Factors predicting osteoporosis treatment initiation in a regionally based cohort.

UNLABELLED: Osteoporosis treatment initiation was assessed during the year after baseline BMD testing in 8,689 previously untreated women. Treatment initiation increased progressively as BMD T-scores decreased, but there was a gradient response rather than step increases at conventional T-score intervention thresholds. INTRODUCTION: Bone mineral density (BMD) testing is used to identify those at high fracture risk and guide osteoporosis treatment (OTx) initiation. Clinical guidelines have used the World Health Organization T-score diagnostic cutoffs as thresholds for treatment intervention. Our objective was to assess whether OTx initiation tracks these T-score cutoffs. METHODS: Eight thousand six hundred and eighty-nine women age > or = 50 years who had not been dispensed any OTx medication in the year prior to baseline BMD were identified from a regionally based database in the Province of Manitoba, Canada, and OTx initiation rates were analyzed. RESULTS: Forty-four percent of women were dispensed OTx in the year after BMD. OTx initiation increased progressively as BMD T-scores decreased (8.2% normal, 41.0% osteopenic, 78.5% osteoporotic, p-for-trend < 0.0001). There was a gradient response to OTx initiation, rather than step increases at conventional T-score intervention thresholds. BMD was strongly associated with OTx (p < 0.0001) while age, weight, and fracture in the last year were not. CONCLUSIONS: Physicians rely heavily on BMD T-score to decide on OTx initiation. Although guidelines suggest using clinical risk factors to guide decision making, we did not see evidence of this. More explicit methods of reporting fracture risk may help physicians select patients who are likely to derive the largest benefit from OTx.

Ibandronate for the prevention of nonvertebral fractures: a pooled analysis of individual patient data.

UNLABELLED: This analysis was conducted to assess the effect of high versus lower doses of ibandronate on nonvertebral fractures. The results were adjusted for clinical fracture, age, and bone density. The treatment effect was dose-dependent. Higher doses of ibandronate significantly reduced the risk of nonvertebral fractures more effectively compared with lower doses. INTRODUCTION: The objective of this study was to assess the efficacy of different doses of ibandronate on nonvertebral fractures in a pooled analysis. METHODS: Eight randomized trials of ibandronate were reviewed for inclusion. Alternative definitions of high versus low doses based on annual cumulative exposure (ACE) were explored. A time-to-event analysis was conducted using Kaplan-Meier methodology. Hazard ratios (HR) were derived using Cox regression and adjusted for covariates. RESULTS: Combining higher ACE doses of > or = 10.8 mg (150 mg once monthly, 3 mg i.v. quarterly, and 2 mg i.v. every 2 months) versus ACE doses of 5.5 mg, from two trials, resulted in an HR 0.62 (95% CI 0.396-0.974, p = 0.038). There was a dose-response trend with increasing ACE doses (7.2-12 mg) versus ACE of 5.5 mg. CONCLUSIONS: A dose-response effect on nonvertebral fractures was observed when comparing high with low ACE doses. A significant reduction in nonvertebral fractures was noted when pooling data from trials using ACE doses of > or = 10.8 mg versus ACE < or = 7.2 mg; and with ACE > or = 10.8 mg versus ACE of 5.5 mg (38% reduction). Higher ibandronate dose levels (150 mg monthly or 3 mg i.v. quarterly) significantly reduced nonvertebral fracture risk in postmenopausal women.

Risk factors for low BMD in healthy men age 50 years or older: a systematic review.

SUMMARY: In this systematic review, we summarize risk factors for low bone mineral density and bone loss in healthy men age 50 years or older. Consistent risk factors were: age, smoking, low weight, physical/functional limitations, and previous fracture. Data specific to men has clinical and policy implications. INTRODUCTION: Osteoporosis is a significant health care problem in men as well as women, yet the majority of evidence on diagnosis and management of osteoporosis is focused on postmenopausal women. The objective of this systematic review is to examine risk factors for low bone mineral density (BMD) and bone loss in healthy men age 50 years or older. MATERIALS AND METHODS: A systematic search for observational studies was conducted in MEDLINE, Cochrane Database of Systematic Reviews, DARE, CENTRAL, CINAHL and Embase, Health STAR. The three main search concepts were bone density, densitometry, and risk factors. Trained reviewers assessed articles using a priori criteria. RESULTS: Of 642 screened abstracts, 299 articles required a full review, and 25 remained in the final assessment. Consistent risk factors for low BMD/bone loss were: advancing age, smoking, and low weight/weight loss. Although less evidence was available, physical/functional limitations and prevalent fracture (after age 50) were also associated with low BMD/bone loss. The evidence was inconsistent or weak for physical activity, alcohol consumption, calcium intake, muscle strength, family history of fracture/osteoporosis, and height/height loss. CONCLUSION: In this systematic review, we identified several risk factors for low BMD/bone loss in men that are measurable in primary practice.

Osteoporosis risk perceptions among patients who have sustained a fragility fracture.

