the manufacturer, Amgen, to place a warning on the EVENITY package label.

FRAME Study: Romosozumab

As Dr. Rubin mentioned, the participants in the FRAME study, were younger than the ARCH study. The research team reported that there were no differences in cardiovascular events.

Dr. Rubin’s Position on Romosozumab

Because of the findings of the ARCH study, Dr. Rubin is using EVENITY in people who she feels really need it because of an elevated risk of fracture.

With younger women who are worried about fractures in the future, she is waiting for more data and finding from the real world application of EVENITY.

She has put many patients on it who have had bad fractures in order to stop them from fracturing again. So far she is pleased with the results, but is not changing her approach to the standard osteoperosis patient until she sees more data.

However, because of the cardiovascular risk potential, Dr. Rubin recommends that a patient who has had a cardiovascular event within the last 12 months, should not receive this drug. That may change in the future as we learn more about the drug.

EVENITY and Bone Quality

EVENITY, because it suppresses sclerostin, stimulates the growth or formation of new, high quality bone.

As Dr. Rubin goes onto state: “If this drug really made bad quality bone, it wouldn’t prevent fractures, which in hundreds of studies these kinds of drugs prevent fractures. That’s why we use them. They are really, really good drugs.”

EVENITY, Forteo and Tymlos

Tymlos and Forteo are both different formulations of a parathyroid hormone (PTH) and bind to the parathyroid hormone receptor.

These drugs are administered daily, As a result, rather than having a sustained hyper-parathyroidism, you get these daily hits of PTH.

Like EVENITY, Forteo and Tymlos stimulate the osteoblasts to make more bone. However, EVENITY has an antiresorptive effect in the long run, whereas the PTH drugs don’t.

EVENITY and Men with Osteoporosis

I asked Dr. Rubin her thoughts on EVENITY for men with osteoporosis.

There are few male studies for EVENITY – but they all suggest similar effects. She mentioned the findings of an efficacy and safety paper published in 2018 in the Journal of Clinical Endocrinology & Metabolism (4).

This was a bridging study to extrapolate the fracture benefit observed in women with osteoporosis in FRAME to men by demonstrating that the BMD profile in the male population is comparable to that in the female population. Amgen sponsored the study.

The study included 245 subjects (163 Romosozumab, 82 placebo). At month 12 of the study, the mean percentage change from baseline in the LS (lumbar spine) and TH (total hip) BMD was significantly greater for the Romosozumab group than for the placebo group (LS, 12.1% vs 1.2%; TH, 2.5% vs 20.5%; P , 0.001).

The adverse events and serious adverse events were balanced between the two group.

However, there was a numerical imbalance in the positively adjudicated cardiovascular serious adverse events [Romosozumab, 8 (4.9%) vs placebo, 2 (2.5%)].

This was similar to the increase in cardiovascular events as in the ARCH study (described above). Dr. Rubin noted that since men have more of these cardiovascular events, she might be more hesitant about using it.

Conclusion and Summary

This article introduces the reader to EVENITY. Dr. Rubin described how EVENITY works, identified potential side effects and described the type of patient she treats with EVENITY.

If you want to learn more about osteoporosis medications, I encourage you to listen to the interview below I did with Dr. Rubin on this topic.

Margaret Martin

References

SOST gene (sclerostin). https://medlineplus.gov/genetics/gene/sost/
Study to Determine the Efficacy and Safety of Romosozumab in the Treatment of Postmenopausal Women With Osteoporosis (ARCH). https://clinicaltrials.gov/ct2/show/NCT01631214
Efficacy and Safety of Romosozumab Treatment in Postmenopausal Women With Osteoporosis (FRAME). https://clinicaltrials.gov/ct2/show/NCT01575834
Lewiecki, et al. A Phase III Randomized Placebo-Controlled Trial to Evaluate Efficacy and Safety of Romosozumab in Men With Osteoporosis, Journal of Clinical Endocrinology & Metabolism. September 2018, 103(9):3183–3193.

The post EVENITY: A Physician’s Perspective appeared first on MelioGuide.

Osteonecrosis of the Jaw and Osteoporosis Drugs

Margaret Martin — Thu, 16 Sep 2021 18:41:08 +0000

Osteonecrosis of the jaw (or ONJ) is a potential side effect of dental surgery while taking osteoporosis medications such as bisphosphonates or denusomab (Prolia).

The objective of this blog post is to give you the information you need about osteonecrosis of the jaw and osteoporosis medications so that you can have an informed discussion with your physician and dentist.

In order to understand the causes, symptoms, and how you can protect yourself against osteonecrosis of the jaw, I approached one of the best oral surgeons in Ottawa, Dr. Hassan Moghadam.

Dr. Hassan Moghadam

Dr. Hassan Moghadam is an oral maxillofacial surgeon. He graduated from McGill University in Montreal and the University of Toronto.

While doing his studies, Dr. Moghadam conducted research on bone regeneration. In addition to his formal training in oral surgery, Dr. Moghdam has a Master’s degree in bone engineering. He spent a lot of time growing bone, understanding how stem cells create bone, and how the body works with bone.

His day practice is dedicated to regenerating bone for dental implants.

Osteonecrosis of the Jaw and Osteoporosis: Key Points

This post (and the video interview) covers a lot of ground. I encourage everyone to read the article and listen to the interview with Dr. Moghadam in their entirety.

However, I recognize that some readers are pressed for time. For those readers, here is a summary of the key points made by Dr. Moghadam.

Osteonecrosis of the jaw (ONJ) means that a region of the jaw bone is dead.
ONJ is not caused by osteoporosis medicine. The ONJ can be brought on after the surgeon has done surgery and the jaw bone has difficulty healing because osteoporosis medications slow the removal of old bone and affect the bone remodelling process.
Get a clean bill of dental health before starting an osteoporosis medication.
Assuming you are on a bisphosphonate or Prolia, the risk of developing ONJ after surgery is very low.
Your risk of developing ONJ when you are on Prolia or a bisphosphonate increases when you have co-morbidities such as diabetes, or you are on an oral steroid (such as Prednisone).
Do not assume that your dentist understands osteoporosis and the subtleties of osteoporosis medications or that your physician understands the implications of dental surgery procedures.
Biomarkers cannot determine the risk of developing ONJ.
Standard dental procedures such as teeth cleaning, fillings, etc are safe to do when you are on a bisphosphonate or Prolia.
If you are on Prolia and are otherwise in good health, you can have a dental surgery provided the surgeon does what is called an atraumatic surgery, where they are extra cautious about traumatizing or heating the bone.
If you are on Prolia but have the co-morbidities listed in point 5 above, you may need to pause Prolia while you get the dental surgery. Your surgeon will need to co-ordinate the treatment protocol with the your physician. In another article I wrote (this time on Prolia), Dr. Rick Adachi suggested delaying the dental surgery until the last month of your Prolia treatment cycle. This may give your dental surgeon enough time to perform the procedure and allow the wound to heal.

Osteonecrosis of the Jaw: Definition and Causes

The American Association of Endodontists, defines osteonecrosis of the jaw (or ONJ) as “a progressive bone destruction in the maxillofacial region”. (1) According to Dr. Moghadam, osteonecrosis of the jaw refers to the death of the bone in jaw region.

There are several ways you can develop osteonecrosis of the jaw. You can get osteonecrosis of the jaw from radiation. This is called radiation-induced osteonecrosis of the jaw.

Another cause of osteonecrosis of the jaw is bacterial infection.

Lastly, you can develop osteonecrosis of the jaw from a dental surgical procedure (i.e., a tooth extraction or a cut of the jaw bone) while on osteoporosis medications. We discuss this in detail below.

Bisphosphonate (or Denusomab) Induced Osteonecrosis of the Jaw

Bisphosphonate related osteonecrosis of the jaw (BRON jaw) was first identified in 2004. During 2005, several research journals published cases of patients who developed osteonecrosis of the jaw while being treated with Alendronate (Fosamax) and other early bisphosphonates for osteoporosis. (2)

In my interview, Dr. Moghdam explained how bisphosphonates affect the bone remodelling process which, in turn, can cause osteonecrosis of the jaw.

Bone Remodelling in the Jaw

During the bone remodelling process, osteoclasts eat holes through the bone (to remove old bone). After that, osteoblasts lay down new bone to replace the old bone. This continuous regeneration process is called bone remodelling.

The family of osteoporosis drugs, including denusomab (Prolia) and bisphosphonate, inhibit osteoclast activity. That is, they stop the removal of old bone. As a result, there are no more holes being made that need to be filled.

This is not a problem if everything stays static and no surgical intervention is required to address dental problems that may arise.

However, imagine you need dental surgery and the oral surgeon has to cut your jaw bone. If a bisphosphonate is active, then the bone remodelling process is hampered and bone repair is impeded.

[The video below is an interview I did with endocrinologist Dr. Janet Rubin. In it, she describes bone remodelling.]

Osteoporosis in the Jaw Bone

Dr. Moghadam explained that he has had patients who have osteoporosis and are concerned that their jaws are weaker (because of the osteoporosis). They believe that they are at risk of a fracture in the jaw if they have a dental surgery, such as dental implants.

Dr. Moghadam stated that this is absolutely not true. The last place your osteoporosis is going to affect is your jaw. This is because your jaw is constantly in motion and your teeth are continually stimulating the bone.

However, if you take all your teeth out, the bone in the jaw bone shrinks significantly because the bone is not being stimulated.

If you have bridges and partial dentures, the jaw bone shrinks. When you take a tooth out, anything under a bridge or under a partial denture will shrink with time. In fact, the bone density is less in an area where there’s no tooth.

A dental implant, on the other hand, is different. When an implant is put in place, the implant provides stimulus to the bone in much the same manner as the original tooth.

Risk of Osteonecrosis of the Jaw

The risk of osteonecrosis of the jaw is elevated when the oral surgeon performs a procedure.

Dr. Moghdam stated in our interview: “Patients come to me and say that they are at risk of osteonecrosis of the jaw because they are on Prolia [or a bisphosphonate]. In my opinion, you’re more at risk if I go and do a procedure on you and I take a tooth out or I cut into your jaw bone.”

For comparison purposes, the risk of spontaneous osteonecrosis of the jaw (that is, a healthy person not taking osteoporosis medications) is very low. Dr. Moghdam estimates the risk at one in 10,000 (or 0.01%).

He estimates the risk of a person developing osteonecrosis of the jaw when someone takes a bisphosphonate and has dental surgery procedure as one in a thousand, or 0.1%. The risk is quite low.

However, the risk of developing osteonecrosis of the jaw increases under the following conditions.

Three Years on a Bisphosphonate or Prolia

During the first three years on a bisphosphonate or Prolia, your risk of having bone necrosis as a result of a surgeon doing a procedure, either a surgery or an extraction, is small. After you have been on the pharmaceutical for three years, the risk increases and it stays elevated.

