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Journal of Clinical Densitometry : the... 2022Osteoporosis is a chronic disease with an increasing prevalence. Anti-sclerostin antibodies are being investigated for the treatment of osteoporosis. The aim of this... (Meta-Analysis)
Meta-Analysis Review
Osteoporosis is a chronic disease with an increasing prevalence. Anti-sclerostin antibodies are being investigated for the treatment of osteoporosis. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of antis-sclerostin antibodies compared to placebo and conventional therapies (alendronate and teriparatide) in the treatment of osteoporosis. Randomized controlled trials were searched from PubMed, EMBASE and Cochrane Central Register of Controlled Trails (CENTRAL) from their inception up to June 2021 by using Medical Subject Headings terms "anti-sclerostin antibody", "romosozumab", "blosozumab", "AMG 785″, "LY2541546", and "osteoporosis". Two investigators independently screened eligible studies, assessed the risk of bias and extracted the data from each study. The I index was used to assess heterogeneity. Meta-analysis was conducted using the Review Manager Software (RevMan, Version 5.4). The GRADE approach was used to rate the quality of evidence for all the pooled outcomes. 8 RCTs with 12,416 patients met the inclusion criteria. Anti-sclerostin antibodies significantly increased lumbar spine, total hip and femoral neck bone mineral density compared to placebo, alendronate and teriparatide at both 6 and 12 mo. Adverse events were comparable between anti-sclerostin antibodies and other treatments, except for the incidence of injection-site reactions that was higher in the anti-sclerostin antibody groups. Anti-sclerostin antibodies represent a valid theurapeutic option in the treatment of osteoporosis. Further studies with longer duration and follow-up are needed to confirm the results of this meta-analysis.
Topics: Alendronate; Bone Density; Bone Density Conservation Agents; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Teriparatide
PubMed: 34920938
DOI: 10.1016/j.jocd.2021.11.005 -
Journal of Investigative Medicine : the... Mar 2022This meta-analysis and systematic review investigated the efficacy of bisphosphonates on the incidence of hip fracture (IHF) in patients of different ages with... (Meta-Analysis)
Meta-Analysis
This meta-analysis and systematic review investigated the efficacy of bisphosphonates on the incidence of hip fracture (IHF) in patients of different ages with osteoporosis or osteopenia. We searched Web of Science, Embase, the Cochrane Database, and PubMed from inception to January 10, 2021, for trials reporting the effects of bisphosphonates on the IHF. We included only randomized, double-blind, placebo-controlled clinical trials. We pooled data using a random-effects meta-analysis with risk ratios (RRs) and reported 95% CIs. We also used the Cochran Q and I² statistics to assess the heterogeneity in the results of individual studies. The primary endpoints were the total numbers of people in the bisphosphonates and placebo groups and the numbers of IHFs during the follow-up periods. Bisphosphonates reduced the IHF with an overall effect (RR: 0.66; 95% CI: 0.56 to 0.77; zoledronic acid: RR: 0.60; 95% CI: 0.46 to 0.78; risedronate: RR: 0.74; 95% CI: 0.59 to 0.94, and alendronate: RR: 0.61; 95% CI: 0.40 to 0.95). The result of the heterogeneity assessment was I²=0, p=0.97. In all age groups (all ages, ≥55 years old, ≥65 years old), bisphosphonates reduced the IHF. In the ≥55 years old and ≥65 years old age groups, the RR and 95% CI were 0.63 and 0.43 to 0.93, and 0.60 and 0.44 to 0.81, respectively. Bisphosphonate reduced the IHF in the general population and all age groups (≥55 years old and ≥65 years old). Zoledronic acid, risedronate and alendronate reduced the IHF in osteoporosis or osteopenia populations. The association between bisphosphonate and the IHF does not appear to be influenced by age.