OBJECTIVE: To explore the perceptions of patients who have sustained a fragility fracture regarding their future fracture risk and the beliefs underlying their perceptions. METHODS: Patients with fragility fracture participated in a telephone interview. Quantitative and qualitative methods were used to characterize patient characteristics and perspectives of future fracture risk. Content analysis of qualitative statements was independently performed by three investigators to identify common themes and contrasting statements, and the findings were discussed to ensure consensus. RESULTS: Consistent themes were identified among participant responses irrespective of whether they responded "yes", "no" or "unsure" when asked whether they were at increased fracture risk: (1) patients' perception of risk was influenced by whether or not they believed they had osteoporosis, which may be altered by interaction with health care providers; (2) patients' had their own perceptions of their bone health; (3) patients' attributed their risk to their own actions or "carefulness"; and (4) patients' had specific beliefs about their fracture and determinants of fracture risk. CONCLUSION: Patients who experience fragility fractures develop perceptions about future fracture risk that are influenced by interactions with health care providers, as well as beliefs about their fracture and beliefs that they can modify their risk. PRACTICE IMPLICATIONS: Health care providers should discuss strategies for fracture prevention with all patients after fragility fracture to ensure that patients understand that participation in preventative behaviours can modify their risk.

A multifaceted intervention to improve treatment of osteoporosis in postmenopausal women with wrist fractures: a cluster randomized trial.

UNLABELLED: In a cluster randomized trial, we evaluated the effect of a multifaceted intervention (directed at both patient and primary care physician) on the rates of testing and treatment of osteoporosis in postmenopausal women within six months of their wrist fracture. Compared to usual care, women in the intervention practices were three times more likely to receive bone mineral density testing and prescribed osteoporosis treatments. INTRODUCTION: Postmenopausal women with wrist fractures are at increased risk of future fragility fractures, yet they frequently do not receive evaluation and treatment for osteoporosis. We set out to evaluate a multifaceted intervention designed to improve management of osteoporosis in older women with recent wrist fractures. METHODS: Cluster randomized trial of 270 women cared for in 119 primary care practices. We recruited postmenopausal women with an acute wrist fracture from the emergency departments of hospitals in southeastern Ontario, Canada. Family practices were randomly assigned to either the intervention or usual care. The intervention consisted of a mailed reminder with a summary of treatment guidelines and letter sent to the primary care physician, in addition to an educational package and letter to the women. The primary outcome was the proportion of women prescribed osteoporosis therapy within 6 months of their fracture. RESULTS: The mean age of women was 69(10.9) years. The intervention increased the proportion of women started on osteoporosis medications (28% vs. 10%) of controls, adjusted OR 3.45, 95% CI, 1.58-7.56, p = 0.002) and the proportion who had a bone mineral density (BMD) test (53.3% vs. 26%) of controls, OR 3.38, 95% CI, 1.83-6.26, p < 0.001). In addition to the intervention, having a female physician was a predictor of increased testing and treatment rates. CONCLUSION: A multifaceted intervention significantly improved rates of osteoporosis treatment and BMD testing in postmenopausal women with wrist fractures.

Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Alendronate belongs to the bisphosphonate class of drugs, which act to inhibit bone resorption by interfering with the activity of osteoclasts. OBJECTIVES: To assess the efficacy of alendronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women. SEARCH STRATEGY: We searched CENTRAL, MEDLINE and EMBASE for relevant randomized controlled trials published between 1966 to 2007. SELECTION CRITERIA: Women receiving at least one year of alendronate, for postmenopausal osteoporosis, were compared to those receiving placebo and/or concurrent calcium/vitamin D. The outcome was fracture incidence. DATA COLLECTION AND ANALYSIS: We undertook study selection and data abstraction in duplicate. We performed meta-analysis of fracture outcomes using relative risks and a > 15% relative change was considered clinically important. We assessed study quality through reporting of allocation concealment, blinding and withdrawals. MAIN RESULTS: Eleven trials representing 12,068 women were included in the review. Relative (RRR) and absolute (ARR) risk reductions for the 10 mg dose were as follows. For vertebral fractures, a significant 45% RRR was found (RR 0.55, 95% CI 0.45 to 0.67). This was significant for both primary prevention, with 45% RRR (RR 0.55, 95% CI 0.38 to 0.80) and 2% ARR, and secondary prevention with 45% RRR (RR 0.55, 95% CI 0.43 to 0.69) and 6% ARR. For non-vertebral fractures, a significant 16% RRR was found (RR 0.84, 95% CI 0.74 to 0.94). This was significant for secondary prevention, with 23% RRR (RR 0.77, 95% CI 0.64 to 0.92) and 2% ARR, but not for primary prevention (RR 0.89, 95% CI 0.76 to 1.04). There was a significant 40% RRR in hip fractures (RR 0.60, 95% CI 0.40 to 0.92), but only secondary prevention was significant with 53% RRR (RR 0.47, 95% CI 0.26 to 0.85) and 1% ARR. The only significance found for wrist was in secondary prevention, with a 50% RRR (RR 0.50 95% CI 0.34 to 0.73) and 2% ARR. For adverse events, we found no statistically significant differences in any included study. However, observational data raise concerns regarding potential risk for upper gastrointestinal injury and, less commonly, osteonecrosis of the jaw. AUTHORS' CONCLUSIONS: At 10 mg per day, both clinically important and statistically significant reductions in vertebral, non-vertebral, hip and wrist fractures were observed for secondary prevention ('gold' level evidence, www.cochranemsk.org). We found no statistically significant results for primary prevention, with the exception of vertebral fractures, for which the reduction was clinically important ('gold' level evidence).

Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts. OBJECTIVES: To assess the efficacy of etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women. SEARCH STRATEGY: We searched CENTRAL, MEDLINE and EMBASE for relevant randomized controlled trials published between 1966 to 2007. SELECTION CRITERIA: Women receiving at least one year of etidronate for postmenopausal osteoporosis were compared to those receiving placebo and/or concurrent calcium/vitamin D. The outcome was fracture incidence. DATA COLLECTION AND ANALYSIS: Study selection and data abstraction was done in duplicate. Meta-analysis of fracture outcomes was performed with data presented as relative risks and a relative change greater than 15% was considered clinically important. Study quality was assessed through the reporting of allocation concealment, blinding and withdrawals. MAIN RESULTS: Eleven studies representing a total of 1248 patients were included in the review.A significant 41% relative risk reduction (RRR) in vertebral fractures across eight studies (RR 0.59, 95% CI 0.36 to 0.96) was found. The six secondary prevention trials demonstrated a significant RRR of 47% in vertebral fractures (RR 0.53, 95% CI 0.32 to 0.87) and a 5% absolute risk reduction (ARR); compared with the pooled result for the two primary prevention trials (RR 3.03, 95% CI 0.32 to 28.44), which was not significant. There were no statistically significant risk reductions for non-vertebral (RR 0.98, 95% CI 0.68 to 1.42), hip (RR 1.20, 95% CI 0.37 to 3.88) or wrist fractures (RR 0.87, 95% CI: 0.32 to 2.36). For adverse events, no statistically significant differences were found in the included studies. However, observational data has led to concerns regarding potential risk for upper gastrointestinal injury. AUTHORS' CONCLUSIONS: Etidronate, at 400 mg per day, demonstrated a statistically significant and clinically important benefit in the secondary prevention of vertebral fractures. No statistically significant reductions in vertebral fractures were observed when it was used for primary prevention. In addition, no statistically significant reductions in non-vertebral, hip, or wrist fractures were found, regardless of whether etidronate was used for primary or secondary prevention. The level of evidence for all outcomes is Silver (www.cochranemsk.org.).

Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Risedronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts. OBJECTIVES: To assess the efficacy of residronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women. SEARCH STRATEGY: We searched CENTRAL, MEDLINE and EMBASE. Relevant randomized controlled trials published between 1966 to 2007 were identified. SELECTION CRITERIA: Women receiving at least one year of risedronate for postmenopausal osteoporosis were compared to those receiving placebo or concurrent calcium/vitamin D or both. The outcome was fracture incidence. DATA COLLECTION AND ANALYSIS: We carried out study selection and data abstraction in duplicate. Study quality was assessed through the reporting of allocation concealment, blinding and withdrawals. Meta-analysis was preformed using relative risks and a >15% relative change was considered clinically important. MAIN RESULTS: Seven trials were included in the review representing 14,049 women. Relative (RRR) and absolute (ARR) risk reductions for the 5 mg dose were as follows. Risk estimates for primary prevention were available only for vertebral and non vertebral fractures and showed no statistically significant effect of risedronate on fractures. For secondary prevention, a significant 39% RRR in vertebral fractures (RR 0.61, 95% CI 0.50 to 0.76) with 5% ARR was found. For non-vertebral fractures, a significant 20% RRR (RR 0.80, 95% CI 0.72 to 0.90) with 2% ARR and for hip fractures there was a significant 26% RRR (RR: 0.74, 95% CI 0.59 to 0.94) with a 1% ARR. When primary and secondary prevention studies were combined, the reduction in fractures remained statistically significant for both vertebral (RR 0.63, 0.51 to 0.77) and non vertebral fractures (RR 0.80, 0.72 to 0.90)For adverse events, no statistically significant differences were found in any of the included studies. However, observational data has led to concerns regarding the potential risk for upper gastrointestinal injury and, less commonly, osteonecrosis of the jaw. AUTHORS' CONCLUSIONS: At 5 mg/day a statistically significant and clinically important benefit in the secondary prevention of vertebral, non-vertebral and hip fractures was observed, but not for wrist. The level of evidence for secondary prevention is Gold (www.cochranemsk.org) for vertebral and non-vertebral and Silver for hip and wrist. There were no statistically significant reductions in the primary prevention of vertebral and non-vertebral fractures. The level of evidence is Silver.

