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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 -
Medicina Oral, Patologia Oral Y Cirugia... Dec 2023To access the occurrence of bisphosphonate-associated osteonecrosis of the jaw (BAONJ) in individuals with rheumatoid arthritis (RA).
BACKGROUND
To access the occurrence of bisphosphonate-associated osteonecrosis of the jaw (BAONJ) in individuals with rheumatoid arthritis (RA).
MATERIAL AND METHODS
Observational studies that evaluated the occurrence of BAONJ in individuals with RA (BAONJ-RA) were considered for inclusion. Electronic searches were performed up to December 2022 in six databases and in the grey literature. The study selection, data extraction, and quality assessment of the included studies according to the Joanna Briggs Institute Critical Appraisal Checklists was performed. The certainty of evidence was evaluated using the GRADE approach.
RESULTS
Five studies were included three cohort and two cross-sectional. The sample size of subjects with RA ranged from 16 to 3201. Together, the studies presented 36 cases of BAONJ-RA. Prevalence of BAONJ-RA ranged from 0.094% to 56.25%. The incidence ranged from 0.4% to 2.21. Women between the 6th and 8th decade of life were the most affected. Alendronate (n=5) and zoledronic acid (n=9), orally and intravenously, respectively, were the most used bisphosphonates. The duration of bisphosphonates use ranged from 2.7 to 8 years. The certainty of evidence was very low.
CONCLUSIONS
The occurrence of BAONJ-RA is low. However, the certainty of the evidence was very low for this outcome.
PubMed: 38150601
DOI: 10.4317/medoral.26373 -
Yakugaku Zasshi : Journal of the... 2022Medical big data are accumulated daily by medical staff in clinical settings. We developed a formulary in 2016 using medical big data from eight hospitals affiliated...
Medical big data are accumulated daily by medical staff in clinical settings. We developed a formulary in 2016 using medical big data from eight hospitals affiliated with Showa University, Japan (3200 beds). In 2019, we revised the procedure from the perspective of authenticity, reproducibility, and clarity to develop a medicine formulary with unbiased data. Briefly, we organized two teams of expert physicians. Team 1 was a systematic review team that conducted a literature search using systematic review. Team 2 was a medical big data team that conducted the analysis using medical big data. Both teams developed a bisphosphonate formulary. First and second team recommendations were alendronic acid and minodronic acid, and alendronic acid and risedronic acid, respectively. Discussion between the two teams yielded alendronic acid only in the bisphosphonate formulary. We developed reports for the bisphosphonate formulary that included conflicts of interest, the role of each staff member in developing the formulary, and the process for determining the formulary. To use our formulary in a community context, we updated the formulary on our website. We tried to substantiate our bisphosphonate formulary and make a recommendation to change the bisphosphonates according to our formulary. The formulary is focused on controlling the economic burden of medical expenses. We believe that the formulary needs to represent authenticity, reproducibility, and clarity in the procedure and conflicts of interest, with unbiased data to preclude context (hospital)-convenient decisions.
Topics: Big Data; Humans; Japan; Reproducibility of Results
PubMed: 35370186
DOI: 10.1248/yakushi.21-00178-2 -
Frontiers in Endocrinology 2020Bisphosphonates (BPs) are first-line therapy for osteoporosis. Adherence is usually low in chronic, asymptomatic diseases, but gastrointestinal (GI) side-effects can... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Bisphosphonates (BPs) are first-line therapy for osteoporosis. Adherence is usually low in chronic, asymptomatic diseases, but gastrointestinal (GI) side-effects can also contribute to low adherence in BP therapy and may necessitate a review by a gastroenterologist with or without gastroscopy.
AIMS
Our meta-analysis aims to determine the risk of severe GI adverse events due to oral BP therapy in osteoporotic patients.
METHODS
A systematic search was conducted in three databases up to September 2020 for randomized controlled trials (RCTs) detailing GI adverse events in adults with osteoporosis on BP compared to placebo. Risk ratios (RRs) with 95% confidence intervals (CI) were calculated for non-severe and severe adverse events indicating endoscopic procedure with the random-effects model. Statistical heterogeneity was assessed using chi and I statistics.
