Fractures in the prodromal period of Parkinson disease

Abstract

Objective: To examine the association between fractures and Parkinson disease (PD) during the 5-year prodromal phase as compared to controls.

Methods: We performed a population-based case-control study of Medicare beneficiaries in the United States from 2004 to 2009. We identified 89,632 incident PD cases and 117,760 comparable controls 66-90 years of age in 2009. PD case status was the outcome, and noncranial fracture the independent variable. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for association between fracture and PD in yearly time intervals prior to PD diagnosis/control reference date, after adjusting for covariates.

Results: There were 39,606 total fractures (25.4% cases, 14.3% controls) over the 5 years prior to the PD diagnosis/control reference date. PD was positively associated with fractures even after adjusting for age, sex, race/ethnicity, Charlson comorbidity index, alcohol use, tobacco use, and osteoporosis. The association between PD and fracture was evident at yearly time windows prior to PD diagnosis/control reference date. The association between PD and each type of fracture strengthened as the PD diagnosis/control reference date approached (all time interaction p values ≤0.02). Among beneficiaries with a mechanism of injury, the majority were attributed to falls (74.6% cases, 72.8% controls).

Conclusion: Fractures occur more commonly during the prodromal period of PD compared to controls, especially as diagnosis date approached, suggesting that patients with PD may experience unrecognized motor and nonmotor symptoms.

Figure. Risk of fracture in relation to time to Parkinson disease (PD) diagnosis

As PD diagnosis approaches, the association between fracture and PD strengthens. The sloping orange line, estimated based on the PD–fracture odds ratios (ORs) at the midpoint of each time window (excluding the final 0–0.25 years window), crosses the horizontal line (OR, 1.0) to indicate the approximate number of years prior to diagnosis at which there is no association between fracture and PD. Panels represent (A) any fracture; (B) spine fracture; (C) torso fracture; (D) pelvis fracture; (E) upper extremity fracture; (F) lower extremity fracture; (G) lower extremity fracture, hip only; and (H) lower extremity fracture, excluding hip.