The Effect of Denosumab on Muscle and Strength and Insulin Sensitivity (DENMUSIN)

December 8, 2025 updated by: Anne Sophie Sølling, Aarhus University Hospital
Randomized, placebo controlled prospective trial evaluating the effect of denosumab on insulin sensitivity and muscle strength.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Denosumab is an antibody against receptor-activator of nuclear factor kappa-B ligand (RANKL) that prevents recruitment and differentiation of mature osteoclasts. Treatment with denosumab markedly decreases bone resorption, increases bone mineral density (BMD), and reduces the risk of vertebral as well as non-vertebral and hip fractures. Osteoclasts produce dipeptidyl peptidase-4 (DPP-4) that degrades glucagon-like peptide-1 (GLP-1) and GLP-1 stimulates insulin production. In accordance with this, animal models have shown a beneficial effect of denosumab on glucose metabolism. However, data from clinical studies in patients with osteoporosis are limited and the results inconsistent. In a small, randomised trial with 52 healthy postmenopausal women, treatment with denosumab for 12 months reduced DPP-4 and increased GLP-1 compared to placebo but no effect was seen on insulin or fasting glucose levels. In the same publication, the authors conducted a non-randomized, observational study in osteoporotic patients with diabetes mellitus or prediabetes that were treated with either denosumab, bisphosphonates, or calcium + vitamin D at the discretion of their physician. Here, treatment with denosumab significantly reduced fasting glucose after 6 months and HbA1c after 12 months compared to bisphosphonates or calcium + vitamin D. Similar findings were seen in another observational study with 20 patients with diabetes. On the other hand, a post hoc analysis of the FREEDOM trial did not find a general effect of denosumab on fasting glucose in postmenopausal women with self-reported diabetes or prediabetes, but only reported a small decrease in fasting glucose in denosumab treated women with diabetes not treated with antidiabetics. This is in line with three small observational studies, in which no clinically relevant effect of denosumab on fasting glucose, insulin level or homeostatic model assessment for insulin resistance (HOMA-IR) was identified.

Overall, the heterogeneity across the studies is large, most of the trials are observational studies and the results are inconsistent. Therefore, randomized, controlled trials are warranted to further elucidate this.

Denosumab has also been shown to improve muscle strength compared to placebo in animal models, however, data from human studies is limited. In an observational study, denosumab decreased the risk of falls and improved sarcopenia measures in 135 patients with osteoporosis compared to 272 patients treated with alendronate or zoledronate assessed at treatment initiation and after 5 years for denosumab and alendronate and 3 years for zoledronate. All outcome measures worsened one years after denosumab discontinuation. In another prospective observational study with 18 postmenopausal women, denosumab treatment for an average of three years improved appendicular lean mass and handgrip strength compared to treatment with bisphosphates or placebo. This is in line with two additional observational studies, in which denosumab improved muscle strength after 6 - 17 months compared to bisphosphonates or vitamin D.

None of the studies evaluating the effect of denosumab on muscle strength are randomised controlled trials, the outcome measures are different and the follow up visits few. Also, none of the studies controlled for exercise.

The investigators therefore want to conduct a randomized, placebo controlled prospective trial evaluating the effect of denosumab on insulin sensitivity and muscle strength.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Anne Sophie Sølling, MD, PhD
  • Phone Number: +45 22 30 05 24
  • Email: annesoel@rm.dk

Study Locations

  • Denmark
      • Aarhus, Denmark
        • Recruiting
        • Aarhus University Hospital
        • Contact:
          • Anne Sophie Sølling, MD, PhD
          • Phone Number: +45 22 30 05 24
          • Email: annesoel@rm.dk

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Postmenopausal women (postmenopausal for at least two years)
  • Age ≥ 40 years
  • BMD T-score ≥ -2.0 (lumbar spine, total hip or femoral neck)
  • At least 2 lumbar vertebrae that can be evaluated by dual-energy x-ray absorptiometry (DXA)
  • Diabetes Mellitus type 2
  • Treatment with metformin as monotherapy

Exclusion Criteria:

