Department of Trauma, Orthopaedic and Plastic Surgery, Georg-August-University of Goettingen, Robert Koch St. No. 40, 37075, Goettingen, Germany.
Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, Tuebingen, Germany.
J Bone Miner Metab. 2023 Nov;41(6):741-751. doi: 10.1007/s00774-023-01453-8. Epub 2023 Jul 6.
The selective androgen receptor modulator ligandrol (LGD-4033 or VK5211) has been shown to improve muscle tissue. In the present study, the effect of ligandrol on bone tissue was investigated in ovariectomized rat model.
Three-month-old Sprague Dawley rats were either ovariectomized (OVX, n = 60) or left intact (NON-OVX, n = 15). After 9 weeks, OVX rats were divided into four groups: untreated OVX (n = 15) group and three OVX groups (each of 15 rats) treated with ligandrol orally at doses of 0.03, 0.3, or 3 mg/kg body weight. After five weeks, lumbar vertebral bodies (L), tibiae, and femora were examined using micro-computed tomographical, biomechanical, ashing, and gene expression analyses.
In the 3-mg ligandrol group, bone structural properties were improved (trabecular number: 38 ± 8 vs. 35 ± 7 (femur), 26 ± 7 vs. 22 ± 6 (L), 12 ± 5 vs. 6 ± 3 (tibia) and serum phosphorus levels (1.81 ± 0.17 vs.1.41 ± 0.17 mmol/l), uterus (0.43 ± 0.04 vs. 0.11 ± 0.02 g), and heart (1.13 ± 0.11 vs. 1.01 ± 0.08 g) weights were increased compared to the OVX group. Biomechanical parameters were not changed. Low and medium doses did not affect bone tissue and had fewer side effects. Body weight and food intake were not affected by ligandrol; OVX led to an increase in these parameters and worsened all bone parameters.
Ligandrol at high dose showed a subtle anabolic effect on structural properties without any improvement in biomechanical properties of osteoporotic bones. Considering side effects of ligandrol at this dose, its further investigation for the therapy of postmenopausal osteoporosis should be reevaluated.
选择性雄激素受体调节剂配体激动剂（LGD-4033 或 VK5211）已被证明能改善肌肉组织。在本研究中，我们研究了配体激动剂对去卵巢大鼠模型中骨组织的影响。
3 月龄 Sprague Dawley 大鼠行卵巢切除术（OVX，n = 60）或假手术（NON-OVX，n = 15）。9 周后，OVX 大鼠分为四组：未治疗的 OVX 组（n = 15）和三组 OVX 组（每组 15 只），经口给予配体激动剂 0.03、0.3 或 3mg/kg 体重。5 周后，采用 micro-CT、生物力学、灰化和基因表达分析检测腰椎体（L）、胫骨和股骨。
在 3mg/kg 配体激动剂组，骨结构特性得到改善（股骨：小梁数分别为 38 ± 8 vs. 35 ± 7，L：26 ± 7 vs. 22 ± 6，胫骨：12 ± 5 vs. 6 ± 3）和血清磷水平（1.81 ± 0.17 vs. 1.41 ± 0.17 mmol/l）、子宫（0.43 ± 0.04 vs. 0.11 ± 0.02 g）和心脏（1.13 ± 0.11 vs. 1.01 ± 0.08 g）重量增加，与 OVX 组相比。生物力学参数无变化。低、中剂量不影响骨组织，副作用较少。配体激动剂不影响体重和食物摄入；OVX 导致这些参数增加，所有骨参数恶化。
高剂量的配体激动剂对结构特性有轻微的合成代谢作用，但对骨质疏松骨的生物力学特性没有改善。考虑到配体激动剂在此剂量下的副作用，其对绝经后骨质疏松症的治疗作用应重新评估。