Diabetes and Steroid Use

People who are diabetic and individuals who use an oral steroid such as Prednisone have an elevated risk. The risk does not apply to nasal spray steroids.

Cancer Treatment

The drug, Zometa (Zoledronic acid), is used as a support medication to treat symptoms of cancer such as hypercalcemia (high blood calcium levels) or to decrease complications (such as fractures or pain) produced by bone metastasis (spread of cancer to the bone). (3)

Zometa is far more potent than the bisphosphonates used in osteoporosis. If the patient is being treated with Zometa, you cannot do any oral surgery procedure unless they stop the drug, according to Dr. Moghadam.

There is almost a 90% chance of having significant necrosis of the jaw if oral surgery is performed while you’re on zoledronic acid IV for cancer.

You have to go off of Zometa for three months before you can have the oral surgery. Even then, there’s still a high risk of necrosis.

After that drug holiday, the surgery can be performed and sometime is needed for the wound to heal. Unfortunately, the metastatic disease is allowed to spread for three months.

Dr. Moghadam recommends that these patients receive a proper dental exam before the application of the Zometa treatment in order to avoid future dental problems.

Oral and IV Bisphosphonates and Osteonecrosis of the Jaw

I asked Dr. Moghadam if he has seen any difference related to osteonecrosis of the jaw between oral bisphosphonates and IV bisphosphonate.

He has found that the IV bisphosphonate is more potent than the oral form of the drug.

Causes of Osteonecrosis of the Jaw

In our interview, Dr. Moghadam stated that we do not know the true cause of osteonecrosis. He told the story of early watchmakers in England painting phosphate onto the dials of the watches only to develop osteonecrosis in their finger tips (they would fall off).

As a result, some scientists believe that phosphate potentially causes the issue for osteonecrosis of the jaw. However, this has not been confirmed.

Exercise Recommendations for Osteoporosis

Exercise is an essential ingredient to bone health. If you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

Denusomab (Prolia) and Osteonecrosis of the Jaw

Dr. Moghdam stated that Prolia (also known as denosumab) can lead to osteonecrosis of the jaw. He pointed out that when Prolia first came out, he and his colleagues we told by the manufacturer, Amgen, that Prolia (a monoclonal antibody and different from a bisphosphonate) will not cause osteonecrosis of the jaw.

The reality is that Dr. Moghadam said that he is seeing more patients from Prolia than patients treated with bisphosphonates for osteoporosis.

However, the risk of developing osteonecrosis of the jaw using either Prolia or a bisphosphonate is still quite low.

Dr. Moghadam states: “If you come to me and you’re on one of those drugs and you are [otherwise] healthy, you don’t smoke, you’re not a diabetic, you don’t drink alcohol, and you are physically active, the chance of developing osteonecrosis of the jaw is extremely rare.”

On the other hand, if you have been on an osteoporosis medication for over three years, you are diabetic and you have been taking an oral steroid, the risk of developing osteonecrosis of the jaw is elevated.

Dental Surgery While on Prolia

If Dr. Moghadam has a patient who requires an extraction, is a diabetic, on Prednisone and Prolia, he will likely ask the physician to pause the Prolia injection for a three month period. This will allow him to perform the surgery and give the wound adequate time to heal.

However, if you are a normal healthy patient who needs an extraction and you’re on Prolia, a drug holiday is not required. He would go ahead and do the surgery.

Regardless of your situation, he suggests an atraumatic dental surgery. This means that your surgeon will take extra precautions during surgery, be careful, minimize exposure of the bone, and limit the drilling and heating of the bone.

An atraumatic surgical procedure is less traumatic and inflammatory to the bone, and less likely to cause osteonecrosis of the jaw.

Biomarkers and Osteonecrosis of the Jaw

Several years ago, Dr. Robert Marx, a dental surgeon in Florida, used the C-terminal telopeptide (CTX) test to detect osteonecrosis of the jaw. (4)

Researchers were able to find a correlation but no one’s been able to properly prove in double blind controlled trials that the biomarker is an indication for people who are going to have problems. As a result, Dr. Moghadam does not use biomarkers to diagnose or determine the risk of developing osteonecrosis of the jaw.

Drug Holidays and Osteonecrosis of the Jaw

Dr. Moghadam used to require a drug holiday (from the bisphosphonate) before a procedure. He would ask that you to pause the drug for three months if you were on the bisphosphonate for greater than three years and you’re a diabetic or you’re on prednisone.

After the three month holiday, they would do your surgery, let it heal, and then have the patient go back on the medication.

However, research has not shown a statistical difference and Dr. Moghadam has stopped following this protocol. One reason is that the bisphosphonate can bind to the bone for as long as 10 years. As a result, a drug holiday is not going to affect the outcome of the surgery.

Osteonecrosis of the Jaw Symptoms

Initially there’s no pain or symptoms if you have osteonecrosis of the jaw. Medical professionals don’t see much clinically when osteonecrosis of the jaw is in its early stages.

The first sign is either exposed bone or an ulcer. The patient might say that they have a sharp piece of bone that they rub their tongue against.

They often do not experience pain. Eventually the ulcer grows bigger and bigger, and it starts taking over more space. An x-ray will show the necrosis or dead bone.

As it spreads and the bigger it is, the harder it is to treat.

Osteonecrosis of the jaw usually occurs in areas where there’s no teeth.

If you get a dental infection and you’re on Prolia, then your bone isn’t re-vascularizing and cleaning itself. That could spread into and becomes an osteomyelitis — a bone infection that can have significant implications.

Bacteria and Osteonecrosis of the Jaw

Osteonecrosis of the jaw starts off with an ulcer and exposed bone, and then the bone gets seeded with bacteria. There are theories that osteonecrosis of the jaw is bacterially related.

Researchers found out that if you culture these areas they have actinomycosis — a type of bacteria. Clinicians thought that six to eight weeks of penicillin was one of the best treatments for it.

Dr. Moghadam uses amoxicillin and clavulanic acid or penicillin-based antibiotic rather than a clindamycin because it has clinical gut issues.

Areas of the Mouth at Risk of Osteonecrosis of the Jaw

Certain areas of the mouth are more prone to developing osteonecrosis of the jaw. The back of the jaw is where it’s most likely to occur because of the anatomy and the blood supply. The blood supply is less in the lower jaw.

It’s very rare in the upper jaw because the blood supply is completely different. High blood supply in the upper jaw, very small blood supply to the lower jaw.

Upper job procedures almost never have an issue. The lower jaw is a riskier location and specifically, the posterior mandible is the highest risk region in the mouth.

Can You Eat and Drink When You Have Osteonecrosis of the Jaw?

Osteonecrosis of the jaw starts off with an ulcer and, perhaps, a little bit of discomfort. Then if it continues to spread and the patient isn’t treated, this becomes so extensive that it involves a large area.

It will spread into the muscle and they get trismus. This means that the patient can’t open their mouth and can’t eat normally.

The patient can have severe pain and it can become very debilitating. Over time, the infection continues to spread and destroys the bone.

How to Prevent Osteonecrosis of the Jaw

If a patient is able to see a dentist every six months, the dentist picks up on the presence of osteonecrosis of the jaw very early. The dentist will send the patient to an oral surgeon, and they treat it.

However, if we have a patient is not able to see a dentist and the osteonecrosis of the jaw spreads, the patient can end up in the hospital. If an infection develops and it’s not treated, then it will lead to a massive procedure.

When caught early, osteonecrosis of the jaw is very treatable. Caught late, it is very difficult to treat.

Forteo and Osteonecrosis of the Jaw

Dr. Moghadam has never seen an osteonecrosis of the jaw with someone treated with Forteo.

Screening for Osteonecrosis of the Jaw

Dr. Moghadam thinks every physician should encourage their patient to go to their dentist for a screening before starting the osteoporosis medication.

For example, let’s say that during an examination your dentist sees a tooth that’s questionable. There might be an abscess that only shows on x-ray but, otherwise, there are no symptoms. You are either going to have a root canal or pull the tooth out.

If you go on a bisphosphonate or Prolia and the abscess becomes problematic, it’s way harder to heal and to fix.

The best thing for anybody who’s going to go on these drugs is to get a thorough dental screening. Tell your dentist that you are going on an osteoporosis medication and they will look at things differently.

Your dentist can see if there is something that’s going to blow up in the next six months to a year. They can tell if there’s a big, deep cavity that might end up in a root canal and might develop an abscess.

Once you get that cleaned up and you’ve had your root canals, your dental health is stable.

Gum disease, on the other hand, is an ongoing, progressive issue. It’s not an acute concern. That is something you can deal with as it surfaces.

Once your dentist clears you and takes care of any of the acute things, then you’re able to go ahead with the osteoporosis medication treatment.

Dental Procedures While on a Bisphosphonate or Prolia

I asked Dr. Moghadam what dental procedures can safely be performed by your dentist while you are on a bisphosphonate or Prolia. He stated that the following procedures are safe but that you should let your dentist know your medication usage and history before any dental intervention or treatment.

Any dental procedure that doesn’t involve surgery.
Fillings.
Cleanings.
Root canal.
Veneers.
Bleaching your teeth.
Crowns.

Avoid any procedure that involves a gum flap, lifting the gums off of the bone, or trauma to the bone by doing an extraction.

Advice and Recommendations

I asked Dr. Moghadam for any final advice for the readers.

“If you’re going to go on one of those drugs, make sure you get the clearance from your dentist. Get a clean bill of health. Have them look at everything and make sure there are no ticking time bombs in that region.”

The factors that change the risk profile for osteonecrosis of the jaw, above and beyond using a bisphosphonate or Prolia, also need to be considered. The risk factors are:

Are you a diabetic?
Do you use steroids?
Is your bisphosphonate an oral or infusion?Are you being treated for cancer with Zometa

Exercise Recommendations for Osteoporosis

Exercise is an essential ingredient to bone health. If you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

Summary and Conclusion

This post covers the relationship between osteonecrosis of the jaw and osteoporosis medications, such as Prolia, bisphosphonates and Forteo.

Dr. Moghadam provided an excellent overview of osteonecrosis of the jaw for people using osteoporosis medications. He covered the risk factors, how to manage the issues, and provided sound advice on how to avoid the development of osteonecrosis of the jaw.

The presence of the following potentially increase the risk of osteonecrosis of the jaw after dental surgery:

Three years of usage of an osteoporosis medication such as a bisphosphonate.
Use of an oral steroid.
Presence of diabetes.
Alcohol use.
Poor overall health.

You can decrease the risk of osteonecrosis of the jaw by:

Regular dental checkups.
Receiving a clean bill of oral health from your dentist before starting an osteoporosis medication.

