SarcopeniaPhase 4MITONCT05666310
Muscle Impact of Treating Osteoporosis
A Phase 4 study testing Denosumab and Zoledronic Acid in people with Sarcopenia and Osteoporosis, run by Nami Safai Haeri at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 65 years and older, women only
- Conditions the study is for
- Sarcopenia, Osteoporosis
- What is being tested?
- Denosumab and Zoledronic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Feb 2023to 4 Aug 2026
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- Women only
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: 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.
- Conditions
- Sarcopenia, Osteoporosis
- Being tested
- Denosumab, Zoledronic Acid, Denosumab Placebo, Zoledronic Acid Placebo
- Medical subject headings
- Sarcopenia, Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Half of study participants will randomly receive denosumab 60 mg subcutaneous injection at month 0 and 6 with zoledronic acid placebo at month 0.
Zoledronic AcidDrug
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 participants will receive zoledronic acid 5 mg intravenous infusion at month 12.
Denosumab PlaceboOther
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.
Zoledronic Acid PlaceboOther
Half of study participants who will randomly receive denosumab 60 mg subcutaneous injection at month 0 and 6 will also receive zoledronic acid placebo.
| Study group | Role | What they receive |
|---|---|---|
| Zoledronic Acid | Active comparator | Zoledronic acid 5 mg IV infusion at month 0, with placebo subcutaneous injections at months 0 and 6. Open-label zoledronic acid 5 mg IV at month 12. Receives: Drug: Zoledronic Acid; Other: Denosumab Placebo |
| Denosumab | Active comparator | Denosumab 60 mg subcutaneous injection at months 0 and 6, with placebo IV infusion at month 0. Open-label zoledronic acid 5 mg IV at month 12. Receives: Drug: Denosumab; Other: Zoledronic Acid Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Urinary D3-creatinine Enrichment (D3-creatine Dilution)
Muscle creatine pool size was estimated by D3-creatine dilution. Participants took a single 30 mg oral dose of deuterium-labeled creatine at baseline and 12 months, with a fasting morning urine sample collected approximately 72 hours later. Urinary D3-creatinine and total creatinine were measured by liquid chromatography-mass spectrometry. Enrichment is the " mol/mol ratio" of D3-creatinine to total creatinine in the same molar units, a dimensionless value from 0 to 1 (baseline values here were approximately 0.03, or 3%). Because about 95% of body creatine is in skeletal muscle, higher enrichment reflects less tracer dilution in a smaller pool and therefore less muscle mass. Reported values are the change (Month 12 minus Baseline), so a positive value is consistent with decreased muscle mass. Enrichment is reported rather than derived muscle mass because derived values showed high intra-individual variability.
Measured: Baseline vs Month 12
Percentage Change From Baseline in Bone Mineral Density (BMD)
BMD is measured by a DXA scan system and a higher BMD is correlated with lower fracture risk
Measured: Baseline vs Month 12
Change From Baseline in Appendicular Lean Mass.
Appendicular lean mass was measured by whole-body dual-energy X-ray absorptiometry and defined as the sum of lean soft tissue mass of both arms and both legs divided by height in meters squared "in kg/m²", excluding bone mineral content and fat mass. Values reported are the change (Month 12 minus Baseline) in appendicular lean mass index; a negative value indicates a decrease.
Measured: Baseline vs Month 12
Change From Baseline in Grip Strength
Grip strength is measure of muscle strength and will be measured by a standard hand dynamometer
Measured: Baseline vs Month 12
Change From Baseline in 4-Meter Walk Time (Gait Speed)
Gait speed is a measure of muscle function and will be measured by standard 4 meter gait speed test
Measured: Baseline vs Month 12
Change From Baseline in Rectus Femoris Muscle Thickness (cm)
This variable will be measured by ultrasound
Measured: Baseline vs Month 12
Change From Baseline in Rectus Femoris Muscle Cross-sectional Surface Area (cm²)
This variable will be measured by ultrasound
Measured: Baseline vs Month 12
CTX Changes
Marker of bone resorption
Measured: Baseline vs Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2022
- Study start14 Feb 2023
- Primary completion5 Jan 2026
- Study completion4 Aug 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SarcopeniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nami Safai Haeri
- Sponsor type
- University, hospital or other
- Collaborators
- The Claude D. Pepper Older Americans Independence Centers, National Institute on Aging (NIA)
- Responsible party
- Sponsor-investigator, Nami Safai Haeri, University of Pittsburgh
- Investigators
- Nami Safai Haeri, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05666310
- Sponsor's protocol ID
- STUDY22080139
- Other IDs
- P30AG024827
- Acronym
- MITO
- Status last verified
- Oct 2026
- First submitted
- 15 Dec 2022
- Last updated