  • Treatment for osteoporosis at any time
  • Other antidiabetic medication than metformin
  • Low-energy vertebral fractures at any time
  • Low-energy hip fracture at any time
  • Ongoing treatment with systemic glucocorticoids
  • Metabolic bone disease (for example osteogenesis imperfecta, Paget's disease of bone, hyperparathyroidism)
  • Treatment affecting bone, calcium metabolism or muscle
  • Active cancer within the last 5 years with the exception of basal cell skin cancer
  • Estimated glomerular filtration rate (eGFR) ≤ 35 mL/min
  • Unable to read and understand Danish
  • Immobility

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Study group 1
Denosumab
Drug: Denosumab
Denosumab 60 mg
Placebo Comparator: Study group 2
Placebo
Drug: Saline (0.9% NaCl)
Placebo
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Insulin sensitivity: HbA1c
Time Frame: 12 months
Changes in Hb1Ac (mmol/mol) from baseline to month 12
12 months
Insulin sensitivity: HOMA-IR
Time Frame: 12 months
Changes in HOMA-IR from baseline to month 12
12 months
Insulin sensitivity: fasting glucose
Time Frame: 12 months
Changes in fasting glucose (mmol/l) from baseline to month 12
12 months
Insulin sensitivity: oral glucose tolerance test
Time Frame: 12 months
Changes in oral glucose tolerance test (OGTT) (mmol/l) from baseline to month 12
12 months
Muscle mass
Time Frame: 12 months
Changes in muscle mass (kg) from baseline to month 12.
12 months
Muscle strength
Time Frame: 12 months
Changes in muscle strength (N) from baseline to month 12.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DPP-4
Time Frame: 12 months
Changes in DPP-4 (U/L) from baseline to month 12.
12 months
GLP-1
Time Frame: 12 months
Changes in GLP-1 (pmol/L) from baseline to month 12.
12 months
Bone turnover markers: CTX
Time Frame: 12 months
Changes in carboxy-terminal collagen crosslinks (CTX) (ug/l) from baseline to month 12.
12 months
Bone turnover markers: PINP
Time Frame: 12 months
Changes in procollagen type I N-terminal propeptide (PINP) (ug/L) from baseline to month 12.
12 months
Bone Mineral Density
Time Frame: 12 months
Change in lumbar spine BMD (g/cm2) from baseline to month 12.
12 months
Advanced glycation end products (AGEs)
Time Frame: 12 months
Change in advanced glycation end products (AGEs) from baseline to month 12.
12 months
Muscle strength
Time Frame: Month 1 and 3
Changes in muscle strength (N) from baseline to month 1 and 3.
Month 1 and 3
Insulin sensitivity: Hb1Ac month 1 and 3
Time Frame: Month 1 and 3
Changes in Hb1Ac (mmol/mol) from baseline to month 1 and 3
Month 1 and 3
Insulin sensitivity: HOMA-IR month 1 and 3
Time Frame: Month 1 and 3
Changes in HOMA-IR from baseline to month 1 and 3
Month 1 and 3
insulin sensitivity: fasting glucose month 1 and 3
Time Frame: Month 1 and 3
Changes in fasting glucose (mmol/l) from baseline to month 1 and 3
Month 1 and 3
Insulin sensitivity: OGTT month 1 and 3
Time Frame: Month 1 and 3
Changes in oral glucose tolerance test (OGTT) (mmol/l) from baseline to month 1 and 3
Month 1 and 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aarhus University Hospital

Collaborators

Sponsor: MD, Professor, DMSc, PhD Bente Lomholt Langdahl

Investigators

  • Principal Investigator: Bente Langdahl, MD, Professor, DMSc, PhD, Aarhus University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 21, 2024

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

November 19, 2025

First Submitted That Met QC Criteria

November 26, 2025

First Posted (Estimated)

December 9, 2025

Study Record Updates

Last Update Posted (Actual)

December 15, 2025

Last Update Submitted That Met QC Criteria

December 8, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTIS: 2024-510637-18-00 (Other Identifier: Aarhus University Hospital, Denmark)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

All results including inconclusive, positive, and negative results will be accessible to the public after the study has ended. As soon as possible and no later than one year after the trial has ended, the trial results will be submitted to the CTIS-portal.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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