Dental surgery is safe if you are on an osteoporosis medication and in, otherwise, good health. There is no need for a drug holiday. However, the surgeon should be careful and perform an atraumatic surgery.

If you are on an osteoporosis medication (specifically Prolia) and also have the additional risks (listed above), then your dental surgeon may ask your physician to implement a drug holiday to allow time for the dental surgery and the healing of the wound.

About Dr. Hassan Moghadam

Dr. Moghadam joined Argyle Associates in 2002 and is the Chief of Dentistry/Oral and Maxillofacial Surgery at the Montfort Hospital. He holds degrees in Dentistry, OMFS, and a Masters degree in Science in Bone Engineering. Dr. Moghadam published the first-ever stem cell regeneration in human jaw bone using BMP and is internationally recognized for his special interest in dental implants and bone reiteration.

He is currently on faculty at McGill, lectures at the University of Ottawa, and is an active staff surgeon at The Ottawa Hospital, The Montfort Hospital, and University of Ottawa’s Faculty of Medicine.

References

American Association of Endodontists. https://www.aae.org/specialty/communique/guidelines-for-medication-related-osteonecrosis-jaw-an-update/
Sarathy, A et al. Bisphosphonate-Associated Osteonecrosis of the Jaws and Endodontic Treatment: Two Case Reports. Jiournal of Endodontics. P759-763, OCTOBER 01, 2005.
chemocare.com website: https://chemocare.com/chemotherapy/drug-info/zometa.aspx
Marx, Robert et al. Oral bisphosphonate-induced osteonecrosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. Journal of Oral Maxillofacial Surgery. 2007 Dec;65(12):2397-410. doi: 10.1016/j.joms.2007.08.003.

The post Osteonecrosis of the Jaw and Osteoporosis Drugs appeared first on MelioGuide.

How Long Can You Take Prolia Injections

Margaret Martin — Wed, 18 Jan 2017 01:07:05 +0000

How long can you take Prolia injections and are there any risks of discontinuing Prolia? What are the Prolia side effects and how long do Prolia side effects last? Can you stop taking Prolia? These are some of the questions individuals struggle with when a physician recommends Prolia.

Many of the patients at my physiotherapy clinic are either taking Prolia injections or considering Prolia to treat their osteoporosis. While the decision to use Prolia is best left to the physician and patient, many of my patients leave their physician’s office with unanswered questions. I wrote this article to address these questions.

[Disclosures: I have no affiliation or relationship (commercial or otherwise) with Amgen — the manufacturer of Prolia. I receive no direct financial or other compensation for this article.]

Prolia Questions

The most common questions that I hear from patients and readers of this blog are:

How does Prolia work?
How long can you take Prolia?
How to discontinue Prolia?
What are the side effects (and potential dangers) of taking Prolia?
How long do Prolia side effects last?
Can Prolia side effects be reversed?
How long does Prolia stay in the body or system?

In order to answer these questions thoroughly, I consulted a number of leading experts on Prolia, delved into the latest independent scientific material on Prolia, and conducted a detailed review of Amgen’s (the manufacturer of Prolia) website. The article reflects the latest publicly available information on Prolia.

Objective of This Article

The objective of this article is to provide you with the information you need to have an intelligent and informed discussion with your physician regarding Prolia as a pharmaceutical treatment for osteoporosis.

After reading this article, you will be in a better position to speak to your physician and decide whether Prolia is right for you or whether you should discontinue Prolia shots.

I have tried to provide a fair assessment of the efficacy of Prolia based on available clinical experience and scientific evidence. I discussed many of the questions associated with Prolia directly with three established experts in the field. These experts are from a wide range of backgrounds including two physicians with direct clinical experience (Dr. Adachi and Dr. Gonzalez-Rodriguez), a recognized researcher (Dr. Gonzalez-Rodriguez), and a clinical pharmacist with over 40 years of experience treating women and men with osteoporosis (Kent MacLeod).

If you are starting Prolia treatment or planning to discontinue Prolia, you should go through this article carefully and consult with your physician.

Before We Start Discussing Prolia

Prolia can be a controversial topic to discuss so I want to make a few points before we start.

First, I am a Physical Therapist who treats patients with osteoporosis, osteopenia and low bone density. Invariably, many of these patients are taking an osteoporosis pharmaceutical, with many of these taking Prolia shots.

Although I do not prescribe medication, I feel it is important that I understand the implications of pharmaceutical intervention when treating my patients.

Second, the article is designed to equip you, the reader, with the information you need to discuss the right pharmaceutical route for you, especially as it pertains to Prolia.

I do not offer advice as to whether you should start, stop, restart or replace Prolia. That is something you have to discuss with your physician. After reading this article, you can have an informed conversation with your physician and arrive at a well-considered and thoughtful decision, one that is right for you.

Third, I have no affiliation or relationship (commercial or otherwise) with Amgen — the manufacturer of Prolia. I receive no direct financial or other compensation for this article. The article was prepared for you so that you can make a good decision about your health.

Sources for Information on Prolia

While preparing this article, I consulted a number of experts with significant clinical and research experience using Prolia.

Dr. Jonathan Adachi

To gain an understanding on the clinical use of Prolia, I consulted Dr. Jonathan Adachi. Dr. Adachi manages a rheumatology practice at St. Joseph’s Healthcare in Hamilton, serves as Actavis Chair for Better Bone Health in Rheumatology, and teaches at the Department of Medicine at McMaster University.

Dr. Adachi is currently involved in the CIHR funded Canadian Multicentre Osteoporosis Study. He is a past president and member of the Scientific Advisory Council of Osteoporosis Canada, was a member of the Council of Scientific Advisors of the International Osteoporosis Foundation (IOF), and was a member of the IOF Board of Directors.

In addition to contributing to this article, Dr. Adachi kindly reviewed the post in its entirety and suggested changes and fixed errors.

Dr. Elena Gonzalez-Rodriguez

To gain a better understanding of the implications of discontinuing Prolia, I consulted Dr. Elena Gonzalez-Rodriguez. Dr. Gonzalez-Rodriguez is a physician and a clinical expert in the area of osteoporosis with the Centre Hospitalier Universitaire Vaudois (CHUV) in Lausanne, Switzerland. She is the author of a recent study on Prolia discontinuance.

Dr. Gonzalez-Rodriguez has published numerous papers on the discontinuation of Prolia, many of them cited in this article.

Kent MacLeod, Clinical Pharmacist

Clinical Pharmacist Kent MacLeod provided a detailed explanation of how Prolia works. Kent is the CEO and founder of NutriChem Compounding Pharmacy and Clinic in Ottawa.

In addition to the interviews mentioned above, I reviewed a number of recent research articles on Prolia. Later in the article, I provide a list of research articles I used.

Finally, I performed a careful read of the Prolia literature on Amgen’s website. That material is referenced in the article.

Key Takeaways on Prolia

Here is an executive summary of the key points made in this Prolia article.

Consult with your physician when and if you should take Prolia injections. Have a conversation with your physician about Prolia. You can use the talking points listed the section below entitled, Prolia and Your Doctor.
A key question patients struggle with is how long can you take Prolia? If you start Prolia injections, you should plan on being on the treatment for life. Discontinuing Prolia usage (without going onto another pharmaceutical to maintain the gains you made) could have serious, irreversible side effects. These side effects include multiple vertebral compression fractures and a lowering of your bone mineral density.
You should work with your physician on an exit plan if you decide to stop using Prolia. Keep in mind that the medical community is still working on the most appropriate and safe way to discontinue Prolia. I discuss these in detail in this article.
If you are at a high risk of osteoporosis fracture and your physician advises Prolia injections, you should consider following her or his advice.
Prolia need not be the treatment of choice if your diagnosis places you in a low or moderate fracture risk category. The right combination of exercise and good nutrition can help you to stay (or move you into) the low risk fracture risk category. With the support of your physician, you should try to delay Prolia injections.
Prolia injection side effects can happen. However, both Dr. Adachi and Amgen state that serious side effects are rare. Dr. Adachi’s experience is that most side effects last a short time (less than 3 months), and many Prolia side effects can be treated and reversed.

Prolia and Your Doctor

Review this article in its entirety before you meet with your physician to discuss Prolia. You should explore the following topics when you meet with your doctor:

Make sure that your physician is confident that Prolia is the right treatment for you — at this time in your life. Do you have the right fracture risk profile? Are there other options you can pursue that allow you to delay the time you start Prolia?
If you experience serious side effects, what is the plan to discontinue Prolia shots and transition to another pharmaceutical treatment?
Can your physician refer you to a Physical Therapist who can construct an osteoporosis exercise program for you that reduces your risk of a fall and chance of a fracture?
Ask your physician to refer you to a Nutritionist who can review your diet to determine you are getting adequate bone building nutrients?
I encourage you to speak with your dentist about any possible dental work that needs to be done before you start on Prolia or a bisphosphonate therapy.

Sudden Stop of Prolia Shot

In the video, above, I discuss a recent study out of Switzerland that indicates that a sudden stop in the usage of Prolia (often because your Physician sees that the medication has been very effective) could lead to incidence of compression fracture. This development could have an impact on how long can you take Prolia.

Later in this article is a detailed update on a new systematic review by the European Calcified Tissue Society (ETCS) on the possible outcomes of discontinuing a Prolia injection treatment program. I also discuss recent developments on potential ways to discontinue Prolia without increasing fracture risk.

Exercise Recommendations for Osteoporosis

Exercise is an essential ingredient to bone health. If you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

How Does Prolia Works

In this section, I define Prolia, explain how it works, discuss how Prolia builds bone, identify Prolia dosage levels, and compare Prolia to another osteoporosis medication, bisphosphonates.

What is Prolia and How Does Prolia Work?

Kent McLeod, pharmacist and owner of NutriChem Pharmacy, defines Prolia as an immunoglobulin monoclonal antibody — a glycoprotein that interferes with the protein RANK ligand (RANKL) and prevents the formation, maturation and survival rates of osteoclasts. RANKL is the molecule blocked by denosumab. (1)

Prolia influences the bone remodelling process by binding to these cells that become osteoclasts. This binding effect leads to the death of the osteoclasts and thus stops bone breakdown.

Osteoclast numbers are greatly reduced and there is virtually no resorption for several months after a Prolia injection.

Dr. Adachi summarized how Prolia works by explaining that:

“Prolia affects bone by inhibiting osteoclast precursor cell maturation and osteoclast function.”

Prolia attaches to lymphocytes but does not affect their function. An intact lymphocyte function is an important part of our immune function.

Does Prolia Build Bone?

A number of a research studies demonstrate that Prolia does build bone. In fact, it is more effective at building bone compared to bisphosphonates (I discuss this in more detail later in the post).

In some individuals, Prolia injections have been shown to increase bone mineral density (BMD) by 20%. A 20% increase in bone density is significant. This means that if you had severe osteoporosis with a T score of -3.5 and were treated with Prolia, you might see your T score improve to -1.5.

