Marc Marty

Is there any scientific evidence for the use of glucosamine in the management of human osteoarthritis

Glucosamine in its acetylated form is a natural constituent of some glycosaminoglycans (for example, hyaluronic acid and keratan sulfate) in the proteoglycans found in articular cartilage, intervertebral disc and synovial fluid. Glucosamine can be extracted and stabilized by chemical modification and used as a drug or a nutraceutical. It has been approved for the treatment of osteoarthritis (OA) in Europe to promote cartilage and joint health and is sold over the counter as a dietary supplement in the United States. Various formulations of glucosamine have been tested, including glucosamine sulfate and glucosamine hydrochloride. In vitro and in vivo studies have uncovered glucosamines mechanisms of action on articular tissues (cartilage, synovial membrane and subchondral bone) and justified its efficacy by demonstrating structure-modifying and anti-inflammatory effects at high concentrations. However, results from clinical trials have raised many concerns. Pharmacokinetic studies have shown that glucosamine is easily absorbed, but the current treatment doses (for example, 1,500 mg/day) barely reach the required therapeutic concentration in plasma and tissue. The symptomatic effect size of glucosamine varies greatly depending on the formulation used and the quality of clinical trials. Importantly, the effect size reduces when evidence is accumulated chronologically and evidence for the structure-modifying effects of glucosamine are sparse. Hence, glucosamine was at first recommended by EULAR and OARSI for the management of knee pain and structure improvement in OA patients, but not in the most recent NICE guidelines. Consequently, the published recommendations for the management of OA require revision. Glucosamine is generally safe and although there are concerns about potential allergic and salt-related side effects of some formulations, no major adverse events have been reported so far. This paper examines all the in vitro and in vivo evidence for the mechanism of action of glucosamine as well as reviews the results of clinical trials. The pharmacokinetics, side effects and differences observed with different formulations of glucosamine and combination therapies are also considered. Finally, the importance of study design and criteria of evaluation are highlighted as new compounds represent new interesting options for the management of OA.

Randomised, controlled trial of avocado–soybean unsaponifiable (Piascledine) effect on structure modification in hip osteoarthritis: the ERADIAS study

Objective To assess the ability of avocado–soybean unsaponifiable—Expanscience (ASU-E) to slow radiographic progression in symptomatic hip osteoarthritis (OA). Methods Prospective, randomised, double blind, parallel group, placebo controlled 3 year trial. Patients with symptomatic (painful ≥1 year, Lequesne Index between 3 and 10) hip OA (American College of Rheumatology criteria) and a minimum joint space width (JSW) of the target hip between 1 and 4 mm on a pelvic radiograph were randomly assigned to 300 mg/day ASU-E or placebo. Standing pelvis, target hip anteroposterior (AP) and oblique views were taken annually. The primary outcome was JSW change at year 3, measured at the narrowest point on pelvic or target hip AP view (manual measure using a 0.1 mm graduated magnifying glass). The full analysis dataset (FAS) included all patients having at least two successive radiographs. An analysis of covariance Mixed Model for Repeated Measurements with Missing at Random (for missing data) was performed to compare adjusted 3 year JSW changes (primary outcome) and the percentages of ‘progressors’ (JSW loss≥0.5 mm) between groups. Results 399 patients were randomised (345 kept in the FAS), aged 62 (35–84) years, 54% women, mean body mass index 27 (SD 4) kg/m2, mean symptom duration 4 (SD 5) years, 0–100 normalised Lequesne Index 30 (SD 9) and global pain visual analogue scale 37 (SD 23) mm. Mean baseline JSW was 2.8 (0.9) mm. There was no significant difference on mean JSW loss (−0.638 mm vs −0.672 mm, p=0.72, in the ASU-E and placebo groups, respectively) but there were 20% less progressors in the ASU-E than in the placebo group (40% vs 50%, respectively, p=0.040). No difference was observed on clinical outcomes. Safety was excellent. Conclusions 3 year treatment with ASU-E reduces the percentage of JSW progressors, indicating a potential structure modifying effect in hip OA to be confirmed, and the clinical relevance requires further assessment. Trial registration number on ClinicalTrial.gov NCT01062737

