The Effect of Denosumab on Muscle and Strength and Insulin Sensitivity

Summary

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

Timeline

Start

2024-05-21

Primary completion

2027-03-01

Completion

2027-03-01

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications