The Effect of Denosumab on Muscle and Strength and Insulin Sensitivity

NCT07271771 | Recruiting Phase 4 DMC

• 1 other identifier: CTIS: 2024-510637-18-00
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, placebo controlled prospective trial evaluating the effect of denosumab on insulin sensitivity and muscle strength.

Conditions

Osteoporosis

Keywords

muscle; insulin sensitivity; denosumab; bone mineral density

Outcome Measures

Primary Outcomes (6)

• Insulin sensitivity: HbA1c

  Changes in Hb1Ac (mmol/mol) from baseline to month 12

  12 months

• Insulin sensitivity: HOMA-IR

  Changes in HOMA-IR from baseline to month 12

  12 months

• Insulin sensitivity: fasting glucose

  Changes in fasting glucose (mmol/l) from baseline to month 12

  12 months

• Insulin sensitivity: oral glucose tolerance test

  Changes in oral glucose tolerance test (OGTT) (mmol/l) from baseline to month 12

  12 months

• Muscle mass

  Changes in muscle mass (kg) from baseline to month 12.

  12 months

• Muscle strength

  Changes in muscle strength (N) from baseline to month 12.

  12 months

Secondary Outcomes (11)

• DPP-4

  12 months

• GLP-1

  12 months

• Bone turnover markers: CTX

  12 months

• Bone turnover markers: PINP

  12 months

• Bone Mineral Density

  12 months

Study Arms (2)

Study group 1

EXPERIMENTAL

Denosumab

Drug: Denosumab

Study group 2

PLACEBO COMPARATOR

Placebo

Drug: Saline (0.9% NaCl)

Interventions

Denosumab DRUG

Denosumab 60 mg

Study group 1

Saline (0.9% NaCl) DRUG

Placebo

Also known as: Placebo

Study group 2

Eligibility Criteria

• Age: 40 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aarhus University Hospital: lead
• Sponsor: MD, Professor, DMSc, PhD Bente Lomholt Langdahl: collaborator

Study Sites (1)

Aarhus University Hospital

Aarhus, Denmark

RECRUITING

Related Publications (15)

• Anastasilakis AD, Papapoulos SE, Polyzos SA, Appelman-Dijkstra NM, Makras P. Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial. J Bone Miner Res. 2019 Dec;34(12):2220-2228. doi: 10.1002/jbmr.3853. Epub 2019 Oct 14.

  PMID: 31433518 BACKGROUND

• Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008 Aug;43(2):222-229. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26.

  PMID: 18539106 BACKGROUND

• Rupp T, von Vopelius E, Strahl A, Oheim R, Barvencik F, Amling M, Rolvien T. Beneficial effects of denosumab on muscle performance in patients with low BMD: a retrospective, propensity score-matched study. Osteoporos Int. 2022 Oct;33(10):2177-2184. doi: 10.1007/s00198-022-06470-3. Epub 2022 Jun 25.

  PMID: 35751664 BACKGROUND

• Phu S, Bani Hassan E, Vogrin S, Kirk B, Duque G. Effect of Denosumab on Falls, Muscle Strength, and Function in Community-Dwelling Older Adults. J Am Geriatr Soc. 2019 Dec;67(12):2660-2661. doi: 10.1111/jgs.16165. Epub 2019 Sep 4. No abstract available.

  PMID: 31483858 BACKGROUND

• Miedany YE, Gaafary ME, Toth M, Hegazi MO, Aroussy NE, Hassan W, Almedany S, Nasr A, Bahlas S, Galal S; Egyptian Academy of Bone Health, Metabolic Bone Diseases. Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia? Clin Rheumatol. 2021 Oct;40(10):4225-4232. doi: 10.1007/s10067-021-05757-w. Epub 2021 May 19.

  PMID: 34008069 BACKGROUND

• Rossini A, Frigerio S, Dozio E, Trevisan R, Perseghin G, Corbetta S. Effect of Denosumab on Glucose Homeostasis in Postmenopausal Women with Breast Cancer Treated with Aromatase Inhibitors: A Pilot Study. Int J Endocrinol. 2020 Nov 6;2020:1809150. doi: 10.1155/2020/1809150. eCollection 2020.

