Introduction: Parkinson’s disease (PD) is the fastest growing neurological disorder globally. Defining features include tremor, muscular rigidity, bradykinesia, and postural instability which contribute to frequent falls. Coupled with a high prevalence of osteoporosis, this drives high fracture rates, particularly at the hip. Osteoporosis guidelines highlight antiparkinsonian medications (i.e. to treat PD motor-symptoms) as being associated with increased fracture-risk; though the extent to which these medications directly impact bone mineral density (BMD) is not clear.
Methods: A systematic search of 4 databases (Embase, MEDLINE, APA PsychInfo, Web of Science) was performed combining PD, antiparkinsonian medications, and bone related search terms. All records were screened by at least two reviewers and risk of bias assessment performed using ROB2/ROBINS-E.
Results: A total of 602 studies were identified, following deduplication. Twenty-seven records underwent full-text review. We included five studies with bone data in people with PD taking Levodopa (L-Dopa). Two studies reported BMD or related surrogates at non-standard sites (hand x-ray, skull HU) severely limiting their clinical relevance. One study reported negative correlations between L-Dopa dosage and hip and lumbar spine aBMD, though no adjustments for PD duration or severity were performed. One observational study and one RCT focused on raised homocysteine (Hcy) caused by L-Dopa therapy as a putative driver of osteoporosis risk in PD. In the observational study, although L-Dopa therapy was associated with higher Hcy, and high Hcy with lower BMD, no causal associations between L-Dopa and aBMD were evident. In the RCT, lowering Hcy was associated with lower annual aBMD loss in patients taking L-Dopa but confounders relating to PD duration, severity, and L-Dopa dosage did not appear to be adjusted for in post-hoc analysis.
Conclusions: The contribution of antiparkinsonian medication to low BMD in PD remains unclear and despite plausible mechanisms of action, evidence of this relationship are lacking.