Devyani Misra

Hand osteoarthritis in relation to mortality and incidence of cardiovascular disease: data from the Framingham Heart Study

Objectives To study whether hand osteoarthritis (OA) is associated with increased mortality and cardiovascular events in a large community based cohort (Framingham Heart Study) in which OA, mortality and cardiovascular events have been carefully assessed. Methods We examined whether symptomatic (≥1 joint(s) with radiographic OA and pain in the same joint) and radiographic hand OA (≥1 joint(s) with radiographic OA without pain) were associated with mortality and incident cardiovascular events (coronary heart disease, congestive heart failure and/or atherothrombotic brain infarction) using Cox proportional hazards models. In the adjusted models, we included possible confounding factors from baseline (eg, metabolic factors, medication use, smoking/alcohol). We also adjusted for the number of painful joints in the lower limb and physical inactivity. Results We evaluated 1348 participants (53.8% women) with mean (SD) age of 62.2 (8.2) years, of whom 540 (40.1%) and 186 (13.8%) had radiographic and symptomatic hand OA, respectively. There was no association between hand OA and mortality. Although there was no significant relation to incident cardiovascular events overall or a relation of radiographic hand OA with events, we found a significant association between symptomatic hand OA and incident coronary heart disease (myocardial infarction/coronary insufficiency syndrome) (HR 2.26, 95% CI 1.22 to 4.18). The association remained after additional adjustment for pain in the lower limb or physical inactivity. Conclusions Symptomatic hand OA, but not radiographic hand OA, was associated with an increased risk of coronary heart disease events. The results suggest an effect of pain, which may be a possible marker of inflammation.

Vitamin K deficiency is associated with incident knee osteoarthritis.

BACKGROUND Osteoarthritis is the most common form of arthritis, with knee osteoarthritis being the leading cause of lower extremity disability among older adults in the US. There are no treatments available to prevent the structural pathology of osteoarthritis. Because of vitamin Ks role in regulating skeletal mineralization, it has potential to be a preventative option for osteoarthritis. We therefore examined the relation of vitamin K to new-onset radiographic knee osteoarthritis and early osteoarthritis changes on magnetic resonance imaging (MRI). METHODS Subjects from the Multicenter Osteoarthritis (MOST) Study had knee radiographs and MRI scans obtained at baseline and 30 months later, and plasma phylloquinone (vitamin K) measured at baseline. We examined the relationship of subclinical vitamin K deficiency to incident radiographic knee osteoarthritis and MRI-based cartilage lesions and osteophytes, respectively, using log binomial regression with generalized estimating equations, adjusting for potential confounders. RESULTS Among 1180 participants (62% women, mean age 62±8 years, mean body mass index 30.1±5.1 kg/m(2)), subclinical vitamin K deficiency was associated with incident radiographic knee osteoarthritis (risk ratio [RR] 1.56; 95% confidence interval [CI], 1.08-2.25) and cartilage lesions (RR 2.39; 95% CI, 1.05-5.40) compared with no deficiency, but not with osteophytes (RR 2.35; 95% CI, 0.54-10.13). Subclinically vitamin K-deficient subjects were more likely to develop osteoarthritis in one or both knees than neither knee (RR 1.33; 95% CI, 1.01-1.75 and RR 2.12; 95% CI, 1.06-4.24, respectively). CONCLUSION In the first such longitudinal study, subclinical vitamin K deficiency was associated with increased risk of developing radiographic knee osteoarthritis and MRI-based cartilage lesions. Further study of vitamin K is warranted given its therapeutic/prophylactic potential for osteoarthritis.