What is the current status of chondroitin sulfate and glucosamine for the treatment of knee osteoarthritis

Chondroitin sulfate and glucosamine sulfate exert beneficial effects on the metabolism of in vitro models of cells derived from synovial joints: chondrocytes, synoviocytes and cells from subchondral bone, all of which are involved in osteoarthritis (OA). They increase type II collagen and proteoglycan synthesis in human articular chondrocytes and are able to reduce the production of some pro-inflammatory mediators and proteases, to reduce the cellular death process, and improve the anabolic/catabolic balance of the extracellular cartilage matrix (ECM). Clinical trials have reported a beneficial effect of chondroitin sulfate and glucosamine sulfate on pain and function. The structure-modifying effects of these compounds have been reported and analyzed in recent meta-analyses. The results for knee OA demonstrate a small but significant reduction in the rate of joint space narrowing. Chondroitin sulfate and glucosamine sulphate are recommended by several guidelines from international societies for the management of knee and hip OA, while others do not recommend these products or recommend only under condition. This comprehensive review clarifies the role of these compounds in the therapeutic arsenal for patients with knee OA.

Forceful sacrococcygeal injections in the treatment of postdiscectomy sciaticaA controlled study versus glucocorticoid injections

UNLABELLED The role of epidural fibrosis in postoperative sciatica is unclear. Few therapeutic trials have been published. We evaluated the mechanical effects of forceful saline injections through the sacrococcygeal hiatus comparatively with glucocorticoid injections. PATIENTS AND METHODS Forty-seven patients with postdiscectomy sciatica but no evidence of compression by computed tomography or magnetic resonance imaging were included in a multicenter, randomized, controlled, parallel-group study comparing forceful injections of saline (20 ml) with or without prednisolone acetate (125 mg) to epidural prednisolone acetate (125 mg) alone. Each of the three treatments was given once a month for three consecutive months. Outcome measures were pain severity on a visual analog scale (VAS) and the scores on the Dallas algofunctional self-questionnaire on day 0, day 60, and day 120. Analysis of variance for repeated measures and Students t test for paired series were used to evaluate the data. RESULTS Forty-seven patients were evaluated. The VAS score improved significantly between day 0 and day 30 in the glucocorticoid group as compared to the forceful injection group (P = 0.01). No other significant differences were found across the groups. The VAS score improved steadily in the forceful injection group, producing a nearly significant difference on day 120 as compared to baseline (P = 0.08). CONCLUSION Forceful epidural injections produced a non-significant improvement in postdiscectomy sciatica four months after surgery. Epidural glucocorticoids used alone induced short-lived pain relief.

Hyaluronan for knee osteoarthritis: an updated meta-analysis of trials with low risk of bias

Background The effectiveness of intra-articular hyaluronic acid (IAHA) injection for knee osteoarthritis (KOA) is debated. Objectives To evaluate the effect of IAHA for patients with KOA by analysing data from trials of IAHA versus placebo with low risk of bias, to provide the highest level of evidence. Methods A systematic review and meta-analysis was conducted. Randomised controlled trials (RCTs) with a low risk of bias (adequate randomisation and concealment and double-blind design) that investigated IAHA versus placebo (saline solution) injection were eligible. The primary efficacy measure was pain intensity and secondary outcome function at 3 months. The treatment effect was summarised with the standardised mean difference (SMD) calculated from differences in means of pain and function measures between treatment and control groups at 3 months. Trials were pooled by a random-effects model with DerSimonian and Laird weights. Statistical heterogeneity was explored by a visual exploration of forest plots and the I2 statistic. Results A total of eight RCTs (2 199 randomised patients) met our inclusion criteria. IAHA significantly reduced the pain intensity (SMD=−0.21, 95% CI (95% CI) −0.32 to −0.10) and improved function (SMD=−0.12, 95% CI −0.22 to −0.02). Trials showed no heterogeneity. Conclusions This meta-analysis of high-quality trials of IAHA versus placebo shows that IAHA provides a moderate but real benefit for patients with KOA.

