Calcium pyrophosphate deposition disease is associated with increased risk of fractures: A retrospective cohort study using electronic health record data.

Objective: To evaluate the risk of fractures in older adults with calcium pyrophosphate deposition (CPPD) disease and osteoarthritis (OA) compared to those with OA alone, and to assess site- and gender-specific fracture risk.

Methods: Using predominantly North American electronic health record data from 2005-2025, we defined CPPD as patients aged ≥60 years with ≥2 administrative codes for CPPD plus OA, excluding other inflammatory arthritides. Comparators were defined analogously with ≥2 OA codes but without CPPD. The primary outcome was any fracture of spine, upper limb, lower limb. We used Cox proportional hazards models 1:1 propensity score-matched for demographics, comorbidities, and medications. Subgroup analyses assessed gender-specific outcomes and site-specific fractures. Sensitivity analyses excluded individuals with prior exposure to glucocorticoids or anti-osteoporosis medications or prior fracture history.

Results: Among 20,176 matched pairs (mean age 73 years, 59% female) with 4015 and 3349 fracture events over 81,291 and 85,802 patient-years, CPPD was associated with 29% increased hazard of any fracture (HR 1.29, 95%CI 1.23, 1.35) which was consistent in males (HR 1.36, 95%CI 1.23, 1.49) and females (HR 1.30, 95%CI 1.23, 1.38). Site-specific analyses similarly showed elevated fracture risks at the upper limb (HR 1.37; 1.28, 1.46), lower limb (HR 1.31; 1.23, 1.39), and spine (HR 1.18; 1.11, 1.26). Results were similar across all sensitivity analyses.

Conclusion: CPPD disease is associated with increased fracture risk across gender and fracture sites. Clinicians should consider screening for bone health in these patients. Future research should clarify underlying mechanisms and refine targeted interventions.