- 27 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Osteoporosis Medications on Muscle Health in Older Adults
- ClinicalTrials.gov ID
- NCT05666310
- Acronym / sponsor ID
- MITO / STUDY22080139
- Conditions
- Sarcopenia, Osteoporosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Nami Safai HaeriUniversity, hospital or other
- Collaborators
- The Claude D. Pepper Older Americans Independence Centers, National Institute on Aging (NIA)
- Study start
- 14 Feb 2023 (actual)
- Primary completion
- 5 Jan 2026 (actual)
- Study completion
- 4 Aug 2026 (actual)
- First posted
- 27 Dec 2022 (actual)
- Results
- Posted 27 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zoledronic Acid | Active comparator | Drug: Zoledronic Acid, Other: Denosumab PlaceboZoledronic acid 5 mg IV infusion at month 0, with placebo subcutaneous injections at months 0 and 6. Open-label zoledronic acid 5 mg IV at month 12. |
| Denosumab | Active comparator | Drug: Denosumab, Other: Zoledronic Acid PlaceboDenosumab 60 mg subcutaneous injection at months 0 and 6, with placebo IV infusion at month 0. Open-label zoledronic acid 5 mg IV at month 12. |
Who may qualify
- Ages
- 65 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabHalf of study participants will randomly receive denosumab 60 mg subcutaneous injection at month 0 and 6 with zoledronic acid placebo at month 0. | Drug | Denosumab |
| Zoledronic AcidHalf of study participants will randomly receive zoledronic acid 5 mg intravenous infusion at month 0 with denosumab placebo at month 0 and 6. All participants will receive zoledronic acid 5 mg intravenous infusion at month 12. | Drug | Zoledronic Acid |
| Denosumab PlaceboHalf 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. | Other | Zoledronic Acid |
| Zoledronic Acid PlaceboHalf of study participants who will randomly receive denosumab 60 mg subcutaneous injection at month 0 and 6 will also receive zoledronic acid placebo. | Other | Denosumab |
Primary outcome
Change From Baseline in Urinary D3-creatinine Enrichment (D3-creatine Dilution)
Time frame: Baseline vs Month 12
Muscle creatine pool size was estimated by D3-creatine dilution. Participants took a single 30 mg oral dose of deuterium-labeled creatine at baseline and 12 months, with a fasting morning urine sample collected approximately 72 hours later. Urinary D3-creatinine and total creatinine were measured by liquid chromatography-mass spectrometry. Enrichment is the " mol/mol ratio" of D3-creatinine to total creatinine in the same molar units, a dimensionless value from 0 to 1 (baseline values here were approximately 0.03, or 3%). Because about 95% of body creatine is in skeletal muscle, higher enrichment reflects less tracer dilution in a smaller pool and therefore less muscle mass. Reported values are the change (Month 12 minus Baseline), so a positive value is consistent with decreased muscle mass. Enrichment is reported rather than derived muscle mass because derived values showed high intra-individual variability.
Percentage Change From Baseline in Bone Mineral Density (BMD)
Time frame: Baseline vs Month 12
BMD is measured by a DXA scan system and a higher BMD is correlated with lower fracture risk
Change From Baseline in Appendicular Lean Mass.
Time frame: Baseline vs Month 12
Appendicular lean mass was measured by whole-body dual-energy X-ray absorptiometry and defined as the sum of lean soft tissue mass of both arms and both legs divided by height in meters squared "in kg/m²", excluding bone mineral content and fat mass. Values reported are the change (Month 12 minus Baseline) in appendicular lean mass index; a negative value indicates a decrease.
Change From Baseline in Grip Strength
Time frame: Baseline vs Month 12
Grip strength is measure of muscle strength and will be measured by a standard hand dynamometer
Change From Baseline in 4-Meter Walk Time (Gait Speed)
Time frame: Baseline vs Month 12
Gait speed is a measure of muscle function and will be measured by standard 4 meter gait speed test
Change From Baseline in Rectus Femoris Muscle Thickness (cm)
Time frame: Baseline vs Month 12
This variable will be measured by ultrasound
Change From Baseline in Rectus Femoris Muscle Cross-sectional Surface Area (cm²)
Time frame: Baseline vs Month 12
This variable will be measured by ultrasound
CTX Changes
Time frame: Baseline vs Month 12
Marker of bone resorption
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Sarcopenia
Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
MF-300 for Treatment of Age-Related Sarcopenia
Sarcopenia in Elderly
Not yet recruitingObservational study
Validation of Uzbek SARC-F and IPAQ-SF Questionnaires in Adults With and Without Hypothyroidism
Hypothyroidism, Psychometrics
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nami Safai Haeri, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Denosumab and Zoledronic Acid in people with Sarcopenia and Osteoporosis, run by Nami Safai Haeri at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Urinary D3-creatinine Enrichment (D3-creatine Dilution) (time frame: Baseline vs Month 12). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.