Topics: Aged; Alendronate; Bone Density Conservation Agents; Diphosphonates; Hip Fractures; Humans; Middle Aged; Osteoporosis; Randomized Controlled Trials as Topic; Risedronic Acid; Zoledronic Acid
PubMed: 34893517
DOI: 10.1136/jim-2021-001961 -
Journal of Indian Society of... 2021Aim of the present meta-analysis was to evaluate the effect of Aloe vera in various forms such as gel, mouthwash, and dentifrice on gingival and plaque index (PI) in...
BACKGROUND
Aim of the present meta-analysis was to evaluate the effect of Aloe vera in various forms such as gel, mouthwash, and dentifrice on gingival and plaque index (PI) in comparison to various allopathic products such as chlorhexidine, metformin, chlorine dioxide, fluoridated toothpaste, and alendronate.
MATERIALS AND METHODS
A comprehensive electronic search was conducted on PubMed/MEDLINE, GOOGLE SCHOLAR, and HAND SEARCH of reference list of archived articles published till January 2020. Randomized controlled trials were searched comparing the product with other products which used PI and gingival index (GI) to evaluate the outcomes. Finally, nine studies assessing PI and four studies evaluating GI were considered for the meta-analysis. After extracting the information, a risk of bias was estimated. The standardized mean differences (SMDs) and fixed and random effect models were obtained from the mean treatment differences.
RESULTS
The estimates of SMD of PI from fixed effects (SMD = 0.271, 95% confidence interval [CI] = 0.00134-0.407, < 0.001) and random effects (SMD = 0.288, 95% CI = 0.048-0.529, = 0.019) were found slightly different, the models showed consistent results yielding positive and significant treatment effects. For GI fixed effects (SMD = 0.27, 95% CI = -0.035-0.575, = 0.0803, not significant) and random effects (SMD = 0.259, 95% CI = 0.049-0.469, = 0.016, significant) were found slightly different and positive. However, one model showed significant and another model showed nonsignificant treatment effects.
CONCLUSION
Results from our meta-analyses confirmed the beneficial effects of in improving the periodontal parameters and hence may be considered as a safe alternative drug delivery agent for the management of periodontal diseases in future.
PubMed: 34667378
DOI: 10.4103/jisp.jisp_40_21 -
Journal of Orthopaedic Surgery and... Aug 2021Osteoporosis affects mostly postmenopausal women, leading to deterioration of the microarchitectural bone structure and low bone mass, with an increased fracture risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoporosis affects mostly postmenopausal women, leading to deterioration of the microarchitectural bone structure and low bone mass, with an increased fracture risk with associated disability, morbidity and mortality. This Bayesian network meta-analysis compared the effects of current anti-osteoporosis drugs on bone mineral density.
METHODS
The present systematic review and network meta-analysis follows the PRISMA extension statement to report systematic reviews incorporating network meta-analyses of health care interventions. The literature search was performed in June 2021. All randomised clinical trials that have investigated the effects of two or more drug treatments on BMD for postmenopausal osteoporosis were accessed. The network comparisons were performed through the STATA Software/MP routine for Bayesian hierarchical random-effects model analysis. The inverse variance method with standardised mean difference (SMD) was used for analysis.
RESULTS
Data from 64 RCTs involving 82,732 patients were retrieved. The mean follow-up was 29.7 ± 19.6 months. Denosumab resulted in a higher spine BMD (SMD -0.220; SE 3.379), followed by pamidronate (SMD -5.662; SE 2.635) and zoledronate (SMD -10.701; SE 2.871). Denosumab resulted in a higher hip BMD (SMD -0.256; SE 3.184), followed by alendronate (SMD -17.032; SE 3.191) and ibandronate (SMD -17.250; SE 2.264). Denosumab resulted in a higher femur BMD (SMD 0.097; SE 2.091), followed by alendronate (SMD -16.030; SE 1.702) and ibandronate (SMD -17.000; SE 1.679).
CONCLUSION
Denosumab results in higher spine BMD in selected women with postmenopausal osteoporosis. Denosumab had the highest influence on hip and femur BMD.
LEVEL OF EVIDENCE
Level I, Bayesian network meta-analysis of RCTs.
