Muscle Impact of Treating Osteoporosis (MITO)

The Impact of Osteoporosis Medications on Muscle Health in Older Adults

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Sarcopenia; Osteoporosis
• Intervention / Treatment: Drug: Zoledronic Acid; Other: Denosumab Placebo; Drug: Denosumab; Other: Zoledronic Acid Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nami Safai Haeri, MD; Phone Number: 412-864-1145; Email: nas287@pitt.edu
• Study Contact Backup: Name: Susan Greenspan, MD; Phone Number: 412-864-1145

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
      • Contact: Nami Safai Haeri, MD; Email: nas287@pitt.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Zoledronic Acid	Drug: Zoledronic 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.; Other: Denosumab 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.
Active Comparator: Denosumab	Drug: Denosumab; Half of study participants will randomly receive denosumab 60 mg subcutaneous injection at month 0 and 6 with zoledronic acid placebo at month 0.; Other: Zoledronic 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nami Safai Haeri
• Collaborators: National Institute on Aging (NIA); The Claude D. Pepper Older Americans Independence Centers
• Investigators: Principal Investigator: Nami Safai Haeri, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: December 15, 2022
• First Submitted That Met QC Criteria: December 22, 2022
• First Posted (Actual): December 27, 2022

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Bone Diseases; Muscular Atrophy; Atrophy; Bone Diseases, Metabolic; Sarcopenia; Osteoporosis; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid; Denosumab
• Other Study ID Numbers: STUDY22080139; P30AG024827 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No