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Rheumatology International Sep 2020Axial spondyloarthropathy (axSpA) is associated with an increased prevalence of osteoporosis, but no recommendations exist to guide management. This systematic review... (Meta-Analysis)
Meta-Analysis
Axial spondyloarthropathy (axSpA) is associated with an increased prevalence of osteoporosis, but no recommendations exist to guide management. This systematic review and meta-analysis aim to assess the efficacy of pharmacological and non-pharmacological interventions on bone mineral density (BMD) in axSpA. Electronic databases were searched from inception to June 2019 for randomised controlled trials (RCTs) and quasi (q)-RCTs with pharmacological and non-pharmacological interventions. Independent reviewers undertook screening, and risk of bias and quality assessments. Primary outcomes of interest were BMD at spine and hip. Eight studies (two RCTs and six qRCTs) were included (602 participants). Moderate level evidence favoured alendronate over placebo at femoral neck [mean difference (MD) 2.01, 95% CI 0.67 to 3.35], but there was low-level evidence showing no effect at the spine. There was moderate level evidence showing no effect of tumour necrosis factor inhibitors (TNFi) on BMD at total hip (MD - 0.01, 95% CI - 0.06 to 0.04). Very low-level evidence demonstrated no effect of TNFi on spine or femoral neck. Moderate level evidence favoured neridronate over infliximab at the spine (MD 3.26, 95% CI 1.14 to 5.38), but low-level evidence showed no effect at the total hip (MD 2.75, 95% CI - 0.21 to 5.71). There were no eligible studies investigating the efficacy of non-pharmacological interventions. We conditionally recommend alendronate for management of low BMD in axSpA. The balance of evidence does not recommend the use of TNF-inhibitors for treating low BMD. There is a lack of high-quality evidence guiding clinicians treating osteoporosis in axSpA.
Topics: Adult; Bone Density; Bone Density Conservation Agents; Female; Humans; Male; Middle Aged; Osteoporosis; Randomized Controlled Trials as Topic; Spondylarthritis; Tumor Necrosis Factor Inhibitors
PubMed: 32556472
DOI: 10.1007/s00296-020-04623-3 -
Clinical Rheumatology Nov 2020Osteoporosis is a chronic skeletal disease with an increasing prevalence. Romosozumab, as a monoclonal anti-sclerostin antibody with a dual function, has been produced.... (Meta-Analysis)
Meta-Analysis Review
Osteoporosis is a chronic skeletal disease with an increasing prevalence. Romosozumab, as a monoclonal anti-sclerostin antibody with a dual function, has been produced. In this meta-analysis, we aimed to examine the efficacy of Romosozumab in patients with low bone mineral density. A systematic search was conducted in the most important electronic search engines like Cochrane Library, PubMed, Web of Science, Scopus, Google Scholar, and ClinicalTrials.gov at the end of July 2019 to retrieve randomized controlled trials (RCTs), which evaluated the effect of Romosozumab in patients with osteoporosis and/or low bone mineral density. After evaluating the quality of articles with the Cochrane checklist, data related to the outcomes of bone mineral density (BMD) of lumbar spine, femoral neck, and total hip, risk of clinical, vertebral and non-vertebral fractures, and risk of adverse events were extracted. Quality of evidence was assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Heterogeneity between studies was evaluated by I2 and Q statistics. The meta-analysis was performed using CMA v.2.0 software. Of all the 671 initially retrieved articles, seven articles were entered into the meta-analysis after removing duplicates and reviewing papers with inclusion and exclusion criteria. The results of the meta-analysis showed that Romosozumab 210, 140, and 70 mg compared with Alendronate, Teriparatide, and placebo can increase the bone mineral density in the lumbar spine, femoral neck, and total hip. The risk of adverse events like adjudicated cardiovascular serious adverse events and adjudicated cardiovascular death was more in Romosozumab 210 mg in comparison with placebo. However, this difference was not statistically significant. Treatment with anti-sclerostin antibodies can be a proper therapeutic option in patients with osteoporosis and low bone mineral density. Based on the results of this meta-analysis, it seems that Romosozumab, with its dual function, has a positive role in the treatment of osteoporosis and low bone mineral density.
Topics: Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Humans; Teriparatide
PubMed: 32385757
DOI: 10.1007/s10067-020-04948-1 -
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 -
Monoclonal Antibodies in... Apr 2020Sclerostin is a protein synthesized mainly by osteocytes whose function is to inhibit bone formation. A recent monoclonal antibody, Romosozumab, is able to block... (Meta-Analysis)
Meta-Analysis
Sclerostin is a protein synthesized mainly by osteocytes whose function is to inhibit bone formation. A recent monoclonal antibody, Romosozumab, is able to block sclerostin. The aim of this meta-analysis is to compare the safety of Romosozumab with placebo and alendronate. Five randomized controlled trials that described the safety of Romosozumab in healthy men and postmenopausal women were analyzed. The measures to be compared were the number of adverse events and the number of serious adverse events. Specific results included injection site reaction, arthralgia, nasopharyngitis, and back pain. A total of 11,741 patients were included in this meta-analysis, in three different groups: Romosozumab, alendronate, and placebo. Significant differences were seen between the groups with regard to injection site reaction: 5.88% in the Romosozumab group versus 3.62% in the placebo group (Mantel-Haenszel [M-H] 1.54, confidence interval [95% CI] 1.22-1.96; < 0.001) and 2.62% in the alendronate group (M-H 1.8, 95% CI 1.32-2.60; < 0.001). In addition, patients treated with Romosozumab had significantly fewer total adverse events than the alendronate group (M-H 0.85, 95% CI 0.74-0.98; < 0.05). In conclusion, Romosozumab may have lower adverse effects compared to alendronate and comparable to a placebo, except injection site reactions. Injection site reactions were more with romosozumab compared to alendronate and compared to the placebo as well. Romosozumab appears to have a similar safety profile to bisphosphonates.
