Risk Of Total Joint Replacement Research Articles

Propranolol reduces risk of knee or hip replacement due to osteoarthritis: A propensity score matched cohort study-using data from the Clinical Practice Research Datalink

Background: There is paucity of safe and effective analgesic drugs for osteoarthritis (OA). β-adrenoreceptor blockers have demonstrated anti-nociceptive effects in several painful conditions. We investigated whether β-blockers are associated with a reduced risk of total joint replacement (TJR) at the knee or the hip in people with incident knee or hip OA. Methods: This was a cohort study. We used data from the Clinical Practice Research Datalink. Participants aged 40 years or older with incident knee or hip OA, prescribed β-blockers following OA diagnosis (new-user design) and their age, sex, OA location and propensity score (PS) for β-blocker prescription matched controls were included in the study. Cox-proportional hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. The analyses were adjusted for factors that influence health-seeking behaviour, progression of OA, and stratified according to β-blocker classification. Data analysis was conducted using STATA-MP v15. Results: Data for 6,970 PS-matched β-blocker exposed and unexposed participants were included. Any β-blocker prescription was not associated with knee or hip TJR (aHR 1.11; 95 % CI 0.98 – 1.25). However, prescription of lipophilic non-selective β-blockers with membrane stabilising effect associated with reduced risk of knee or hip TJR (aHR 0.69; 95 % CI 0.52 – 0.93). Of these, there was a protective effect for propranolol (aHR 0.71; 95 % CI 0.53 – 0.95), the commonest prescribed drug in this class. The number needed to treat (95%CI) with propranolol for two years, in order to prevent one TJR was 32 (23–52). Conclusions: The non-selective β-blocker propranolol reduces the risk of knee or hip TJR, consistent with its analgesic effects demonstrated in other conditions. A randomised controlled trial is required to further evaluate the analgesic potential of propranolol in OA.

Metformin use and associated risk of total joint replacement in patients with type 2 diabetes: a population-based matched cohort study.

It is uncertain whether metformin use is associated with reduced risk of joint replacement in patients with type 2 diabetes mellitus. We aimed to establish whether metformin use was associated with a reduced risk of total knee replacement (TKR) or total hip replacement (THR) among these patients. We selected patients with type 2 diabetes mellitus that was diagnosed between 2000 and 2012 from the Taiwan National Health Insurance Research Database. We used prescription time-distribution matching and propensity-score matching to balance potential confounders between metformin users and nonusers. We assessed the risks of TKR or THR using Cox proportional hazards regression. We included 20 347 participants who were not treated with metformin and 20 347 who were treated with metformin, for a total of 40 694 participants (mean age 63 yr, standard deviation 11 yr; 49.8% were women) after prescription time-distribution matching. Compared with participants who did not use metformin, those who used metformin had lower risks of TKR or THR (adjusted hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.60-0.81 for TKR or THR; adjusted HR 0.71, 95% CI 0.61-0.84 for TKR; adjusted HR 0.61, 95% CI 0.41-0.92 for THR) after adjustment for covariates. Propensity-score matching analyses (10 163 participants not treated with metformin v. 10 163 treated with metformin) and sensitivity analyses using inverse probability of treatment weighting and competing risk regression showed similar results. Metformin use in patients with type 2 diabetes mellitus was associated with a significantly reduced risk of total joint replacement. Randomized controlled clinical trials in patients with osteoarthritis are warranted to determine whether metformin is effective in decreasing the need for joint replacement.

Metformin Use and Risk of Total Joint Replacement in Patients with Type 2 Diabetes: A Population-Based Cohort Study

Metformin Use and Risk of Total Joint Replacement in Patients with Type 2 Diabetes: A Population-Based Cohort Study

Urinary CTX-II predicts the risk of total joint replacement in postmenopausal women: a 18-year longitudinal study

Purpose: Identifying objective risk-factors for total joint replacement (TJR) is useful to enrich population at high risk in osteoarthritis (OA) clinical trials. In this study, we investigated the value of urinary CTX-II, a biochemical marker of cartilage breakdown, to predict TJR in postmenopausal women.

