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Fractures in Patients With Acute Calcium Pyrophosphate Crystal Arthritis Versus Matched Comparators in a Large Cohort Study

Sara K. Tedeschi

Corresponding Author

Sara K. Tedeschi

Brigham and Women's Hospital, Boston, Massachusetts

Address correspondence via email to Sara K. Tedeschi, MD, MPH, at [email protected].

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Keigo Hayashi

Keigo Hayashi

Brigham and Women's Hospital, Boston, Massachusetts

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Ann Rosenthal

Ann Rosenthal

Medical College of Wisconsin, Milwaukee, Wisconsin

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Muneet Gill

Muneet Gill

Brigham and Women's Hospital, Boston, Massachusetts

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Javier Marrugo

Javier Marrugo

Brigham and Women's Hospital, Boston, Massachusetts

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Sho Fukui

Sho Fukui

Brigham and Women's Hospital, Boston, Massachusetts

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Ellen Gravallese

Ellen Gravallese

Brigham and Women's Hospital, Boston, Massachusetts

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Daniel H. Solomon

Daniel H. Solomon

Brigham and Women's Hospital, Boston, Massachusetts

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First published: 14 January 2024

Supported by the NIH (grants K23-AR-075070, L30-AR-070514, and R03-AR-081309 to Dr Tedeschi and grant P30-AR-072577 to Dr Solomon).

Additional supplementary information cited in this article can be found online in the Supporting Information section (http://onlinelibrary.wiley.com/doi/10.1002/art.42798).

Author disclosures are available at https://onlinelibrary.wiley.com/doi/10.1002/art.42798.

Abstract

Objective

Calcium pyrophosphate deposition (CPPD) disease was associated with osteopenia in two cross-sectional studies. We compared fracture risks in patients with acute calcium pyrophosphate (CPP) crystal arthritis versus matched comparators.

Methods

We performed a longitudinal cohort study using electronic health record data from a single large academic health system, with data from 1991 to 2023. Patients with one or more episodes of acute CPP crystal arthritis were matched to comparators on the index date (first documentation of “pseudogout” or synovial fluid CPP crystals or matched encounter) and first encounter in the health system. The primary outcome was first fracture at the humerus, wrist, hip, or pelvis. We excluded patients with fracture before the index date. Covariates included demographics, body mass index, smoking, comorbidities, health care use, glucocorticoids, and osteoporosis treatments. We estimated incidence rates and adjusted hazard ratios for fracture. Sensitivity analyses excluded patients prescribed glucocorticoids, patients prescribed osteoporosis treatments, or patients with rheumatoid arthritis and additionally adjusted for chronic kidney disease.

Results

We identified 1,148 patients with acute CPP crystal arthritis matched to 3,730 comparators, with a mean age of 73 years. Glucocorticoids and osteoporosis treatments were more frequent in the acute CPP crystal arthritis cohort. Fracture incidence rates were twice as high in the acute CPP crystal arthritis cohort (11.7 per 1,000 person-years) versus comparators (5.5 per 1,000 person-years). After multivariable adjustment, fracture relative risk was twice as high in the acute CPP crystal arthritis cohort (hazard ratio 1.8 [95% confidence interval 1.3–2.3]); results were similar in sensitivity analyses.

Conclusion

In this first published study of fractures and CPPD, fracture risk was nearly doubled in patients with acute CPP crystal arthritis.