Knee Osteoarthritis and Frailty: Findings From the Multicenter Osteoarthritis Study and Osteoarthritis Initiative

BACKGROUND Knee osteoarthritis (OA) and frailty are two conditions that are associated with functional limitation and disability in elders, yet their relation to one another is not known. METHODS We included participants from two large, multicenter studies enriched with community dwelling older adults with knee OA (Multicenter Osteoarthritis Study and Osteoarthritis Initiative). Knee OA was defined radiographically (ROA) and symptomatically (SOA). Frailty was defined using the Study of Osteoporotic Fracture index as the presence of ≥2 of the following: (i) weight loss >5% between two consecutive visits; (ii) inability to arise from chair five times without support; (iii) poor energy. Cross-sectional and longitudinal associations of knee OA with prevalent and incident frailty, respectively, were examined using binomial regression with robust variance estimation, adjusting for potential confounders. RESULTS In the cross-sectional analyses, frailty was more prevalent among participants with ROA (4.39% vs 2.77%; PR 1.60 [1.07, 2.39]) and SOA (5.88% vs 2.79%; PR 1.92 [1. 35, 2.74]) compared with those without ROA or SOA, respectively. In the longitudinal analyses, risk of developing frailty was greater among those with ROA (4.73% vs 2.50%; RR 1.45 [0.91, 2.30]) and SOA (6.30% vs 2.83%; RR 1.66 [1.11, 2.48]) than those without ROA or SOA, respectively. CONCLUSIONS Knee OA is associated with greater prevalence and risk of developing frailty. Understanding the mechanisms linking these two common conditions of older adults would aid in identifying novel targets for treatment or prevention of frailty.

Total joint arthroplasty and the risk of myocardial infarction: a general population, propensity score-matched cohort study.

To replicate recent findings indicating that total knee arthroplasty (TKA) or total hip arthroplasty (THA) surgery will substantially reduce the risk of serious cardiovascular events among patients with osteoarthritis.

Matrix Gla Protein Polymorphism, But Not Concentrations, Is Associated with Radiographic Hand Osteoarthritis

Objective. Factors associated with mineralization and osteophyte formation in osteoarthritis (OA) are incompletely understood. Genetic polymorphisms of matrix Gla protein (MGP), a mineralization inhibitor, have been associated clinically with conditions of abnormal calcification. We therefore evaluated the relationship of MGP concentrations and polymorphisms at the MGP locus to hand OA. Methods. Ours was an ancillary study to a 3-year randomized trial assessing the effect of vitamin K supplementation on vascular calcification and bone loss among community-dwelling elders. We studied participants who had serum MGP concentration measured and DNA genotyped for 3 MGP genetic polymorphisms (rs1800802, rs1800801, and rs4236), and who had hand radiographs. We evaluated the cross-sectional associations of serum MGP and the 3 MGP genetic polymorphisms, respectively, with radiographic hand OA using logistic regression with generalized estimating equations, adjusting for potential confounders. Results. Radiographic hand OA in ≥ 1 joint was present in 71% of the 376 participants (mean age 74 years, mean body mass index 28 kg/m2, 59% women). No significant association between serum MGP concentrations and radiographic hand OA was found [adjusted OR 1.0 (ref), 1.40, 1.21, and 1.21 for quartiles 1–4, respectively]. Homozygosity of the rs1800802 minor allele was associated with 0.56 times lower prevalence of hand OA compared with having ≥ 1 major allele at this locus (95% CI 0.32–0.99, p = 0.046). Conclusion. There may be an association between hand OA and genetic polymorphism at the MGP locus that is not reflected by total MGP serum concentrations. Further studies are warranted to replicate and elucidate potential mechanisms underlying these observed associations.

The independent impact of congestive heart failure status and diuretic use on serum uric acid among men with a high cardiovascular risk profile: a prospective longitudinal study.

OBJECTIVE To evaluate the independent impact of congestive heart failure (CHF) status (compensation or decompensation) on serum uric acid levels among men with high cardiovascular risk profile. METHOD We analyzed 11,681 men from the Multiple Risk Factor Interventional Trial, using data prospectively collected at baseline and annually over 6 years (64,644 visits). We evaluated the impact of change in CHF status during study follow-up, as compared with study baseline, on hyperuricemia (serum uric acid ≥7 mg/dL) and serum uric acid levels, using generalized estimating equations, adjusting for age, race, weight, weight change, education, alcohol intake, diuretic use, hypertension, serum creatinine level, and dietary factors. Similarly, we evaluated the independent impact of change in diuretic use (initiation or discontinuation). RESULTS At baseline, mean serum uric acid was 6.88 mg/dL. Compared with no change in CHF status, odds ratios of hyperuricemia were 1.67 (95% CI, 1.21 to 2.32) for CHF decompensation and 0.21 (95% CI, 0.08 to 0.55) for compensation. The corresponding uric acid differences were 0.41 (95% CI, 0.20 to 0.62) and -1.00 (95% CI, -1.72 to -0.27), respectively. The odds ratios for initiation and discontinuation of diuretic were 3.32 (95% CI, 3.06 to 3.61) and 0.39 (95% CI, 0.35 to 0.44). CONCLUSIONS CHF decompensation and diuretic use are both independently associated with increased odds of hyperuricemia among men with a high cardiovascular risk profile, whereas CHF recovery and diuretic discontinuation are associated with substantially lower odds of hyperuricemia.

