Effect of Selective Androgen Receptor Modulator Enobosarm on Bone Healing in a Rat Model for Aged Male Osteoporosis
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ORIGINAL RESEARCH
Effect of Selective Androgen Receptor Modulator Enobosarm on Bone Healing in a Rat Model for Aged Male Osteoporosis Marina Komrakova1 · Janek Nagel1 · Daniel Bernd Hoffmann1 · Wolfgang Lehmann1 · Arndt Friedrich Schilling1 · Stephan Sehmisch1 Received: 20 May 2020 / Accepted: 14 August 2020 © The Author(s) 2020
Abstract Enobosarm (ostarine, MK-2866, or GTx-024) is a non-steroidal selective androgen receptor modulator. This study evaluated the effect of various regimens of enobosarm (EN) on bone healing in an orchiectomized rat model for aged male osteoporosis and compared it to testosterone (T) treatment. Ninety eight-month-old male Sprague Dawley rats were either orchiectomized (Orx) or left intact (Non-Orx) and divided into groups (n = 15/group): (1) Non-Orx; (2) Orx; (3) Orx+T-th; (4) Orx+EN-th; (5) Orx+T-pr; and (6) Orx+EN-pr. Prophylaxis (Pr) treatments were applied immediately after Orx for up to 18 weeks. Therapy (Th) treatments were applied 12 weeks after Orx for up to 6 weeks. Bilateral tibia osteotomy with plate osteosynthesis was performed 12 weeks after Orx in all groups. EN and T were mixed with the diet; the daily dosage was 0.35 ± 0.06 and 41 ± 8 mg/kg BW, respectively. Both T treatments improved bone healing by increasing callus volume and area, bone volume and density, and cortical width; they had no effect on prostate or levator ani weight. EN-pr increased the callus area and callus density and decreased cortical density, but increased prostate weight. The effect of T-pr and T-th on bone was stronger than EN-pr. EN-th affected bone healing negatively by reducing callus density and area and delaying osteotomy bridging. Levator ani weight was increased in both EN groups. EN treatment after fracture is not advisable in aged males. EN-pr treatment as a therapy for bone healing in men could be further investigated; endocrinological side effects must be closely monitored. Keywords Selective androgen receptor modulator · Enobosarm · Testosterone · Bone healing · Male osteoporosis
Introduction Fractured bones impair the quality of life of patients, and osteoporosis impedes normal bone healing processes [1, 2]. Despite increasing recognition of the problem of male osteoporosis, postmenopausal osteoporosis has been the focus of research, and most treatments have been developed for women. In men, there are only a few options for osteoporosis treatment. Non-pharmacologic treatment includes diet and lifestyle changes to reduce the risk of fracture [3, 4]. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00223-020-00751-x) contains supplementary material, which is available to authorized users. * Marina Komrakova [email protected]‑goettingen.de 1
Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Goettingen, Robert‑Koch Str. 40, 37075 Goettingen, Germany
Therapeutic options include the administration of bisphosphonates, human parathyroid hormone, teriparatide, denosumab, or romosozumab. T
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