[Read our FRAX Calculator and Score Interpretation article to learn more about T score.]

Dr. Jonathan Adachi — a leading osteoporosis physician at St. Joseph’s Healthcare in Hamilton, Ontario — points at research that shows a 70% reduction in spine fractures and a 40% reduction in hip fractures after three years of Prolia usage.

A study published in 2017 (2) by a team of Japanese researchers looked at the effect of denosumab (Prolia) on bone mineral density and bone turnover markers in Japanese postmenopausal women with osteoporosis.

(Denosumab is the medical term for the human monoclonal antibody medication, while Prolia is the name trademarked by Amgen. They are one and the same thing and I use them interchangeably in this article.)

The team examined the efficacy of three doses of Prolia over a 12 month period compared to a placebo. They reported that “denosumab (Prolia in 14, 60, and 100 mg doses) showed significant increases in percent BMD (bone mineral density) values of lumbar spine and total hip from baseline in 12 months. Distal 1/3 radius BMD (bone mineral density) was also significantly increased except at the 100-mg dose.”

They concluded that “Denosumab (Prolia) [in 60 mg doses] could be an effective dose for Japanese postmenopausal women with osteoporosis, as was shown in the Caucasian population.”

Prolia, Bone Density and Bone Quality

Prolia treatment increases bone density but there is no evidence that it influences bone quality. (I encourage you to read my article on bone quality to learn about that important bone health topic.)

Bone quality is influenced by a number of factors such as appropriate exercise and hormonal balance. Hormones are the only prescription medication that have a positive influence on bone quality. (3)

Should You Take Prolia for Osteoporosis Treatment?

Asked how he decides who should be prescribed Prolia, Dr. Adachi stated that Prolia should be instituted if the patient is at high risk for fracture.

In his opinion, it is the best available medication for the treatment of osteoporosis. In fact, there is data going out ten years showing that ongoing Prolia treatment leads to sustained benefit for the patient.

He also mentioned that there are patients who are so afraid of Prolia side effects that they refuse to take Prolia or other medications. The unfortunate result is that some patients go on to experience a fracture.

In other words, sometimes the side effects of not taking Prolia exceed the side effects of taking Prolia.

Prolia Injection and Recommended Dosage

The Endocrine Society, the world’s largest and most established organization of endocrine clinicians and scientists, recommends a dosage of 60 mg of Prolia every 6 months.

The medication is administered via subcutaneous injection. The injection locations include the upper arm, upper thigh and the abdomen.

Endocrine Society 2019 Recommendations on Prolia Usage

In March of 2019, the Endocrine Society released clinical recommendations on the use of Prolia. The report, entitled Pharmacologic Management of Osteoporosis in Postmenopausal Women, include the following recommendations:

Postmenopausal women with osteoporosis who are at high risk for osteoporotic fractures should use denosumab (Prolia) as an alternative initial treatment.
Administration of denosumab should not be delayed or stopped without subsequent antiresorptive (e.g., bisphosphonate, hormone therapy or selective estrogen receptor modulator) or other therapy administered in order to prevent a rebound in bone turnover and to decrease the risk of rapid bone mineral density loss and an increased risk of fracture.

This thinking is consistent with that of Dr. Adachi. He indicates that if Prolia is effective, there is no reason to discontinue the treatment.

If, on the other hand, there is a reason to discontinue Prolia, the termination should not be sudden and a clear alternative treatment plan should be in place.

Who is the Manufacturer of Prolia?

Amgen is the manufacturer of Prolia. It is an American biopharmaceutical company headquartered in Thousand Oaks, California.

Who Should be Prescribed Prolia?

Amgen states that Prolia is for the treatment of low bone mass in:

Women diagnosed with postmenopausal osteoporosis (and a high risk for fracture) or receiving adjuvant aromatase inhibitor therapy for breast cancer.
Men at high risk for fracture due to osteoporosis or receiving androgen deprivation therapy for nonmetastatic prostate cancer.
Men and women at high risk for fracture from Glucocorticoid-induced osteoporosis.

Is Prolia a Bisphosphonate and How Do The Two Compare?

In some ways, Prolia’s mechanism is similar in action to that of bisphosphonates.

Prolia, however, is not a bisphosphonate. It works by binding to RANKL and prevents it from binding to the RANK receptor on osteoclasts and their precursor cells. In doing so, they prevent the activation of these cells and prevent bone breakdown or osteoclastic bone resorption.

As I mentioned in the section above, Prolia is an immunoglobulin — a glycoprotein that works by binding to the cells that become osteoclasts. When they bind to these cells, this leads to the death of the osteoclasts cells and thus stops bone breakdown.

Bisphosphonates, on the other hand, reduce osteoclast activity. This, in turn, leads to a slowdown in the turnover of bone and removal of old bone.

Differences Between Bisphosphonates and Prolia

A bisphosphonate, like Prolia, is a medication for the treatment of osteoporosis (Actonel, Fosamax, etc). However, bisphosphonates differ from Prolia in four important ways.

1. Effect on Osteoclast Cells

First, Prolia and bisphosphonates differ in how they affect osteoclast cells.

Osteoclast cells are the cleaners of old bone. The newly formed osteoclast cells join mature osteoclasts to perform an important role: the breakdown of the old bone.

Bisphosphonate medications bind directly to bone at sites of active bone breakdown and are then ingested by osteoclasts. When ingested, the osteoclasts die and bone breakdown is prevented.

Prolia, on the other hand, interferes with the cells that make osteoclasts, thus limiting their production.

2. Prolia, Bisphosphonates and Increase in Bone Density

Second, a number of studies (4, 5) that compare Prolia to bisphosphonates demonstrate that Prolia leads to a greater increase in bone mineral density (BMD) and reduced bone turnover markers (BTM) .

3. Prolia, Bisphosphonates and Reduction of Hip Fracture Rate

In one study from Denmark, Prolia demonstrated similar results in hip fracture reduction rate when compared to the bisphosphonate, Alendronate. (6)

The research team also performed a cost-effectiveness analysis of the two treatments and found that the “”cost-effectiveness of denosumab (Prolia) treatment compared with alendronate is an argument for prescribing denosumab (Prolia) rather than alendronate to prevent hip fractures.”

4. Retention in the Body

Dr. Adachi points out that one major difference between Prolia and bisphosphonates is how long each is retained in the body after discontinuation. Prolia is in the body for approximately five months, whereas bisphosphonates can linger in the body for several years.

Because of Prolia’s more robust bone density changes, physicians often transition their patients from a bisphosphonate to Prolia. It is recommended that individuals take a drug holiday from a bisphosphonate after 5 to 7 years.

To learn more about bisphosphonates, please refer to my Bisphosphonates Osteoporosis Guidelines blog post.

Prolia, however, is not as strong a medication as Forteo or Evenity. Forteo and Evenity will be discussed later in the blog post.

How Long Does Prolia Stay in Your System (Body)?

In our 2020 exchange, I asked Dr. Adachi how long Prolia stays in your system. He stated that Prolia is unlike bisphosphonates that stay in bone for years. Prolia is metabolized in three to four months and within five months it is largely gone from your body.

How Long Can You Take Prolia?

In 2017, after Prolia had been available for a decade, I asked Dr. Jonathan Adachi how long a patient can take Prolia. At that time, Dr. Adachi recommended that patients that start Prolia should continue the treatment for ten years.

Now that we have more experience with Prolia, Dr. Adachi indicates that anyone currently on Prolia should plan on continuing Prolia for life. Once started, Prolia should not be discontinued.

The reason: a sudden stop in usage of Prolia (without a proper termination plan) can have significant irreversible side effects. These irreversible side effects include multiple vertebral fractures and a reduction of your bone mineral density.

Dr. Adachi was clear to point out that if you are unable to continue your Prolia treatments, your physician should have a plan to transition your Prolia injections to another pharmaceutical.

If you decide that you want to either terminate your use of Prolia or take a “drug holiday”, you should discuss your concerns with your Physician before making such a move.

Can You Discontinue Prolia?

A sudden discontinuance of Prolia can lead to serious side effects including multiple vertebral fractures and a reduction of your bone mineral density.

Clinicians and researchers have found that a sudden termination of Prolia can result in a “rebound effect” that could lead to further bone loss and increased risk of fractures. (7)

As a result, researchers are investigating how to reduce the risk of a rebound of bone loss and fracture upon discontinuation of Prolia.

Exercise Recommendations for Osteoporosis

Exercise is an essential ingredient to bone health. If you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

Prolia Discontinuance

A group of clinicians in Switzerland and a working group of clinicians and researchers from the European Calcified Tissue Society (ETCS) have explored the possible implications of discontinuing Prolia osteoporosis treatment (8).

Reasons to Discontinue Prolia

In their 2019 research publication, Lamy, Gonzalez-Rodriguez and colleagues (9) identify several clinical reasons to stop Prolia.

Women who are treated for breast cancer via adjuvant AI (aromatase inhibitors) therapy often take Prolia for bone preservation reasons. When the AI therapy terminates, Prolia is supposed to be discontinued.
Some physicians discontinue Prolia when the patient achieves the target T-Score that places them outside the osteoporosis category. This could lead to multiple vertebral compression fractures and a lowering of your bone mineral density, and should be avoided.
In some rare cases, the risk of osteonecrosis of the jaw (ONJ) and atypical femoral fractures increases with Prolia treatment. If this happens, the risk of ONJ and atypical fractures potentially exceeds the benefits of Prolia.

Potential Risks of Discontinuing Prolia Injections

The potential risks of discontinuing Prolia injections treatment include an increased risk of fracture, including compression fractures. Two recent research studies shed some light on this question.

In the first study, the researchers noticed that when people came off of Prolia (within nine to sixteen months of discontinuing Prolia), they experienced numerous compression fractures.

In the second study, the researchers noticed an increased risk of multiple vertebral fractures after discontinuation of Prolia.

I cover the two studies in detail next.

Prolia Injection Discontinuance Results • 2016

In the Spring of 2016, a research team from Switzerland presented case studies (10) from their practice at the annual Endocrinology Conference. In the case studies, seven women had been put on Prolia.

Some of the women had just received two to four Prolia injections. They were not on Prolia for very long because shortly after starting Prolia, their doctor noticed the improvement in bone density. The physician prematurely, and without realizing the consequences, discontinued the Prolia injection treatments.

The researchers noticed that when people came off of Prolia (within nine to sixteen months of discontinuing Prolia), that they fractured and experienced numerous compression fractures.

The paper indicated that the seven women, mentioned above, had 28 fractures in total between them.

When they presented an updated version of the paper a half-a-year later in the Fall of 2016, they stated that there were nine women, with on average, five-and-a-half fractures per individual.