Comparison of general practitioners and rheumatologists' prescription patterns for patients with knee osteoarthritis

BackgroundTo compare the prescription modalities of general practitioners (GPs) and rheumatologists (RHs) for symptomatic knee osteoarthritis (OA) and to determine correlates with prescription of low-dose NSAIDs.MethodsThis observational, prospective, national survey was carried out among a national representative sample of GPs (n = 808) and RHs (n = 134). Each physician completed a medical questionnaire for the 2 most recent patients fulfilling the ACR criteria for knee OA.ResultsGPs and RHs included 1,570 and 251 patients, respectively. Mean pain level of the knee (on a VAS, 0-100 mm) was greater for GP patients than for RH patients (49.8 ± 16.3 vs. 46.2 ± 17.1 mm, respectively; p < 0.01). As compared with patients of RHs, those of GPs more frequently had another joint affected by OA: 71.2% vs. 63.7% (p < 0.0001) and more often had hypertension and diabetes mellitus (p < 0.05).As compared with RHs, GPs more frequently prescribed low-dose NSAIDs (p < 0.0001), oral NSAIDs (p < 0.05), and topical NSAIDs (p < 0.0001) but less frequently symptomatic slow-acting drugs for OA (p < 0.01). Moreover, GPs more frequently recommended rehabilitation (p < 0.01) and loss of weight (p < 0.0001). Logistic regression analysis revealed an association of low-dose NSAIDs prescription and prescription by GPs, prescription of topical NSAIDs, no prescription of oral NSAIDs or coxibs and no intra-articular injection of steroids.ConclusionsThis study identified speciality-related variability in some aspects of the management of knee OA. The clinical profile of patients with knee OA differed between GPs and RHs.

“Let’s Talk about OA Pain”: A Qualitative Analysis of the Perceptions of People Suffering from OA. Towards the Development of a Specific Pain OA-Related Questionnaire, the Osteoarthritis Symptom Inventory Scale (OASIS)

Introduction Pain is the primary outcome measurement in osteoarthritis, and its assessment is mostly based on its intensity. The management of this difficult chronic condition could be improved by using pain descriptors to improve analyses of painful sensations. This should help to define subgroups of patients based on pain phenotype, for more adapted treatment. This study draws upon patients’ descriptions of their pain, to identify and understand their perception of osteoarthritis pain and to categorize pain dimensions. Methods This qualitative study was conducted with representative types of patients suffering from osteoarthritis. Two focus groups were conducted with a sample of 14 participants, with either recent or chronic OA, at one or multiple sites. Focus groups were semi-structured and used open-ended questions addressing personal experiences to explore the experiences of patients with OA pain and the meanings they attributed to these pains. Results Two main points emerged from content analyses: -A major difficulty in getting patients to describe their osteoarthritis pain: perception that nobody wants to hear about it; necessity to preserve one’s self and social image; notion of self-imposed stoicism; and perception of osteoarthritis as a complex, changing, illogical disease associated with aging. -Osteoarthritis pains were numerous and differed in intensity, duration, depth, type of occurrence, impact and rhythm, but also in painful sensations and associated symptoms. Based on analyses of the verbatim interviews, seven dimensions of OA pain emerged: pain sensory description, OA-related symptoms, pain variability profile, pain-triggering factors, pain and physical activity, mood and image, general physical symptoms. Summary In osteoarthritis, pain analysis should not be restricted to intensity. Our qualitative study identified pain descriptors and defined seven dimensions of osteoarthritis pain. Based on these dimensions, we aim to develop a specific questionnaire on osteoarthritis pain quality for osteoarthritis pain phenotyping: the OsteoArthritis Symptom Inventory Scale (OASIS).

