Department of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Goettingen, Robert-Koch Str. 40, 37075, Goettingen, Germany.
Calcif Tissue Int. 2020 Dec;107(6):593-602. doi: 10.1007/s00223-020-00751-x. Epub 2020 Sep 2.
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.
依诺司他（Ostarine，MK-2866，或 GTx-024）是一种非甾体类选择性雄激素受体调节剂。本研究评估了依诺司他（EN）在去势雄性骨质疏松症老年雄性大鼠模型中的不同方案对骨愈合的影响，并与睾酮（T）治疗进行了比较。98 月龄雄性 Sprague Dawley 大鼠行去势（Orx）或假手术（Non-Orx），并分为以下几组（每组 n=15）：（1）Non-Orx；（2）Orx；（3）Orx+T-th；（4）Orx+EN-th；（5）Orx+T-pr；和（6）Orx+EN-pr。预防（Pr）治疗在去势后立即进行，最多持续 18 周。治疗（Th）治疗在去势后 12 周开始，最多持续 6 周。所有组均在去势后 12 周行双侧胫骨骨折切开复位钢板内固定术。EN 和 T 混合在饲料中给药；每日剂量分别为 0.35±0.06 和 41±8mg/kg BW。两种 T 治疗均通过增加骨痂体积和面积、骨体积和密度以及皮质宽度来改善骨愈合；它们对前列腺或肛提肌重量无影响。EN-pr 增加了骨痂面积和骨痂密度，降低了皮质密度，但增加了前列腺重量。T-pr 和 T-th 对骨骼的影响强于 EN-pr。EN-th 对骨愈合有负面影响，降低了骨痂密度和面积，并延迟了骨折愈合。两种 EN 组的肛提肌重量均增加。对于老年男性，骨折后不建议使用依诺司他治疗。可以进一步研究 EN-pr 作为男性骨愈合治疗的方法；必须密切监测内分泌副作用。