Clinical and biochemical factors associated with risk of total joint replacement and radiographic progression in osteoarthritis: Data from two phase III clinical trials

ObjectivesClinical trials of new disease-modifying treatments for osteoarthritis should demonstrate a positive effect on a functional outcome or reduction in joint failure in order to be considered successful. Total joint replacement (TJR) surgery may be considered as joint failure, but great variation in the incidence of TJR complicates its use as a study endpoint. Factors predicting elevated risk of TJR could potentially be used to enrich such outcome-trials. MethodsUsing cumulative data from two phase three clinical trials with urine samples from 1255 knee OA patients followed for two years, we assessed the value of a series of baseline clinical variables including the uCTX-II biomarker, as predictors of joint-space narrowing, Kellgren-Lawrence-grade progression, and total joint replacement. ResultsA prediction-model incorporating age, sex, BMI, CTX-II and KL-grade predicted TJR within the two-year period with an AUC of 0.75 (95% CI: 0.72–0.77). The participants with a cumulative KL-grade between knees of 5, 6, or 7 had a more than 3 times higher risk of TJR in the study period compared to lower (HR: 3.03, 95% CI: 1.54 to 5.96, p = 0.001). Age was associated with increased TJR risk (per 5 years of age: HR: 1.28, 95% CI: 1.03–3.79, p = 0.05). Baseline u-CTX-II was associated with elevated risk of radiographic progression in terms of both JSN and KL-grade. ConclusionsA composite model combining baseline age, sex, BMI, u-CTX-II and KL-grade was able to acceptably predict TJR during a two-year period. In the absence of baseline radiographic OA severity, u-CTX-II independently contributed to prediction of TJR. Baseline urine CTX-II was associated with risk of radiographic progression.

Urate-lowering treatment and risk of total joint replacement in patients with gout

ObjectivesTo examine whether gout is an independent risk factor for total joint replacement (TJR) and whether urate-lowering treatment (ULT) reduces this risk. MethodsUsing the Taiwan National Health Insurance database and the UK Clinical Practice Research Datalink, 74 560 Taiwan patients and 34 505 UK patients with incident gout were identified and age and sex matched to people without gout. Cox proportional hazards models and condition logistic regression were used to examine the risk of TJR in gout patients and the association between cumulative defined daily dose (cDDD) of ULT and TJR.ResultsThe prevalence rates of TJR in the patients at the time of diagnosis of gout and in people without gout were 1.16% vs 0.82% in Taiwan and 2.61% vs 1.76% in the UK. After a gout diagnosis, the incidence of TJR was higher in the patients with gout compared with those without (3.23 vs 1.91 cases/1000 person-years in Taiwan and 6.87 vs 4.61 cases/1000 person-years in the UK), with adjusted HRs of 1.56 (95% CI 1.45, 1.68) in Taiwan and 1.14 (1.05, 1.22) in the UK. Compared with patients with gout with <28 cDDD ULT, the adjusted ORs for TJR were 0.89 (95% CI 0.77, 1.03) for 28–90 cDDD, 1.03 (0.85, 1.24) for 90–180 cDDD and 1.12 (0.94, 1.34) for >180 cDDD ULT in Taiwan. In the UK, the respective ORs were 1.09 (0.83, 1.42), 0.93 (0.68, 1.27) and 1.08 (0.94, 1.24).ConclusionThis population-based study provides evidence from two nation populations that gout confers significant TJR risk, which was not reduced by current ULT.

Severity of Diabetes Mellitus and Total Hip or Knee Replacement: A Population-Based Case-Control Study.