RESULTS
Forty-two RCTs with 39,047 patients with 9,999 non-severe and 1,503 severe GI adverse events were included. The incidence of non-severe and severe adverse events ranged between 0.3-54.9 and 0-10.3%, respectively. There was no difference between BP and control groups in terms of the risk of non-severe or severe side effects: RR=1.05 (CI: 0.98-1.12), I = 48.1%, and RR=1.01 (CI: 0.92-1.12), I = 0.0%, respectively. Subgroup analysis of the most commonly used BP, once-weekly alendronate 70 mg, revealed an association between bisphosphonates and the risk of non-severe GI adverse events, RR=1.16 (CI: 1.00-1.36), I = 40.7%, while the risk of severe GI side effects was not increased in this subgroup, RR=1.20 (CI: 0.83-1.74), I = 0.0%.
CONCLUSION
Our results show that bisphosphonates do not increase the risk of severe GI adverse events. However, the marked variability of the screening for side effects in the included studies, and the fact that in most of the studies GI diseases were exclusion criteria limits the strenght of evidence of our results. The conclusions drawn from the meta-analysis are therefore restricted to selected populations, and the results must be interpreted with caution.
Topics: Administration, Oral; Bone Density Conservation Agents; Diphosphonates; Gastrointestinal Diseases; Humans; Osteoporosis; Publication Bias
PubMed: 33240217
DOI: 10.3389/fendo.2020.573976 -
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 -
The Cochrane Database of Systematic... Dec 2020Different bone-modifying agents like bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are used as supportive treatment in men... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Different bone-modifying agents like bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are used as supportive treatment in men with prostate cancer and bone metastases to prevent skeletal-related events (SREs). SREs such as pathologic fractures, spinal cord compression, surgery and radiotherapy to the bone, and hypercalcemia lead to morbidity, a poor performance status, and impaired quality of life. Efficacy and acceptability of the bone-targeted therapy is therefore of high relevance. Until now recommendations in guidelines on which bone-modifying agents should be used are rare and inconsistent.
OBJECTIVES
To assess the effects of bisphosphonates and RANKL-inhibitors as supportive treatment for prostate cancer patients with bone metastases and to generate a clinically meaningful treatment ranking according to their safety and efficacy using network meta-analysis.
SEARCH METHODS
We identified studies by electronically searching the bibliographic databases Cochrane Controlled Register of Trials (CENTRAL), MEDLINE, and Embase until 23 March 2020. We searched the Cochrane Library and various trial registries and screened abstracts of conference proceedings and reference lists of identified trials.
SELECTION CRITERIA
We included randomized controlled trials comparing different bisphosphonates and RANKL-inihibitors with each other or against no further treatment or placebo for men with prostate cancer and bone metastases. We included men with castration-restrictive and castration-sensitive prostate cancer and conducted subgroup analyses according to this criteria.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the quality of trials. We defined proportion of participants with pain response and the adverse events renal impairment and osteonecrosis of the jaw (ONJ) as the primary outcomes. Secondary outcomes were SREs in total and each separately (see above), mortality, quality of life, and further adverse events such as grade 3 to 4 adverse events, hypocalcemia, fatigue, diarrhea, and nausea. We conducted network meta-analysis and generated treatment rankings for all outcomes, except quality of life due to insufficient reporting on this outcome. We compiled ranking plots to compare single outcomes of efficacy against outcomes of acceptability of the bone-modifying agents. We assessed the certainty of the evidence for the main outcomes using the GRADE approach.
