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Inadequate pain relief and large functional loss among patients with knee osteoarthritis: evidence from a prospective multinational longitudinal study of osteoarthritis real-world therapies.

18 September 2018

OBJECTIVE: To estimate the prevalence of inadequate pain relief (IPR) among patients with symptomatic knee OA prescribed analgesic therapy and to characterize patients with IPR. METHODS: Patients ≥50 years old with physician-diagnosed knee OA who had taken topical or oral pain medication for at least 14 days were recruited for this prospective non-interventional study in six European countries. Pain and function were assessed using the Brief Pain Inventory (BPI) and the WOMAC; quality of life (QoL) was assessed using the 12-item short form. IPR was defined as an average pain score of >4 out of 10 on BPI question 5. RESULTS: Of 1187 patients enrolled, 68% were female and the mean age was 68 years (s.d. 9); 639 (54%) met the definition of IPR. Patient responses for the BPI average pain question were well correlated with responses on the WOMAC pain subscale (Spearman r = 0.64, P < 0.001). In multivariate logistic regression, patients with IPR had greater odds of being female [adjusted odds ratio (adjOR) 1.90 (95% CI 1.46, 2.48)] and having OA in both knees [adjOR 1.48 (95% CI 1.15, 1.90)], higher BMI, longer OA duration, depression or diabetes. Patients with IPR (vs non-IPR) were more likely to have worse QoL, greater function loss and greater pain interference. CONCLUSION: IPR is common among patients with knee OA requiring analgesics and is associated with large functional loss and impaired QoL. Patients at particular risk of IPR, as characterized in this study, may require greater attention towards their analgesic treatment options. TRIAL REGISTRATION: https://clinicaltrials.gov/ (NCT01294696).

What is the risk of having a total hip or knee replacement for patients with lupus?

18 September 2018

Individuals with systemic lupus erythematosus (SLE) frequently have arthralgia but joint damage leading to surgery is thought to be less common. In addition to inflammatory damage, other reasons like avascular necrosis (AVN), which is often associated with steroid use, excessive alcohol intake and antiphospholipid syndrome (APS), may increase the likelihood of large joint failure. In this study we aimed to determine the likelihood of having a total hip replacement (THR) or total knee replacement (TKR) for individuals with SLE compared to those without lupus, by performing a retrospective matched case control study of all THRs and TKRs that were performed between 1991 and 2011 and recorded in the General Practice Research Database (GPRD). Individuals with inflammatory arthritis due to any other causes were excluded and the results were adjusted for steroid use, alcohol consumption (drinking status) and APS. The results show that patients with lupus who had a THR or TKR were younger than their peers without lupus. In addition, they appeared to have a significantly increased risk of TKR but the increased risk of THR did not remain after adjustment for steroid use, alcohol consumption and APS.

Cam impingement: defining the presence of a cam deformity by the alpha angle: data from the CHECK cohort and Chingford cohort.

18 September 2018

INTRODUCTION: Cam impingement is characterized by abnormal contact between the proximal femur and acetabulum caused by a non-spherical femoral head, known as a cam deformity. A cam deformity is usually quantified by the alpha angle; greater alpha angles substantially increase the risk for osteoarthritis (OA). However, there is no consensus on which alpha angle threshold to use to define the presence of a cam deformity. AIM: To determine alpha angle thresholds that define the presence of a cam deformity and a pathological cam deformity based on development of OA. METHODS: Data from both the prospective CHECK cohort of 1002 individuals (45-65 years) and the prospective population-based Chingford cohort of 1003 women (45-64 years) with respective follow-up times of 5 and 19 years were combined. The alpha angle was measured at baseline on anteroposterior radiographs, from which a threshold for the presence of a cam deformity was determined based on its distribution. Further, a pathological alpha angle threshold was determined based on the highest discriminative ability for development of end-stage OA at follow-up. RESULTS: A definite bimodal distribution of the alpha angle was found in both cohorts with a normal distribution up to 60°, indicating a clear distinction between normal and abnormal alpha angles. A pathological threshold of 78° resulted in the maximum area under the ROC curve. CONCLUSION: Epidemiological data of two large cohorts shows a bimodal distribution of the alpha angle. Alpha angle thresholds of 60° to define the presence of a cam deformity and 78° for a pathological cam deformity are proposed.

Decision making in knee arthroplasty.

18 September 2018

A randomized saline-controlled trial of NASHA hyaluronic acid for knee osteoarthritis.