Long-term dalteparin in pregnancy not associated with a decrease in bone mineral density: substudy of a randomized controlled trial.

BACKGROUND: The risk of decreased bone mineral density (BMD) with prophylactic dose long-term low-molecular-weight heparin (LMWH) is unknown. OBJECTIVES: We sought to determine whether long-term prophylactic dalteparin in pregnancy leads to loss of BMD. PATIENTS/METHODS: Patients in a substudy of an ongoing multicenter randomized trial investigating the effect of antepartum dalteparin prophylaxis on pregnancy outcomes in thrombophilic pregnant women were randomized to either dalteparin 5000 U s.c. daily until 20 weeks and then 5,000 U s.c. q12 h until >37 weeks or to the control group. The primary outcome was absolute spine BMD at six weeks postpartum. RESULTS: Of 77 patients eligible for the BMD substudy, 62 were analyzed. 33 patients received a mean of 212 days of dalteparin in the intervention group. 29 patients received a mean of 38 days of postpartum dalteparin in the control group. There was no difference in mean BMD between the intervention (1.11 g cm(-2)) and the control groups (1.14 g cm(-2)). Similarly, there was no difference in T-scores; the difference of -0.34 (95% confidence interval -0.93 to +0.25) in favor of the control group excludes a clinically important increase in fracture risk. CONCLUSIONS: Our results suggest that the use of long-term prophylactic dalteparin in pregnancy is not associated with a significant decrease in BMD. CLINICAL TRIAL REGISTRATION: ISRCTN87441504 at http://www.controlled-trials.com.

WITHDRAWN: Etidronate for treating and preventing postmenopausal osteoporosis.

BACKGROUND: Osteoporosis is a clinical syndrome of reduced bone mass and increased fracture susceptibility. There are now a number of options, including etidronate which can decrease the risk of fractures. OBJECTIVES: To systematically review the efficacy of etidronate on bone density, fractures and toxicity in postmenopausal women. SEARCH STRATEGY: We searched MEDLINE from 1966 to December 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. SELECTION CRITERIA: We included thirteen trials (with 1010 participants) that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least one year. DATA COLLECTION AND ANALYSIS: For each trial, three independent reviewers assessed the methodological quality and abstracted data. MAIN RESULTS: The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.60% (95% CI 0.41 to 0.88). There was no effect on non-vertebral fractures (pooled relative risk 1.00, (95% CI 0.68 to 1.42)). Etidronate, relative to control, increased bone density after three years of treatment in the lumbar spine by 4.27% (95% CI 2.66 to 5.88), in the femoral neck by 2.19% (95% CI 0.43, 3.95) and in the total body by 0.97% (95% CI 0.39, 1.55). Effects were larger at 4 years, though the number of patients followed was much smaller. AUTHORS' CONCLUSIONS: Etidronate increases bone density in the lumbar spine and femoral neck. The pooled estimates of fracture reduction with etidronate are consistent with a reduction in vertebral fractures, but no effect on non-vertebral fractures.

WITHDRAWN: Risedronate for the prevention and treatment of postmenopausal osteoporosis.

BACKGROUND: Postmenopausal osteoporosis results in an increased susceptibility to low-trauma fractures due to reduced bone volume and microarchitectural deterioration. Risedronate, a third generation bisphosphonate, has been shown in multiple clinical trials to reduce fracture risk and improve bone mineral density in postmenopausal women with osteoporosis. First and second generation bisphosphonates are known to have gastrointestinal side-effects and risedronate may be better tolerated. OBJECTIVES: To systematically review the efficacy of risedronate on bone density, and fracture reduction in postmenopausal women. SEARCH STRATEGY: The Cochrane Controlled Trials Registry Medline, and Current Contents were searched from 1990 - 2001. The electronic search was supplemented by handsearching four osteoporosis journals and their conference proceedings, as well as contacting content experts and industry sources for unpublished data. SELECTION CRITERIA: We included eight trials that randomised women to risedronate or an alternative (placebo or calcium and /or vitamin D) and measured bone mineral density for at least one year. DATA COLLECTION AND ANALYSIS: For each trial three independent reviewers assessed the methodological quality and abstracted data. Data was extracted for outcomes of fracture, bone mineral density and adverse events. The more conservative random effects model was used to pool data. The quality of trials was assessed according to the Jadad five-point scale. MAIN RESULTS: Both vertebral and non-vertebral fractures were statistically and clinically reduced with risedronate. Eleven out of one hundred women who received risedronate had a vertebral fracture compared to 17 out of one hundred of those who received calcium and vitamin D (pooled relative risk for vertebral fractures of 0.64 (95% CI 0.52 - 0.77). Three percent of participants who received risedronate had a non-vertebral fracture compared to 4.6% of those who received calcium and vitamin D (pooled relative risk for nonvertebral fractures of 0.73 (95% CI 0.61 - 0.87). The weighted mean difference for the percent change from baseline for bone mineral density with 5 mg daily for lumbar spine, femoral neck and trochanter was 4.54% (95%CI 4.12 - 4.97), p<0.01; 2.75% (95% CI 2.32 - 3.17), p<0.01; and 4.38% (95% CI 3.51 - 5.25), p<0.01 respectively. AUTHORS' CONCLUSIONS: There is good evidence for the efficacy of risedronate in the reduction of both vertebral and non-vertebral fractures. In addition, there is evidence from randomized trials that risedronate is able to achieve this without increasing risk for overall withdrawals due to adverse effects.