Effect of bisphosphonates on knee replacement surgery

Purpose Bone remodelling as a therapeutic target in knee osteoarthritis (OA) has gained much interest, but the effects of antiresorptive agents on knee OA have been conflicting, with no studies to date examining the effects of bisphosphonate use on the clinically relevant endpoint of knee replacement (KR) surgery. Methods We used data from The Health Improvement Network (THIN), a general practitioner electronic medical records representative of the general UK population. We identified older women who had initiated bisphosphonate use after their incident knee OA diagnosis. Each bisphosphonate initiator was propensity score-matched with a non-initiator within each 1-year cohort accrual block. The effect of bisphosphonates on the risk of KR was assessed using Cox proportional hazard regression. Sensitivity analyses to address residual confounding were also conducted. Results We identified 2006 bisphosphonate initiators, who were matched to 2006 non-initiators(mean age 76, mean body mass index 27), with mean follow-up time of 3 years. The crude incidence rate of KR was 22.0 per 1000 person-years among the initiators, and 29.1 among the non-initiators. Bisphosphonate initiators had 26% lower risk of KR than non-initiators(HR 0.74, 95% CI 0.59 to 0.93); these results were similar when additionally adjusted for potential confounders in the propensity score (HR 0.76, 95% CI 0.60 to 0.95). Results of sensitivity analyses supported this protective effect. Conclusions In this population-based cohort of older women with incident knee OA, those with incident bisphosphonate users had lower risk of KR than non-users of bisphosphonates, suggesting a potential beneficial effect of bisphosphonates on knee OA.

Does knee replacement surgery for osteoarthritis improve survival? The jury is still out

Background The relation of knee replacement (KR) surgery to all-cause mortality has not been well established owing to potential biases in previous studies. Thus, we aimed to examine the relation of KR to mortality risk among patients with knee osteoarthritis (OA) focusing on identifying biases that may threaten the validity of prior studies. Methods We included knee OA subjects (ages 50–89 years) from The Health Improvement Network, an electronic medical records database in the UK. Risk of mortality among KR subjects was compared with propensity score-matched non-KR subjects. To explore residual confounding bias, subgroup analyses stratified by age and propensity scores were performed. Results Subjects with KR had 28% lower risk of mortality than non-KR subjects (HR 0.72, 95% CI 0.66 to 0.78). However, when stratified by age, protective effect was noted only in older age groups (>63 years) but not in younger subjects (≤63 years). Further, the mortality rate among KR subjects decreased as candidacy (propensity score) for KR increased among subjects with KR, but no such consistent trend was noted among non-KR subjects. Conclusions While a protective effect of KR on mortality cannot be ruled out, findings of lower mortality among older KR subjects and those with higher propensity scores suggest that prognosis-based selection for KR may lead to intractable confounding by indication; hence, the protective effect of KR on all-cause mortality may be overestimated.

Risk of knee oa with obesity, sarcopenic obesity and sarcopenia

Obesity, defined by anthropometric measures, is a well‐known risk factor for knee osteoarthritis (OA), but there is a relative paucity of data regarding the association of body composition (fat and muscle mass) with risk of knee OA. We undertook this study to examine the longitudinal association of body composition categories based on fat and muscle mass with risk of incident knee OA.

Response to: ‘Bisphosphonates reduce the risk of knee replacement: we need more analyses!’ by Li et al

We thank Dr Li and colleagues1 for their interest in our paper. As outlined in our paper,2 we used data from a large general practitioner electronic health records database for our study. These data are collected and recorded as part of routine clinical care with diagnostic codes. As such, factors such as willingness to undergo and …