18 September 2018

OBJECTIVE: NASHA hyaluronic acid is administered as a single intra-articular injection to treat the symptoms of osteoarthritis (OA). In a previous trial, post-hoc analysis indicated that NASHA provides significantly greater pain relief than saline in patients with OA confined to the study knee. We aimed to evaluate the safety and efficacy of NASHA in patients with unilateral knee OA. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, saline-controlled trial. All patients had knee OA confirmed by American College of Rheumatology criteria and a WOMAC pain score of 7-17 in the study knee, but no pain in the previous 3 months in the non-study knee. Treatment comprised a single intra-articular injection of NASHA or saline control. The follow-up period was 6 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01806207. MAIN OUTCOME MEASURES: The primary efficacy endpoint was the responder rate, defined as the percentage of patients with ≥40% improvement from baseline in WOMAC pain score and an absolute improvement of ≥5 points. RESULTS: A total of 218 patients received study treatment (NASHA: 108, saline: 110). In the main intention-to-treat (ITT) analysis, no statistically significant difference in responder rate was found between the two groups at 6 weeks (NASHA: 30.6%; saline: 26.4%). A post-hoc subgroup analysis of patients without clinical effusion in the study knee at baseline showed a significantly higher 6 week responder rate with NASHA than with saline: 40.6% versus 19.7% (p = 0.0084). A total of 68 adverse events were reported among 44 patients in the NASHA group, compared with 69 adverse events among 44 patients in the saline group. The main weakness of the study was the short, 6 week follow-up duration. In addition, image guidance was not used to ensure injection as intended into the intra-articular space. CONCLUSIONS: Single-injection NASHA was well tolerated and, although there was no significant benefit versus saline control in the primary analysis, post-hoc analysis showed a statistically significant improvement in pain relief at 6 weeks among patients without clinical effusion at baseline.

The hereditary predisposition to hip osteoarthritis and its association with abnormal joint morphology.

18 September 2018

OBJECTIVE: Genetic factors and abnormalities of joint morphology are important in the aetiology of hip osteoarthritis (OA). The extent to which genetic influences are manifest through joint morphology has undergone limited investigation. Using a cohort with an hereditary predisposition to end-stage hip OA and a control group with no inherited risk, we aimed to identify associations with abnormal joint morphology and clinical features. DESIGN: One hundred and twenty-three individuals (mean age 52 years) with a family history of total hip arthroplasty (THA) (termed 'sibkids') were compared with 80 spouse controls. Morphology was assessed using standardised radiographs and cam, dysplasia, and pincer deformities defined. Regression modelling described the association of cohort with abnormal joint morphology, adjusting for confounders [age, gender, body mass index (BMI), OA, and osteophyte]. RESULTS: Sibkids had an odds ratio of 2.1 [95%confidence interval (CI) 1.3-3.5] for cam deformity. There were no differences in the prevalence of dysplasia or pincer deformities. In both groups, hips with cam deformities or dysplasia were more likely to have clinical features than normal hips [odds ratio (OR) 4.46 (1.8-11.3), and 4.40 (1.4-14.3) respectively]. Pincer deformity was associated with positive signs in the sibkids but not in the controls (OR 3.0; 1.1-8.2). DISCUSSION: After adjustment for confounders that cause secondary morphological change, individuals with an hereditary predisposition to end-stage hip OA had a higher prevalence of morphological abnormalities associated with hip OA. Sibkids were more likely to demonstrate clinical features in the presence of pincer deformity, suggesting that the genes are acting not only through abnormal morphology but also through other factors that influence the prevalence of pain.

The feasibility of performing a randomised controlled trial for femoroacetabular impingement surgery.

18 September 2018

OBJECTIVES: The number of surgical procedures performed each year to treat femoroacetabular impingement (FAI) continues to rise. Although there is evidence that surgery can improve symptoms in the short-term, there is no evidence that it slows the development of osteoarthritis (OA). We performed a feasibility study to determine whether patient and surgeon opinion was permissive for a Randomised Controlled Trial (RCT) comparing operative with non-operative treatment for FAI. METHODS: Surgeon opinion was obtained using validated questionnaires at a Specialist Hip Meeting (n = 61, 30 of whom stated that they routinely performed FAI surgery) and patient opinion was obtained from clinical patients with a new diagnosis of FAI (n = 31). RESULTS: Clinical equipoise was demonstrated when surgeons were given clinical scenarios and asked whether they would manage a patient operatively or non-operatively. A total of 23 surgeons (77%) who routinely perform FAI surgery were willing to recruit patients into a RCT, and 28 patients (90%) were willing to participate. 75% of responding surgeons believed it was appropriate to randomise patients to non-operative treatment for ≥ 12 months. Conversely, only eight patients (26%) felt this was acceptable, although 29 (94%) were willing to continue non-operative treatment for six months. More patients were concerned about their risk of developing OA than their current symptoms, although most patients felt that the two were of equal importance. CONCLUSIONS: We conclude that a RCT comparing operative and non-operative management of FAI is feasible and should be considered a research priority. An important finding for orthopaedic surgical trials is that patients without life-threatening pathology appear willing to trial a treatment for six months without improvement in their symptoms.