This indicates that bone density gains experienced during Prolia treatment should not be a reason to prematurely terminate Prolia. You should discuss this with your physician if the topic of discontinuance surfaces.

Prolia Injection Discontinuance • 2018 Follow On Report

In 2018, the Swiss research team (above) reported on the cases of 35 patients (34 women and one man between the ages of 66 and 76) who received 60 mg doses of Prolia every six months. The total number of doses ranged between two to eleven total doses. (11)

All of the patients used both calcium and Vitamin D during the time they were receiving Prolia, as well as after the discontinuance of the Prolia injections.

The research team reported the following:

After Prolia discontinuation, women below the age of 65 years had a higher number of spontaneous clinical vertebral fractures (SCVF) and in a shorter period than women over 65 years.
SCVF are a very severe and frequent clinical complication after Prolia discontinuation.
Bisphosphonates may decrease the rebound effect at Prolia discontinuation.

Prolia Discontinuation and Fracture Risk

At the September 2018 American Society for Bone and Mineral research (ASBMR) conference in Montreal, I asked Dr. Elena Gonzalez-Rodriguez — a researcher and physician in the area of osteoporosis — two questions I often get from my patients:

Can you stop taking Prolia?
What happens if you stop taking Prolia?

Dr. Gonzalez-Rodriguez is the author of the study, Is Denosumab Discontinuation Associated with a Severe Increase in Fracture Risk? (12)

She identified two separate circumstances for the patient to consider:

The period after they have had only one Prolia shot.
After they have had more than one Prolia shot.

The answer is very different under each circumstance.

Can You Stop Taking Prolia if You Have Had Only One Prolia Injection?

I asked Dr. Gonzalez-Rodriguez what do you tell someone who has changed their mind after they receive their first Prolia injection? I also asked her if a patient can stop taking Prolia without undesirable consequences.

Dr. Gonzalez-Rodriguez indicated that the choice for an osteoporotic treatment has to be taken by the physician and the patient. If Prolia treatment is discontinued after a single injection, Dr. Gonzalez-Rodriguez states that all scientific evidence suggests that there is no risk for biological, densitometric or clinical (vertebral fractures risk) rebound.

In 2017, I asked Dr. Adachi the same question. Dr. Adachi stated:

“You can probably discontinue the Prolia treatment after a single dose. However, if they have started Prolia there must have been a good reason for terminating the treatment. Stopping any drug after one injection, or a couple of weeks of bisphophonate treatment, is going to leave them at risk for fracture because their osteoporosis status will not have changed.”

Can You Stop Taking Prolia if You Have Had More Than One Prolia Injection?

I asked Dr. Gonzalez-Rodriguez what she tells someone who has received two or more Prolia injections and wants to stop. Is it possible for them to stop taking Prolia without undesirable consequences?

She stated that once a patient received two or more Prolia injections, there is a risk of the rebound effect (i.e., rapid bone loss and increased risk of fracture) at the discontinuation of Prolia. As far as it is known, there is no difference between the rebound effect after two or more injections.

Dr. Gonzalez-Rodriguez stated that if Prolia is well-tolerated and the treatment indication is clear, there is no reason to stop Prolia treatment because of the existence of the rebound effect.

Like Dr. Adachi, she further stated that Prolia is a very efficacious treatment, and once initiated with two or more injections, the patient should take advantage of its benefits.

Dr. Gonzalez-Rodriguez concluded by stating that it is very important for patients that Prolia injections are strictly given every six months, and that no Prolia injection is missed.

If you decide to stop Prolia, it should always be done in a controlled manner. There should be very close follow up by the treating physician who will explain to the patient the protocol to be followed.

Can You Avoid Bone Loss and Fracture After Stopping Prolia?

A number of women have contacted me and stated that they have sustained multiple vertebral fractures after they have been removed from Prolia.

In light of reported findings from small studies, such as the one presented at the European League Against Rheumatism (EULAR), that looked at the best approach to transition someone off of Prolia, I asked Dr. Adachi what he recommends for the discontinuation of Prolia.

He emphasized that “Prolia should not be discontinued. [However] if they need to discontinue Prolia treatment, I would start a bisphosphonate around five months after the last Prolia shot or injection.”

A recent analysis (13) presented at the Annual European Congress of Rheumatology (EULAR 2019) demonstrated promising results from bisphosphonate use.

The team found that women who had received an infusion of zoledronate, an intravenous bisphosphonate, before starting Prolia and after discontinuing Prolia, had a better chance of maintaining the bone density gained during the Prolia phase of their treatment.

Bisphosphonate Infusion Therapy and Prolia

A study (14) presented at the European League Against Rheumatism conference in Madrid, Spain in June of 2019, indicated that an injection of an infusion bisphosphonate, zolendronic acid (Reclast®), before or after the Prolia treatment protocol could offset the rebound effects associated with sudden Prolia discontinuance.

The research team found that “denosumab (Prolia) withdrawal without subsequent bisphosphonate treatment seems to be related to a rebound effect: a rapid decrease in mineral density in bone densitometry (DEXA).”

The team stated in their conclusion that “denosumab (Prolia) withdrawal without subsequent antiresorptive treatment produces a rapid decrease in [bone mineral density] DEXA values in our patients. This phenomenon appears to diminish in patients who have received denosumab (Prolia) for a longer period.”

Transitioning Off of Prolia to a Bisphosphonate

In the past, Dr. Adachi mentioned that an oral bisphosphonate should be prescribed once someone is taken off of Prolia. A bisphosphonate could reduce the possibility of a fracture risk.

During my 2020 exchange with Dr. Adachi, I referenced the studies mentioned above and asked if he preferred an oral bisphosphonate (like Fosamax or Actonel ) or the injectable bisphosphonate (such as zolendronic acid).

He responded by stating that he “[uses] Actonel DR as it is covered by the Ontario government, and may be taken with food.”

(Please note that Dr. Adachi is referring to medical coverage provided by the government of Ontario and that the insurance coverage in your jurisdiction will likely differ.)

He went on further to say that “the problem with an IV bisphosphonate is that it has more side effects and is more difficult to set up.”

Zolendronic and Prolia

In May 2020, a Danish research team published a study (15) that “investigated if treatment with zoledronate could prevent bone loss (after Prolia discontinuance) and if the timing of the zoledronate infusion influenced the outcome.”

Dr. Anne Sophie Soelling of Aarhus University Hospital in Denmark and her team ran the trial for a two year period. Sixty-one postmenopausal women and men who discontinued Prolia after six years of treatment were selected for the trial.

The participants were randomly assigned to two groups. The first group received a single injection of zoledronate six months and the second group received a single injection of zoledronate nine months after the most recent Prolia injection or “when bone turnover had increased beyond a certain threshold”.

A third observational group was used in the study for comparative purposes.

Dr. Soelling used DEXA scores and bone turnover markers to track the participants bone health. Fifty-nine of the original sixty-one participants completed the trial.

Findings: Zolendronic and Prolia

The trial found that there was significant loss of bone mineral density (BMD) reported for all groups.

The loss at the lumbar spine was 30% in the six-month cohort and 45% in the nine-month cohort. The observational group experienced a 47% decline.
Bone mineral density loss in the hip region occurred in 5% of the six-month group, 25% of the nine-month group, and 11% of the observational group. (16)

The team concluded that “treatment with zoledronate, irrespective of the timing, did not fully prevent loss of BMD in patients discontinuing denosumab (Prolia).”

Dr. Soelling stated that “we speculate that some patients would benefit from a second treatment with zoledronate three to six months later. This needs to be investigated in a clinical trial.”

The study has come under some criticism, including that the trial size was too small to make major conclusions and recommendations.

At time of publication, the research team indicated that the study trial was still ongoing.

Multiple Spontaneous Vertebral Fractures

Cases have been reported where physicians have prematurely taken their patients off Prolia only to cause multiple vertebral fractures.

When I asked Dr. Adachi what his pharmaceutical approach would be for someone who was in that situation after prematurely stopping Prolia, he indicated that he would recommend Evenity to the patient.

Prolia Side Effects

In this section, I identify the major and minor Prolia side effects. This section also includes a discussion of recently identified Prolia side effects published on Amgen’s website.

To be clear, many people find success with Prolia and experience few, if any, side effects during their course of treatment.

According to Dr. Adachi, Prolia side effects are rare and far fewer than what we see with bisphosphonates, such as alendronate or risedronate.

Dr. Adachi’s experience with Prolia side effects is the following:

Acute symptoms like rash and low blood calcium occur early within the first couple of weeks.
Long-term side effects like osteonecrosis of the jaw (ONJ) may occur at any time, but are extremely rare.
Atypical femoral fractures occur when Prolia use is greater than 5 years. He estimates that atypical femoral fractures occur within around 8 years based on clinical experience with bisphosphonates.

In the rare instance where there are Prolia side effects, the patient may experience:

A rash, itching, blistering or reddening of skin.
Hives.
Bone, joint, back or muscle pain (myalgias).
Low blood calcium levels may occur in those with chronic kidney disease or malabsorption. As a result, your physician may encourage you to increase your vitamin D and calcium intake while you are being treated with Prolia.
Osteonecrosis of the jaw (ONJ) and atypical femoral fractures may also occur — but these are rare.
Allergic reaction including low blood pressure; impaired breathing; or swelling in the face, tongue or lips.
Skin infections or inflammations.
Difficulty urinating; including pain, burning or irritation while urinating.
Frequent urge to urinate.

The Mayo Clinic provides a detailed list of Prolia side effects from common to less common.

Exercise Recommendations for Osteoporosis

Exercise is an essential ingredient to bone health. If you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

How to Reverse Prolia Side Effects

Dr. Adachi recommends a small amount of prednisone to reduce the duration of a rash or myalgias that results from Prolia shots.

Secondly, he mentioned that if your calcium levels drop, you can increase your vitamin D and calcium intake while you are being treated with Prolia.

How Long Do Prolia Side Effects Last?

According to Dr. Adachi, in the rare cases when they occur, Prolia side effects last up to three months. They do not persist for more than five months (the length of time Prolia is in your body).

In general, the vast majority of Prolia side effects are resolved within three months. Acute symptoms like rash and low blood calcium occur early within the first couple of weeks.

If you are experiencing an acute symptom that you believe to be a Prolia side effect and it persists for longer than three to six months, you should consult with your physician.

Keep in mind that the condition you are experiencing might not be related to your Prolia injection and should be attended to in a timely manner.

Does Prolia Cause Dental Problems?

Long-term side effects like osteonecrosis of the jaw may occur at any time but are extremely rare.

In 2020 I mentioned to Dr. Adachi that I know of individuals who have been asked to discontinue Prolia by their dentist (oral surgeon) to reduce osteonecrosis of the jaw. I asked Dr. Adachi how long you should wait after oral surgery before your next Prolia shot.

