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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is studying how medications for weak bones might also help improve muscle health in older adults with both weak bones and muscles. Researchers believe these medications could benefit muscle strength and function by affecting the way bones and muscles work together.

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 data supports the effectiveness of the drug Denosumab and Zoledronic Acid for muscle health in osteoporosis?

Research shows that Denosumab and Zoledronic Acid are effective in increasing bone mineral density and reducing fractures in people with osteoporosis. These drugs are also used in cancer patients to prevent bone-related issues, indicating their strength in maintaining bone health. ^{1 2 3 4 5}

Is it safe to use Denosumab and Zoledronic Acid for osteoporosis?

Denosumab and Zoledronic Acid are generally considered safe for treating osteoporosis, but they can have side effects. Denosumab may have effects on kidney function, and Zoledronic Acid can cause low calcium levels and flu-like symptoms after the first dose. ^{1 2 6 7 8}

How is the drug treatment with Denosumab and Zoledronic Acid unique for osteoporosis?

Denosumab and Zoledronic Acid are unique because they are injectable drugs that offer convenient administration and long-lasting effects, with Zoledronic Acid requiring only once-yearly intravenous treatment. This makes them different from other osteoporosis treatments that may require more frequent dosing or oral administration. ^{1 2 3 6 9}

Research Team

Nami Safai Haeri, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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 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 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]

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 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]

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

Annual zoledronic acid for osteoporosis. [2018]

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

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

4. 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]

5. 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]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Outcomes of Zoledronic Acid Use in Paediatric Conditions. [2021]

8. Japan pubmed.ncbi.nlm.nih.gov

A quality improvement project to address the challenges surrounding zoledronic acid use in children. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

[Drugs for osteoporosis.] [2018]