Florent Richy

Health-related quality of life in total hip and total knee arthroplasty: A qualitative and systematic review of the literature

BACKGROUND Total hip and total knee arthroplasties are well accepted as reliable and suitable surgical procedures to return patients to function. Health-related quality-of-life instruments have been used to document outcomes in order to optimize the allocation of resources. The objective of this study was to review the literature regarding the outcomes of total hip and knee arthroplasties as evaluated by health-related quality-of-life instruments. METHODS The Medline and EMBASE medical literature databases were searched, from January 1980 to June 2003, to identify relevant studies. Studies were eligible for review if they met the following criteria: (1). the language was English or French, (2). at least one well-validated and self-reported health-related quality of life instrument was used, and (3). a prospective cohort study design was used. RESULTS Of the seventy-four studies selected for the review, thirty-two investigated both total hip and total knee arthroplasties, twenty-six focused on total hip arthroplasty, and sixteen focused on total knee arthroplasty exclusively. The most common diagnosis was osteoarthritis. The duration of follow-up ranged from seven days to seven years, with the majority of studies describing results at six to twelve months. The Short Form-36 and the Western Ontario and McMaster University Osteoarthritis Index, the most frequently used instruments, were employed in forty and twenty-eight studies, respectively. Seventeen studies used a utility index. Overall, total hip and total knee arthroplasties were found to be quite effective in terms of improvement in health-related quality-of-life dimensions, with the occasional exception of the social dimension. Age was not found to be an obstacle to effective surgery, and men seemed to benefit more from the intervention than did women. When improvement was found to be modest, the role of comorbidities was highlighted. Total hip arthroplasty appears to return patients to function to a greater extent than do knee procedures, and primary surgery offers greater improvement than does revision. Patients who had poorer preoperative health-related quality of life were more likely to experience greater improvement. CONCLUSIONS Health-related quality-of-life data are valuable, can provide relevant health-status information to health professionals, and should be used as a rationale for the implementation of the most adequate standard of care. Additional knowledge and scientific dissemination of surgery outcomes should help to ensure better management of patients undergoing total hip or total knee arthroplasty and to optimize the use of these procedures.

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.

Vitamin D analogs versus native vitamin D in preventing bone loss and osteoporosis-related fractures: a comparative meta-analysis