Topics: Alendronate; Bayes Theorem; Bone Density; Bone Density Conservation Agents; Denosumab; Female; Humans; Ibandronic Acid; Network Meta-Analysis; Osteoporosis; Osteoporosis, Postmenopausal; Pharmaceutical Preparations
PubMed: 34452621
DOI: 10.1186/s13018-021-02678-x -
Oral Diseases Jan 2023To determine the frequency of osteonecrosis of the jaw in bisphosphonate users submitted to dental procedures. (Review)
Review
OBJECTIVE
To determine the frequency of osteonecrosis of the jaw in bisphosphonate users submitted to dental procedures.
METHODS
This systematic review searched the sources: MEDLINE, EMBASE, Web of Science, Scopus, and Virtual Health Library, with no restriction on language or publication date. Reviewers, in pairs and independently, selected the studies, extracted their data, and assessed the risk of bias. Meta-analyses were pooled using the DerSimonian and Laird random effects model.
RESULTS
A total of 27 studies (5391 participants) were included. The most reported bisphosphonates were zoledronate (n = 17 studies) and alendronate (n = 19) for treating cancers (n = 11) and osteoporosis (n = 16), respectively. Twelve studies were of low methodological quality. The frequency of osteonecrosis was 2.7% (95% CI: 0.9-5.2%) and proved higher for intravenous [6.9% (0.7-17.3%)] than oral [0.2% (0.9-5.2%)] bisphosphonate use. No association between longer treatment duration and greater frequency of osteonecrosis was observed.
CONCLUSIONS
Higher frequency of osteonecrosis was observed in intravenous bisphosphonate users submitted to dental extraction. Further studies collecting more detailed information on the bisphosphonates used and of greater methodological rigor are warranted to confirm these findings and better inform prescribers, dental surgeons, and other professionals on risks of bisphosphonate use in this patient group.
Topics: Humans; Diphosphonates; Bone Density Conservation Agents; Osteonecrosis; Zoledronic Acid; Osteoporosis; Bisphosphonate-Associated Osteonecrosis of the Jaw
PubMed: 34402147
DOI: 10.1111/odi.14003 -
Frontiers in Pharmacology 2021Herein, we purposed to evaluate the efficacy along with the safety of Xianling Gubao capsule (XLGB) combined with alendronate (ALE) for primary osteoporosis (POP) from...
The Efficacy and Safety of Chinese Herbal Medicine Xianling Gubao Capsule Combined With Alendronate in the Treatment of Primary Osteoporosis: A Systematic Review and Meta-Analysis of 20 Randomized Controlled Trials.
Herein, we purposed to evaluate the efficacy along with the safety of Xianling Gubao capsule (XLGB) combined with alendronate (ALE) for primary osteoporosis (POP) from the current literature. We carried out a search for electronic literature in the PubMed, Chinese National Knowledge Infrastructure, EMBASE, Wanfang Web of Science, Chinese Biomedical Literature Database, Cochrane Library, as well as Chinese VIP databases targeting articles published from inception to December 2020. Only randomized controlled trials (RCTs) were enrolled into the study. Alkaline phosphatase (ALP), visual analogue scale (VAS), serum phosphorus (S-P), bone gla protein (BGP), serum calcium (S-Ca) and bone mineral density (BMD) were the primary outcome variable. The total clinical effective rate along with the adverse drug reaction (ADR) were the secondary outcome variables. The meta-analysis was conducted using RevMan 5.3 and STATA 12.0. GRADE pro3.6.1 software was used for the assessment of evidence quality. Overall, 20 RCTs focusing on 1911 patients were enrolled into the study. Our meta-analysis demonstrated that XLGB combined with ALE remarkably increased BMD ( < 0.001), BGP ( < 0.001), S-Ca ( < 0.001), S-P ( < 0.001) and effective rate ( < 0.001) than ALE alone in patients with POP. Moreover, ALP ( < 0.001) and VAS ( < 0.001) were overtly by decreased XLGB. However, XLGB combined with ALE would not markedly increase the rate of ADR in contrast with ALE alone ( = 0.499). The results of our study demonstrated that XLGB is a potential candidate for OP treatment. We recommend that rigorous, as well as high-quality trials involving large samples sizes should be conducted to confirm our findings.
