Osteoporosis Medication for Muscle Health in Older Adults

Overseen By Susan Greenspan, MD

Age: 65+

Sex: Any

Trial Phase: Phase 4

Sponsor: Susan L. Greenspan

Must not be taking: Bisphosphonates, Denosumab, Teriparatide, others

Disqualifiers: Subacute illnesses, Hypocalcemia, Glucocorticoids, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

155 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Denosumab (also known as Prolia or Xgeva) might improve or maintain muscle health, strength, mobility, and function in frail older adults with osteoporosis. The researchers compare Denosumab to Zoledronic Acid (also known as Zometa or Reclast) to determine which better supports muscle health. Individuals living in nursing homes or assisted living facilities with a diagnosis of osteoporosis or low bone mass might be suitable candidates. As a Phase 4 trial, this research aims to understand how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

You may need to stop certain medications if you are currently on a related therapy like bisphosphonates, Denosumab, teriparatide, abaloparatide, or romosozumab. However, you can continue taking anticonvulsants, hormone replacement, raloxifene, and use protective hip pads. It's suggested to stop calcitonin due to cancer concerns.

What is the safety track record for these treatments?

Research shows that both Denosumab and Zoledronic Acid are generally safe treatments for osteoporosis and might also improve muscle health in older adults.

Denosumab increases bone strength over time and carries a low risk of causing fractures. Common side effects include back pain, pain in the arms and legs, and high cholesterol. Serious side effects are rare but can involve low calcium levels in the blood and serious infections.

Zoledronic Acid also strengthens bones and may benefit muscle health. Some studies have reported side effects like fever, muscle pain, and flu-like symptoms after the first dose. There is a small risk of heart-related side effects.

In summary, both Denosumab and Zoledronic Acid have been well-studied and are considered safe for treating conditions like osteoporosis. However, like any treatment, they can have side effects. It's important to consult a healthcare provider to understand what these might mean for individual cases. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Denosumab and Zoledronic Acid for muscle health in older adults because these treatments might offer unique benefits compared to traditional osteoporosis medications. Denosumab is a monoclonal antibody that works by inhibiting a protein involved in bone resorption, which is different from many standard treatments that mostly focus on bone density. Zoledronic Acid, on the other hand, is administered via a once-yearly IV infusion, providing convenience and potentially better adherence compared to daily or weekly pill regimens. This new approach could enhance muscle health while providing bone protection, offering a dual benefit that current treatments don't typically address.

What evidence suggests that this trial's treatments could be effective for muscle health in older adults?

Research has shown that denosumab, one of the treatments in this trial, can significantly lower the risk of fractures in people with osteoporosis. Specifically, one study found a 36% reduction in hip fractures for those taking denosumab. Over 10 years, patients experienced steady improvements in bone strength, indicating stronger bones.

Zoledronic acid, another treatment option in this trial, also improves bone health. Studies have demonstrated that it increases bone strength and reduces the risk of spine and hip fractures. Evidence suggests that zoledronic acid can enhance muscle health, benefiting those concerned about muscle strength. Both treatments effectively support bone and muscle health, which could be advantageous for older adults. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for ambulatory men and women aged 65 or older living in institutions like nursing homes, who have osteoporosis or low bone mass at risk of fractures. They must have a diagnosis based on bone density scores, history of certain fractures, or high fracture risk as per specific criteria.

Inclusion Criteria

I am 65 or older with osteoporosis or at risk for fractures, living in a care facility.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Denosumab or Zoledronic acid to evaluate efficacy in preserving muscle health, strength, mobility, and function

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with all receiving Zoledronic acid to prevent potential bone loss

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Denosumab
• Zoledronic Acid

Trial Overview The study tests the effectiveness of Denosumab in improving muscle health and strength compared to Zoledronic Acid in frail elderly adults with osteoporosis. It aims to see if Denosumab can help maintain mobility and function.

How Is the Trial Designed?

Group I: Denosumab Experimental Treatment 1 Intervention

Denosumab 60mg SQ with placebo zoledronic acid

Group II: Zoledronic acid Active Control 1 Intervention

Zoledronic acid 5mg IV with Denosumab placebo

Denosumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Prolia for:

• Osteoporosis in postmenopausal women
• Bone loss associated with hormone ablation therapy for prostate cancer
• Bone loss associated with hormone ablation therapy for breast cancer

Approved in United States as Prolia for:

• Treatment of postmenopausal women with osteoporosis at high risk for fracture
• Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

Approved in Canada as Prolia for:

• Treatment of osteoporosis in postmenopausal women at high risk for fracture
• Treatment to increase bone mass in men with osteoporosis at high risk for fracture

Approved in Japan as Prolia for:

• Treatment of osteoporosis in postmenopausal women
• Treatment of bone loss associated with hormone ablation therapy for prostate cancer

Who Is Running the Clinical Trial?

Susan L. Greenspan

Lead Sponsor

Trials

6

Recruited

990+

Published Research Related to This Trial

In a study involving 5543 patients with advanced cancer and bone metastases, denosumab was found to significantly reduce the risk of skeletal-related events (SREs) compared to zoledronic acid, across various patient subgroups.

Denosumab demonstrated consistent efficacy in preventing both the first and subsequent SREs, regardless of factors such as performance status, number of bone metastases, and presence of visceral metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics. Lipton, A., Fizazi, K., Stopeck, AT., et al.[2022]

In a study involving 643 postmenopausal women with osteoporosis, transitioning to denosumab resulted in significantly greater increases in bone mineral density (BMD) compared to zoledronic acid after 12 months, with improvements seen at the lumbar spine, total hip, femoral neck, and one-third radius.