Is volition the missing link in the management of low back pain

Patients with nonspecific chronic low back pain are typically prescribed a regimen of regular physical exercises to improve pain and function, increase workability, and prevent pain recurrence. However, adherence to home exercise programs is often partial at best. Patients often fail to translate their intention to exercise (motivation) into action (implementation). Volition is the mental activity by which intentions are implemented. In this review, we argue that volition may be crucial to the successful rehabilitation of patients with low back pain. Obstacles to the implementation of intentions are described, as well as factors that promote implementation, most notably the conscious formation of implementation intentions.

Validation of the KOFUS (Knee Osteoarthritis Flare-Ups Score)

OBJECTIVE To develop a diagnostic score for knee osteoarthritis flare-ups and to evaluate its sensitivity and specificity. METHODS We used two epidemiological databases built using the same methodology. One database was from a general-practice study and served to develop the score, whereas the other was from a rheumatology study and served to validate the score. Physicians determined the flare-up status of each patient. The rheumatologist diagnosis was the reference standard. Logistic regression was performed to identify factors significantly associated with having a flare-up. RESULTS Of the 6085 patients in the general-practice database, 52.3% had a knee osteoarthritis flare-up. The score was built by assigning points to features that were present, with a weighting system based on the odds ratio of each feature for having a flare-up (0, feature absent; 1, morning stiffness for longer than 20 min; 2, pain causing nocturnal awakenings and knee effusion; 3, limping, joint swelling, and increased warmth over the knee). The score could range from 0 to 14. The receiver-operating characteristic curve showed that 7 was the best cutoff for diagnosing a flare-up. In the rheumatologist database, the numbers of patients having a flare-up were 274 (46.4%) based on the score and 270 (45.7%) based on the rheumatologist diagnosis. Sensitivity of the score was 87.0%, specificity 87.9%, positive predictive value 85.8%, and negative predictive value 89.0%. The Youden index was 0.75. CONCLUSION A score equal to or greater than 7 points correlated well with a rheumatologist diagnosis of flare-up. Our score may constitute a valid objective criterion for standardizing the diagnosis of knee osteoarthritis flare-up, most notably when screening patients for inclusion in therapeutic trials.

Ecological or recalled assessments in chronic musculoskeletal pain? A comparative study of prospective and recalled pain assessments in low back pain and lower limb painful osteoarthritis.

OBJECTIVES The objective of this study was to compare ecological and recalled pain intensity assessments over 29 days in hip and knee osteoarthritis (O) and chronic low back pain (L). PATIENTS AND METHODS Rheumatologists were asked to enroll patients with O and L, with pain intensity above 40 mm, in a prospective study for 29 days. Pain intensity was assessed with physicians on Days 1 and 29, and ecologically, over the intervening 28-day period, by random phone calls. RESULTS We carried out correlation analyses for 353 (159 O, 194 L) patients: Overall recalled daily pain was strongly correlated with calculated 3-day mean pain assessments (r=0.96 [O]; 0.93 [L]) and evening pain (r=0.96 [O], 0.90 [L]). Correlations between ecological and recalled measures were stronger for recall over the last 7 days than for recall over the last 28 days in osteoarthritis patients (r=0.78, r=0.63), but were similar for both recall periods in low back pain patients (r=0.70, r=0.72). Correlations between assessments for the last 7 and 28 days were stronger for ecological (r=0.88 [O], 0.91 [L]) than for clinical (r=0.77 [O]; 0.86 [L]) assessments. After adjustment for current pain intensity, correlations remained significant for ecological assessments, but not for clinical assessments. Recalled pain assessments were more accurate when made after 24 hours (r=0.71 [O]; 0.70 [L]) than when made after 48 hours (r=0.63 [O]; 0.61 [L]). CONCLUSIONS For both low back pain and osteoarthritis, overall daily pain recall is a reliable measurement correlated with daily ecological measurements, whereas a rapid decrease in recall occurs after 48 hours. The most reliable period for pain recall was 7 days, but the results obtained were influenced by current pain.