Clinical significance of the long-term symptom-modifying effects of glucosamine sulfate: comment on the article by Brandt and Mazzuca.
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Arthralgia↗
Biomedical subjects
Olivier Bruyere
Publications and source records attributed to Olivier Bruyere.
Controlled whole body vibration to decrease fall risk and improve health-related quality of life of nursing home residents.
OBJECTIVE: To investigate the effects of whole body vibration in the elderly. DESIGN: Randomized controlled trial. SETTING: Nursing home. PARTICIPANTS: Forty-two elderly volunteers. INTERVENTIONS: Six-week vibration intervention plus physical therapy (PT) (n=22) or PT alone (n=20). MAIN OUTCOME MEASURES: We assessed gait and body balance using the Tinetti test (maximum scores of 12 for gait, 16 for body balance, 28 for global score), motor capacity using the Timed Up & Go (TUG) test, and health-related quality of life (HRQOL) using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: After 6 weeks, the vibration intervention group improved by a mean +/- standard deviation of 2.4+/-2.3 points on the gait score compared with no score change in the control group ( P <.001). The intervention group improved by 3.5+/-2.1 points on the body balance score compared with a decrease of 0.3+/-1.2 points in the control group ( P <.001). TUG test time decreased by 11.0+/-8.6 seconds in the treated group compared with an increase of 2.6+/-8.8 seconds in the control group ( P <.001). The intervention group had significantly greater improvements from baseline on 8 of 9 items on the SF-36 compared with the control group. CONCLUSIONS: Controlled whole body vibration can improve elements of fall risk and HRQOL in elderly patients.
Accidental Falls↗
Strontium ranelate (Fujisawa/Servier).
Strontium ranelate (PROTELOS), a divalent strontium salt, has been developed and launched by Servier for the treatment of osteoporosis. Fujisawa Pharmaceutical is developing the drug in Japan; in November 2004, phase II Japanese trials were ongoing.
Animals↗
Fracture prevention in postmenopausal women.
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Aged↗
Current concepts in the therapeutic management of osteoarthritis with glucosamine.
Over the last 10 years, several studies have investigated the ability of glucosamine sulfate to improve the symptoms (pain and function) and to delay the structural progression of osteoarthritis. There is now a large, convergent body of evidence that glucosamine sulfate, given at a daily oral dose of 1,500 mg, is able to significantly reduce the symptoms of osteoarthritis in the lower limbs and spine. This effect is usually seen with a minimal time for the onset of significant action - around 2 weeks. A similar dose of glucosamine sulfate has also been shown, in two independent studies, to prevent the joint space narrowing observed at the femorotibial compartment in patients with mild to moderate knee osteoarthritis. This effect, which is not affected by the radiographic technique used for the assessment of joint space width, also translated into a 50% reduction in the incidence of osteoarthritis-related surgery of the lower limbs during a 5-year period following the withdrawal of the treatment. There is a high degree of consistency in the literature showing that when glucosamine sulfate is used for the treatment of osteoarthritis, an efficacious response with minimum side effects can be expected. Since some discrepancies have been described between the results of studies performed with a patent-protected formulation of glucosamine sulfate distributed as a drug and those having used glucosamine preparations purchased from global suppliers, packaged, and sold over-the-counter as nutritional supplements (not regulated as drugs and with some potential issues concerning the reliability of their content), caution should be used when extrapolating conclusive results obtained with prescription drugs to over-the-counter or food supplements.
Drug Prescriptions↗
Primary prevention of osteoporosis: mass screening scenario or prescreening with questionnaires? An economic perspective.