To avoid any complications, Dr. Adachi stated that he “typically has the patient do the dental surgery five months after a Prolia shot and then delay the next Prolia injection until the tissue heals. [This often takes] around four to six weeks; at which time I would [continue] the Prolia shots again.”

Prolia’s Effect on the Immune System

I asked Dr. Adachi if he had concerns about Prolia relative to the impact on the immune system.

He stated that there were some initial concerns Prolia could affect the immune system. At that time there were some skin infections that occurred in the Prolia treated group and not in the placebo group.

Time has passed and there is longer term data on Prolia treatment. The ten year data suggest that there is not a long term risk for infection or malignancy.

Further, there does not appear to be an increase in infection risk in the breast cancer population treated with very high doses of Prolia.

In patients with rheumatoid arthritis who are on immunosuppressive therapy and Prolia, clinicians have not reported significant increases in infection.

Prolia and COVID-19

A joint guidance statement issued in May of 2020 by the American Society for Bone and Mineral Research (ASBMR), the American Association of Clinical Endocrinologists, the Endocrine Society, the European Calcified Tissue Society, and the National Osteoporosis Foundation stated that:

“there is no evidence that any osteoporosis therapy (including Prolia) increases the risk or severity of COVID-19 infection or alters the disease course.” (17)

Amgen’s Prolia Side Effects Warnings and Precautions

In March of 2020, Amgen updated its documentation on Prolia side effects. (18) The company identified ten warnings and precautions in its prescription information sheet. Below I highlight five of the ten that I think are most applicable to the reader.

Multiple Vertebral Fractures

Amgen states in its prescription information sheet that “following [the] discontinuation of Prolia treatment, fracture risk increases, including the risk of multiple vertebral fractures.”

This Prolia side effect is becoming known among the medical community. Your physician should be aware that sudden discontinuation of Prolia can be problematic.

Amgen, explains that “treatment with Prolia results in significant suppression of bone turnover and cessation of Prolia treatment results in increased bone turnover above pretreatment values 9 months after the last dose of Prolia. Bone turnover then returns to pretreatment values 24 months after the last dose of Prolia.”

Further, it states that “new vertebral fractures occurred as early as 7 months (on average 19 months) after the last dose of Prolia. Prior vertebral fracture was a predictor of multiple vertebral fractures after Prolia discontinuation.”

It advises physicians to “evaluate an individual’s benefit-risk before initiating treatment with Prolia.” In other words, you should expect that your doctor will work with you to fully evaluate whether you are a candidate for this treatment.

Finally, Amgen advises physicians that “if Prolia treatment is discontinued, patients should be transitioned to an alternative antiresorptive therapy.”

Bone Remodelling Suppression

Amgen states that clinical trials of postmenopausal women with osteoporosis who were treated with Prolia “resulted in significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry.”

They indicate that the “significance of these findings and the effect of long-term treatment with Prolia are unknown.” It is possible that bone modelling suppression could, over the long term, lead to a number of problems, including:

Osteonecrosis of the jaw (ONJ).
Atypical fractures.
Delayed fracture healing.

Atypical Fractures

Amgen states that “atypical low energy or low trauma fractures of the shaft have been reported in patients receiving Prolia. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution.”

This means that you can have a fracture from things as gentle as walking. Fractures can occur anywhere between your knee and your hip. Finally, the fracture may be straight or on an angle and there can be more than one fracture.

Amgen states that the atypical femoral fractures “most commonly occur with minimal or no trauma to the affected area. They may be bilateral, and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs.”

In other words, there can be no apparent reason for the fracture to occur. The first symptoms will be a dull, aching thigh pain that can go on for weeks or months before the bone actually fractures enough that it breaks.

The causality of these fractures has not been determined since “these fractures also occur in osteoporotic patients who have not been treated with antiresorptive agents.”

Further, Amgen indicates that a “number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture.”

Dr. Adachi observes that atypical femoral fractures occur when Prolia use is greater than 5 years. He estimates that atypical femoral fractures occur within around 8 years based on clinical experience with bisphosphonates.

If you experience dull, aching thigh pain anywhere from your knee to your hip, you need to speak to your doctor about this possible side effect. Your physician should order a test to see if you have a hairline fracture and measures should be taken to reduce the risk of it developing into a complete fracture.

Musculoskeletal Pain

The prescription information sheet states that “severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking Prolia. The time to onset of symptoms varied from one day to several months after starting Prolia.”

Amgen advises medical professionals to “consider discontinuing (Prolia) use if severe symptoms develop.”

Besides the uncomfortable sensations associated with this pain, this side effect can limit your desire to exercise and move, at a time when you need to maintain an exercise program that promotes balance, posture, strength and overall well-being.

Hypocalcemia

Hypocalcemia is a medical condition in which the patient experiences lower-than-average levels of calcium in their blood. Dr. Adachi mentioned this side effect earlier in the post.

The prescription information sheet states that “hypocalcemia may be exacerbated by the use of Prolia.”

Amgen suggests that physicians take the following steps:

Pre-existing hypocalcemia must be corrected prior to initiating therapy with Prolia.
Clinical monitoring of calcium and mineral levels (phosphorus and magnesium) is highly recommended within 14 days of Prolia injection for patients predisposed to hypocalcemia and disturbances of mineral metabolism.
Adequately supplement all patients with calcium and vitamin D.

Prolia, Forteo and Evenity

In this section, I discuss Prolia in the context of two other osteoporosis pharmaceuticals, Forteo and Evenity. I also cover the link between PPI’s and fragility fractures.

Difference Between Forteo and Prolia

Teriparatide (or Forteo) is an anabolic agent, a drug that builds bone. Denosumab (or Prolia) is an antiresorptive drug, one that prevents the breakdown of bone.

Here is a summary of the differences between Forteo and Prolia:

Patients with multiple fractures with very low bone density use Forteo.
If you have undergone radiation therapy or who have Paget’s disease, you should not use Forteo.
Prolia should be used with caution in those who have low calcium levels. These are usually seen in individuals with malabsorption or severe renal disease.
Forteo is given daily for two years and Prolia every six months via subcutaneous injection for life.
In the short term, Forteo is more expensive than Prolia.

EVENITY

In October 2019 Health Canada approved a third potent bone-building drug for the treatment of individuals who are at a high risk of fracture, Evenity.

In April of 2020, I asked Dr. Adachi how he decides when a patient should take Denosumab (Prolia) instead of Teriparatide (Forteo) or Romosozumab (EVENITY).

Dr. Adachi stated that

“Forteo is the most expensive [osteoporosis medication] and it is hard to get private insurance to cover its cost. Evenity is less expensive and has more private coverage but does not have public funding by the government (of Ontario or Canada). Prolia is covered by both private and government insurance programs. EVENITY provides the greatest increase in bone mineral density (BMD).”

To learn more about EVENITY, please read (and listen to) my interview with endocrinologist Dr. Janet Rubin.

Link Between PPI’s and Fragility Fractures

Many people are on proton pump inhibitors (PPI’s) for gastroesophageal reflux. There are a few studies that tenuously establish a link between PPI’s (such as Nexium) and fragility fractures.

I asked Dr. Adachi what he tells his clients who are on PPI’s. Should they increase their calcium intake?

There is evidence that there may be an association between PPI’s and fractures. This remains controversial. If they are taking the PPI intermittently, it is probably less of a concern.

However if they require high doses of their PPI, Dr. Adachi suggests that they increase their dietary calcium intake so that they get three to four dairy products a day.

If they have osteoporosis and are at high risk for fractures or have had fractures, Dr. Adachi recommends treatment with either a bisphosphonate or Prolia.

Exercise Recommendations for Osteoporosis

Exercise is an essential ingredient to bone health. If you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

Should You Take Prolia?

A key question for many patients, besides how long can you take Prolia, is should I take Prolia at all? This is a complex question and I strongly suggest you discuss this with your physician.

Many women do not make their bone health a priority until a life event, such as a diagnosis of osteoporosis, forces a change. They often find that their physician recommends that they take an osteoporosis medication such as Prolia, Evenity or Prolia.

The decision to take an osteoporosis medication, such as Prolia, is an important health decision that you should discuss with your Physician.

The following story is about a patient of mine who was in a position to hold off on Prolia injections because she was in a low fracture risk category.

Nina Completes a Bone Mineral Density Test

Nina (not her real name or picture) schedules her annual physical around her birthday. This year, she turned sixty-five and her physician recommended she have a bone mineral density (BMD) test.

When the results came back, they showed that Nina’s bone density was lower than anticipated. As a result, her physician suggested she take Prolia to increase her bone density and reduce her risk of a fracture.

Is Osteoporosis Medication Right for Nina?

Nina had reservations about taking the pharmaceutical route. She did some research and found that although the osteoporosis medications claimed to increase bone density, there were some side effects that made her uncomfortable.

Pharmaceuticals may be appropriate for individuals in urgent need of an increase in bone density because they are at an elevated or high risk of fracture.

However, Nina knows that pharmaceuticals will not improve her bone quality, her balance or strength, and will certainly not reduce her risk of a fall.

Also, since Nina is still at a low risk of a fracture and has many years ahead of her, she decided that the best route was to commit to a program of exercise and nutrition that, as best she could, keep her in the low risk category.

A Plan to Reduce Fracture Risk

Nina asked me to provide her a safer, healthier approach to strengthen her bones and reduce her fracture risk.

After reviewing her bone mineral density test and her current exercise routine, I recommended that Nina incorporate more weight bearing in her exercise program.

As a result, Nina exchanged some of her swimming sessions for other activities such as brisk walking, hiking, and step classes.

Bone Quality

Research into bone strength has found that it is not only the density of bone that determines the strength of bones but also the quality of bones. Safe, frequent loading of bones through strength training (lifting something heavy enough so that the pull from the muscle demands a response from your bones) as well as weight bearing, positively impacts bone quality.

While osteoporosis pharmaceuticals do a good job of building bone density, exercise does a better job of improving bone quality. And as an added benefit, exercise only has positive side effects!

Micro and Macro Trauma Guidelines

One key recommendation I make for many clients is that to avoid a macro trauma to their bones, they need to improve their balance. I also recommend that they work on their posture and modify their movements (during activities of daily living) to avoid a micro trauma to their spine.

Improve Agility with Balance Exercises

I also recommended that Nina improve her balance. Her bone density was low and she needed good balance and strength to regain her footing in case of a trip or slip.

Activities of Daily Living and Nutrition

We also needed to change the way Nina moved when she performed daily activities such as housework and gardening. Proper movement and postural alignment play a key role in preventing spinal fractures.

Nina had to practice mindfulness and relearn how she did her day-to-day activities.

Finally, Nina needed to optimize her food choices to ensure that she had all the essential nutrients needed for her muscles and bones.