A discrete-choice experiment of United Kingdom patients' willingness to risk adverse events for improved function and pain control in osteoarthritis.

18 September 2018

OBJECTIVE: To assess patient preferences for treatment-related benefits and risks associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA). DESIGN: Using a chronic-illness panel in the United Kingdom, patients 45 years or older with a self-reported diagnosis of OA were eligible to participate in the study. Patient preferences were assessed using a discrete-choice experiment that compared hypothetical treatment profiles of benefits and risks consistent with NSAID use. Benefit outcomes (ambulatory pain, resting pain, stiffness, and difficulty doing daily activities) were presented on a 0-to-100 mm scale. Risk outcomes (bleeding ulcer, stroke, and myocardial infarction [MI]) were expressed as probabilities over a fixed time period. Each patient answered 10 choice tasks comparing different treatment profiles. Preference weights were estimated using a random-parameters logit model. RESULTS: Final sample included 294 patients. Patients ranked reductions in ambulatory pain and difficulty doing daily activities (both: 6.32; 95% confidence interval [CI]: 5.0-7.6) as the most important benefit outcomes, followed by reductions in resting pain (2.80; 95% CI: 1.8-3.8) and stiffness (2.65; 95% CI: 0.9-4.4). Incremental changes (3%) in the risk of MI or stroke were assessed as the most important risk outcomes (10.00; 95% CI: 8.2-11.8; and 8.90; 95% CI: 7.3-10.5, respectively). CONCLUSION: Patients ranked ambulatory pain as a more important benefit than resting pain; likely due to its impact on ability to do daily activities. For a 25-mm reduction, patients were willing to accept four times the risk of MI in ambulatory pain vs resting pain.

Knee arthroplasty and risk of hip fracture: a population-based, case-control study.

18 September 2018

The majority of knee arthroplasties (KAs) are performed in patients with osteoarthritis (OA). Although bone mass may be increased in these patients, subjects with knee OA may have an increased risk of hip fracture, possibly due to an increased severity of falls. However, in patients with KAs, risk of hip fracture has not been studied extensively. We evaluated the association between KAs and hip fracture risk in a population-based case-control study using the Dutch PHARMO Record Linkage System (1991-2002, n = 33,104). Cases were patients with a first admission for hip fracture; controls were matched by age, gender, and geographic location. Neither group had a previous history of fracture. Time since first KA was calculated. Analyses were adjusted for disease and drug history. A 54% increased hip fracture risk was found in patients who underwent KA (adjusted [adj.] OR = 1.54, 95% CI 1.19-2.00). We found a strong effect modification by age in these patients: the youngest patients (aged 18-70 years) were at more increased risk for hip fracture (adj. OR = 2.76, 95% CI 1.16-6.59), while we could not detect a statistical increase in patients aged >80 years. Furthermore, the association tended to be greater during the first few years after surgery, although it did not reach statistical significance. We found that KAs are associated with a 54% increased risk of hip fracture, in particular among adult patients aged <71 years old. Fracture risk assessment could be considered in patients who are about to undergo a KA.

Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study.

18 September 2018

Aromatase inhibitor (AI)-associated arthralgia limits adherence to therapy in breast cancer. The pathophysiology may involve vitamin D status. We wished to establish the optimal concentration of 25(OH)D that prevents or minimizes arthralgia. We used a prospective cohort of 290 women starting AI in whom baseline vitamin D was measured. All received daily vitamin D(3) (800 IU) with calcium. Women with baseline 25(OH)D concentration <30 ng/ml also received 16,000 IU of D(3) orally every 2 weeks. The primary outcome was incident or worsening joint pain derived from baseline and 3-month visual analogic scale (VAS) for joint pain. Regression models were used to analyse the association between vitamin D concentrations at 3 months and pain adjusting for age, BMI, season when the sample was drawn, aromatase inhibitor (exemestane vs. letrozole/anastrozole), prior tamoxifen therapy, baseline NTX, and previous fracture. 90% of women had a 25(OH)D <30 ng/ml at baseline. After supplementation (daily 800 IU and additional 16,000 IU every 2 weeks), 50% of them still failed to reach adequate concentrations at 3 months. In the whole cohort, there was an increase in joint pain (mean 1.16 points SD 2.66; P < 0.001) and the increase was significantly (P = 0.02) attenuated in those that reached concentrations of 25(OH)D of ≥40 ng/ml, with a lower risk of incident arthralgia (OR 0.12 ** [0.03 to 0.40]). A target concentration of 40 ng/ml 25OHD may prevent development of AI arthralgia but higher loading doses are required to attain this level in women with deficiency at baseline.