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

Abstract

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.

Urinary proteome profiling for stratifying patients with familial Parkinson’s disease

“…Inhibitors of the closely related family member cyclophilin D (CypD) are considered as therapeutic agents against several neurodegenerative diseases including PD (Fayaz et al, 2015). Most other proteins associated with the GO term "bone development" were downregulated in PD patients, in line with recent findings that PD patients frequently suffer from osteoporosis and osteopenia (Torsney et al, 2014;Handa et al, 2019). Going forward, it would be important to examine the relationship between PD progression and bone health more closely, as this connection is currently underexplored.…”

Crosstalk of Brain and Bone—Clinical Observations and Their Molecular Bases

“…As a result, the majority of PD patients are prone not only to neurological impairment and postural imbalance but also an increased fracture risk [ 18 , 86 ]. Along with correlating vitamin D deficiency, reduced body weight [ 87 ] and female gender [ 88 ], recent evidence propose a direct effect of PD on bone through degeneration of dopaminergic neurons, resulting in accelerated osteoclastogenesis and suppressed bone formation [ 89 ].…”

Urinary proteome profiling for stratifying patients with familial Parkinson’s disease

“…Inhibitors of the closely related family member cylophilin D (CypD) are considered as therapeutic agents against several neurodegenerative diseases including PD [57]. Most other proteins associated with the GO-term 'bone development' were downregulated in PD patients, in line with recent findings that PD patients frequently suffer from osteoporosis and osteopenia [46,58]. Going forward, it would be important to examine the relationship between PD profession and bone health more closely, as this connection is currently underexplored.…”