OBJECTIVETo evaluate if type 2 diabetes is an independent risk predictor for severe osteoarthritis (OA).RESEARCH DESIGN AND METHODSPopulation-based cohort study with an age- and sex-stratified random sample of 927 men and women aged 40–80 years and followed over 20 years (1990–2010).RESULTSRates of arthroplasty (95% CI) were 17.7 (9.4–30.2) per 1,000 person-years in patients with type 2 diabetes and 5.3 (4.1–6.6) per 1,000 person-years in those without (P < 0.001). Type 2 diabetes emerged as an independent risk predictor for arthroplasty: hazard ratios (95% CI), 3.8 (2.1–6.8) (P < 0.001) in an unadjusted analysis and 2.1 (1.1–3.8) (P = 0.023) after adjustment for age, BMI, and other risk factors for OA. The probability of arthroplasty increased with disease duration of type 2 diabetes and applied to men and women, as well as subgroups according to age and BMI. Our findings were corroborated in cross-sectional evaluation by more severe clinical symptoms of OA and structural joint changes in subjects with type 2 diabetes compared with those without type 2 diabetes.CONCLUSIONSType 2 diabetes predicts the development of severe OA independent of age and BMI. Our findings strengthen the concept of a strong metabolic component in the pathogenesis of OA.

Objective. To determine the prevalence, clinical picture, and disease burden of arthritis in patients with hereditary hemochromatosis.Methods. In this cross-sectional observational study of 199 patients with hemochromatosis and iron overload, demographic and disease-specific variables, genotype, and organ involvement were recorded. The prevalence, intensity, and localization of joint pain were assessed, and a complete rheumatologic investigation was performed. Radiographs of the hands, knees, and ankles were scored for joint space narrowing, erosions, osteophytes, and chondrocalcinosis. In addition, the number and type of joint replacement surgeries were recorded.Results. Joint pain was reported by 72.4% of the patients. Their mean ؎ SD age at the time of the initial joint symptoms was 45.8 ؎ 13.2 years. If joint pain was present, it preceded the diagnosis of hemochromatosis by a mean ؎ SD of 9.0 ؎ 10.7 years. Bony enlargement was observed in 65.8% of the patients, whereas synovitis was less common (13.6%). Joint space narrowing and osteophytes as well as chondrocalcinosis of the wrist and knee joints were frequent radiographic features of hemochromatosis. Joint replacement surgery was common, with 32 patients (16.1%) undergoing total joint replacement surgery due to severe OA. The mean ؎ SD age of these patients was 58.3 ؎ 10.4 years at time of joint replacement surgery. Female sex, metacarpophalangeal joint involvement, and the presence of chondrocalcinosis were associated with a higher risk of early joint failure (i.e., the need for joint replacement surgery).Conclusion. Arthritis is a frequent, early, and severe symptom of hemochromatosis. Disease is not confined to involvement of the metacarpophalangeal joints and often leads to severe damage requiring the replacement of joints.

Objective. To investigate the different patterns of bone spur formation in psoriatic arthritis (PsA) and hand osteoarthritis (OA), using high-resolution peripheral quantitative computed tomography (QCT).Methods. The study group comprised 70 subjects (25 patients with PsA, 25 patients with hand OA, and 20 healthy controls). The 2 patient groups were similar with regard to age and sex distribution and clinical involvement of the metacarpophalangeal (MCP) joints. All patients underwent high-resolution peripheral QCT scanning of the second, third, and fourth MCP joints of the dominantly affected hand. Demographic and disease-specific data were recorded, and the number, size, and distribution of bone spurs were assessed and compared between patients with PsA and patients with hand OA.Results. The overall number and size of bone spurs were similar in patients with PsA and patients with hand OA. However, localization of lesions within individual joints was substantially different between patients with PsA and those with hand OA. In PsA, bone spurs dominated the radial sides of the joints (for the metacarpal head of the second joint, P < 0.001 versus hand OA; for the base of the second phalangeal joint, P < 0.001 versus hand OA), whereas the palmar and dorsal quadrants were the predilection sites in hand OA. Detailed anatomic analysis showed that bone spurs in the entheseal regions were prominent in patients with PsA but rare in patients with hand OA, and that bone spurs in patients with hand OA typically emerged at the cartilage-bone interphase and the joint margins.Conclusion. Our findings show that the overall number and size of bone spurs are similar in patients with PsA and patients with hand OA. Nonetheless, the anatomic sites of bone proliferation are different between these 2 groups of patients.

Genome-wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention. Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2 and Chr2p14) in recent GWAS and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden. Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (P = 1.02 × 10(-5)) in the German cohort with genotypic odds ratios of 3.56 (95% CI 1.29-9.77) for CG heterozygotes and 5.38 (95% CI 2.39-12.10) for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (P = 0.014; ORallelic = 1.82 (95% CI 1.12-2.95) but not in Swedish patients. Post hoc combined analyses of German/Swiss/Austrian patients with available liver histology (N = 244, P = 0.00014, ORallelic = 2.84) and of males only (N = 431, P = 2.17 × 10(-5), ORallelic = 2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH. PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutation.

The histological picture of the synovium in HH arthropathy largely resembles a process reminiscent of OA. Neutrophil invasion is, however, markedly increased in HH arthropathy, especially in joints with iron deposition. Accumulation of neutrophils may be crucial for the production of matrix enzymes, which enables cartilage degradation and more rapidly progressive articular damage.