WITHDRAWN: Calcium supplementation on bone loss in postmenopausal women.

BACKGROUND: Although calcium is one the simplest and least expensive strategies for preventing osteoporotic fractures calcium supplementation is nevertheless not without controversy (Kanis 1989; Nordin 1990). The Food and Drug Administration in the US has permitted a bone health claim for calcium-rich foods, and the NIH in its Consensus Development Process approved a statement that high calcium intake reduces the risk of osteoporosis. OBJECTIVES: To assess the effects of calcium on bone density and fractures in postmenopausal women. SEARCH STRATEGY: We searched Cochrane Controlled Register, MEDLINE and EMBASE up to 2001, and examined citations of relevant articles and proceedings of international meetings. SELECTION CRITERIA: Trials that randomized postmenopausal women to calcium supplementation or usual calcium intake in the diet and reported bone mineral density of the total body, vertebral spine, hip, or forearm or recorded the number of fractures, and followed patients for at least one year were considered for inclusion. DATA COLLECTION AND ANALYSIS: Three independent reviewers assessed the methodologic quality and extracted data for each trial. For each bone density site (lumbar spine, total body, combined hip and combined forearm), we calculated the weighted mean difference in bone density between treatment and control groups using the percentage change from baseline. We constructed regression models in which the independent variables were year and dose, and the dependent variable was the effect size. This regression was used to determine the years across which pooling was appropriate. Heterogeneity was assessed. For each fracture analysis we calculated a risk ratio. MAIN RESULTS: Fifteen trials, representing 1806 participants, were included. Calcium was more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05% (95% CI 0.24 to 3.86) for total body bone density, 1.66% (95% CI 0.92 to 2.39) for the lumbar spine at 2 years, 1.60% (95% CI 0.78 to 2.41) for the hip, and 1.91% (95% CI 0.33 to 3.50) for the distal radius. The relative risk of fractures of the vertebrae was 0.79 (95% CI 0.54 to 1.09); the relative risk for non-vertebral fractures was 0.86 (95% CI 0.43 to 1.72). AUTHORS' CONCLUSIONS: Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but it is unclear if calcium reduces the incidence of non vertebral fractures.

Bisphosphonate therapy for children and adolescents with secondary osteoporosis.

BACKGROUND: Children with chronic illnesses are at increased risk for reductions in bone strength and subsequent fractures (osteoporosis), either due to the impact of the underlying condition on skeletal development or due to the osteotoxic effect of medications (e.g., glucocorticoids) used to treat the chronic illness. Bisphosphonates are being administered with increasing frequency to children with secondary osteoporosis; however, the efficacy and harm of these agents remains unclear. OBJECTIVES: To examine the efficacy and harm of bisphosphonate therapy in the treatment and prevention of secondary osteoporosis in children and adolescents. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Issue 4, 2006), MEDLINE, EMBASE, CINAHL and ISI Web of Science (inception-December 2006). Further literature was identified through expert contact, key author searches, scanning reference lists of included studies, and contacting bisphosphonate manufacturers. SELECTION CRITERIA: Randomized, quasi-randomized, controlled clinical trials, cohort, and case controls of bisphosphonate(s) in children 0-18 years of age with at least one low-trauma fracture event or reductions in bone mineral density in the context of secondary osteoporosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed quality. Case series were used for supplemental harms-related data. MAIN RESULTS: Six RCTs, two CCTs, and one prospective cohort (n=281 children) were included and classified into osteoporosis due to: 1) neuromuscular conditions (one RCT) and 2) chronic illness (five RCTs, two CCTs, one cohort). Bisphosphonates examined were oral alendronate, clodronate, and intravenous (IV) pamidronate. Study quality varied. Harms data from 23 case series (n=241 children) were used. Heterogeneity precluded statistically combining the results. Percent change or Z-score change in lumbar spine areal BMD from baseline were consistently reported. Two studies carried out between-group analyses; one showed no significant difference (using oral alendronate in anorexia nervosa) while the other demonstrated a treatment effect on lumbar spine with IV pamidronate in burn patients. Frequently reported harms included the acute phase reaction, followed by gastrointestinal complaints, and bone/muscle pain. AUTHORS' CONCLUSIONS: The results justify further evaluation of bisphosphonates among children with secondary osteoporosis. However, the evidence does not support bisphosphonates as standard therapy. Short-term (3 years or less) bisphosphonate use appears to be well-tolerated. An accepted criterion for osteoporosis in children, a standardized approach to BMD reporting, and examining functional bone health outcomes (e.g., fracture rates) will allow for appropriate comparisons across studies.