UNLABELLED: This study focuses on the controversy surrounding selective approaches to screen for osteoporosis. Seven screening approaches were compared in terms of cost-effectiveness and incremental cost-effectiveness ratios in a sample of 4035 postmenopausal women. Our results show that certain prescreening strategies are more efficient than DXA-based approaches. These results are of considerable value for health policy decision-makers and the scientific community. INTRODUCTION: There is no general consensus on the most efficient strategy to use bone densitometry for osteoporosis screening. Two distinct approaches have progressively emerged: mass screening using DXA and prescreening strategies using user-friendly risk indices. This study was designed to compare the efficiency of these approaches. MATERIALS AND METHODS: A database of 4035 medical records from postmenopausal women above 45 years was analyzed. In the first scenario, women were systematically referred to DXA if above 45, 50, or 65 years of age. The second scenario involved the validated prescreening tools SCORE, ORAI, OST, and OSIRIS and assessed two separate ways of handling their results (theoretical and pragmatic). The cost of a DXA test was set as the median Belgian value: 40.14 Euros. All strategies were compared in terms of cost exposed per osteoporotic patient detected and in terms of incremental cost-effectiveness ratios. RESULTS: In the systematic DXA strategies, the cost per patient detected ranged from 123 Euros when measuring all women >45 years of age to 91 Euros when focusing on women >65 years of age. The corresponding percentage of cases detected ranged from 100% (age > 45 years) to 50% (age > 65 years). When considering prescreening under the theoretical and pragmatic scenarios, the OSIRIS index provided the best efficiency, with costs of 74 Euros (theoretical) to 85 Euros (pragmatic) per case detected, followed by ORAI (75 Euros and 96 Euros), OST (84 Euros and 94 Euros), and SCORE (96 Euros and 103 Euros). The corresponding percentage of cases detected ranged from 89% (SCORE) to 75% (OSIRIS). The cost-effectiveness analysis showed that mass screening strategies over 50 and 65 years of age and using ORAI were best. CONCLUSIONS: Our study sets the grounds for considering, in a health economics perspective, prescreening tools as valuable, cost-effective, approaches to significantly reduce the economic burden of osteoporosis screening.
Absorptiometry, Photon↗
Efficacy of alphacalcidol and calcitriol in primary and corticosteroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate.
Vitamin D metabolites alphacalcidol and calcitriol (D-hormones) have been investigated for two decades, but few and conflicting results are available from high-quality randomized controlled trials. Our objectives were to provide an evidence-based update quantitatively summarizing their efficacy on bone mineral density (BMD) and fracture rate. We performed a systematic research of any randomized controlled trial containing relevant data, peer review, data extraction and quality scoring blinded for authors and data sources, and comprehensive meta-analyses of the relevant data. Inclusion criteria were: randomized controlled study, calcitriol or alphacalcidol, BMD or fractures in healthy/osteopenic/osteoporotic patients exposed or not to corticosteroids (CS). Analyses were performed in a conservative fashion using professional dedicated softwares and stratified by outcome, target patients, study quality, and control-group type. Results were expressed as effect size (ES) for bone loss or relative risk (RR) for fracture while allocated to D-hormones vs control. Publication bias and robustness were investigated. Of the trials that were retrieved and subsequently reviewed, 17 papers fitted the inclusion criteria and were assessed. Quality scores ranged from 20 to 100%, the mean (standard deviation) being 72 (22)%. Calcitriol and alphacalcidol were found to have the same efficacy on all outcomes at p>0.13. We globally assessed D-hormones effects in preventing bone loss in patients not exposed to CS, and found positive effect: ES=0.39 ( p<0.001). For lumbar spine, this particular effect was 0.43 ( p<0.001). D-hormones significantly reduced the overall fracture rates: RR=0.52 (0.46; 0.59) and both vertebral and non-vertebral fractures: RR=0.53 (0.47; 0.60) and RR=0.34 (0.16; 0.71), respectively. No statistical difference in response was observed between results from studies on healthy and osteoporotic patients or depending on the fact that controls were allowed to calcium supplementation. Treatment with D-hormones was evaluated for maintaining spinal bone mass in five trials of patients with CS-induced osteoporosis, and provided ES=0.43 at p<0.001. Only two studies specifically addressed the effects of calcitriol on spinal fracture rate. None of them provided significant results, and the global RR did not reach the significance level as well: RR=0.33 (0.07; 1.51). Our data demonstrated efficacy for DH on bone loss and fracture prevention in patients not exposed to CS and on bone loss in patients exposed to CS, in the light of the most reliable scientific evidence. Their efficacy in reducing the number of fractures in patients exposed to CS remains to be determined.