Take Control of Your Bone Health

The balance and strength training, her improved body awareness during her daily activities, and her nutrition program have made Nina feel more confident and in control of her bone health. Plus she has made a commitment to keep her bones healthy and in the low risk fracture category.

Prolia Shot Conclusion

This article answers many questions patients have about Prolia, including how long can you take Prolia. We also explored other topics related to the use of Prolia. We provided a definition of Prolia and we compared Prolia to Forteo, Evenity and bisphosphonates.

I encourage you to review this article before you meet with your physician to discuss Prolia. You should explore the following topics when you meet with your doctor:

Make sure that your physician is confident that Prolia is the right treatment for you — at this time in your life. Do you have the right fracture risk profile? Are there other options you can pursue that allow you to delay the time you start Prolia?
If you experience serious side effects, what is the plan to discontinue Prolia shots and transition to another pharmaceutical treatment?
Can your physician refer you to a Physical Therapist who can construct an exercise program for you that reduces your risk of a fall and chance of a fracture?
Can your physician refer you to a Nutritionist who can review your diet to determine you are getting adequate bone building nutrients?
I encourage you to speak with your dentist about any possible dental work that needs to be done before you start on Prolia a bisphosphonate therapy.

I want to thank Dr. Jonathan Adachi, Dr. Gonzalez-Rodriguez and Kent MacLeod for taking time to address these questions in detail.

References

References for this article on how long can you take Prolia and how long do Prolia side effects last:

Per Aspenberg, Denosumab and atypical femoral fractures. Acta Orthopaedica. 2014 Feb; 85(1): 1. Published online 2014 Feb 25. doi: 10.3109/17453674.2013.859423
Nakamura T, et al. Dose-response Study of Denosumab on Bone Mineral Density and Bone Turnover Markers in Japanese Postmenopausal Women With Osteoporosis. Osteoporos Int. 2012 Mar;23(3):1131-40. doi: 10.1007/s00198-011-1786-8. Epub 2011 Sep 17.
Fatemeh Abdi, et al. The Effects of Transdermal Estrogen Delivery on Bone Mineral Density in Postmenopausal Women: A Meta-analysis. Iran Journal of Pharmaceutical Research. 2017 Winter; 16(1): 380–389.
Benjamin B, Benjamin MA, Swe M, Sugathan S. Review on the comparison of effectiveness between denosumab and bisphosphonates in post-menopausal osteoporosis. Osteoporos Sarcopenia. 2016;2(2):77-81.
Lin T, Wang C, Cai XZ, et al. Comparison of clinical efficacy and safety between denosumab and alendronate in postmenopausal women with osteoporosis: a meta-analysis. Int J Clin Pract. 2012;66(4):399-408
Pedersen, AB, et al. Comparison of Risk of Osteoporotic Fracture in Denosumab vs Alendronate Treatment Within 3 Years of Initiation. AMA Netw Open. 2019;2(4):e192416. doi:10.1001/jamanetworkopen.2019.2416
Lamy, O., Stoll, D., Aubry-Rozier, B., Gonzalez-Rodriguez E. Current Osteoporos Rep (2019) 17: 8. https://doi.org/10.1007/s11914-019-00502-4
Tsourdi, Elena, et al. Discontinuation of Denosumab Therapy for Osteoporosis: A Systematic Review and Position Statement by European Calcified Tissue Society (ECTS). Bone. Volume 105, December 2017, pp 11 to17.
Lamy, O. Et al. Stopping Denosumab. Current Osteoporosis Reports. 2019 Feb;17(1):8-15. doi: 10.1007/s11914-019-00502-4
Lamy O, Gonzalez-Rodriguez E, Stoll D, Hans D, Aubry-Rozier B. Severe Rebound-associated Vertebral Fractures After Denosumab Discontinuation: Nine Clinical Cases Report. J Clin Endocrinol Metab. 2016 Oct 12.
Aubry-Rozier B, Liebich G, Stoll D, et al. Can we avoid the loss of bone mineral density one year after denosumab discontinuation? The REOLAUS Bone Project: Abstract OP0085
Gonzalez-Rodriguez E, Stoll D, Aubry-Rozier B, Hans D, Lamy O. Is Denosumab Discontinuation Associated with a Severe Increased of Fracture Risk? about 7 Women with 28 Spontaneous Vertebral Fractures 9 to 16 Months after the Last Dose of Denosumab, Endocrine Society’s 98th Annual Meeting and Expo, April 1–4, 2016.
Ian R. Reid et al, Bone Loss After Denosumab: Only Partial Protection with Zoledronate, Calcified Tissue International (2017). DOI: 10.1007/s00223-017-0288-x
Irati, Urionaguena & Sandra, P & Gallo, Chinchilla & Hernandez Gomez, Sandra & Garcia-Llorente, Jose & Aizpurua Manso, Izaskun & Vegas Revenga, Nuria. (2019). AB0857 DENSITOMETRY VALUES CHANGE WHEN STOPPING DENOSUMAB. Annals of the Rheumatic Diseases. 78. 1896.1-1896. 10.1136/annrheumdis-2019-eular.4338.
Soelling AS, et al. Treatment with zoledronate subsequent to denosumab in osteoporosis: a randomized trial. Journal of Bone and Mineral Research. 27 May 2020 https://doi.org/10.1002/jbmr.4098
Zoledronate After Denosumab Does Not Fully Prevent Bone Loss. MedScape. June 18, 2020.
JOINT GUIDANCE ON OSTEOPOROSIS MANAGEMENT IN THE ERA OF COVID-19 FROM THE ASBMR, AACE, ENDOCRINE SOCIETY, ECTS & NOF. https://www.asbmr.org/ASBMRStatementsDetail/joint-guidance-on-osteoporosis-management-in-era-o
Amgen. Highlights of Prescribing Information. https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/prolia/prolia_pi.pdf

About Dr. Jonathan Adachi

Dr. Jonathan (Rick) Adachi shares his time between his rheumatology practice at St. Joseph’s Healthcare in Hamilton, serving as Actavis Chair for Better Bone Health in Rheumatology and teaching for the Department of Medicine at McMaster University.

Dr. Adachi is currently involved in the CIHR funded Canadian Multicentre Osteoporosis Study. Dr. Adachi’s studies peripheral quantitative computer tomography (pQCT) and peripheral magnetic resonance imaging (pMRI) for structural analysis of bone and cartilage.

Osteoporosis Guidelines

For more information on topics related to osteoporosis (including how long can you take Prolia), check out my Osteoporosis Guidelines.

The post How Long Can You Take Prolia Injections appeared first on MelioGuide.

Bisphosphonates Osteoporosis Guidelines

Margaret Martin — Wed, 07 Sep 2011 20:08:32 +0000

An increasing number of my patients with low to moderate fracture risk have been prescribed a bisphosphonate. To help readers of this blog, I have prepared this post with my recommended bisphosphonates osteoporosis guidelines.

Bisphosphonates Osteoporosis Guidelines

I am a Physiotherapist and I treat many patients with osteoporosis. My preferred modality is safe and effective osteoporosis physiotherapy treatment for the individual. However, most of my patients have taken or are prescribed an osteoporosis medication such as a bisphosphonate, Prolia or Forteo.

I am not philosophically against the use of pharmaceutical intervention. In many cases, it is the appropriate course for individuals who are at an elevated risk of fracture. However, I believe that all health care professionals who treat this population be familiar with these medications.

In this post, I will address several questions and topics related to bisphosphonate use:

What Are Bisphosphonates
Use of Bisphosphonates
When to Stop Bisphosphonates • Bisphosphonate Drug Holiday
Long Term Bisphosphonate Use
Bisphosphonate Femur Fracture
Alternatives to Bisphosphonates

What Are Bisphosphonates

Let’s start with a definition of bisphosphonates.

Bisphosphonates arrest the loss of bone density. They bind to the surface of bone and reduce the effects of bone loss caused by osteoclasts (cells that erode bone). Osteoblasts (cells that build bone) can be more effective when it comes to creating bone.

How do they work? An abstract on PubMed explains in more technical detail:

At the tissue level, they decrease the rate of bone resorption and turnover, increase bone mineral density, and maintain or improve structural and material properties of bone and thereby reduce the risk of fractures.

Popular brand name bisphosphonates include: Fosamax, Actonel, Boniva and Reclast and are also referred to as alendronate, risedronate, ibandronate and zoledronate.

Use of Bisphosphonates

The Endocrine Society issued its recommendations about bisphosphonate use in March of 2019. They recommend the following:

We recommend initial treatment with bisphosphonates for postmenopausal women at high risk of fractures.
Reassess fracture risk after 3 to 5 years of treatment. This applies to postmenopausal women with osteoporosis who are taking bisphosphonates. Women who remain at high risk of fractures should continue therapy, whereas those who are at low-to-moderate risk of fractures should be considered for a “bisphosphonate holiday.”

A bisphosphonate holiday is a temporary discontinuation of bisphosphonate for up to 5 years. This period may be longer depending on the bone mineral density and clinical circumstances of the individual patient.

These recommendations clearly indicate that individuals at a high risk of fracture start a bisphosphonate treatment program.

FDA Review

The US Federal Drug Administration initiated a review of the long term use of bisphosphonates and raised concerns associated with their use. They noticed an elevated risk of atypical femur fractures and esophageal cancer.

Why are people with low to moderate fracture risk prescribed an osteoporosis medication?

This question has become increasingly confusing and frustrating for people with low bone density. In a recent article in the New York Times on bisphosphonates even the physicians who are quoted disagree on appropriate bisphosphonate use.

FRAX Assessment

The World Health Organization has developed a tool called FRAX to assist individuals in determining their fracture risk. This is a good starting point and you should consult this tool to determine your fracture risk.

Pharmacist Kent MacLeod recommends that patients and their physicians use the online FRAX to determine fracture risk.

In the US, bisphosphonates should be considered for an individual whose 10 hip year fracture risk is above 3% or their major fracture risk is above 20%.
In Canada, bisphosphonates should be considered when an individual’s major fracture risk is above 20%. For individuals whose fracture risk is moderate (10 to 20%) pharmaceutical intervention may be considered dependent upon additional risk factors.

The decision has become more complicated now that studies are showing an increased risk of femoral shaft fractures for people who take bisphosphonates for an extended period of time.

In addition, the FDA recently announced an updated warning on kidney impairment associated with the use of Reclast.

Bisphosphonates or Prolia

In a recent interview I had with one of Canada’s leading Osteoporosis Specialists, Dr. Jonathan Adachi, I asked him why many physicians are switching patients from bisphosphonate treatment to Prolia.

He indicated that a physician should make the switch when “patients have side effects to the bisphosphonate, when there are declines in bone mineral density (BMD) or when patients sustain a fracture on bisphosphonates.”

