Systematic review finds limited and mixed evidence that antiparkinsonian medications—particularly L‑Dopa via elevated homocysteine—may influence bone mineral density, but causal links are not established.

Low immediate value for PD therapeutic discovery, but clinically relevant for fracture risk management and suggests a testable biomarker (homocysteine) and adjunctive intervention opportunity rather than a direct disease‑modifying target.

INTRODUCTION: Parkinson's disease (PD) is associated with elevated fracture risk, particularly at the hip. Antiparkinsonian medications have also been associated with increased fracture risk; although their direct effects on bone mineral density (BMD) remains unclear. OBJECTIVE: Investigate whether antiparkinsonian medications influence BMD. METHODS: A systematic search of four databases (Embase, MEDLINE, APA PsycINFO, Web of Science) was conducted up to 24/11/2025 using terms related to PD, antiparkinsonian medications and bone. RESULTS: A total of 748 records were identified, with 543 screened following deduplication. Fourteen studies underwent full-text review, of which seven met inclusion criteria. Three studies assessed bone mineral content or surrogate measures at non-standard sites (hand radiographs or skull Hounsfield Units) and reported no associations with L-Dopa therapy. Four studies reported areal BMD (aBMD) from dual energy x-ray absorptiometry (DXA). One study showed negative correlations between L-Dopa dosage with aBMD at the hip and spine. Two studies (RCT and cross-sectional) implicated elevated serum homocysteine (Hcy) levels induced by L-Dopa as a potential mechanism for osteoporosis risk in PD. In the cross-sectional study, although L-Dopa therapy was associated with higher Hcy and lower aBMD, there were no causal associations between L-Dopa and hip aBMD. In the RCT, lower Hcy was associated with reduced annual aBMD loss with L-Dopa therapy. One further study found no associations between L-Dopa therapy and aBMD at any site. CONCLUSIONS: The contribution of antiparkinsonian medication to low BMD in PD remains unclear. Despite plausible mechanisms of action, evidence of causal associations is lacking.