Calcium Pyrophosphate Deposition Disease and Associated Medical Comorbidities: A National Cross-Sectional Study of US Veterans.

OBJECTIVE: Calcium pyrophosphate deposition disease (CPDD) is a common cause of acute and chronic arthritis, yet there are few large epidemiologic studies of CPDD. We sought to characterize CPDD in the national Veterans Affairs (VA) population. METHODS: Using data from the Department of VA Corporate Data Warehouse, patients with International Classification of Diseases, Ninth Revision, codes for CPDD seen at any VA medical center from 2010 through 2014 were matched by age and sex with control patients without CPDD. We used multivariate analysis to compare the prevalence and odds ratios (ORs) of various comorbidities, substance use, medication exposures, and arthroplasties among patients with and without CPDD. RESULTS: We identified 25,157 patients with CPDD, yielding a point prevalence of 5.2 per 1,000. The mean ± SD age was 68.1 ± 12.3 years, and 95% were male. The strongest positive associations with CPDD were hyperparathyroidism (OR 3.35 [95% confidence interval (95% CI) 2.96-3.79]), gout (OR 2.82 [95% CI 2.69-2.95]), osteoarthritis (OR 2.26 [95% CI 2.15-2.37]), rheumatoid arthritis (OR 1.88 [95% CI 1.74-2.03]), and hemochromatosis (OR 1.87 [95% CI 1.57-2.24]). Positive associations were also seen with higher odds for osteoporosis (OR 1.26 [95% CI 1.16-1.36]), hypomagnesemia (OR 1.23 [95% CI 1.16-1.30]), chronic kidney disease (OR 1.12 [95% CI 1.07-1.18]), and calcium supplementation (OR 1.15 [95% CI 1.06-1.24). Negative associations were seen with proton-pump inhibitors (OR 0.58 [95% CI 0.55-0.60]) and loop diuretics (OR 0.80 [95% CI 0.76-0.84]). CONCLUSION: Using a large national data set, we confirmed known associations with CPDD, provided support for positive associations with rheumatoid arthritis, hypomagnesemia, and osteoporosis, and suggested potential novel negative associations with commonly used medications.

Diabetes and rheumatic diseases.

PURPOSE OF REVIEW: This review summarizes recent advances in the field of diabetes and rheumatic disease. These conditions exert a significant healthcare burden on our society and much remains to be learned regarding their pathophysiology and treatment. RECENT FINDINGS: We summarize new insights into diabetes and its association with osteoarthritis, rheumatoid arthritis, carpal tunnel syndrome, osteoporosis, diffuse idiopathic skeletal hyperostosis, crystalline arthropathy, neuropathic arthropathy, and tendinopathy. Diabetes has major effects on connective tissues, which have significant impact on both the development and outcome of these diseases of cartilage, bone, ligament, and tendon. An improved understanding of the mechanisms through which diabetes alters connective tissue metabolism should lead to better preventive and therapeutic interventions. SUMMARY: Incremental progress has been made in understanding the interactions between diabetes and common musculoskeletal syndromes. Although this review highlights exciting areas of future interest, more work in this field is certainly warranted.

Regulation of transglutaminase activity in articular chondrocytes through thrombin receptor-mediated factor XIII synthesis.

Transglutaminases are a family of enzymes that catalyze the formation of epsilon-(gamma-glutamyl)lysine isopeptide bonds in proteins, an activity that has been implicated in the pathogenesis of cartilage matrix mineralization in degenerative arthritis. Type II transglutaminase and thrombin-activatable factor XIII have been identified in articular cartilage. Thrombin, a coagulation protease, is found in pathological synovial fluids, and is known to stimulate transglutaminase activity in non-articular tissues. We investigated the effects of thrombin on transglutaminase activity in porcine articular chondrocytes. Direct addition of thrombin to chondrocyte lysates resulted in increased transglutaminase activity due to proteolytic conversion of factor XIII to XIIIa. Thrombin-treated chondrocyte cultures (0.001 to 2.0 U/ml) also showed increased transglutaminase activity. Thrombin treatment of chondrocyte cultures increased transglutaminase activity as early as 15 minutes after addition, an effect that we attributed to factor XIII activation. Additional stimulatory effects of thrombin were observed in cultured chondrocytes at 4 and 24 hours. A thrombin receptor agonist peptide (TRAP) which activates the PAR1 thrombin receptor mimicked these later effects. Thrombin treatment of chondrocyte cultures increased factor XIII mRNA and protein levels, without affecting levels of type II transglutaminase. Thus, thrombin stimulates transglutaminase activity in articular cartilage by directly cleaving factor XIII and by receptor-mediated up-regulation of factor XIII synthesis. Such increases in potential transglutaminase activity may facilitate pathological matrix calcification in degenerative arthritis.