It has been suggested that early postmenopausal women and patients treated with steroids should receive preventive therapy (calcium, vitamin D, vitamin D analogs, estrogens, or bisphosphonates) to preserve their bone mineral density (BMD) and to avoid fragility fractures. We designed the present study to compare the effects of native vitamin D to its hydroxylated analogs alfacalcidol 1-α(OH)D and calcitriol 1,25(OH)2D. All randomized, controlled, double-blinded trials comparing oral native vitamin D and its analogs, alfacalcidol or calcitriol, to placebo or head-to-head trials in primary or corticosteroids-induced osteoporosis were included in the meta-analysis. Sources included the Cochrane Controlled Trials Register, EMBASE, MEDLINE, and a hand search of abstracts and references lists. The study period January 1985 to January 2003. Data were abstracted by two investigators, and methodological quality was assessed in a similar manner. Heterogeneity was extensively investigated. Results were expressed as effect-size (ES) for bone loss and as rate difference (RD) for fracture while allocated to active treatment or control. Publication bias was investigated. Fourteen studies of native vitamin D, nine of alfacalcidol, and ten of calcitriol fit the inclusion criteria. The two vitamin D analogs appeared to exert a higher preventive effect on bone loss and fracture rates in patients not exposed to glucocorticoids. With respect to BMD, vitamin D analogs versus placebo studies had an ES of 0.36 (P < 0.0001), whereas native vitamin D versus placebo had an ES of 0.17 (P = 0.0005), the interclass difference being highly significant (ANOVA-1, P < 0.05). When restricted to the lumbar spine, this intertreatment difference remained significant: ES = 0.43 (P = 0.0002) for vitamin D analogs and ES = 0.21 (P = 0.001) for native vitamin D (analysis of variance [ANOVA-1], P = 0.047). There were no significant differences regarding their efficacies on other measurement sites (ANOVA-1, P = 0.36). When comparing the adjusted global relative risks for fracture when allocated to vitamin D analogs or native vitamin D, alfacalcidol and calcitriol provided a more marked preventive efficacy against fractures: RD = 10% (95% Confidence interval [CI-2] to 17) compared to RD = 2% (95% CI, 1 to 2), respectively. The analysis of the spinal and nonspinal showed that fracture rates differed between the two classes, thereby confirming the benefits of vitamin D analogs, with significant 13.4% (95% CI 7.7 to 19.8) and. 6% (95% CI 1 to 12) lower fracture rates for vitamin D analogs, respectively. In patients receiving corticosteroid therapy, both treatments provided similar global ESs for BMD: ES = 0.38 for vitamin D analogs and ES = 0.41 for native vitamin D (ANOVA-1, P = 0.88). When restriced to spinal BMD, D analogs provided significant effects, whereas native vitamin D did not: ES = 0.43 (P < 0.0001) and ES = 0.33 (P = 0.21), respectively. The intertreatment difference was nonsignificant (ANOVA-1, P = 0.52). Neither D analogs for native vitamin D significantly prevented fractures in this subcategory of patients: RD = 2.6 (95%CI, −9.5 to 4.3) and RD = 6.4 (95%CI, −2.3 to 10), respectively. In head-to-head studies comparing D analogs and native vitamin D in patients receiving corticosteroids, significant effects favoring D analogs were found for femoral neck BMD: ES = 0.31 at P = 0.02 and spinal fractures: RD = 15% (95%CI, 6.5 to 25). Publication bias was not significant. Our analysis demonstrates a superiority of the D analogs atfacalcidol and calcitriol in preventing bone loss and spinal fractures in primary osteoporosis, including postmenopausal women. In corticosteroid-induced osteoporosis, the efficacy of D analogs differed depending on the comparative approach: indirect comparisons led to nonsignificant differences, whereas direct comparison did provide significant differences. In this setting, D analogs seem to prevent spinal fractures to a greater extent than do native vitamin D, but this assumption should be confirmed on a comprehensive basis in multiarm studies including an inactive comparator.

Subchondral tibial bone mineral density predicts future joint space narrowing at the medial femoro-tibial compartment in patients with knee osteoarthritis

Preliminary studies have shown that dual-energy X-ray absorptiometry (DXA) produces images of sufficient quality for a precise and accurate measurement at density of the subchondral bone. The objective of this study was to investigate the relationship between baseline subchondral tibial bone mineral density (BMD) and joint space narrowing observed after 1 year at the medial femoro-tibial compartment of the knee joint. Fifty-six consecutive patients, from both genders, with knee osteoarthritis diagnosed according to the American College of Rheumatology criteria, were included in the study. Radiographic posteroanterior views were taken, at baseline and after 1 year of follow-up. Minimum joint space width (JSW) measurement, at the medial femoro-tibial joint, was performed with a 0.1-mm graduated magnifying lens. Baseline BMD of the subchondral tibial bone was assessed by DXA. The mean +/- SD age of the patients was 65.3 +/- 8.7 years, with a body mass index of 28.0 +/- 4.9 kg/m(2). The minimum JSW was 3.5 +/- 1.5 mm and the mean BMD of the subchondral bone was 0.848 +/- 0.173 g/cm(2). There was a significant negative correlation between subchondral BMD and 1-year changes in minimum JSW (r = -0.43, p = 0.02). When performing a multiple regression analysis with age, sex, body mass index, and minimum JSW at baseline as concomitant variables, BMD of the subchondral bone as well as JSW at baseline were independent predictors of 1-year changes in JSW (p = 0.02 and p = 0.005, respectively). Patients in the lowest quartile of baseline BMD (<0.73 g/cm(2)) experienced less joint space narrowing than those in the highest BMD quartile (>0.96 g/cm(2)) (+0.61 +/- 0.69 mm versus -0.13 +/- 0.27 mm; p = 0.03). Assessment of BMD of the subchondral tibial bone is significantly correlated with future joint space narrowing and could be used as a predictor of knee osteoarthritis progression.