Adrenal Cortex Hormones↗
Combination/sequential therapy in osteoporosis.
Combination therapy includes the concomitant or sequential use of compounds sharing the same mode of action (eg, two or more inhibitors of bone resorption) or with distinct pathways of activity (eg, an inhibitor of resorption plus an anabolic agent). Combination use of antiresorptive agents may generate concerns, because of the risk of inducing oversuppression of bone turnover. However, if low doses of estrogen, used for the management of climacteric symptoms, are insufficient to normalize bone turnover, the addition of a bisphosphonate to hormone therapy may prove to be useful to achieve this objective. Patients pretreated with inhibitors of resorption, who have not achieved a full therapeutic response, are good candidates for treatment with anabolic agents. The increase in bone turnover that comes after the introduction of parathyroid hormone (PTH) in patients treated with an antiresorptive agent is similar to that observed in treatment-naïve patients and the pattern of bone mineral density (BMD) increase is also identical, with the exception of a 6 month delay in the spine and hip BMD changes observed in prior alendronate-treated subjects. Current data discourage the concomitant use of alendronate and PTH since the bisphosphonate appears to blunt (in men and women) the anabolic action of PTH. Whether this applies to other bisphosphonates or inhibitors of resorption, remains unknown. The use of an inhibitor of bone resorption after completion of PTH treatment seems an appropriate way to maintain the skeletal benefits gained during therapy. Long-term clinical studies, using fractures as an endpoint should be initiated to better understand the clinical and pharmaco-economic interest of combination therapies in the management of osteoporosis.
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Recommendations for the use of new methods to assess the efficacy of disease-modifying drugs in the treatment of osteoarthritis.
BACKGROUND: Recent innovations in the pharmaceutical drug discovery environment have generated new chemical entities with the potential to become disease modifying drugs for osteoarthritis (DMOAD's). Regulatory agencies acknowledge that such compounds may be granted a DMOAD indication, providing they demonstrate that they can slow down disease progression; progression would be calibrated by a surrogate for structural change, by measuring joint space narrowing (JSN) on plain X-rays with the caveat that this delayed JSN translate into a clinical benefit for the patient. Recently, new technology has been developed to detect a structural change of the OA joint earlier than conventional X-rays. OBJECTIVE: The Group for the Respect of Ethics and Excellence in Science (GREES) organized a working party to assess whether these new technologies may be used as surrogates to plain x-rays for assessment of DMOADs. METHODS: GREES includes academic scientists, members of regulatory authorities and representatives from the pharmaceutical industry. After an extensive search of the international literature, from 1980 to 2002, two experts meetings were organized to prepare a resource document for regulatory authorities. This document includes recommendations for a possible update of guidelines for the registration of new chemical entities in osteoarthritis. RESULTS: Magnetic resonance imaging (MRI) is now used to measure parameters of cartilage morphology and integrity in OA patients. While some data are encouraging, correlation between short-term changes in cartilage structure observed with MRI and long-term radiographic or clinical changes are needed. Hence, the GREES suggests that MRI maybe used as an outcome in phase II studies, but that further data is needed before accepting MRI as a primary end-point in phase III clinical trials. Biochemical markers of bone and cartilage remodelling are being tested to predict OA and measure disease progression. Recently published data are promising but validation as surrogate end-points for OA disease progression requires additional study. The GREES suggests that biochemical markers remain limited to 'proof of concept' studies or as secondary end-points in phase II and III clinical trials. However, the GREES emphasizes the importance of acquiring additional information on biochemical markers in order to help better understand the mode of action of drugs to be used in OA. Regulatory agencies consider that evidence of improvement in clinical outcomes is critical for approval of DMOAD. Time to total joint replacement surgery is probably the most relevant clinical end-point for the evaluation of efficacy of a DMOAD. However, at this time, time to surgery can not be used in clinical trials because of bias by non disease-related factors like patient willingness for surgery or economic factors. At this stage, it appears that DMOAD should demonstrate a significant difference compared to placebo. Benefit should be measured by 3 co-primary end-points: JSN, pain and function. Secondary end-points should include the percentage of patients who are 'responder' (or 'failure'). The definition of a 'failure' patient would be someone with progression of JSN>0.5mm over a period of 2-3 years or who has a significant worsening in pain and/or function, based on validated cut-off values. The definition of the clinically relevant cut-off points for pain and function must be based on data evaluating the natural history of the disease (epidemiological cohorts or placebo groups from long-term studies). These cut-offs points should reflect a high propensity, for an individual patient, to later require joint replacement. CONCLUSION: GREES has outlined a set of guidelines for the development of a DMOAD for OA. Although these guidelines are subject to change as new information becomes available, the information above is based on the present knowledge in the field with the addition of expert opinion.