  PMID: 33204260 BACKGROUND

• Lasco A, Morabito N, Basile G, Atteritano M, Gaudio A, Giorgianni GM, Morini E, Faraci B, Bellone F, Catalano A. Denosumab Inhibition of RANKL and Insulin Resistance in Postmenopausal Women with Osteoporosis. Calcif Tissue Int. 2016 Feb;98(2):123-8. doi: 10.1007/s00223-015-0075-5. Epub 2015 Oct 24.

  PMID: 26498169 BACKGROUND

• Passeri E, Benedini S, Costa E, Corbetta S. A Single 60 mg Dose of Denosumab Might Improve Hepatic Insulin Sensitivity in Postmenopausal Nondiabetic Severe Osteoporotic Women. Int J Endocrinol. 2015;2015:352858. doi: 10.1155/2015/352858. Epub 2015 Mar 19.

  PMID: 25873952 BACKGROUND

• Napoli N, Pannacciulli N, Vittinghoff E, Crittenden D, Yun J, Wang A, Wagman R, Schwartz AV. Effect of denosumab on fasting glucose in women with diabetes or prediabetes from the FREEDOM trial. Diabetes Metab Res Rev. 2018 May;34(4):e2991. doi: 10.1002/dmrr.2991. Epub 2018 Apr 16.

  PMID: 29430796 BACKGROUND

• Abe I, Ochi K, Takashi Y, Yamao Y, Ohishi H, Fujii H, Minezaki M, Sugimoto K, Kudo T, Abe M, Ohnishi Y, Mukoubara S, Kobayashi K. Effect of denosumab, a human monoclonal antibody of receptor activator of nuclear factor kappa-B ligand (RANKL), upon glycemic and metabolic parameters: Effect of denosumab on glycemic parameters. Medicine (Baltimore). 2019 Nov;98(47):e18067. doi: 10.1097/MD.0000000000018067.

  PMID: 31764838 BACKGROUND

• Bonnet N, Bourgoin L, Biver E, Douni E, Ferrari S. RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass. J Clin Invest. 2019 May 23;129(8):3214-3223. doi: 10.1172/JCI125915.

  PMID: 31120440 BACKGROUND

• Weivoda MM, Chew CK, Monroe DG, Farr JN, Atkinson EJ, Geske JR, Eckhardt B, Thicke B, Ruan M, Tweed AJ, McCready LK, Rizza RA, Matveyenko A, Kassem M, Andersen TL, Vella A, Drake MT, Clarke BL, Oursler MJ, Khosla S. Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism. Nat Commun. 2020 Jan 7;11(1):87. doi: 10.1038/s41467-019-14003-6.

  PMID: 31911667 BACKGROUND

• Bone HG, Wagman RB, Brandi ML, Brown JP, Chapurlat R, Cummings SR, Czerwinski E, Fahrleitner-Pammer A, Kendler DL, Lippuner K, Reginster JY, Roux C, Malouf J, Bradley MN, Daizadeh NS, Wang A, Dakin P, Pannacciulli N, Dempster DW, Papapoulos S. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017 Jul;5(7):513-523. doi: 10.1016/S2213-8587(17)30138-9. Epub 2017 May 22.

  PMID: 28546097 BACKGROUND

• Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65. doi: 10.1056/NEJMoa0809493. Epub 2009 Aug 11.

  PMID: 19671655 BACKGROUND

• Lacey DL, Boyle WJ, Simonet WS, Kostenuik PJ, Dougall WC, Sullivan JK, San Martin J, Dansey R. Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab. Nat Rev Drug Discov. 2012 May;11(5):401-19. doi: 10.1038/nrd3705.

  PMID: 22543469 BACKGROUND

MeSH Terms

Conditions

Osteoporosis; Insulin Resistance

Interventions

Denosumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperinsulinism; Glucose Metabolism Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Bente Langdahl, MD, Professor, DMSc, PhD

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne Sophie Sølling, MD, PhD

CONTACT

+45 22 30 05 24; annesoel@rm.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, postdoc

Model Details: The study is a randomized double-blind, interventional study in 40 postmenopausal with diabetes mellitus type 2. The patients will be randomized at baseline to denosumab 60 mg (n=20) or placebo (n=20), which will administrated at base-line and month 6.

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 9, 2025
• Study Start: May 21, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)