MAIN RESULTS
Twenty-five trials fulfilled our inclusion criteria. Twenty-one trials could be considered in the quantitative analysis, of which six bisphosphonates (zoledronic acid, risedronate, pamidronate, alendronate, etidronate, or clodronate) were compared with each other, the RANKL-inhibitor denosumab, or no treatment/placebo. By conducting network meta-analysis we were able to compare all of these reported agents directly and/or indirectly within the network for each outcome. In the abstract only the comparisons of zoledronic acid and denosumab against the main comparator (no treatment/placebo) are described for outcomes that were predefined as most relevant and that also appear in the 'Summary of findings' table. Other results, as well as results of subgroup analyses regarding castration status of participants, are displayed in the Results section of the full text. Treatment with zoledronic acid probably neither reduces nor increases the proportion of participants with pain response when compared to no treatment/placebo (risk ratio (RR) 1.46, 95% confidence interval (CI) 0.93 to 2.32; per 1000 participants 121 more (19 less to 349 more); moderate-certainty evidence; network based on 4 trials including 1013 participants). For this outcome none of the trials reported results for the comparison with denosumab. The adverse event renal impairment probably occurs more often when treated with zoledronic acid compared to treatment/placebo (RR 1.63, 95% CI 1.08 to 2.45; per 1000 participants 78 more (10 more to 180 more); moderate-certainty evidence; network based on 6 trials including 1769 participants). Results for denosumab could not be included for this outcome, since zero events cannot be considered in the network meta-analysis, therefore it does not appear in the ranking. Treatment with denosumab results in increased occurrence of the adverse event ONJ (RR 3.45, 95% CI 1.06 to 11.24; per 1000 participants 30 more (1 more to 125 more); high-certainty evidence; 4 trials, 3006 participants) compared to no treatment/placebo. When comparing zoledronic acid to no treatment/placebo, the confidence intervals include the possibility of benefit or harm, therefore treatment with zoledronic acid probably neither reduces nor increases ONJ (RR 1.88, 95% CI 0.73 to 4.87; per 1000 participants 11 more (3 less to 47 more); moderate-certainty evidence; network based on 4 trials including 3006 participants). Compared to no treatment/placebo, treatment with zoledronic acid (RR 0.84, 95% CI 0.72 to 0.97) and denosumab (RR 0.72, 95% CI 0.54 to 0.96) may result in a reduction of the total number of SREs (per 1000 participants 75 fewer (131 fewer to 14 fewer) and 131 fewer (215 fewer to 19 fewer); both low-certainty evidence; 12 trials, 5240 participants). Treatment with zoledronic acid and denosumab likely neither reduces nor increases mortality when compared to no treatment/placebo (zoledronic acid RR 0.90, 95% CI 0.80 to 1.01; per 1000 participants 48 fewer (97 fewer to 5 more); denosumab RR 0.93, 95% CI 0.77 to 1.11; per 1000 participants 34 fewer (111 fewer to 54 more); both moderate-certainty evidence; 13 trials, 5494 participants). Due to insufficient reporting, no network meta-analysis was possible for the outcome quality of life. One study with 1904 participants comparing zoledronic acid and denosumab showed that more zoledronic acid-treated participants than denosumab-treated participants experienced a greater than or equal to five-point decrease in Functional Assessment of Cancer Therapy-General total scores over a range of 18 months (average relative difference = 6.8%, range -9.4% to 14.6%) or worsening of cancer-related quality of life.
AUTHORS' CONCLUSIONS
When considering bone-modifying agents as supportive treatment, one has to balance between efficacy and acceptability. Results suggest that Zoledronic acid likely increases both the proportion of participants with pain response, and the proportion of participants experiencing adverse events However, more trials with head-to-head comparisons including all potential agents are needed to draw the whole picture and proof the results of this analysis.
Topics: Adult; Alendronate; Antineoplastic Agents, Hormonal; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Bone Neoplasms; Clodronic Acid; Denosumab; Diphosphonates; Etidronic Acid; Humans; Male; Network Meta-Analysis; Pamidronate; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Quality of Life; RANK Ligand; Randomized Controlled Trials as Topic; Risedronic Acid; Zoledronic Acid
PubMed: 33270906
DOI: 10.1002/14651858.CD013020.pub2 -
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