Fragility fractures and the osteoporosis care gap: an international phenomenon.

OBJECTIVES: To describe practice patterns in the management of osteoporosis after fragility fracture. METHODS: Systematic review of articles in MEDLINE, EMBASE, Cochrane, and CINAHL databases (1996 to February 2005). Diagnostic outcomes included clinical osteoporosis diagnoses, laboratory tests, and bone density scans. Treatment outcomes included initiation of calcium, vitamin D, hormone replacement therapy, bisphosphonates, calcitonin, raloxifene and falls assessments. RESULTS: Thirty-five studies met our inclusion criteria and demonstrated that adults who experience fragility fracture are not receiving osteoporosis management. An osteoporosis diagnosis was reported in 1 to 45% of patients with fractures; laboratory tests were ordered for 1 to 49% and 1 to 32% of patients had bone density scans. Calcium/vitamin D and pharmacological therapy was reported in 2 to 62% and 1 to 65% of patients, respectively. Osteoporosis treatment was recommended more often in women than men, and more often in patients with vertebral fractures than in patients with nonvertebral fractures. Older patients were more likely to be diagnosed with osteoporosis, but treatment was more likely in younger patients. A history of prior fracture was reported in 7 to 67% of patients. Between 1 and 22% of patients had a subsequent fracture during follow-up periods of 6 months to 5 years. Falls assessments were not often reported; when they were, they were infrequently performed. A greater proportion of patients were diagnosed/treated during follow-up studies than in studies evaluating diagnosis/treatment on discharge from acute care. CONCLUSIONS: The majority of individuals who sustain fragility fractures are not receiving adequate osteoporosis management. Future research should address barriers to appropriate management and the efficacy of implementation strategies designed to close the osteoporosis care gap. RELEVANCE: This article is of particular importance to health care professionals who provide care for patients with fragility fracture.

Strontium ranelate for preventing and treating postmenopausal osteoporosis.

BACKGROUND: Strontium ranelate is a new anti-osteoporosis therapy therefore, its benefits and harms need to be known. OBJECTIVES: To determine the efficacy and safety of strontium ranelate for the treatment and prevention of postmenopausal osteoporosis. SEARCH STRATEGY: We searched MEDLINE (1996 to March 2005), EMBASE (1996 to week 9 2005), the Cochrane Library (1996 to Issue 1 2005), reference lists of relevant articles and conference proceedings from the last two years. Additional data was sought from authors and industry sponsors. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of at least one year duration comparing strontium ranelate versus placebo reporting fracture incidence, bone mineral density (BMD), health related quality of life and/or safety outcomes in postmenopausal women. Treatment (versus prevention) population was defined as women with prevalent vertebral fractures and/or lumbar spine BMD T score < -2.5 SD. DATA COLLECTION AND ANALYSIS: Two reviewers independently determined study eligibility, assessed trial quality and extracted the relevant data. Disagreements were resolved by consensus. RCTs were grouped by dose of strontium ranelate and treatment duration. Where possible, meta-analysis was conducted using the random effects model. MAIN RESULTS: A total of four trials met our inclusion criteria, three of which investigated the effects of strontium ranelate compared to placebo in a treatment population (doses ranged from 0.5 to 2 g daily) and one, in a prevention population (doses 0.125, 0.5 and 1 g daily). In osteoporotic, postmenopausal women a 37% reduction in vertebral fractures (two trials, n = 5082, RR 0.63, 95% CI 0.56 to 0.71) and a 14% reduction in non-vertebral fractures (two trials, n = 6572, RR 0.86, 95% CI 0.75 to 0.98) was demonstrated over a three year period with 2 g of strontium ranelate daily. An increase in BMD at all sites was shown with the same dose: lumbar spine BMD (two trials, n = 1614, WMD adjusted for strontium content 5.44, 95% CI 3.41 to 7.46 and WMD not adjusted 11.29, 95% CI 10.22 to 12.37 over two years), femoral neck and total hip (two trials, n = 4230, WMD 8.25, 95% CI 7.84 to 8.66 and WMD 9.83, 95% CI 9.39 to 10.26 respectively over three years). One gram of strontium ranelate daily in postmenopausal women without osteoporosis increased BMD at all sites over a two year period: lumbar spine (one trial, n = 59, WMD adjusted for strontium content 2.39, 95% CI 0.15 to 4.63 and WMD not adjusted 6.68, 95% CI 5.16 to 8.20), femoral neck (one trial, n= 60, WMD 2.52, 95%CI 0.96 to 4.09) and total hip (one trial, n = 60, WMD 1.02, 95% CI 0.48 to 1.56). In both the treatment and prevention populations, lower doses of strontium ranelate were superior to placebo with the highest dose of strontium ranelate demonstrating the greatest reduction in vertebral fractures and increase in BMD. There is some evidence to suggest that 2 g of strontium ranelate daily compared to placebo may have a beneficial effect on health related quality of life in postmenopausal women after three years of treatment. Two grams of strontium ranelate daily increased the risk of diarrhea (RR 1.38%, 95% CI 1.02 to 1.87); however, adverse events did not affect the risk of discontinuing strontium ranelate nor did it increase the risk of serious side effects, gastritis or death. Additional data obtained suggests that the risk of vascular system disorders including venous thromboembolism (two trials, n = 6669, 2.2% versus 1.5%, OR 1.5, 95% CI 1.1 to 2.1) and pulmonary embolism (two trials, n = 6669, 0.8% versus 0.4%, OR 1.7, 95% CI 1.0 to 3.1) as well as nervous system disorders such as headaches (3.9% versus 2.9%), seizures (0.3% versus 0.1%), memory loss (2.4% versus 1.9%) and disturbance in consciousness (2.5% versus 2.0%) is slightly increased with taking 2 g of strontium ranelate daily over a 3 to 4 year period. AUTHORS' CONCLUSIONS: There is silver level evidence to support the efficacy of strontium ranelate for the reduction of vertebral fractures (and to a lesser extent non-vertebral fractures) in postmenopausal osteoporotic women and an increase in BMD (all sites) in postmenopausal women with and without osteoporosis. Diarrhea may occur however, adverse events leading to study withdrawal were not significantly increased in the strontium ranelate group. Potential risks to the vascular and neurological system associated with taking 2 g of strontium ranelate daily need to be further explored and quantified.

