Risk of Injurious Fall and Hip Fracture up to 26 y before the Diagnosis of Parkinson Disease: Nested Case-Control Studies in a Nationwide Cohort

Notwithstanding the issues around case ascertainment and differentiation from atypical Parkinson's this is really interesting. In fact even if atypical Parkinson's did explain some of the association, one would not expect the effect to be present up to 10 years before diagnosis. 

Certainly prominent falling should still raise the possibility of atypical Parkinson's in individual patients, but this study suggests the presence of motor features many years before eventual diagnosis. We have been saying this for some time... subtle motor dysfunction ought to be present if looked for and the notion of 'premotor' PD may not hold true. Only if you have looked at people with prodromal or pre-diagnostic disease (without bias) and can find no hint of motor problems, then waited to see motor dysfunction subsequently emerge can one be confident of a premotor phase.

Whether the association with fracture risk suggests common disease mechanisms between osteoporosis and PD, or whether subtle reduction in mobility increases fracture risk will remain unclear... but given the lag time between fracture and PD, l-dopa, undernutrition and lack of sunlight exposure should not be playing a role...

PLoS Med. 2016 Feb 2;13(2):e1001954. doi: 10.1371/journal.pmed.1001954. eCollection 2016.

Nyström H, Nordström A, Nordström P.

BACKGROUND:

Low muscle strength has been found in late adolescence in individuals diagnosed with Parkinson disease (PD) 30 y later. This study investigated whether this lower muscle strength also may translate into increased risks of falling and fracture before the diagnosis of PD.

METHODS AND FINDINGS:

Among all Swedish citizens aged ≥50 y in 2005, two nested case-control cohorts were compiled. In cohort I, individuals diagnosed with PD during 1988-2012 (n = 24,412) were matched with up to ten controls (n = 243,363), and the risk of fall-related injuries before diagnosis of PD was evaluated. In cohort II, individuals with an injurious fall in need of emergency care during 1988-2012 (n = 622,333) were matched with one control (n = 622,333), and the risk of PD after the injurious fall was evaluated. In cohort I, 18.0% of cases and 11.5% of controls had at least one injurious fall (p < 0.001) prior to PD diagnosis in the case. Assessed by conditional logistic regression analysis adjusted for comorbid diagnoses and education level, PD was associated with increased risks of injurious fall up to 10 y before diagnosis (odds ratio [OR] 1.19, 95% CI 1.08-1.31; 7 to <10 y before diagnosis) and hip fracture ≥15 y before diagnosis (OR 1.36, 95% CI 1.10-1.69; 15-26 y before diagnosis). In cohort II, 0.7% of individuals with an injurious fall and 0.5% of controls were diagnosed with PD during follow-up (p < 0.001). The risk of PD was increased for up to 10 y after an injurious fall (OR 1.18, 95% CI 1.02-1.37; 7 to <10 y after diagnosis). An important limitation is that the diagnoses were obtained from registers and could not be clinically confirmed for the study.

CONCLUSIONS:

The increased risks of falling and hip fracture prior to the diagnosis of PD may suggest the presence of clinically relevant neurodegenerative impairment many years before the diagnosis of this disease.