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Orthopaedic Surgery Aug 2020To assess the effectiveness and safety of oral bisphosphonates in increasing bone mineral density (BMD), reducing fractures, and improving clinical function in patients... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the effectiveness and safety of oral bisphosphonates in increasing bone mineral density (BMD), reducing fractures, and improving clinical function in patients with osteogenesis imperfecta (OI).
METHODS
Studies were eligible for inclusion if they were randomized controlled trials of directly comparing oral bisphosphonate therapy with placebo-group in OI patients. Data synthesis regarding to bone mineral density as measured by dual-energy X-ray absorptiometry (DEXA), decreased fracture incidence, change in biochemical markers of bone and mineral metabolism, bone histology, growth, bone pain, quality of life, and others were assessed, and meta-analysis done when possible.
RESULTS
From 98 potential references and six randomized controlled studies a total of 263 participants receiving oral bisphosphonates and 143 placebo treatments contributed data to meta-analysis. Pooled meta-analysis of three studies suggested that there was significant difference between bisphosphonate treated group and placebo in number of patients with at least one fracture (mean difference 0.53, 95% confidence interval 0.32-0.89, P = 0.02). Pooled meta-analysis of two studies suggested that significant difference was noted between bisphosphonate treated group and placebo in mean percentage change in spine BMD (T-score) (mean difference 28.43, 95% confidence interval 7.09-49.77, P = 0.009). The similar effect was shown in the term of mean change (Z-score) in spine BMD.
CONCLUSIONS
Significant improvement in lumbar areal BMD in patients affected with OI has been shown when treated with oral bisphosphonates, even though only a small population was enrolled. We cannot draw a definite conclusion that the increase in BMD can be translated into fracture reduction and clinical functional improvement. The optimal method, dose, type, initiation, and duration of oral bisphosphonates therapy still remains unclear. Well-designed, adequately-powered, placebo-controlled RCTs investigating the effects of oral bisphosphonates on fractures reduction and improvement in quality of life in both children and adults are studied here.
Topics: Bone Density; Bone Density Conservation Agents; Diphosphonates; Fractures, Bone; Humans; Osteogenesis Imperfecta; Randomized Controlled Trials as Topic
PubMed: 32589343
DOI: 10.1111/os.12611 -
Journal of Traditional Chinese Medicine... Feb 2020The aim of this study was to evaluate the effectiveness of Chinese herbal medicines for invigorating the kidney (CHMIK) on senile osteoporosis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to evaluate the effectiveness of Chinese herbal medicines for invigorating the kidney (CHMIK) on senile osteoporosis.
METHODS
We searched for studies in English-language databases (PubMed, the Cochrane Library, and Web of Science) and Chinese-language databases (China National Knowledge Infrastructure, Wan Fang Data, VIP Chinese periodical service platform, and China Biology Medicine disc from their inception to September 2017. Randomized controlled trials comparing the effectiveness of Traditional Chinese Medicine therapies (alone or in combination) and conventional clinical medicine therapies among older adult patients with osteoporosis were identified. We conducted a network Meta-analysis with a Bayesian hierarchical random-effects model using RStudio software, Version 3.4.1.
RESULTS
Forty-three randomized controlled trials assessing the differences between Traditional Chinese Medicine and conventional clinical medicine were identified, including 15 treatments and involving 3316 patients. The results of the network Meta-analysis indicated that alendronate (odds ratio [OR] = 0.20, 95% confidence interval [CI]: 0.047-0.73) and calcium (OR = 0.18, 95% CI: 0.11-0.30) are significantly more effective if combined with oral CHMIK. CHMIK alone is significantly more effective than both alendronate (OR = 0.34, 95% CI: 0.10-1.0) and calcium (OR = 0.13, 95% CI: 0.056-0.28). Moreover, CHMIK + tuina + calcium is more effective than CHMIK + calcium + vitamin D + alendronate (OR = 18.0, 95% CI: 1.1-2.7e + 02).
CONCLUSION
The present network Meta-analysis found that alendronate and calcium are more effective if combined with oral CHMIK and that oral CHMIK alone may be more effective than alendronate or calcium. Tuina may have an advantage over oral medicines. Oral CHMIK and calcitonin show the most potential for treating senile osteoporosis.
Topics: Humans; Medicine, Chinese Traditional; Osteoporosis; Randomized Controlled Trials as Topic
PubMed: 32227762
DOI: No ID Found -
JBMR Plus Oct 2019Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder that results in bone fragility and deformity. Management is multi-disciplinary. Although...
Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder that results in bone fragility and deformity. Management is multi-disciplinary. Although pharmacologic intervention with bisphosphonates (BP) is a standard of care for individuals with severe OI, no consensus or reviews were found that focus on the effects of bisphosphonates on function and mobility. PubMed, CINAHL, Cochrane Library, Web of Science, and PEDro databases were searched for eligible articles for this review. Methodological quality was assessed using the Cochrane Collaboration's tool for risk of bias. Twenty-six studies (801 children) were reviewed and five showed a low risk of bias. Included studies showed significant variability among clinical protocols for administering BP. Randomized controlled trials did not demonstrate a significant improvement in function and mobility with oral BP administration, while non-randomized open-label uncontrolled studies demonstrated that oral and intravenous BP administration objectively improved function and mobility. The most common outcome measure used by the studies included in this review was the Bleck score. Effect sizes (d = 0.28 - 4.5) varied among studies. This systematic review also summarized the apparent confounding variables affecting results of previous studies and provided suggestions to improve the quality of future studies.
PubMed: 31687649
DOI: 10.1002/jbm4.10216 -
BMC Musculoskeletal Disorders Aug 2019Bone loss with aging and menopause increases the risk of fragile vertebral fracture, osteoporotic vertebral compression fracture (OVCF). The fracture causes severe pain,... (Meta-Analysis)
Meta-Analysis
Effect of medications on prevention of secondary osteoporotic vertebral compression fracture, non-vertebral fracture, and discontinuation due to adverse events: a meta-analysis of randomized controlled trials.
BACKGROUND
Bone loss with aging and menopause increases the risk of fragile vertebral fracture, osteoporotic vertebral compression fracture (OVCF). The fracture causes severe pain, impedes respiratory function, lower the quality of life, and increases the risk of new fractures and deaths. Various medications have been prescribed to prevent a secondary fracture, but few study summarized their effects. Therefore, we investigated their effects on preventing subsequent OVCF via meta-analyses of randomized controlled trials.
METHODS
Electronic databases, including MEDLINE, EMBASE, CENTRAL, and Web of Science were searched for published randomized controlled trials from June 2015 to June 2019. The trials that recruited participants with at least one OVCF were included. We assessed the risk of bias of every study, estimated relative risk ratio of secondary OVCF, non-vertebral fracture, gastrointestinal complaints and discontinuation due to adverse events. Finally, we evaluated the quality of evidence.
RESULTS
Forty-one articles were included. Moderate to high quality evidence proved the effectiveness of zoledronate (Relative Risk, RR: 0.34; 95% CI, 0.17-0.69, p = 0.003), alendronate (RR: 0.54; 95% CI: 0.43-0.68; p < 0.0001), risedronate (RR: 0.61; 95% CI: 0.51-0.73; p < 0.0001), etidronate (RR, 0.50; 95% CI, 0.29-0.87, p < 0.01), ibandronate (RR: 0.52; 95% CI: 0.38-0.71; p < 0.0001), parathyroid hormone (RR: 0.31; 95% CI: 0.23-0.41; p < 0.0001), denosumab (RR, 0.41; 95% CI, 0.29-0.57; p < 0.0001) and selective estrogen receptor modulators (Raloxifene, RR: 0.58; 95% CI: 0.44-0.76; p < 0.0001; Bazedoxifene, RR: 0.66; 95% CI: 0.53-0.82; p = 0.0002) in preventing secondary fractures. Moderate quality evidence proved romosozumab had better effect than alendronate (Romosozumab vs. alendronate, RR: 0.64; 95% CI: 0.49-0.84; p = 0.001) and high quality evidence proved that teriparatide had better effect than risedronate (risedronate vs. teriparatide, RR: 1.98; 95% CI: 1.44-2.70; p < 0.0001).
CONCLUSION
Zoledronate, alendronate, risedronate, etidronate, ibandronate, parathyroid hormone, denosumab and selective estrogen receptor modulators had significant secondary prevention effects on OVCF. Moderate quality evidence proved romosozumab had better effect than alendronate. High quality evidence proved PTH had better effect than risedronate, but with higher risk of adverse events.
Topics: Bone Density Conservation Agents; Fractures, Compression; Gastrointestinal Diseases; Humans; Oligopeptides; Osteoporosis; Osteoporotic Fractures; Prevalence; Randomized Controlled Trials as Topic; Spinal Fractures; Withholding Treatment
PubMed: 31472671
DOI: 10.1186/s12891-019-2769-8 -
Frontiers in Pharmacology 2019Several epidemiological articles have reported the correlations between anti-osteoporosis medication and the risks of fractures in male and female subjects, but the...