Strontium ranelate for preventing and treating postmenopausal osteoporosis.

BACKGROUND: Strontium ranelate is a new treatment for osteoporosis therefore, its benefits and harms need to be known. OBJECTIVES: To determine the efficacy and safety of strontium ranelate for the treatment and prevention of postmenopausal osteoporosis. SEARCH STRATEGY: We searched MEDLINE (1996 to March 2005), EMBASE (1996 to week 9 2005), the Cochrane Library (1996 to Issue 1 2005), reference lists of relevant articles and conference proceedings from the last two years. Additional data was sought from authors. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of at least one year duration comparing strontium ranelate versus placebo reporting fracture incidence, bone mineral density (BMD), health related quality of life or safety in postmenopausal women. Treatment (versus prevention) population was defined as women with prevalent vertebral fractures and/or lumbar spine BMD T score < -2.5 SD. DATA COLLECTION AND ANALYSIS: Two reviewers independently determined study eligibility, assessed trial quality and extracted the relevant data. Disagreements were resolved by consensus. RCTs were grouped by dose of strontium ranelate and treatment duration. Where possible, meta-analysis was conducted using the random effects model. MAIN RESULTS: Four trials met the inclusion criteria. Three included a treatment population (0.5 to 2 g of strontium ranelate daily) and one a prevention population (0.125 g, 0.5 g and 1 g daily). A 37% reduction in vertebral fractures (RR 0.63, 95% CI 0.56, 0.71) and a 14% reduction in non-vertebral fractures (RR 0.86, 95% CI 0.75, 0.98) were demonstrated over three years with 2 g of strontium ranelate daily in a treatment population. An increase in BMD was shown at all BMD sites after two to three years in both populations. Lower doses of strontium ranelate were superior to placebo and the highest dose demonstrated the greatest reduction in vertebral fractures and increase in BMD. An increased risk of diarrhea with 2 g of strontium ranelate was found; however, adverse events did not affect the risk of discontinuing treatment nor did it increase the risk of serious side effects, gastritis or death. Additional data suggests that the risk of vascular and nervous system side-effects is slightly increased with taking 2 g of strontium ranelate daily over three to four years. AUTHORS' CONCLUSIONS: There is silver level evidence (www.cochranemsk.org) to support the efficacy of strontium ranelate for the reduction of fractures (vertebral and to a lesser extent non-vertebral) in postmenopausal osteoporotic women and an increase in BMD in postmenopausal women with/without osteoporosis. Diarrhea may occur however, adverse events leading to study withdrawal were not significantly increased with taking 2 g of strontium ranelate daily. Potential vascular and neurological side-effects need to be further explored.

The use of Neoral in rheumatoid arthritis.

Neoral (a microemulsion-based formulation) is an immunomodulator that possesses a more predictable and improved absorption than the conventional oral formulation (Sandimmun). The increased bioavailability of Neoral could result in improved efficacy. The pharmacokinetics of cyclosporin and efficacy of cyclosporin in rheumatoid arthritis are reviewed in this article. Current guidelines for the use of Neoral in the treatment of rheumatoid arthritis patients are outlined.

Cost effectiveness of nasal calcitonin in postmenopausal women: use of Cochrane Collaboration methods for meta-analysis within economic evaluation.

