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

Trial Summary

What is the purpose of this trial?

Our goal is to demonstrate efficacy of the novel agent Denosumab to improve or preserve muscle health, strength, mobility and function in frail older adults.

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 data supports the effectiveness of the drug for muscle health in older adults?

Research shows that denosumab and zoledronic acid are effective in increasing bone mineral density and reducing fractures in patients with osteoporosis, which may indirectly support muscle health by improving overall skeletal strength. ^{1 2 3 4 5}

Is the osteoporosis medication safe for humans?

Denosumab (Prolia, Xgeva) and zoledronic acid (Reclast, Zometa) have been used in treating osteoporosis and preventing bone issues in cancer patients. They are generally considered safe, but factors like kidney function and potential side effects should be discussed with a healthcare provider. ^{1 2 4 6 7}

How is the drug for osteoporosis different from other treatments?

Denosumab and zoledronic acid are unique because they are injectable drugs that offer convenient administration and are effective in increasing bone density. Denosumab works by reversibly reducing a protein called RANKL, which is involved in bone breakdown, while zoledronic acid is administered once a year intravenously, providing long-term protection against fractures. ^{1 4 7 8 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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 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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy, adverse effects, and cost of zoledronic acid and denosumab in the treatment of osteoporosis. [2021]

2. England 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Denosumab versus zoledronic acid in elderly patients after hip fracture. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Annual zoledronic acid for osteoporosis. [2018]

5. Korea (South) 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). [2022]

6. England pubmed.ncbi.nlm.nih.gov

Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Denosumab versus zoledronic acid in patients previously treated with zoledronic acid. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates. [2022]