Effect of anamorelin, a ghrelin receptor agonist, on muscle and bone in adults with osteosarcopenia

Authors: DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BARGER, KATHRYN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; REITSHAMER, ELISE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; EVANS, WILLIAM - University Of California Berkeley; CEGLIA, LISA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/27/2023
Publication Date: 12/6/2023
Citation: Dawson-Hughes, B., Barger, K., Reitshamer, E., Fielding, R.A., Evans, W., Ceglia, L. 2023. Effect of anamorelin, a ghrelin receptor agonist, on muscle and bone in adults with osteosarcopenia. Journal of Clinical Endocrinology and Metabolism. https://doi.org/10.1210/clinem/dgad702.
DOI: https://doi.org/10.1210/clinem/dgad702

Interpretive Summary: Low muscle mass and low bone mass contribute to loss of function and fractures in older adults. Anamorelin, a ghrelin receptor agonist known to stimulate the pulsatile release of growth hormone (GH) from the pituitary, has the potential to improve musculoskeletal health in adults with low bone and muscle mass (osteosarcopenia, OS). This small study was done to determine the effect of anamorelin treatment for one year on muscle mass and strength and on biochemical markers of bone turnover in adults with OS. In 26 older men and women with OS, treatment with anamorelin, compared with placebo, had no effect on muscle mass; however, it increased leg strength by 20% and increased an indicator of bone formation by 75%. These changes appeared to result from changes in the production of the growth factor, IGF-1, which increased by 50%. This small study found no significant impact of anamorelin on muscle mass, but potential improvements in muscle strength in the legs and in bone formation. Further study is needed to assess these potential improvements in a larger population of adults with OS.

Technical Abstract: Anamorelin, a ghrelin receptor agonist known to stimulate the pulsatile release of growth hormone (GH) from the pituitary, has the potential to improve musculoskeletal health in adults with osteosarcopenia. Objective: To determine the effect of anamorelin treatment for one year on muscle mass and strength and on biochemical markers of bone turnover in adults with osteosarcopenia (OS). Design: Randomized, placebo-controlled, 1-year anamorelin intervention trial Setting: The Bone Metabolism Laboratory at the USDA Nutrition Center at Tufts University. Participants: 26 men and women, age 50 years and older, with OS Main outcome measures: muscle mass by D3-creatine dilution and lean body mass (LBM) by dual energy X-ray absorptiometry, muscle strength, and bone turnover markers, serum procollagen 1 intact N-terminal (P1NP) and C-terminal telopeptide (CTX) Results: Anamorelin did not have a significant effect on muscle mass or LBM; it significantly increased knee flexion torque at 240 0/S by 20% (P = 0.013) and had a similar non-statistically significant change in knee extension; it increased bone formation (P1NP) by 75% (P = 0.006), and had no significant effect on placebo group (P = 0.0001 for group difference). Conclusions: This pilot study indicates that anamorelin is a promising agent to potentially improve musculoskeletal health in adults with osteosarcopenia and that further study of anamorelin in this population is warranted.