A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats

• Published in: Journal of endocrinological investigation 2022-12, Vol.45 (12), p.2299-2311
• Main Authors: Komrakova, M., Büchler, G., Böker, K. O., Lehmann, W., Schilling, A. F., Roch, P. J., Taudien, S., Hoffmann, D. B., Sehmisch, S.
• Format: Article
• Language: English
• Subjects: Androgen receptors; Androgens; Biomechanics; Body weight; Bone loss; Computed tomography; Endocrinology; Estrogen receptors; Estrogens; Food intake; Gene expression; Internal Medicine; Kidneys; Liver; Mechanical properties; Medicine; Medicine & Public Health; Metabolic Diseases; Original; Original Article; Osteoporosis; Prostate; Raloxifene; Spine (lumbar)
• ISSN: 1720-8386; 0391-4097; 1720-8386
• DOI: 10.1007/s40618-022-01865-9

Purpose Enobosarm (EN), a selective androgen receptor modulator and raloxifene (RAL), a selective estrogen receptor modulator, have been shown to improve bone tissue in osteoporotic males. The present study evaluated the effects of a combination therapy of EN and RAL on bone properties in orchiectomized rats compared to the respective single treatments. Methods Eight-month-old male Sprague–Dawley rats were either left intact (Non-Orx) or orchiectomized (Orx). The Orx rats were divided into four groups (n = 15 each): 1) Orx, 2) EN treatment (Orx + EN), 3) RAL treatment (Orx + RAL), 4) combined treatment (Orx + EN + RAL). EN and RAL (0.4 mg and 7 mg/kg body weight/day) were applied immediately after Orx with a soy-free pelleted diet for up to 18 weeks. The lumbar spine and femora were examined by micro-CT, biomechanical, histomorphological, ashing, and gene expression analyses. Results EN exhibited an anabolic effect on bone, improving some of its parameters in Orx rats, but did not affect biomechanical properties. RAL exhibited antiresorptive activity, maintaining the biomechanical and trabecular parameters of Orx rats at the levels of Non-Orx rats. EN + RAL exerted a stronger effect than the single treatments, improving most of the bone parameters. Liver weight increased after all treatments; the kidney, prostate, and levator ani muscle weights increased after EN and EN + RAL treatments. BW was reduced due to a decreased food intake in the Orx + RAL group and due a reduced visceral fat weight in the Orx + EN + RAL group. Conclusion The EN + RAL treatment appeared to be promising in preventing male osteoporosis, but given the observed side effects on liver, kidney, and prostate weights, it requires further investigation.