OBJECTIVE: To assess the cost effectiveness of nasal calcitonin (Miacalcin) compared with no therapy, alendronate or etidronate in the treatment of postmenopausal women with previous osteoporotic fracture. DESIGN AND SETTING: Meta-analysis followed by economic analysis. PERSPECTIVE: A Canadian provincial Ministry of Health. METHODS: The meta-analysis of randomised controlled clinical trials was based on the recommendations of the Cochrane Collaboration. Economic analysis was conducted within a Markov model using probabilities and costs derived from Canadian sources. RESULTS: The meta-analysis found evidence of the positive effect of both nasal calcitonin and alendronate in reducing the risks of hip, wrist and vertebral fractures in postmenopausal women. However, there was a lack of evidence of the effect of etidronate on hip and wrist fractures. For a 65-year-old woman, with 5 years' therapy, the incremental cost per quality-adjusted life-year (QALY) gained for nasal calcitonin was 46,500 Canadian dollars ($Can) compared with no therapy and $Can32,600 compared with etidronate (1998 values). Comparison with alendronate was highly sensitive to the inclusion of one specific trial. CONCLUSIONS: Given the results of the analysis, based on current evidence, nasal calcitonin can be considered at the margins of being cost effective when compared with no therapy. Compared with active therapy, nasal calcitonin can be considered more cost effective than etidronate, but its cost effectiveness versus alendronate is inconclusive.

Calcium and vitamin D for corticosteroid-induced osteoporosis.

OBJECTIVES: To assess the effects of calcium and vitamin D compared to calcium alone or placebo in the prevention of bone loss in patients taking systemic corticosteroids. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal trials register, Cochrane Controlled Trials Register, EMBASE and Medline up to 1996. We also conducted a hand search of abstracts from various scientific meetings and reference lists of selected trials. SELECTION CRITERIA: All randomized trials comparing calcium and vitamin D to calcium alone or placebo in patients taking systemic corticosteroids. DATA COLLECTION AND ANALYSIS: Data was abstracted from trials by two investigators. Methodological quality was assessed in a similar manner. Analysis was performed using fixed effects models. MAIN RESULTS: Five trials were included, with 274 patients. The analysis was performed at two years after starting calcium and vitamin D. There was a significant weighted mean difference (WMD) between treatment and control groups in lumbar (WMD 2.6 (95% CI 0.7, 4.5), and radial bone mineral density (WMD 2.5 (95% CI 0.6, 4.4). The other outcome measures (femoral neck bone mass, fracture incidence, biochemical markers of bone resorption) were not significantly different. REVIEWER'S CONCLUSIONS: This meta-analysis demonstrated a clinically and statistically significant prevention of bone loss at the lumbar spine and forearm with vitamin D and calcium in corticosteroid treated patients. Because of low toxicity and cost all patients being started on corticosteroids should receive prophylactic therapy with calcium and vitamin D.

Bisphosphonates for steroid induced osteoporosis.

OBJECTIVES: To assess the effects of bisphosphonates for the prevention and treatment of corticosteroid-induced osteoporosis. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Group trials register, Medline up to 1997 and Embase1988-1997), and selected hand searching of reference lists was conducted. Hand searching of scientific abstracts from relevant meetings for the last five years was also done. An electronic search in Current Contents was done for the last six months. The Cochrane Controlled Trials Register (CCTR) will be searched for future updates. All languages were included in the search. For practical reasons only those in English were included, but all languages will be retrieved and translated for future updates. SELECTION CRITERIA: All controlled clinical trials (CCTs) dealing with prevention or treatment of corticosteroid-induced osteoporosis with bisphosphonates of any type and reporting the outcomes of interest were assessed. Trials had to involve adults only, and subjects had to be taking a mean steroid dose of 7.5 mg/day or more. DATA COLLECTION AND ANALYSIS: All data extraction was performed by two independent reviewers. Outcomes of interest included change in bone mineral density (BMD) at the lumbar spine and femoral neck at six and 12 months. If present, data on number of new fractures and withdrawals due to adverse effects were also extracted. All data extraction was performed by two independent reviewers. Both continuous and dichotomous data were analyzed using fixed effects models. When significant heterogeneity was present, a random effects model was used. MAIN RESULTS: A total of 13 trials, including 842 patients are included in this meta-analysis. Results are reported as a weighted mean difference of the percent change in BMD between the treatment and placebo groups, with trials being weighted by the inverse of their variance. The 95% confidence intervals (95% CI) are presented. At the lumbar spine, the weighted mean difference of BMD between the treatment and placebo groups was 4.3% (95% CI 2.7, 5.9). At the femoral neck, the weighted mean difference was 2.1% (95%CI 0. 01, 3.8). Although there was a 24% reduction in odds of spinal fractures [OR 0.76 (95%CI 0.37, 1.53)], this result was not statistically significant. REVIEWER'S CONCLUSIONS: Bisphosphonates are effective at preventing and treating corticosteroid-induced bone loss at the lumbar spine and femoral neck. Efficacy regarding fracture prevention cannot be concluded from this analysis, although bone density changes are correlated with fracture risk.