Osteoporosis Medications for Muscle Health in Osteoporosis

(MITO Trial)

Overseen By Susan Greenspan, MD

Age: 65+

Sex: Female

Trial Phase: Phase 4

Sponsor: Nami Safai Haeri

Must be taking: Osteoporosis medications

Must not be taking: Oral bisphosphonates, Intravenous bisphosphonates

Disqualifiers: Severe liver disease, Men, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how osteoporosis medications, specifically Denosumab (Prolia or Xgeva) and Zoledronic Acid (Zometa or Reclast), impact muscle health in older adults. The focus is on understanding the relationship between bone and muscle health, especially in those treated for osteoporosis. Suitable participants are adults aged 65 or older with osteoporosis, a history of certain bone fractures, or a high risk of fractures. As a Phase 4 trial, this research helps determine how these FDA-approved treatments can benefit more patients.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, it seems that participants who have been on certain osteoporosis medications like oral bisphosphonates for the past year or intravenous bisphosphonates for the past two years are excluded, which might imply a need to stop these specific medications.

What is the safety track record for these treatments?

Research has shown that both denosumab and zoledronic acid are well-researched treatments for osteoporosis.

Denosumab effectively reduces fractures, but some safety concerns exist. Studies have found that while it lowers fracture risk, it might increase the risk of serious heart problems by 36%. Patients should discuss this with their doctor, especially if they have heart issues.

Zoledronic acid also effectively increases bone strength and reduces fractures. Most research indicates it is generally safe, with safety outcomes similar to denosumab. Both treatments have FDA approval for osteoporosis, indicating a strong safety record for this condition.

Patients should always consult a healthcare provider to understand the risks and benefits for their personal health situation. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments because Denosumab and Zoledronic Acid offer unique approaches to muscle health in osteoporosis that differ from traditional treatments like bisphosphonates. Denosumab works by inhibiting a protein called RANKL, which plays a key role in bone resorption, potentially providing a more targeted action on bone density and strength. Zoledronic Acid, on the other hand, is a bisphosphonate that is administered once a year, which can improve patient compliance compared to more frequent dosing schedules. These treatments have the potential to enhance muscle health as well, offering a dual benefit for individuals with osteoporosis.

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

This trial will compare the effects of Denosumab and Zoledronic Acid on muscle health in individuals with osteoporosis. Studies have shown that both Denosumab and Zoledronic Acid effectively treat osteoporosis by increasing bone strength and reducing fracture risk. Participants may receive Denosumab, which significantly lowers the chance of major bone breaks. Some research suggests it might also improve muscle strength, though other studies found no noticeable improvement in muscle size or function. Alternatively, participants may receive Zoledronic Acid, which strengthens bones and has been found to increase muscle size over time. Both treatments are proven to improve bone health, and there are indications they might help with muscle health, although results are mixed. ^{2 4 6 7 8}

Who Is on the Research Team?

Nami Safai Haeri, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for adults aged 65 or older with osteoporosis, diagnosed either by a previous spine or hip fracture, or low bone density scores. It's open to those who need treatment based on their risk of fractures. Men and people with severe kidney issues, contraindications for the drugs being tested, recent bisphosphonate use, planned tooth extractions, or severe liver disease cannot participate.

Inclusion Criteria

I have had a fracture in my spine or hip from a minor injury as an adult.

I am at high risk for major bone fractures according to FRAX scores.

Your bone density in your spine, hip, or forearm is very low, indicating osteoporosis.

Exclusion Criteria

I cannot take bisphosphonates or denosumab due to health reasons.

I have been taking oral bisphosphonates for 1 year or intravenous bisphosphonates for 2 years.

I am scheduled for a tooth extraction to prevent jaw bone damage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive osteoporosis medications to assess their impact on muscle health

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Denosumab
• Zoledronic Acid

Trial Overview The study tests how osteoporosis medications affect muscle health in older adults. Participants will receive either Denosumab or Zoledronic Acid versus placebos to see if these treatments have an impact on muscle strength and function as well as bone health.

How Is the Trial Designed?

Group I: Zoledronic Acid Active Control 2 Interventions

Group II: Denosumab Active Control 2 Interventions

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?

Nami Safai Haeri

Lead Sponsor

Trials

1

Recruited

20+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

The Claude D. Pepper Older Americans Independence Centers

Collaborator

Trials

11

Recruited

350+

Published Research Related to This Trial

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 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]

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]

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]

Citations

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

Denosumab in the Treatment of Osteoporosis: 10 Years Later The available data show that denosumab has a favorable benefit/risk profile and is a versatile agent for preventing osteoporotic fractures in the short and ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S8756328225001644

Impact of denosumab on muscle health in older adults ... Denosumab did not significantly improve muscle mass, strength, or function compared to placebo. •. Both the denosumab and placebo groups experienced declines in ...

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

Long-Term Efficacy and Safety of Denosumab Thus, in the virtual model, the risk of fractures in all areas was reduced over 10 years in the denosumab treatment group [22]. Predicting ...

4. 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9546982/

Beneficial effects of denosumab on muscle performance in ... We demonstrated in a cohort of 150 patients with low BMD that Dmab results in increased muscle strength in the upper and lower limbs, indicating ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39761590/

Cardiovascular Safety and Fracture Prevention ... It was estimated that, compared with oral bisphosphonates, denosumab lowered the risk for fractures by 45% and increased the risk for MACE by 36%.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4069896/

Safety of denosumab in postmenopausal women with ... Conclusions: Compared to placebo, denosumab treatment significantly decreased the risk of non-vertebral fracture but increased the risk of SAE related to ...

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

Denosumab for Prevention of Fractures in Postmenopausal ... Results. As compared with placebo, denosumab reduced the risk of new radiographic vertebral fracture, with a cumulative incidence of 2.3% in the denosumab group ...