Research Summary

Fracture Risk Doubles For Patients With Acute Calcium Pyrophosphate Crystal Arthritis

Anthony Calabro, MA

Researchers observed double the fracture risk in patients with acute calcium pyrophosphate (CPP) crystal arthritis vs matched comparators. The first-of-its-kind study was presented at the ACR Convergence 2023 Annual Meeting in San Diego, California.1

Although previous studies noted a positive association between calcium pyrophosphate deposition (CPPD) disease and osteopenia, the risk of fractures has not been evaluated. There are many manifestations of CPPD, the most common of which is CPP crystal arthritis (also known as “pseudogout”).2

Researchers developed a matched cohort study using electronic health records from a large academic medical center spanning the years 1991 to 2017. The primary objective was to assess the risk of fragility fractures, focusing on specific anatomical sites, in patients with acute CPP crystal arthritis compared with well-matched counterparts. Fragility fractures were identified through established algorithms, with a positive predictive value exceeding 90%.

Tedeschi and colleagues matched patients with acute CPP crystal arthritis to comparators without this condition based on the index date and the year of electronic health record entry. Notably, comparators were allowed to have other types of arthritis. The index date was defined as the first mention of "pseudogout" in notes or the first synovial fluid analysis with CPP crystals, whichever occurred first.

Researchers identified 1148 patients with acute CPP crystal arthritis and 3730 carefully matched comparators. Women represented more than half of the patients in both cohorts. The mean age in both cohorts was 73 years.  The cohort of patients with acute CPP crystal arthritis had higher frequencies of glucocorticoid and osteoporosis treatments, suggesting potential associations between these therapies and the disease.

The results showed that the acute CPP crystal arthritis cohort experienced fracture rates twice as high as their comparators (11.2 vs 5.6 per 1000 person-years). Even after adjusting for covariates, the study results demonstrated a doubling in fracture risk in the acute CPP crystal arthritis cohort compared with comparators (hazard ratio [HR] = 1.8, [95% CI; 1.4 - 2.4]).

“In this first-ever study of fractures and CPPD, we observed a doubling of fracture risk in patients with acute CPP crystal arthritis,” the authors concluded. “Future studies evaluating bone turnover markers and changes in bone density over time in patients with CPPD are needed.”



  1. Tedeschi S, Hayashi K, Rosenthal A, et al. Fractures in patients with acute cpp crystal arthritis versus matched comparators in a large cohort study. Paper presented at: American College of Rheumatology Convergence 2023; November 10-15, 2023; San Diego, CA.
  2. Rosenthal AK. Patient education: calcium pyrophosphate crystal deposition (CPPD) disease (beyond the basics). Uptodate. Updated December 14, 2023. Accessed January 26, 2024.