Several epidemiological articles have reported the correlations between anti-osteoporosis medication and the risks of fractures in male and female subjects, but the specific efficacy of anti-osteoporosis medication for male subjects remains largely unexplored. The aim of this study was to evaluate the correlation between anti-osteoporosis medication and the risk of fracture in relation to low bone mass [including outcomes of osteoporosis, fracture, and bone mineral density (BMD) loss] in male subjects analyzed in studies within the updated literature. Randomized controlled trials (RCTs) that analyzed the effectiveness of a treating prescription for male subjects with osteoporosis (or low BMD) and that focused on the outcomes of fracture were included. Relevant studies from Embase, Web of Science, PubMed, and Chinese database of CNKI were retrieved from inception to January 30th, 2019. Two staff members carried out the eligibility assessment and data extraction. The discrepancies were settled by consultation with another researcher. We calculated the pooled relative risks (RRs) based on 95% confidence intervals (CIs). Twenty-seven documents (28 studies) with 5,678 subjects were identified. For the category of bisphosphonates, significant results were observed in pooled analyses for decreased risk of the vertebral fracture domain (RR, 0.44 [95% CI, 0.31-0.62]), nonvertebral fracture domain (RR, 0.63 [95% CI, 0.46-0.87]), and clinical fracture domain (RR, 0.59 [95% CI, 0.48-0.72]) compared with those of controls. Participants with bisphosphonates had a 56% (95% CI = 38-69%) lower risk of vertebral fractures, 37% (95% CI = 13-54%) lower risk of nonvertebral fractures, and 41% (95% CI = 28-52%) lower risk of clinical fractures. Furthermore, meta-analyses also demonstrated a decreased risk of the vertebral fracture domain treatment with risedronate (RR, 0.45 [95% CI, 0.28-0.72]) and alendronate (RR, 0.41 [95% CI, 0.23-0.74]), but not with calcitriol, calcitonin, denosumab, ibandronate, monofluorophosphate, strontium ranelate, teriparatide, or zoledronic acid, compared with that of controls. This systematic review confirms that bisphosphonates were connected with a decreased risk of vertebral fractures, nonvertebral fractures, and clinical fractures for male subjects with osteoporosis. Future research is needed to further elucidate the role of nonbisphosphonates in treating fractures of osteoporosis subjects.
PubMed: 31447677
DOI: 10.3389/fphar.2019.00882 -
Journal of the American Dental... Aug 2019The authors' aim in this systematic review was to evaluate the validity of using preoperative serum C-terminal cross-linking telopeptide (CTX) levels as a predictive... (Meta-Analysis)
Meta-Analysis Review
Serum C-terminal cross-linking telopeptide level as a predictive biomarker of osteonecrosis after dentoalveolar surgery in patients receiving bisphosphonate therapy: Systematic review and meta-analysis.
BACKGROUND
The authors' aim in this systematic review was to evaluate the validity of using preoperative serum C-terminal cross-linking telopeptide (CTX) levels as a predictive factor of increased risk of developing medication-related osteonecrosis of the jaw (MRONJ) in patients receiving bisphosphonate (BP) therapy who underwent invasive dental procedures.
TYPES OF STUDIES REVIEWED
The authors searched PubMed, MEDLINE, and Web of Science and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The authors conducted a meta-analysis on the risk ratio. The authors used the methodological index for nonrandomized studies and Quality Appraisal of Reliability Studies checklist to assess quality.
RESULTS
The authors included 18 clinical trials involving 2,301 patients. Most patients received alendronate or risedronate for an average of 62.14 months. The average serum CTX level in patients who received BP before surgery was 198.25 picograms per milliliter. Meta-analysis results showed that the cutoff in CTX level (150 pg/mL) was not predictive of MRONJ risk. The sensitivity of CTX values lower than 150 pg/mL was 34.26%, and the specificity was 77.08%.
CONCLUSIONS AND PRACTICAL IMPLICATIONS
The use of CTX levels to diagnose MRONJ risk after dental procedures in patients receiving BP is not justified. The cutoff of 150 pg/mL in serum CTX levels is not predictive of MRONJ. Further studies are needed to develop other reliable biomarkers.
Topics: Biomarkers; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Collagen Type I; Diphosphonates; Humans; Osteonecrosis; Peptides; Reproducibility of Results
PubMed: 31256803
DOI: 10.1016/j.adaj.2019.03.006 -
Annals of Internal Medicine Jul 2019Optimal long-term osteoporosis drug treatment (ODT) is uncertain.
BACKGROUND
Optimal long-term osteoporosis drug treatment (ODT) is uncertain.
PURPOSE
To summarize the effects of long-term ODT and ODT discontinuation and holidays.
DATA SOURCES
Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies.
STUDY SELECTION
48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB).
DATA EXTRACTION
Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy.
DATA SYNTHESIS
Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapy reduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE).