Development and Validation of a Markov Microsimulation Model for the Economic Evaluation of Treatments in Osteoporosis.

OBJECTIVE Markov models are increasingly used in economic evaluations of treatments for osteoporosis. Most of the existing evaluations are cohort-based Markov models missing comprehensive memory management and versatility. In this article, we describe and validate an original Markov microsimulation model to accurately assess the cost-effectiveness of prevention and treatment of osteoporosis. METHODS We developed a Markov microsimulation model with a lifetime horizon and a direct health-care cost perspective. The patient history was recorded and was used in calculations of transition probabilities, utilities, and costs. To test the internal consistency of the model, we carried out an example calculation for alendronate therapy. Then, external consistency was investigated by comparing absolute lifetime risk of fracture estimates with epidemiologic data. RESULTS For women at age 70 years, with a twofold increase in the fracture risk of the average population, the costs per quality-adjusted life-year gained for alendronate therapy versus no treatment were estimated at €9105 and €15,325, respectively, under full and realistic adherence assumptions. All the sensitivity analyses in terms of model parameters and modeling assumptions were coherent with expected conclusions and absolute lifetime risk of fracture estimates were within the range of previous estimates, which confirmed both internal and external consistency of the model. CONCLUSION Microsimulation models present some major advantages over cohort-based models, increasing the reliability of the results and being largely compatible with the existing state of the art, evidence-based literature. The developed model appears to be a valid model for use in economic evaluations in osteoporosis.

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.

Development and Validation of the ORACLE Score to Predict Risk of Osteoporosis

OBJECTIVE To develop and validate a composite index, the Osteoporosis Risk Assessment by Composite Linear Estimate (ORACLE), that includes risk factors and ultrasonometric outcomes to screen for osteoporosis. SUBJECTS AND METHODS Two cohorts of postmenopausal women aged 45 years and older participated in the development (n = 407) and the validation (n = 202) of ORACLE. Their bone mineral density was determined by dual energy x-ray absorptiometry and quantitative ultrasonometry (QUS), and their historical and clinical risk factors were assessed (January to June 2003). Logistic regression analysis was used to select significant predictors of bone mineral density, whereas receiver operating characteristic (ROC) analysis was used to assess the discriminatory performance of ORACLE. RESULTS The final logistic regression model retained 4 biometric or historical variables and 1 ultrasonometric outcome. The ROC areas under the curves (AUCs) for ORACLE were 84% for the prediction of osteoporosis and 78% for low bone mass. A sensitivity of 90% corresponded to a specificity of 50% for identification of women at risk of developing osteoporosis. The corresponding positive and negative predictive values were 86% and 54%, respectively, in the development cohort. In the validation cohort, the AUCs for identification of osteoporosis and low bone mass were 81% and 76% for ORACLE, 69% and 64% for QUS T score, 71% and 68% for QUS ultrasonometric bone profile index, and 76% and 75% for Osteoporosis Self-assessment Tool, respectively. ORACLE had the best discriminatory performance in identifying osteoporosis compared with the other approaches (P < .05). CONCLUSION ORACLE exhibited the highest discriminatory properties compared with ultrasonography alone or other previously validated risk indices. It may be helpful to enhance the predictive value of QUS.

Efficacy and safety of piroxicam revisited: a global meta-analysis of randomised clinical trials

