Bone loss caused by dopaminergic degeneration and levodopa treatment in Parkinson’s disease model mice

• Published in: Scientific reports 2019-09, Vol.9 (1), p.13768-16, Article 13768
• Main Authors: Handa, Kazuaki, Kiyohara, Shuichi, Yamakawa, Tomoyuki, Ishikawa, Koji, Hosonuma, Masahiro, Sakai, Nobuhiro, Karakawa, Akiko, Chatani, Masahiro, Tsuji, Mayumi, Inagaki, Katsunori, Kiuchi, Yuji, Takami, Masamichi, Negishi-Koga, Takako
• Format: Article
• Language: English
• Subjects: 38/61; 38/77; 631/80/304; 64/60; 692/308/1426; 96/106; 96/31; Animals; Antiparkinson Agents - adverse effects; Antiparkinson Agents - pharmacology; Bone Diseases, Metabolic - chemically induced; Bone Diseases, Metabolic - etiology; Bone Diseases, Metabolic - metabolism; Bone growth; Bone loss; Bone turnover; Disease Models, Animal; Dopamine - metabolism; Dopamine receptors; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - pathology; Estrogens; Female; Hormone replacement therapy; Humanities and Social Sciences; Levodopa; Levodopa - adverse effects; Levodopa - pharmacology; Male; Malnutrition; Menopause; Metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Motor activity; Movement disorders; multidisciplinary; Muscle strength; Neurodegeneration; Neurodegenerative diseases; Neurotoxins; Osteoclastogenesis; Osteogenesis; Osteoporosis; Osteoporosis - chemically induced; Osteoporosis - metabolism; Osteoporosis - pathology; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Post-menopause; Prolactin; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• 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.