Anthraquinones↗
Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis.
OBJECTIVE: To assess the structural and symptomatic efficacy of oral glucosamine sulfate and chondroitin sulfate in knee osteoarthritis through independent meta-analyses of their effects on joint space narrowing, Lequesne Index, Western Ontario MacMaster University Osteoarthritis Index (WOMAC), visual analog scale for pain, mobility, safety, and response to treatment. METHODS: An exhaustive systematic research of randomized, placebo-controlled clinical trials published or performed between January 1980 and March 2002 that assessed the efficacy of oral glucosamine or chondroitin on gonarthrosis was performed using MEDLINE, PREMEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Contents, BIOSIS Previews, HealthSTAR, EBM Reviews, manual review of the literature and congressional abstracts, and direct contact with the authors and manufacturers of glucosamine and chondroitin. Inclusion, quality scoring, and data abstraction were performed systematically by 2 independent reviewers who were blinded to sources and authors. Conservative approaches were used for clear assessment of potential efficacy. RESULTS: Our results demonstrated a highly significant efficacy of glucosamine on all outcomes, including joint space narrowing and WOMAC. Chondroitin was found to be effective on Lequesne Index, visual analog scale pain, mobility, and responding status. Safety was excellent for both compounds. CONCLUSIONS: Our study demonstrates the structural efficacy of glucosamine and indistinguishable symptomatic efficacies for both compounds. Regarding the relatively sparse data on glucosamine and joint space narrowing and the absence of data on structural effects of chondroitin, further studies are needed to investigate the relationship among time, dose, patient baseline characteristics, and structural efficacy for an accurate, disease-modifying characterization of these 2 compounds.
Administration, Oral↗
Interest of biochemical markers of bone turnover for long-term prediction of new vertebral fracture in postmenopausal osteoporotic women.
OBJECTIVE: To analyse the interest of baseline levels and short-term (3-months) changes in serum osteocalcin (BGP), serum bone-specific alkaline phosphatase (BALP) and urinary C-telopeptide of type I collagen/creatinine ratio (U-CTX) to predict 3-years changes in bone mineral density (BMD) and spinal deformity index (SDI) in postmenopausal osteoporotic women. METHODS: Data were derived from a cohort of 603 osteoporotic women corresponding to the placebo arm of a 3-years prospective, double-blind study. RESULTS: Baseline values of BALP, BGP and U-CTX were negatively and significantly correlated with baseline spinal BMD. Significant correlations were also observed between the changes in BMD observed after 36 months at the spine and baseline BALP (r=0.20, P=0.0001), BGP (r=0.09, P=0.05) and U-CTX (r=-0.11, P=0.02). At 3 years, 71 women (15.9%) showed an increase in their SDI, corresponding to the occurrence of at least one new vertebral deformity. Baseline values of the four bone turnover markers (BTM) were not significantly related to the occurrence of new vertebral deformities. However, when considering the changes in the BTM observed after 3-months of follow-up, BGP (P=0.003) and U-CTX (P=0.047) were identified as significant predictors of an increase of SDI. The associated odds ratios (95% confidence interval (CI)) were 10.922 (2.218-53.78) for unit changes of log BGP and 1.369 (1.003-1.867) for unit changes of logU-CTX. The relative risk (RR) (IC 95%) of having a new vertebral fracture over 36 months was 0.31 (0.15-0.65) when being in the lowest quartile of 3-months changes in BGP as compared with the highest. CONCLUSION: We conclude that two sequential measurements of BGP and U-CTX performed at 3-months intervals could be of interest to identify postmenopausal osteoporotic women with the highest risk to present new vertebral deformities.
