Patients with ‘pseudogout’ have double the risk for fracture vs controls
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SAN DIEGO — Patients with acute calcium pyrophosphate crystal arthritis demonstrate double the risk for fractures vs. matched comparators, according to data presented at ACR Convergence 2023.
“CPPD disease, which stands for calcium pyrophosphate deposition disease, is a very common crystalline arthritis that affects 8 million to 10 million adults over the age of 60,” Sara Tedeschi, MD, MPH, of Brigham and Women’s Hospital, in Boston, said at a press conference during the meeting. “That means that the prevalence of CPPD disease is really similar to the prevalence of gout. And we know much about gout, whereas in contrast we know very little about CPPD disease.
“There are several manifestations of CPPD disease,” she added. “The one that is most classically recognized has been called ‘pseudogout’ for many years — now it’s called acute CPP crystal arthritis, which is a real mouthful. There have been a number of studies that have looked at whether CPPD is related to the progression of osteoarthritis, with conflicting results. Our group was interested in thinking about the effects of CPPD disease outside of the joint. And in this current work, we focused on the risk of fracture.”
To compare fracture risk between patients with calcium pyrophosphate (CPP) crystal arthritis and healthy controls, Tedeschi and colleagues conducted a matched cohort study of electronic health record data at a large academic medical center. The researchers matched 1,148 patients with at least one episode of acute CPP crystal arthritis from 1991 to 2017 with 3,730 comparators without pseudogout, based on index date and year of EHR entry. Patients with existing fragility fracture at baseline were excluded.
The index date was defined as the first mention of “pseudogout” in notes or first synovial fluid analysis with CPP crystals. For the control participants, an encounter +/- 30 days acted as the index date.
The primary outcome was the first fragility fracture of the humerus, wrist, hip or pelvis. Secondary outcomes included the first fracture at each separate site. The researchers identified fragility fractures through published algorithms using diagnosis and procedural codes with a positive predictive value of more than 90%. For participants with more than one fracture, just the earliest was included. A baseline period of at least 180 days from EHR entry through the index date was required.
Age, sex, race, smoking, rheumatoid arthritis, hyperparathyroidism, health care visits, multimorbidity index, BMI, oral glucocorticoid use, osteoporosis treatment and proton pump inhibitor use were assessed as covariates. The sensitivity analyses excluded participants with RA or who received glucocorticoids or osteoporosis treatment.
According to the researchers, the fracture incidence rate was twice as high among patients with acute CPP crystal arthritis, at 11.2 per 1,000 person-years, compared with the matched control group, which demonstrated a rate of 5.6 per 1,000 person-years. In addition, cumulative incidence curves increasingly diverged over time, highlighting greater fracture rates in the acute CPP crystal arthritis group.
Fracture risk remained twice as high in patients with acute CPP crystal arthritis even after adjusting for covariates (HR = 1.8; 95% CI, 1.4-2.4). The sensitivity analyses returned similar results, the researchers wrote.
“This was specifically driven by fractures of the wrist, where there was actually a four-fold increased risk,” Tedeschi said. “I think this is really interesting. We were not able to assess for fragility and we were not able to assess for falls using this dataset, but I do think it could be a possibility that people who have an acute episode of CPP crystal arthritis — being that they are in acute pain — fall and brace themselves with their arm and they may break their wrist. That’s one possibility.
“It’s also interesting that CPPD commonly affects the wrist,” she added. “Could it be that there are local factors and potentially locally decreased bone density specific to the wrist? So future work is going to involve looking at bone turnover markers in patients with CPPD and looking at bone mineral density scores.”
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Tedeschi S. Abstract 235. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego.
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