It is generally thought that people with diabetes mellitus (DM) are more likely to suffer from osteoarthritis (OA) due to an increased body mass index (BMI), resulting in mechanical destruction of cartilage. However, previous studies have suggested a coexisting metabolic causality.To evaluate the risk of hip or knee replacement, as a proxy for severe OA, in patients with DM. We additionally evaluated the risk of total joint replacement (TJR) with various proxies for increased DM severity.A population-based case-control study was performed, using the Clinical Practice Research Datalink (CPRD). Cases (n = 94,609) were defined as patients >18 years who had undergone TJR between 2000 and 2012. Controls were matched by age, gender, and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) surgery associated with use of antidiabetic drugs (ADs). We additionally stratified current AD users by proxies for DM severity.Current AD use was significantly associated with a lower risk of TKR (OR = 0.86 (95% CI = 0.78-0.94)) and THR (OR = 0.90 (95% CI = 0.82-0.99)) compared to patients not using ADs. Moreover, risk of TKR and THR was decreased with increasing HbA1c.This study does not support the theory that DM patients are more likely to suffer from severe OA as compared to patients without diabetes. Moreover, risk of severe OA necessitating TJR decreases with increasing DM severity. This is possibly due to dissimilarities in methodology, a decrease in eligibility for surgery, or variability of OA phenotypes.

Use of thiazolidinediones and the risk of elective hip or knee replacement: a population based case-control study.

Osteoarthritis (OA) is the most common musculoskeletal condition in the elderly population. However, no disease modifying drug exists for this disease. In vivo animal studies have suggested that thiazolidinediones (TZD) may be used as disease modifying osteoarthritis drugs (DMOADs). To our knowledge, this has not yet been examined in humans before. The aim was to determine the risk of total joint replacement (TJR) in patients using TZDs compared with diabetic patients using other antidiabetic drugs. A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n=94609) were defined as patients >18years of age who had undergone total knee (TKR) or hip replacement (THR) between 2000 and 2012. Controls were matched by age, gender and practice/surgery. Conditional logistic regression analyses were used to estimate the risk of TKR and THR with the use of TZDs in patients currently using one or more antidiabetic drugs. In order to determine effect with prolonged use, we also stratified TZD users by total number of prescriptions prior to surgery. We statistically adjusted our analyses for lifestyle factory, comorbidities and concomitant drug use. There was no difference in risk of TKR (OR 1.09, 95% CI 0.93, 1.27) and THR (OR 0.92, 95% CI 0.76, 1.10) when TZD users were compared with other AD users. Furthermore, we did not find an association with prolonged use of TZDs and TJR. Despite promising results from animal in vivo studies, this study did not find any evidence for a disease modifying osteoarthritic effect of TZDs.

Involvement of different risk factors in clinically severe large joint osteoarthritis according to the presence of hand interphalangeal nodes

To quantify the differences in risk factors influencing total hip replacement (THR) and total knee replacement (TKR) based on the presence versus absence of multiple interphalangeal nodes in 2 or more rays of the fingers of each hand in patients with large joint osteoarthritis (OA). A group of 3,800 patients with large joint OA who underwent total joint replacement (1,201 of whom had the nodal phenotype) and 1,906 control subjects from 2 case-control studies and a population-based cohort in the UK were studied. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for the risk of total joint replacement in association with age, sex, body mass index (BMI), height, and prevalence of the T allele in the GDF5 rs143383 polymorphism. ORs for total joint replacement were compared between cases of nodal OA and cases of non-nodal OA and between patients who underwent TKR and those who underwent THR. Age, sex, and BMI had significantly higher ORs for an association with total joint replacement in nodal OA cases than in non-nodal OA cases. The GDF5 polymorphism was significantly associated with THR in cases of nodal OA, but not in cases of non-nodal OA, and increased height was a risk factor for THR in non-nodal OA cases only. Female sex was a protective risk factor for TKR in non-nodal OA cases (OR 0.60, 95% CI 0.52-0.70) but was predisposing for TKR in the nodal form of OA (OR 1.83, 95% CI 1.49-2.26). The nodal phenotype was associated with a significantly higher risk of undergoing both THR and TKR (OR 1.46, 95% CI 1.09-1.94) and also a significantly higher risk of bilateral TKR (OR 1.70, 95% CI 1.37-2.11), but, paradoxically, was associated with a lower risk of bilateral THR (OR 0.72, 95% CI 0.56-0.91). Nodal and non-nodal forms of large joint OA have significantly different risk factors and outcomes, indicating a different etiology for the 2 forms of OA. With regard to the likelihood of undergoing THR, this appears to be, at least in part, genetically determined.