Aged↗
Inhaled corticosteroids effects on bone in asthmatic and COPD patients: a quantitative systematic review.
Deleterious effect of oral corticosteroids on bone has been well documented, whereas this remains debated for inhaled ones (ICS). Our objectives were to analyze the effects of ICS on bone mineral density, fracture risk and bone markers. We performed an exhaustive systematic research of all controlled trials potentially containing pertinent data, peer-reviewed by a dedicated WHO expert group, and comprehensive meta-analyses of the data. Inclusion criteria were ICS, and BMD/markers/fractures in asthma/chronic obstructive pulmonary diseases (COPD) and healthy patients. Analyses were performed in a conservative fashion using professional dedicated softwares and stratified by outcome, study design and ICS type. Results were expressed as standardized mean difference/effect size (ES), relative risk (RR) or odds ratio (OR), depending on study design and outcome units. Publication bias was investigated. Twenty-three trials were reviewed; 11 papers fit the inclusion criteria and were assessed for the main analysis. Quality scores for the randomized controlled trials (RCTs) were 80%, 71% for the prospective cohort studies, and 78% for the retrospective cohort and cross-sectional studies. We globally assessed ICS effects on BMD and found deleterious effects: ES=0.61 ( p=0.001) for healthy subjects, and ES=0.27 ( p<0.001) for asthma/COPD patients. For these patients, this effect was 0.21 ( p<0.01) at the lumbar spine, and 0.26 ( p<0.001) at the hip or femoral neck. A single study evaluated the impact of ICS on hip fracture and reported an increased OR of 1.6 (1.24; 2.03). Lumbar fracture rate differences did not reach the level of statistical significance: 1.87 (0.5; 6.94). Osteocalcin and PICP were decreased and ICTP, pyridinoline and deoxypyridinoline levels were not significantly affected. Budesonide (BUD) appeared to be the ICS inducing the less deleterious effects on bone, followed by beclomethasone dipropionate (BDP) and triamcinolone (TRI). Publication bias investigation provided non-significant results. In our meta-analyses, BUD at a mean daily dose (SD) of 686 microg (158 microg), BDP at 703 microg (123 microg) and TRI at 1,000 microg (282 microg) were found to affect bone mineral density and markers in patients suffering from the two major respiratory diseases. These findings could have practical implication in the long-term management of asthmatic and COPD patients.
Administration, Inhalation↗
Naturocetic (glucosamine and chondroitin sulfate) compounds as structure-modifying drugs in the treatment of osteoarthritis.
PURPOSE OF REVIEW: Several entities have been investigated carefully for the symptomatic and structural management of osteoarthritis. This review reports recent findings suggesting that such compounds may delay the structural progression of osteoarthritis. RECENT FINDINGS: The most compelling evidence of a potential for inhibiting the structural progression of osteoarthritis has been obtained with glucosamine sulfate, whereas preliminary results obtained in patients with osteoarthritis of the hands also suggest that chondroitin sulfate could be used in the same indication. At any rate, these two compounds have clearly demonstrated a symptomatic action, mainly in osteoarthritis of the lower limbs. Patients with the less severe radiographic osteoarthritis will experience, in the long run, the most dramatic disease progression in terms of joint space narrowing. Such patients may be particularly responsive to structure-modifying drugs. SUMMARY: Glucosamine sulfate has demonstrated its ability to reduce the progression of osteoarthritis in the lower limbs. The preliminary results obtained in the hands suggest that chondroitin sulfate could also be of interest in this indication. An important issue is that all the conclusive studies with such chemical entities resulted from the use of prescription medicines, not over-the-counter pills or food supplements.
