Osteoprotective Effects of Melatonin on Bone Loss Associated with Dopaminergic Neuron Degeneration in a Rat Model of Parkinson Disease.

Publication date: Nov 05, 2025

Public health problems regarding the potential association between Parkinson’s disease (PD) and the increased prevalence of osteoporosis have been raised. However, the exact relationship, as well as potential treatment strategies, remains unclear and requires further investigation. Melatonin (MLT) is known for its beneficial effects on bone metabolism and its strong neuroprotective properties. Therefore, this study aimed to evaluate the potential role of MLT in the prevention and treatment of bone loss associated with PD using an hemiparkinsonian rat model induced by the destruction of dopaminergic neurons following intracerebral injection of 6-hydroxydopamine (6-OHDA). Forty male Wistar rats were divided into 5 groups: Control (CTR), 6-OHDA, MLT, 6-OHDA + MLT 1, and 6-OHDA + MLT 15. MLT (20 mg/kg/day) was administered intraperitoneally from Day 1 or Day 15, depending on the group. The effects on locomotor performance, oxidative status, bone structure, collagen accumulation, mineralization and the expression of bone marker proteins and genes were examined. Our results showed that the degeneration of dopaminergic neurons caused by 6-OHDA significantly impaired locomotor performance and induced marked alterations in bone parameters. Early MLT treatment (Day 1) mitigated these bone alterations by preserving structural integrity, enhancing collagen accumulation, and modulating bone marker expression. Importantly, beneficial effects on bone were also observed when MLT was administered later (Day 15), despite the absence of significant improvement in motor deficits. These findings suggest that dopaminergic neuron degeneration can negatively influence bone health and that MLT may exert a direct osteoprotective effect, supporting its possible therapeutic utility in managing bone fragility associated with PD.

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