Topics: Antibodies, Monoclonal; Female; Humans; Male; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause
PubMed: 32195618
DOI: 10.1089/mab.2019.0049 -
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 -
Bone Jan 2020To determine the clinical effectiveness of denosumab (DEN), raloxifene (RLX), romosozumab (ROMO) and teriparatide (TPTD), within their licensed (or anticipated licensed)... (Meta-Analysis)
Meta-Analysis
Clinical effectiveness of denosumab, raloxifene, romosozumab, and teriparatide for the prevention of osteoporotic fragility fractures: A systematic review and network meta-analysis.
OBJECTIVES
To determine the clinical effectiveness of denosumab (DEN), raloxifene (RLX), romosozumab (ROMO) and teriparatide (TPTD), within their licensed (or anticipated licensed) indications, for the treatment of osteoporosis.
METHODS
A systematic review was conducted. Nine electronic databases and trial registries were searched up to the end of July 2018. Studies were eligible for inclusion if they were randomised controlled trials (RCT) in a population at risk of osteoporotic fracture, comparing these four non-bisphosphonates DEN, RLX, ROMO, or TPTD with each other, a non-active treatment, or the bisphosphonates alendronate (ALN), risedronate (RIS), ibandronate (IBN) and zoledronic acid (ZOL). Quality of included studies was assessed using the Cochrane Risk of Bias tool. Network meta-analyses (NMA) were used to determine the relative effectiveness of treatments.
RESULTS
The systematic review identified 7898 citations. Forty-six RCTs of non-bisphosphonates met the inclusion criteria for the review and provided data for analyses. Additionally 49 RCTs of bisphosphonates were used in the NMAs. Forty-six RCTs were included in the NMA of vertebral fracture data, 23 RCTs for hip fractures and 73 RCTs in the NMA of femoral neck bone mineral density (FN BMD). For vertebral fractures, all four non-bisphosphonates showed statistically significant benefit relative to placebo: TPTD HR 0.23 (95% credible internal (CrI) 0.16, 0.32); ROMO followed by ALN 0.25 (95% CrI 0.15, 0.43); DEN HR 0.30 (95% CrI 0.21, 0.43); RLX HR 0.61 (95% CrI 0.44, 0.80). The four non-bisphosphonates interventions studied also showed statistically significant benefit relative to placebo for FN BMD, and for hip fractures TPTD, ROMO followed by ALN, and DEN showed statistically significant benefit relative to placebo.
CONCLUSIONS
The four non-bisphosphonate interventions studied were all statistically significantly clinically effective for reducing vertebral fractures when compared to placebo, and were beneficial for change in FN BMD compared to placebo. All reduced hip fractures, and this was statistically significant for TPTD, ROMO followed by ALN, and DEN.
Topics: Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Denosumab; Diphosphonates; Humans; Network Meta-Analysis; Osteoporotic Fractures; Raloxifene Hydrochloride; Teriparatide; Treatment Outcome
PubMed: 31626995
DOI: 10.1016/j.bone.2019.115081 -
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 -
Journal of Clinical Densitometry : the... 2020Osteoporosis is a common complication of primary biliary cholangitis (PBC) yet evidence for effective therapy is lacking. We sought to review all randomized controlled... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Osteoporosis is a common complication of primary biliary cholangitis (PBC) yet evidence for effective therapy is lacking. We sought to review all randomized controlled trials evaluating pharmacotherapy against placebo or no intervention for treatment of osteoporosis in PBC.
METHODOLOGY
A comprehensive database search was conducted from inception through 29 March 2017. The primary outcome was incidence of fractures; secondary outcomes were change in bone mineral density (BMD) and adverse events. We assessed studies for risk of bias, graded quality of evidence, and used meta-analysis to obtain overall effect by pooling studies of the same drug class.
RESULTS
We identified 11 randomized controlled trials evaluating bisphosphonates (3), hormone replacement therapy (2), ursodeoxycholic acid (1), obeticholic acid (1), cyclosporin A (1), vitamin K (1), calcitriol (1), and sodium fluoride (1). No intervention significantly reduced fractures compared to control. Although significant improvement in BMD was seen in one study with alendronate, a third-generation bisphosphonate, no significant improvement was seen on pooled analysis of all bisphosphonates including first-generation bisphosphonates (standard mean difference 0.41, p = 0.68). On pooled analysis, hormone replacement therapy modestly improved lumbar BMD (standard mean difference 0.69, p = 0.02), but with significantly increased adverse events (odds ratio 8.82, p = 0.01).
CONCLUSIONS
There is a lack of high-quality evidence supporting the efficacy of any treatment of osteoporosis in PBC. This may be explained by lack of power in the included studies. However, our current understanding of PBC-related osteoporosis indicates that it results from decreased bone formation, which may explain the attenuated effect of traditional antiresorptive agents. Future studies should investigate newer anabolic bone agents.
Topics: Bone Density; Bone Density Conservation Agents; Diphosphonates; Hormone Replacement Therapy; Humans; Liver Cirrhosis, Biliary; Osteoporosis; Osteoporotic Fractures; Risk Factors
PubMed: 31146965
DOI: 10.1016/j.jocd.2019.05.003