CPDD: VA Study Confirms Most Classic Associations

January 3, 2017

Study supports associations between crystal deposition disease, rheumatoid arthritis and osteoporosis.

A study of calcium pyrophosphate crystal deposition disease in the national veterans administration population confirms classic disease associations and epidiology, while refuting past research suggesting positive associations with loop diuretic use. The study findings also support associations between crystal deposition disease and rheumatoid arthritis and osteoporosis, according to authors writing in Arthritis Care and Research.

While crystal deposition disease is a common cause of acute and chronic arthritis, few large epidemiologic studies have been conducted. The authors note that crystal deposition disease is common in aging adults, and that classic risk factors are hyperparathyroidism, osteoarthritis and hemochromatosis. Other associations such as with osteoporosis, hypomagnesemia, and calcium supplementation have remained controversial. Negative relationships between CPDD and PPI and loop diuretic use have been reported recently.

In order to identify patient characteristics, comorbid conditions, and medications associated with crystal deposition disease (CPDD), the authors matched 25,157 VA CPDD patients (2010-2014) by gender and age with patients without CPDD. Average patient age for CPDD patients was 69 years (95% male). The point prevalence for CPDD was 5.2 per 1000.

Associations between CPDD and hyperparathyroidism (OR 3.35; 95% CI, 2.96, 3.79) and hemochromatosis (OR 1.87; 95% CI, 1.57, 2.24) were strongly positive. The association between CPDD and hypomagnesemia was also positive (OR 1.23; 95% CI, 1.16, 1.30), although less strong than in previous research.

Among comorbidities and health behaviors examined, osteoarthritis (OR 2.26; 95% CI, 2.15, 2.37), rheumatoid arthritis (OR 1.88; 95% CI, 1.74, 2.03), and osteoporosis (OR 1.26; 95% CI, 1.16, 1.36) had significantly higher prevalence in CPDD patients. Negative associations were found between CPDD and alcohol abuse (OR 0.62; 95% CI, 0.58, 0.65) and tobacco use (OR 0.73; 95% CI, 0.70, 0.76). CPDD prevalence was not increased in the presence of hypothyroidism, congestive heart failure, hypertension, and diabetes, and was only slightly higher with chronic kidney disease.

The authors wrote an “interesting” negative association between CPDD and use of PPIs (OR 0.58; 95% CI, 0.55-0.60) was observed, despite small PPI risk for producing hypomagnesemia and minimal effects on calcium absorption. PPIs were the most commonly used medications among those studied (60.3% in CPDD patients and 71.9% in controls).

Osteoporosis was more common in the CPDD cohort than in controls, supporting the idea that CPDD may be a systemic disorder associated with pyrophosphate level dysregulation. Also, calcium supplementation was more common in the CPDD cohort, suggesting that study of a potential connection is merited, the authors noted. A slight positive association of calcium supplementation with CPDD (OR 1.15; 95% CI, 1.05, 1.24) was observed, and bisphosphonate use showed a negative association in multivariate analyses (OR 0.85; 95% CI, 0.78, 0.93).

Associations between CPDD and PPIs (OR 0.58; 95% CI, 0.55, 0.60); thiazide diuretics (OR 0.84; 95% CI, 0.81, 0.88); and loop diuretics (OR 0.80; 95% CI, 0.76, 0.84) were all negative.

The CPDD cohort had knee arthroplasties (but not hip and shoulder arthroplasties) more commonly than controls (12.2% versus 6.7%) even after controlling for the presence of OA in the multivariate model.

The study, the authors concluded, confirmed classic associations and recent ones associating RA and osteoporosis. “Additional studies of risk factors and associations will advance our understanding of CPDD pathogenesis and inform developing evidence-based treatment strategies for this common disease.”



Crystal Kleiber Balderrama MD, Ann K. Rosenthal MD, et al. "Calcium pyrophosphate deposition disease and associated medical co-morbidities: A national cross-sectional study of us veterans,Arthritis Care and Research. Accepted manuscript online: 29 November 2016. DOI: 10.1002/acr.23160