Antirheumatic Agents↗
Biochemical markers of bone and cartilage remodeling in prediction of longterm progression of knee osteoarthritis.
OBJECTIVE: To investigate the relationship between biochemical markers of bone and cartilage remodeling and severity or progression (symptoms and structure) of knee osteoarthritis (OA). METHODS: Mean and minimal joint space width (JSW) of the femorotibial joint were measured from standardized radiographs taken at baseline and at the end of a 3-year longitudinal study of patients with knee OA. Pain, stiffness, and physical function subscales of the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index were assessed at the same time points. Biochemical markers [serum keratan sulfate (KS), serum hyaluronic acid (HA), urine pyridinoline (PYD) and deoxypyridinoline (DPD), serum osteocalcin (OC), cartilage oligomeric matrix protein (COMP)] were assessed at baseline and after 1 year. RESULTS: At baseline, no significant correlations were observed between values of biochemical markers and JSW or any of the WOMAC scores. Baseline markers were not correlated with 3-year percentage changes observed in mean or minimal JSW and WOMAC scores. Changes observed after 1 year in OC and HA were significantly correlated with 3-year progression in mean JSW (r = -0.24, p = 0.04 and r = 0.27, p = 0.02, respectively) and in minimal JSW (r = -0.31, p = 0.01 and r = 0.24, p = 0.04, respectively). In patients from the lowest quartile of 1-year changes in HA (< -21.22 ng/ml), mean JSW decreased after 3 years by 0.76 (1.23) mm compared to an increase of 0.11 (0.83) mm in patients in the highest quartile (> +14.34 ng/ml) (p = 0.03). CONCLUSION: The 3-year radiological progression of knee OA could be predicted by a 1-year increase in OC or a 1-year decrease in HA levels.
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New perspectives in the management of osteoarthritis. structure modification: facts or fantasy?
Several entities have been carefully investigated for the symptomatic and structural management of osteoarthritis (OA). The most compelling evidence of a potential for inhibiting the structural progression of OA has been obtained with glucosamine sulfate, while some preliminary results also suggest that other compounds could be used in the same indication. At any rate, several medications have clearly demonstrated a symptomatic action, mainly in OA of the lower limbs, including pain relief and improvement of functional disability. An important issue is that all conclusive studies with such chemical entities resulted from the use of prescription medicines and not over-the-counter or nutriceutical supplements.
Anthraquinones↗
Fracture prevention in postmenopausal women.
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Calcitonin↗
Fracture prevention in postmenopausal women.
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Aged↗
Radiologic features poorly predict clinical outcomes in knee osteoarthritis.
OBJECTIVES: To assess the impact of radiographic severity and progression on pain and disability. METHODS: Measurements of mean joint space width (JSW), narrowest join space (NJS) point and assessment of symptoms by the WOMAC questionnaire were performed at baseline and after three years in 212 subjects over 50 years with primary knee OA. RESULTS: At baseline, JSW and NJS were not significantly correlated with the scores recorded for the WOMAC global index or its pain, stiffness or function subscales. A statistically significant correlation was observed between the joint space narrowing over three years and the changes observed in the pain subscale of the WOMAC during the same period. The three-year changes in the global WOMAC index in patients within the lowest and the highest quartiles of mean joint space width at baseline showed, in both cases, a statistically (p<0.05) significant favorable difference between patients treated with glucosamine sulphate and those having received placebo. CONCLUSION: Radiographic and clinical progressions of the disease are significantly associated but the clinical relevance of the association is questionable.
Aged↗