Effect of a GH secretagogue, anamorelin, on serum irisin and inflammation levels in osteosarcopenic adults

Authors: DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; KONIECZYNSKI, ELSA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; REITSHAMER, ELISE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; CEGLIA, LISA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of the Endocrine Society
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/9/2024
Publication Date: 2/23/2024
Citation: Dawson-Hughes, B., Konieczynski, E.M., Reitshamer, E., Ceglia, L. 2024. Effect of a GH secretagogue, anamorelin, on serum irisin and inflammation levels in osteosarcopenic adults. Journal of the Endocrine Society. https://doi.org/10.1210/jendso/bvae028.
DOI: https://doi.org/10.1210/jendso/bvae028

Interpretive Summary: There may be an association between growth hormone (GH) secretion and circulating levels of the hormone, irisin, although evidence is mixed. Irisin is produced in muscle and blood levels of irisin increase in response to exercise. The impact of compounds that stimulate growth hormone release, GH secretagogues, on irisin levels is unknown. The objective of this study was to determine whether treatment with the GH secretagogue, anamorelin, altered serum levels of irisin in older adults with low bone and muscle mass (osteosarcopenia), and to assess whether irisin levels modulate the increase in blood glucose that occurs with anamorelin treatment. This study was conducted in older adults with osteosarcopenia who participated in a 12-month trial to determine the effect of anamorelin vs placebo on bone and muscle. The effect of anamorelin on inflammation markers was also assessed. Treatment with anamorelin did not significantly alter irisin levels or levels of inflammation markers. Further study is needed to confirm whether increasing irisin levels by becoming more physically active will lower the risk of hyperglycemia in older adults being treated with a GH secretagogue to improve their bone and muscle health.

Technical Abstract: Background: Data suggest an association between growth hormone (GH) secretion and circulating levels of the myokine, irisin, and inflammatory cytokines, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP). The impact of GH secretagogues on these markers is unknown. Objectives: To determine the effect of treatment with the GH secretagogue, anamorelin, on 12-month changes in serum irisin, IL-6 and hsCRP levels, and to assess whether baseline irisin levels modulate the glycemic response to treatment with anamorelin. Methods: This is an ancillary study in 26 older adults with osteosarcopenia who participated in a 12-month trial examining the effect of anamorelin 100 mg/day vs placebo on musculoskeletal outcomes. Serum irisin, IL-6, and hsCRP were measured at baseline and 12 months. Results: Treatment with anamorelin, compared with placebo, did not significantly alter irisin levels [12-month change = 0.50= +/-1.2 (SD) ng/mL in anamorelin group and -0.08 +/-2.3 ng/mL in placebo; P=0.191]. Baseline irisin levels were not significantly correlated with 2-month change in fasting glucose levels in the anamorelin group (r=-0.222, P=0.46) or the placebo group (r=0.30, P=0.34); however, the slopes of the two regression lines describing the relationship by group tended to differ (P=0.0547). Anamorelin treatment for 12 months had no significant effect on serum IL-6 or hsCRP levels. Conclusion: In this small sample of older adults with osteosarcopenia, treatment with the GH secretagogue anamorelin did not significantly alter levels of irisin, IL-6 or hsCRP. Higher baseline irisin levels may attenuate the glycemic response to anamorelin treatment; however, a larger study is needed to confirm this possibility.