LIMITATION
No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays.
CONCLUSION
Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-term bisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms.
PRIMARY FUNDING SOURCE
National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).
Topics: Alendronate; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Diphosphonates; Drug Administration Schedule; Duration of Therapy; Female; Hip Fractures; Humans; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Spinal Fractures; Zoledronic Acid
PubMed: 31009947
DOI: 10.7326/M19-0533 -
Osteoporosis International : a Journal... Apr 2019We performed a systematic review on the effect of drug holidays (discontinuation) on bone mineral density (BMD) and fracture risk. Bisphosphonate discontinuation may be... (Meta-Analysis)
Meta-Analysis
UNLABELLED
We performed a systematic review on the effect of drug holidays (discontinuation) on bone mineral density (BMD) and fracture risk. Bisphosphonate discontinuation may be considered for women who do not have low hip BMD after 3-5 years of initial treatment, while women who have low hip BMD may benefit from treatment continuation.
INTRODUCTION
We performed a systematic review and meta-analysis on the effect of drug holidays (discontinuation) on BMD and fracture risk.
METHODS
We searched PubMed, Embase, and Cochrane Library databases to locate controlled clinical trials and cohort studies evaluating the effect of drug holidays/discontinuation versus osteoporosis treatment continuation. We performed random-effects meta-analyses of hazard ratios of hip and any clinical osteoporotic fracture for individuals who discontinued bisphosphonates compared to persistent users.
RESULTS
Thirteen records reporting results from eight different studies met inclusion criteria. The FLEX study found a reduced clinical vertebral fracture risk with 10 years of alendronate therapy compared to 5 (RR 0.45, 95% CI 0.24-0.85), and the HORIZON extension studies found a reduced risk of morphometric vertebral fracture with 6 years of zoledronic acid therapy compared to 3 (OR = 0.51, 95% CI 0.26-0.95); subgroup analyses showed that women with low hip BMD T-scores after the initial treatment period benefitted from continued treatment in terms of reduced vertebral fracture risk. Meta-analysis of adjusted hazard ratios of hip and any clinical osteoporotic fracture for women who discontinued bisphosphonates revealed no significant differences in the risk of hip fracture (summary estimate of HR 1.09, 95% CI 0.87-1.37) or any clinical fracture (summary estimate of HR 1.13, 95% CI 0.75-1.70) compared to persistent users.
CONCLUSIONS
Bisphosphonate discontinuation may be considered for women who do not have low hip BMD after 3 to 5 years of initial treatment, while women who have low hip BMD may benefit from treatment continuation.
Topics: Bone Density; Bone Density Conservation Agents; Clinical Decision-Making; Diphosphonates; Drug Administration Schedule; Humans; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Risk Assessment; Withholding Treatment
PubMed: 30623214
DOI: 10.1007/s00198-018-4791-3 -
Medicine Oct 2018Alendronate has been used to prevent or treat glucocorticoid-induced osteoporosis (GIO), data regarding its efficacy are inconsistent. We conducted the current... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alendronate has been used to prevent or treat glucocorticoid-induced osteoporosis (GIO), data regarding its efficacy are inconsistent. We conducted the current systematic review and meta-analysis to evaluate both efficacy and safety of alendronate in the treatment of GIO.
METHODS
PubMed, Embase, the Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing Databases were searched up through March 1, 2018. Randomized controlled trials (RCTs) involving patients which received alendronate treatment were included. Outcome measures were bone mineral density (BMD) changes, bone fractures, and adverse reactions. Data from the individual studies were pooled using random or fixed effect models based on heterogeneity. Effect size was reported as standardized mean differences (SMD) for continuous outcomes and pooled odds ratios (OR) for dichotomous outcomes, with 95% confidence interval (CI).
RESULTS
Overall, 10 studies involving 1002 patients were included in the present investigation. Alendronate treatment significantly increased BMD of the lumbar spine and femoral neck during 6 to 24 months. These beneficial effects were apparent at 12 months after treatment for the lumbar spine but not the femoral neck BMD. Alendronate treatment did not significantly change fracture risk nor induce significant differences in adverse gastrointestinal effects.
CONCLUSION
Alendronate significantly increases BMD of the lumbar spine and femoral neck in patients with GIO, but does not appear to reduce the risk of fractures. As relatively insufficient data regarding the GIO fracture incidence has been reported, more RCTs need to be carried out to determine the efficacy of alendronate in the prevention of GIO fracture.
Topics: Alendronate; Bone Density; Bone Density Conservation Agents; Female; Glucocorticoids; Humans; Male; Osteoporosis; Osteoporotic Fractures; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30334952
DOI: 10.1097/MD.0000000000012691