BACKGROUND The relative efficacy/safety profiles of traditional (non-selective) NSAIDs (t-NSAIDs) have been repeatedly challenged. To better understand the efficacy and safety profile of piroxicam, a widely used NSAID, a meta-analysis of comparative RCTs was carried out according to the QUOROM guidance. METHODS A systematic comprehensive research (years 1980-2006) of any comparative randomised controlled trial (of over 7-day duration) with piroxicam for the treatment of osteoarticular conditions was conducted. Conservative analyses were stratified by comparator, outcome, indication, duration, and doses. Publication bias and robustness were exhaustively investigated. RESULTS Seventy-five comparative trials were ultimately included for analyses. Regarding global efficacy, piroxicam was more effective than naproxen [OR=1.37 (1.05; 1.77)] and nabumetone [OR=1.72 (1.26; 2.34)], while equivalent to other NSAIDS [OR=1.06 (0.96; 1.18)]. For pain and articular swelling, piroxicam was statistically equivalent to all other NSAIDs. For mobility, piroxicam appeared to be more effective than indomethacin, while equivalent to all other NSAIDs. Piroxicam was globally safer than other NSAIDs OR=0.83 [0.73; 0.96], notably indomethacin [OR=0.53 (0.43; 0.64], naproxen [OR=0.75 (0.65; 0.85)] and salicylates [OR=0.36 (0.17; 0.75)]. From a global GI safety point of view, piroxicam was better tolerated than indomethacin [OR=0.46 (0.36; 0.58)], naproxen [OR=0.66 (0.53; 0.83)] and salicylates [OR=0.45 (0.27; 0.78)] while less tolerated when compared to meloxicam [OR=1.49 (1.05; 2.13)]. Major GI effects were comparable among piroxicam users as in comparator drugs users [OR=1.33 (0.96; 1.84)], except for meloxicam [OR=2.37 (1.13; 4.97)]. The skin safety of piroxicam was statistically comparable to those of comparators [OR=1.01 (0.68; 1.51)]. CONCLUSION This meta-analysis of RCTs support a similar to more favourable efficacy/safety profile of piroxicam as compared to other t-NSAIDs.

D-Hormone analog alfacalcidol: an update on its role in post-menopausal osteoporosis and rheumatoid arthritis management

Alfacalcidol (1-alpha-hydroxyvitamin D3 is a non-endogenous analog of vitamin D which can bypass the renal and intestinal regulatory mechanisms that control the production of calcitriol (1,25-hydroxyvitamin D3, the active form of vitamin D, D-Hormone). Alfacalcidol may be metabolized into calcitriol with a limited risk of hypercalcemia. Alfacalcidol and calcitriol have been evaluated in animal and human studies assessing their effects on bone mineral density and fracture rates. More recently, they have been shown to produce beneficial effects in muscle, immune system, and autoimmune diseases, including rheumatoid arthritis. This paper discusses the therapeutic efficacy of alfacalcidol in reports in which it has been proposed as an interesting alternative to vitamin D or calcitriol. Some recent findings about general metabolism and regulation of vitamin D and its analogs are discussed. The biological and clinical effects of alfacalcidol in post-menopausal osteoporosis are reviewed, followed by critical appraisal of its efficacy in preventing bone loss and falls in the elderly. The last two sections discuss the role of D-analogs in regulating the immune system, with particular regard to rheumatoid arthritis. The main results of this review show that alfacalcidol may have a wider range of therapeutic applicability, beyond simply restricting it to patients in hemodialysis or peritoneal dialysis with high serum levels of intact PTH.

Efficacy and safety profiles of manidipine compared with amlodipine: A meta-analysis of head-to-head trials

Abstract The aim of this meta-analysis was to compare the efficacy and safety profile of manidipine 20 mg with that of amlodipine 10 mg. A systematic research of quantitative data produced or published between 1995 and 2009 was performed. Head-to-head randomized controlled trials (RCTs) of 12 months minimum duration reporting comparative efficacy (changes in systolic and diastolic blood pressure) and safety (total adverse events and ankle oedema), were included. Four high-quality RCTs, accounting for 838 patients (436 received manidipine and 402 received amlodipine) were included. The efficacy of manidipine and amlodipine was statistically equivalent: effect size for DBP = −0.08 (p = 0.22) and SBP = −0.01 (p = 0.83). The global safety of manidipine was significantly better than amlodipine: the relative risk (RR) for adverse event was 0.69 (0.56–0.85), and particularly for ankle oedema RR was 0.35 (0.22–0.54). Publication bias was not significant and the robustness of the analyses was good. These data suggest a better efficacy/safety ratio of manidipine over amlodipine.