Exercise Recommendations for Osteoporosis

Exercise is an essential ingredient to bone health. If you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

When to Stop Bisphosphonates and Take a Drug Holiday

In 2013 the Journal Therapeutic Advances in Musculoskeletal Disease published a study (1) on bisphosphonate drug holiday. The study was by Diab and Watts, Bisphosphonate Drug Holiday.

The authors state that “it is difficult to find evidence to support the need for a drug holiday or to establish the effectiveness of treatment after restarting therapy.”

However, the authors do believe that “there is logic to support the following clinical scenarios.” The scenarios that Diab and Watts refer to in their bisphosphonate drug holiday study reflect the degree of risk of a fracture. Diab and Watts identify four risk levels and provide guidance for each risk level as it relates to the questions of when to stop bisphosphonates use.

Low Risk Fracture

Bisphosphonate treatment is not needed. Bisphosphonate treatment should be discontinued and not resumed until the patient meets treatment guidelines.

Mild Risk of Fracture

Use bisphosphonates for a 3 to 5 year period and then stop. The bisphosphonate drug holiday can continue until there has been a “significant loss” of bone mineral density.

Moderate Risk of Fracture

Use bisphosphonates for a 5 to 10 year period. At that point “offer a bisphosphonate drug holiday of 3 to 5 years or until there is significant loss of bone mineral density or the patient has a fracture, whichever comes first.”

High Risk of Fracture

Diab and Watts recommend “treat with bisphosphonate for 10 years, offer a ‘drug holiday’ of 1 to 2 years, until there is significant loss of bone mineral density or the patient has a fracture, whichever comes first.”

Long Term Bisphosphonate Use

What about long term bisphosphonate use and what about the possible implications?

On May 9, 2012 the U.S Food and Drug Administration (FDA) published an analysis on bisphosphonates longterm use in post-menopausal women.

According to the FDA, while bisphosphonate therapy has demonstrated “efficacy in preventing fractures in registration trials lasting 3 to 4 years … data on safety have raised concern regarding the optimal duration of use for achieving and maintaining protection against fractures”.

These safety concerns include increased risk of femoral shaft fractures, esophageal cancer and osteonecrosis of the jaw.

Long Term Bisphosphonate Use • Findings and Recommendation

The findings of this analysis were presented to a joint meeting of two FDA committees. The committees jointly decided that the data from the analysis “did not support a regulatory restriction on the duration of drug use”.

However, the joint committees did recommend that the labeling on bisphosphonate drugs be updated. Bisphophonate drugs now contain an “Important Limitation of Use” definition that states:

The optimal duration of use has not been determined. All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis.

What is the FDA Saying?

This recommendation can appear to fall short in terms of specifics. The recommendations probably reflect the fact that the study data reviewed by the FDA was, at times, inconsistent and incomplete.

In addition, the behaviour of bisphosphonate is quite complex and can vary from person to person and from brand to brand. Since bisphosphonates are absorbed into the bone during the treatment phase, they can persist for years – even after cessation of treatment. Further, there have been no long terms studies of the effects of bisphosphonates after cessation.

Basically, the FDA researchers state that more work and study has to be done. Individuals should consult, on a regular basis, with their health provider on what is right for them.

This regular evaluation should include an individual assessment of the risks and benefits of bisphosphonate therapy and patient preference. A good source for your health provider to use in evaluating your fracture risk is the online FRAX tool developed by the World Health Organization and the International Osteoporosis Foundation.

Clearly, the FDA and researchers are grappling with this complex issue.

Bisphosphonates Osteoporosis Guidelines • FDA

The New England Journal of Medicine published another article to accompany the FDA review. This article was written by a group of physicians at a number of medical institutes across the United States.

In the article, the physicians review the data and shed more light on the results. They state the following:

Vertebral Fractures (i.e., fractures of the spine): Although evidence is limited regarding the risk of fracture with the continuation of bisphosphonate therapy beyond 3 to 5 years, data from randomized controlled trials generally suggest that the risk of vertebral fracture is reduced.
Nonvertebral Fractures (i.e., fractures of the wrist, ribs, hip, etc): The consistent evidence of a statistically significant reduction in nonvertebral fractures with the continuation of bisphosphonates is lacking.

Further, this team provides guidance regarding continued use of bisphosphonates. The caveat is that these recommendations could change as more research is published.

Patients with low bone mineral density at the femoral neck (T score below −2.5) after 3 to 5 years of treatment are at the highest risk for vertebral fractures and therefore appear to benefit most from continuation of bisphosphonates.
Patients with an existing vertebral fracture who have a somewhat higher (although not higher than −2.0) T score for bone mineral density may also benefit from continued therapy.
Patients with a femoral neck T score above −2.0 have a low risk of vertebral fracture and are unlikely to benefit from continued treatment.

As you can see, these physicians recommend that patients with osteoporosis and a high fracture risk should continue bisphosphonate therapy. Those with low or moderate risk of fracture will probably not see material benefit from continued use of this therapy.

Long Term Bisphosphonate Use • Recommendation

Since each individual’s medical profile is unique, I strongly encourage you to discuss this issue with your physician. Hopefully, articles like this one make you a more informed patient.

As a general rule, if you are at a high risk of fracture, continued use of bisphosphonates is probably the prudent path.

If you are at low or moderate risk of fracture, you need to weigh the risks associated with long term use of this drug (as defined earlier in this article). Research is showing that there is no evidence that bisphoshonates cause a significant reduction in nonvertebral fractures.

A well designed osteoporosis exercise program is something that everyone should be following.

Conclusion

Expect to hear more about this debate in the coming years as researchers spend more resources examining the long term effects of this drug. Clearly, people within the FDA and researchers in the field have concerns with the continued long term use of this drug and its effectiveness when it comes to reducing fracture risk. The problem today is that there is not enough data to provide definitive guidance or change the FDA’s regulatory position with regard to this drug.

FDA Review in More Detail

The FDA article goes into a lot of detail as to what the study involved. For those of you not interested in reviewing the article but still interested in the mechanics of the study, here is a brief summary.

The FDA examined the long term effects of three bisphosphonates: Fosamax, Reclast and Actonel. One study group took the bisphosphonate and the other took a placebo. The FDA studied the effect of the various bisphosphonates on changes in the bone density in the femoral neck and the lumbar spine. They also looked the effect on vertebral fractures.

The FDA found that continued use of bisphosphonate therapy beyond five years lead to “maintenance of bone mineral density in the femoral neck and further increases in bone mineral density at the lumbar spine”.

However, the FDA review found that the “data raise[s] the question of whether continued bisphosphonate therapy imparts additional fracture-prevention benefit, relative to cessation of therapy after 5 years.” It was this finding that caused the FDA to issue the label change mentioned above.

Exercise Recommendations for Osteoporosis

Exercise is an essential ingredient to bone health. If you have osteoporosis, therapeutic exercise needs to be part of your osteoporosis treatment program.

I cover important topics related to osteoporosis exercise including:

Can exercise reverse osteoporosis?
Stop the stoop — how to avoid kyphosis and rounded shoulders.
Key components of an osteoporosis exercise program.
Key principles of bone building.
Exercises you should avoid if you have osteoporosis.
Yoga and osteoporosis — should you practice yoga if you have osteoporosis?
Core strength and osteoporosis — why is core strength important if you have osteoporosis?

Bisphosphonate Femur Fracture

Can you experience a femur fracture as a result of bisphosphonate treatment?

A study was just recently released in the Journal of the American Medical Association (JAMA) on prolonged bisphosphonate therapy and the increased risk of femoral shaft fractures in older women. Treatment for five years or longer was associated with an increased risk of femoral shaft fracture.

In the following video, I discuss this study and its implications for you. The study can be found at the JAMA website.

Atypical Fracture Bisphosphonate

Today, I’d like to talk about a recent study that was published in JAMA, the Journal of the American Medical Association. They spoke about unusual fractures related to bisphosphonate use.

As a person with osteoporosis, or low bone density, if you’re on a bisphosphonate, you might be a little bit concerned about this study.

First of all, I’d like to take you into the anatomy of where these fractures are occurring.

Anatomy of Fracture

We’re going to zoom right in to the bones of the lower leg, specifically the thighbone or femur. Most typical osteoporotic fractures occur in the neck of the femur.

Typical Osteoporotic Fracture

The typical osteoporotic fracture occurs in that part of the femur because that’s the part of the femur that has more trabecular bone. The study showed that these unusual fractures were in the region of the femur below the intertrochanteric area, or also referred to as the shaft of the femur.

What’s concerning is that the shaft of the femur has a lot more cortical bone, which is usually known as really good, hard bone.

People who are on bisphosphonates for over five years, have an effect not just on the trabecular bone, but also on the cortical bone.

Effect of Bisphosphonates

If you are at all concerned, you should definitely talk to your doctor before you discontinue your medication.

Chances are your doctor might recommend that you continue your bisphosphonate if you are already at a high fracture risk, and you haven’t been taking a bisphosphonate for five years.

If you are at a moderate fracture risk or a low-moderate fracture risk, you should definitely have a discussion with your doctor as to whether or not a bisphosphonate is the best approach for you.

Whether you are at a low, moderate, or high fracture risk, we know that exercise helps build quality of bone.

But exercise is going to help you recover from a fracture as well, so you really should consider starting an exercise program.

Exercise, Safe Daily Activities, Nutrition and Vitamin D

The choice to take a bisphosphonate prescription (or any other osteoporosis medication) is yours. However, you should always follow a prescribed exercise program for osteoporosis.

All individuals, regardless of fracture risk, should:

Follow a prescribed osteoporosis exercise plan that not only includes weight bearing for bone building but also includes balance, posture, strength and flexibility exercises that reduce the chance of a fall.
Practice perfect posture and modify how they do their household chores (known as their activities of daily living), exercise routine, yoga practice, and pilates moves that can increase their risk of fracture.
Determine whether you are getting adequate Vitamin D.
Follow a proper nutrition program for your bone health.

Prolia Injections

Dr Adachi indicated that many physicians are shifting their patients from bisphosphonates to Prolia. However, Prolia is not without its challenges as discussed in my post, How Long Can You Take Prolia.

References

Diab, Dima and Watts, Nelson, Bisphosphonate Drug Holiday, Therapeutic Advances in Musculoskeletal Disease, 2013 Jun.

Conclusion

These bisphosphonates osteoporosis guidelines have covered a wide range of questions my clients have about bisphosphonate use including

when to stop bisphosphonates.
the implications of long term bisphosphonate use.
bisphosphonate femoral fracture.
alternatives to bisphosphonates.

Osteoporosis Guidelines

For more information, check out my Osteoporosis Guidelines.

The post Bisphosphonates Osteoporosis Guidelines appeared first on MelioGuide.

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