Department of Orthopaedic Surgery, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
Department of Pharmacology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
Sci Rep. 2019 Sep 24;9(1):13768. doi: 10.1038/s41598-019-50336-4.
Accumulating evidence have shown the association of Parkinson's disease (PD) with osteoporosis. Bone loss in PD patients, considered to be multifactorial and a result of motor disfunction, is a hallmark symptom that causes immobility and decreased muscle strength, as well as malnutrition and medication. However, no known experimental evidence has been presented showing deleterious effects of anti-PD drugs on bone or involvement of dopaminergic degeneration in bone metabolism. Here, we show that osteoporosis associated with PD is caused by dopaminergic degeneration itself, with no deficit of motor activity, as well as treatment with levodopa, the current gold-standard medication for affected patients. Our findings show that neurotoxin-induced dopaminergic degeneration resulted in bone loss due to accelerated osteoclastogenesis and suppressed bone formation, which was associated with elevated prolactin. On the other hand, using an experimental model of postmenopausal osteoporosis, dopaminergic degeneration did not result in exacerbation of bone loss due to estrogen deficiency, but rather reduction of bone loss. Thus, this study provides evidence for the regulation of bone metabolism by the dopaminergic system through both gonadal steroid hormone-dependent and -independent functions, leading to possible early detection of osteoporosis development in individuals with PD.
越来越多的证据表明帕金森病 (PD) 与骨质疏松症有关。PD 患者的骨丢失被认为是多种因素的结果，是运动功能障碍的结果，是导致活动能力下降、肌肉力量减弱、营养不良和药物治疗的标志性症状。然而，目前尚无已知的实验证据表明抗 PD 药物对骨骼有有害影响，或涉及多巴胺能退化对骨代谢的影响。在这里，我们表明与 PD 相关的骨质疏松症是由多巴胺能退化本身引起的，与运动活动不足无关，也与左旋多巴的治疗无关，左旋多巴是目前受影响患者的黄金标准药物。我们的研究结果表明，神经毒素诱导的多巴胺能退化导致骨丢失，原因是破骨细胞生成加速和骨形成受到抑制，这与催乳素升高有关。另一方面，在绝经后骨质疏松症的实验模型中，多巴胺能退化并没有导致雌激素缺乏引起的骨丢失加重，而是减少了骨丢失。因此，这项研究为通过多巴胺能系统的性腺类固醇激素依赖和非依赖功能对骨代谢的调节提供了证据，这可能导致对 PD 患者骨质疏松症发展的早期检测。