Denosumab also showed greater inhibition of bone turnover markers compared to zoledronic acid, indicating a more effective mechanism for reducing bone remodeling, while both treatments had similar safety profiles with no significant differences in adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates. Miller, PD., Pannacciulli, N., Brown, JP., et al.[2022]

Zoledronic acid is the first bisphosphonate approved in the UK for once-yearly intravenous treatment of postmenopausal osteoporosis, highlighting its convenience and potential for improved patient compliance.

Promotional claims suggest that zoledronic acid offers significant fracture reduction over three years at key sites, indicating its efficacy in providing long-term osteoprotection for women with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Annual zoledronic acid for osteoporosis. [2018]

A study of 304 adult oncology patients receiving denosumab for preventing skeletal-related events showed that 93% met the health system's formulary restrictions, indicating appropriate use in most cases.

Among patients eligible for alternative treatment, 84% could have received the less expensive zoledronic acid instead of denosumab, suggesting potential cost savings and the need for better education on treatment options, especially for those with multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of denosumab in adult oncology patients for the prevention of skeletal related events across a large academic health system. Sproat, MR., Burton, B., Burdalski, C., et al.[2022]

In a study of 282 geriatric patients with hip fractures, denosumab showed a significantly greater increase in bone mineral density (BMD) compared to zoledronic acid after 2 years (p < 0.001).

Patients treated with denosumab also demonstrated a higher persistence rate in treatment adherence compared to those receiving zoledronic acid (p = 0.01), suggesting denosumab may be a more favorable option for long-term management of osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab versus zoledronic acid in elderly patients after hip fracture. Kim, SJ., Kim, JW., Lee, DW.[2023]

In a study of 107 patients comparing denosumab and zoledronic acid for osteoporosis treatment, denosumab resulted in a significantly greater increase in spine bone mineral density (BMD) after one year (0.060 g/cm2 vs. 0.021 g/cm2 for ZA).

The zoledronic acid group experienced a higher incidence of mild flu-like symptoms (29% vs. 0% in the denosumab group), indicating that denosumab may be better tolerated in terms of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy, adverse effects, and cost of zoledronic acid and denosumab in the treatment of osteoporosis. Sheedy, KC., Camara, MI., Camacho, PM.[2021]

In postmenopausal women previously treated with zoledronic acid, both denosumab and zoledronic acid resulted in similar increases in lumbar spine bone mineral density (BMD) after one year, with mean increases of 4.5% and 4.4%, respectively.

Denosumab was more effective in reducing bone turnover markers, significantly decreasing levels of CTx and P1NP, and it also caused a substantial reduction in sRANKL levels, indicating a strong mechanism of action in inhibiting bone resorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab versus zoledronic acid in patients previously treated with zoledronic acid. Anastasilakis, AD., Polyzos, SA., Gkiomisi, A., et al.[2020]

In a study of 75 patients with osteoporosis and decreased kidney function, treatment with denosumab (Prolia®) over an average of 5.3 years led to significant improvements in bone mineral density, with a 12% increase in the lumbar spine and a 7% increase in the hip T scores.

The treatment was generally well tolerated, although 20% of patients experienced new fractures and 21% had biochemical hypocalcemia, indicating the need for monitoring calcium levels during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of osteoporosis with denosumab in patients with decreased kidney function. Svendsen, OL.[2023]

In a study of 585 postmenopausal women with osteoporosis, denosumab (DEN) resulted in a significantly greater increase in bone mineral density (BMD) compared to zoledronic acid (ZOL) after two years (P < 0.001).

DEN also led to a greater improvement in trabecular bone score (TBS) and a more significant reduction in bone turnover marker CTX compared to ZOL, indicating a more effective inhibition of bone remodeling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Denosumab and Zoledronic Acid in Postmenopausal Women With Osteoporosis: Bone Mineral Density (BMD) and Trabecular Bone Score (TBS). Kang, T., Park, SY., Lee, SH., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39777487/

Denosumab and clinical outcomes among men with ... This real-world study shows direct evidence of fracture risk reduction among men with osteoporosis (36% of hip fracture reduction with denosumab) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8799550/

Denosumab in the Treatment of Osteoporosis: 10 Years Later In the 10-year FREEDOM Extension study, denosumab treatment produced progressive incremental increases in BMD, sustained low rates of vertebral ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2405525517300043

Review Article Denosumab for the treatment of osteoporosis In postmenopausal women with osteoporosis, denosumab effectively and quickly reduces the risk of important fractures related to osteoporosis, and that fracture ...

4. academic.oup.com academic.oup.com/jbmr/article/39/7/826/7675442

Comparative effectiveness of denosumab vs alendronate ... Overall, denosumab reduced the risk of MOP by 39%, hip by 36%, NV by 43%, NHNV by 50%, and HV fractures by 30% compared with alendronate.

5. prolia.com prolia.com/proven-results/real-world-study

Real-World Study Results | Prolia® (denosumab) The overall risk of major osteoporotic fracture was 10.5% for women taking Prolia® compared to 17.2% for women who took alendronate. Major osteoporotic ...

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Denosumab for osteoporosis treatment: when, how, ... Denosumab produces a continuous increase in bone mineral density over ten years, associated with a low risk of vertebral and non-vertebral fractures.

7. e-enm.org e-enm.org/journal/view.php?number=2567

Long-Term Efficacy and Safety of Denosumab The Endocrine Society's guideline indicates that patients at high risk for fracture after 5 to 10 years of denosumab use should continue the treatment or other ...

8. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1358592/full

Analysis of adverse drug reactions of Denosumab (Prolia) ... Objective: To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa0809493

Denosumab for Prevention of Fractures in Postmenopausal ... Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women ...