Primary Hyperparathyroidism and the Risk of Fracture: A Population-Based Study

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Abstract
While severe primary hyperparathyroidism (HPT) is clearly associated with osteitis fibrosa cystica, it remains uncertain whether mild, asymptomatic primary HPT adversely affects the skeleton. Thus, we assessed the incidence of age-related fractures in a large, population-based inception cohort of 407 cases of primary HPT (93 men and 314 women) recognized during the 28-year period, 1965–1992. Fracture risk was assessed by comparing new fractures at each site to the number expected from gender- and age-specific fracture incidence rates for the general population (standardized incidence ratios, SIRs). These community patients with primary HPT mostly had mild disease (mean ± SD serum calcium, 10.9 ± 0.6 mg/dl). Altogether, 471 fractures occurred during 5766 person-years of follow-up. Overall fracture risk was significantly increased in these patients (SIR 1.3, 95% confidence interval [CI] 1.1–1.5). Primary HPT was associated with an increased risk of vertebral (SIR 3.2, 95% CI 2.5–4.0), distal forearm (SIR 2.2, 95% CI 1.6–2.9), rib (SIR 2.7, 95% CI 2.1–3.5), and pelvic fractures (SIR 2.1, 95% CI 1.1–3.5). The risk of proximal femur fractures was only marginally increased (SIR 1.4, 95% CI 1.0–2.0). By univariate analysis, increasing age and female gender were significant predictors of fracture risk, although higher serum calcium levels were also associated with increased fracture risk, and parathyroid surgery may have had a protective effect. By multivariate analysis, however, only age (relative hazard [RH] per 10-year increase, 1.6, 95% CI 1.4–1.9) and female gender (RH 2.3, 95% CI 1.2–4.1) remained significant independent predictors of fracture risk. Thus, primary HPT among unselected patients in the community is associated with a significant increase in the risk of vertebral, Colles', rib, and pelvic fractures. These data have important implications for the current trend to recommend nonsurgical management for patients with mild primary HPT.