Osteoporosis, Sarcopenia
Conditions
Brief summary
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.
Interventions
DRUGDenosumab
Half of study participants will randomly receive denosumab 60 mg subcutaneous injection at month 0 and 6 with zoledronic acid placebo at month 0.
DRUGZoledronic Acid
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.
OTHERDenosumab Placebo
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.
OTHERZoledronic Acid Placebo
Half of study participants who will randomly receive denosumab 60 mg subcutaneous injection at month 0 and 6 will also receive zoledronic acid placebo.
Sponsors
The Claude D. Pepper Older Americans Independence Centers
National Institute on Aging (NIA)
Nami Safai Haeri
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Ambulatory adults age ≥65 years including those using assistive devices to maximize generalizability, if they have criteria for treating osteoporosis including: 1. Osteoporosis by axial bone density (spine, hip or forearm BMD T-score ≤-2.5 SD) or 2. A previous adult fragility fracture of the spine or hip or 3. 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
1. Patients with a calculated creatinine clearance \< 35 ml/min or 2. Who have a contraindication for bisphosphonates or denosumab or 3. Those who are scheduled for a tooth extraction to avoid jaw osteonecrosis or 4. Subjects with severe liver disease or 5. 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 6. Men
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change from baseline in muscle mass (kg) measured by D3-Creatine | Baseline vs Month 12 | D3-Creatine dilution method is a novel method to measure muscle mass |
| Percentage change from baseline in appendicular lean mass (ALM/body mass index) | Baseline vs Month 12 | Appendicular lean mass is measured by whole body DXA scan and is an index of skeletal muscle mass |
| Percentage change from baseline in trabecular bone score (TBS) | Baseline vs Month 12 | 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 |
| Percentage change from baseline in bone mineral density (BMD) (g/cm²) | Baseline vs Month 12 | BMD is measured by a DXA scan system and a higher BMD is correlated with lower fracture risk |
| Percentage change from baseline in grip strength (kgf) | Baseline vs Month 12 | Grip strength is measure of muscle strength and will be measured by a standard hand dynamometer |
| Percentage change from baseline in gait speed (m/s) | Baseline vs Month 12 | Gait speed is a measure of muscle function and will be measured by standard 4 meter gait speed test |
| Percentage change from baseline in rectus femoris muscle thickness (cm) | Baseline vs Month 12 | This variable will be measured by ultrasound |
| Percentage change from baseline in rectus femoris muscle cross-sectional surface area (cm²) | Baseline vs Month 12 | This variable will be measured by ultrasound |
Countries
United States
Outcome results
None listed