Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis – meta-analysis

SummaryObjectiveTo evaluate the therapeutic trajectory of intra-articular hyaluronic acid (IAHA) vs placebo for knee osteoarthritis (OA).DesignOur data sources include Medline, EMBASE, CINAHL, BIOSIS, Web of Science, Google Scholar, Cochrane database; hand searched reviews, manuscripts, and, supplements; author contacts for unpublished data. Randomized trials that reported effects of IAHA vs placebo on knee OA were selected based on inclusion criteria. We computed effect sizes for change from baseline at 4, 8, 12, 16, 20 and 24 weeks, using Bayesian random effects model. We performed multivariate analyses adjusting for correlation between time points. Meta-regressions were performed adjusting for potential confounders.ResultsThe 54 eligible trials included 7545 participants. The conduct and quality of these trials varied in number of aspects. The effect size (ES) favored IAHA by week 4 (0.31; 95% CI 0.17, 0.45), reaching peak at week 8 (0.46; 0.28, 0.65), and then trending downwards, with a residual detectable effect at week 24 (0.21; 0.10, 0.31). This therapeutic trajectory was consistent among the subset of high quality trials and on multivariate analysis adjusting for correlation between time points.ConclusionsOur meta-analysis highlights a therapeutic trajectory of IAHA for knee OA pain over 6 months post-intervention. With this additional perspective, we are able to infer that IAHA is efficacious by 4 weeks, reaches its peak effectiveness at 8 weeks and exerts a residual detectable at 24 weeks. On the other hand, the peak effect size (0.46; 0.28, 0.65), is greater than published effects from other OA analgesics [acetaminophen (ES=0.13; 0.04, 0.22); NSAIDs (ES=0.29; 0.22, 0.35); COX-2 inhibitors (ES=0.44; 0.33, 0.55)]. An effect size above 0.20 is considered to be clinically relevant on an individual patient basis in chronic pain conditions such as knee OA. Thus, its properties could have utility for certain clinical situations, or in combination with other therapies

Cross-sectional DXA and MR measures of tibial periarticular bone associate with radiographic knee osteoarthritis severity

SummaryObjectiveWe evaluated the relationship of medial proximal tibial periarticular areal bone mineral density (paBMD) and trabecular morphometry and determined whether these bone measures differed across radiographic medial joint space narrowing (JSN) scores.Methods482 participants of the Osteoarthritis Initiative (OAI) Bone Ancillary Study had knee dual X-ray absorptiometry (DXA) and trabecular bone 3T magnetic resonance imaging (MRI) exams assessed at the same visit. Medial proximal tibial paBMD was measured on DXA and apparent trabecular bone volume fraction (aBV/TV), thickness (aTb.Th), number (aTb.N), and spacing (aTb.Sp) were determined from MR images. Radiographs were assessed for medial JSN scores (0–3). We evaluated associations between medial paBMD and trabecular morphometry. Whisker plots with notches of these measures versus medial JSN scores were generated and presented.ResultsMean age was 63.9 (9.2) years, BMI 29.6 (4.8) kg/m2, and 53% were male. The Spearman correlation coefficients between DXA-measured medial paBMD and aBV/TV was 0.61 [95% confidence interval (CI) 0.55–0.66]; between paBMD and aTb.Th was 0.38 (95%CI 0.30–0.46); paBMD and aTb.N was 0.65 (95%CI 0.60–0.70); paBMD and aTb.Sp was −0.65 (95%CI −0.70 to −0.59). paBMD and the trabecular metrics were associated with medial JSN scores.ConclusionThe moderate associations between periarticular trabecular bone density and morphometry and their relationship with greater severity of knee OA support hypotheses of remodeling and/or microscopic compression fractures in the natural history of OA. Longitudinal studies are needed to assess whether knee DXA will be a predictor of OA progression. Further characterization of the periarticular bone in OA utilizing complementary imaging modalities will help clarify OA pathophysiology

Physiological effects of oral glucosamine on joint health: Current status and consensus on future research priorities

The aim of this paper was to provide an overview of the current knowledge and understanding of the potential beneficial physiological effects of glucosamine (GlcN) on joint health. The objective was to reach a consensus on four critical questions and to provide recommendations for future research priorities. To this end, nine scientists from Europe and the United States were selected according to their expertise in this particular field and were invited to participate in the Hohenheim conference held in Aug

How can we explain the differences between the OARSI and ESCEO Guidelines for the management of knee osteoarthritis?

peer reviewe

Individual patient data meta-analysis of trials investigating the effectiveness of intra-articular glucocorticoid injections in patients with knee or hip osteoarthritis

Based on small to moderate effect sizes for the wide range of symptomatic treatments in osteoarthritis (OA), and on the heterogeneity of OA patients, treatment guidelines for OA have stressed the need for research on clinical predictors of response to different treatments. A meta-analysis to quantify the effect modified by the predictors using individual patient data (IPD) is suggested. The initiative to collect and analyze IPD in OA research is commenced by the OA Trial Bank. The study aims are therefore: to evaluate the efficacy of intra-articular glucocorticoids for knee or hip OA in specific subgroups of patients with severe pain and (mild) inflammatory signs, over both short-term and long-term follow-up, using IPD from existing studies; to reach consensus on the rules for cooperation in a consortium; and to develop and explore the methodological issues of meta-analysis with individual OA patient data. For the current IPD analysis we will collect and synthesize IPD from randomized trials studying the effect of intra-articular glucocorticoid injections in patients with hip or knee OA. Subgroup analyses will be performed for the primary outcome of pain at both short-term and long-term follow-up, in the subgroups of patients with and without severe pain and with and without inflammatory signs. This study protocol includes the first study of the OA Trial Bank, an international collaboration that initiates meta-analyses on predefined subgroups of OA patients from existing literature. This approach ensures a widely supported initiative and is therefore likely to be successful in data collection of existing trials. The collaboration developed (that is, the OA Trial Bank) may also lead to future IPD analyses on subgroups of patients with several intervention strategies applied in OA patients

The OA Trial Bank: Meta-analysis of individual patient data from knee and hip osteoarthritis trials show that patients with severe pain exhibit greater benefit from intra-articular glucocorticoids

Objective: To evaluate the efficacy of intra-articular (IA) glucocorticoids for knee or hip osteoarthritis (OA) in specific subgroups of patients with severe pain and inflammatory signs using individual patient data (IPD) from existing trials. Design: Randomized trials evaluating one or more IA glucocorticoid preparation in patients with knee or hip OA, published from 1995 up to June 2012 were selected from the literature. IPD obtained from original trials included patient and disease characteristics and outcomes measured. The primary outcome was pain severity at short-term follow-up (up to 4 weeks). The subgroup factors assessed included severe pain (≥70 points, 0-100 scale) and signs of inflammation (dichotomized in present or not) at baseline. Multilevel regression analyses were applied to estimate the magnitude of the effects in the subgroups with the individuals nested within each study. Results: Seven out of 43 published randomized clinical trials (n = 620) were included. Patients with severe baseline pain had a significantly larger reduction in short-term pain, but not in mid- and long-term pain, compared to those with less severe pain at baseline (Mean Difference 13.91; 95% Confidence Interval 1.50-26.31) when receiving IA glucocorticoid injection compared to placebo. No statistical significant interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo and to tidal irrigation at all follow-up points. Conclusions: This IPD meta-analysis demonstrates that patients with severe knee pain at baseline derive more benefit from IA glucocorticoid injection at short-term follow-up than those with less severe pain at baseline