Muscle Impact of Treating Osteoporosis

Study Overview
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Brief Summary
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Osteosarcopenia is a geriatric musculoskeletal syndrome characterized by co-existence of osteoporosis and sarcopenia (low skeletal muscle mass, strength, and/or functional capacity). There is strong evidence of overlap between the pathophysiology of osteoporosis and sarcopenia (muscle-bone crosstalk). This research plan will further explore the relationship between bone and muscle, and provide new information about effect of osteoporosis medications on muscle health in older adults who are under treatment for osteoporosis.

Official Title
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The Impact of Osteoporosis Medications on Muscle Health in Older Adults

Conditions
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Sarcopenia, Osteoporosis

Intervention / Treatment
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* Drug: Denosumab
* Drug: Zoledronic Acid
* Other: Denosumab Placebo
* Other: Zoledronic Acid Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory adults age ≥65 years including those using assistive devices to maximize generalizability, if they have criteria for treating osteoporosis including: Osteoporosis by axial bone density (spine, hip or forearm BMD T-score ≤-2.5 SD) or A previous adult fragility fracture of the spine or hip or Would be treated based on FRAX National Osteoporosis Foundation treatment thresholds of a 10-year risk of ≥ 20% for a major osteoporotic fracture or ≥ 3% for hip fracture using femoral neck BMD. Exclusion Criteria: Patients with a calculated creatinine clearance < 35 ml/min or Who have a contraindication for bisphosphonates or denosumab or Those who are scheduled for a tooth extraction to avoid jaw osteonecrosis or Subjects with severe liver disease or Those who have been on oral bisphosphonates for the past 1 year and intravenous bisphosphonates for the past 2 years prior to the study or Men

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Zoledronic Acid<br> | Drug: Zoledronic Acid<br>* Half of study participants will randomly receive zoledronic acid 5 mg intravenous infusion at month 0 with denosumab placebo at month 0 and 6. All forty participants will receive zoledronic acid 5 mg intravenous infusion at month 12.<br>Other: Denosumab Placebo<br>* Half of study participants who will randomly receive zoledronic acid 5 mg intravenous infusion at month 0 will also receive denosumab placebo at month 0 and 6.<br>|
| Active Comparator: Denosumab<br> | Drug: Denosumab<br>* Half of study participants will randomly receive denosumab 60 mg subcutaneous injection at month 0 and 6 with zoledronic acid placebo at month 0.<br>Other: Zoledronic Acid Placebo<br>* Half of study participants who will randomly receive denosumab 60 mg subcutaneous injection at month 0 and 6 will also receive zoledronic acid placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline in muscle mass (kg) measured by D3-Creatine | D3-Creatine dilution method is a novel method to measure muscle mass | Baseline vs Month 12 | 
| Percentage change from baseline in appendicular lean mass (ALM/body mass index) | Appendicular lean mass is measured by whole body DXA scan and is an index of skeletal muscle mass | Baseline vs Month 12 | 
| Percentage change from baseline in trabecular bone score (TBS) | TBS is measure of bone microarchitecture and is measured by a DXA system. A value of ≥ 1.35 indicates a normal architecture while TBS ≤ 1.20 indicates degraded microarchitecture | Baseline vs Month 12 | 
| Percentage change from baseline in bone mineral density (BMD) (g/cm²) | BMD is measured by a DXA scan system and a higher BMD is correlated with lower fracture risk | Baseline vs Month 12 | 
| Percentage change from baseline in grip strength (kgf) | Grip strength is measure of muscle strength and will be measured by a standard hand dynamometer | Baseline vs Month 12 | 
| Percentage change from baseline in gait speed (m/s) | Gait speed is a measure of muscle function and will be measured by standard 4 meter gait speed test | Baseline vs Month 12 | 
| Percentage change from baseline in rectus femoris muscle thickness (cm) | This variable will be measured by ultrasound | Baseline vs Month 12 | 
| Percentage change from baseline in rectus femoris muscle cross-sectional surface area (cm²) | This variable will be measured by ultrasound | Baseline vs Month 12 |