PubMed: 34335260
DOI: 10.3389/fphar.2021.695832 -
The Archives of Bone and Joint Surgery May 2021Atypical femoral fractures are the femoral fractures located anywhere between the lesser trochanter and the supracondylar flare of the femur. Long-term bisphosphonates,... (Review)
Review
BACKGROUND
Atypical femoral fractures are the femoral fractures located anywhere between the lesser trochanter and the supracondylar flare of the femur. Long-term bisphosphonates, as the most common preventive and treatment medications for osteoporosis, are thought to have an important role in these fractures. Most of the fractures should be treated surgically, and the complications are considerable.
METHODS
We searched Medline, CENTRAL, Embase, and DART on February 26, 2020. One author reviewed and retrieved citations from these four databases for irrelevant and duplicate studies, and two other authors independently extracted data from the studies and rated their quality.Patients with surgical treatment of bisphosphonate-related atypical femoral fracture, according to the American Society for Bone and Mineral Research definition, were included. Animal studies, case reports, studies with high-energy trauma, pathological fracture, or malignancy-related fractures were excluded.
RESULTS
In total, 316 patients (348 fractures) were included in this study. Mean age of patients was 70.47 years, and 97.5% of them were female. Duration of using bisphosphonates was 4.04 to 8.8 years, and Alendronate was the most common type. Moreover, 65.27% and 34.72% of the reported fractures were in diaphyseal and subtrochanteric, respectively. Moreover, the most common fixation type was intramedullary. Rate of complication was 17.52%, and the most frequent one was non-union, followed by implant failure. The main limitation of this research was that most of the studies did not have a high level of evidence.
CONCLUSION
An increase in the rate of atypical femoral fracture with its challenging management makes it an important issue to be noted by orthopedic surgeons. Based on the results of this study, subtrochanteric fractures might have more complications post-operatively and are suggested to be operated on by more experienced surgeons. It was also found that extra-medullary fixation increases the risk of complications. Future studies on union time, outcomes of different surgical methods, and teriparatide therapy may help shed more light on the surgical management of these fractures.
PubMed: 34239955
DOI: 10.22038/abjs.2020.52698.2608 -
The Cochrane Database of Systematic... Jul 2021Chronic kidney disease (CKD) is an independent risk factor for osteoporosis and is more prevalent among people with CKD than among people who do not have CKD. Although... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic kidney disease (CKD) is an independent risk factor for osteoporosis and is more prevalent among people with CKD than among people who do not have CKD. Although several drugs have been used to effectively treat osteoporosis in the general population, it is unclear whether they are also effective and safe for people with CKD, who have altered systemic mineral and bone metabolism.
OBJECTIVES
To assess the efficacy and safety of pharmacological interventions for osteoporosis in patients with CKD stages 3-5, and those undergoing dialysis (5D).
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 25 January 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials comparing any anti-osteoporotic drugs with a placebo, no treatment or usual care in patients with osteoporosis and CKD stages 3 to 5D were included.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, assessed their quality using the risk of bias tool, and extracted data. The main outcomes were the incidence of fracture at any sites; mean change in the bone mineral density (BMD; measured using dual-energy radiographic absorptiometry (DXA)) of the femoral neck, total hip, lumbar spine, and distal radius; death from all causes; incidence of adverse events; and quality of life (QoL). Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Seven studies involving 9164 randomised participants with osteoporosis and CKD stages 3 to 5D met the inclusion criteria; all participants were postmenopausal women. Five studies included patients with CKD stages 3-4, and two studies included patients with CKD stages 5 or 5D. Five pharmacological interventions were identified (abaloparatide, alendronate, denosumab, raloxifene, and teriparatide). All studies were judged to be at an overall high risk of bias. Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture (RR 0.52, 95% CI 0.39 to 0.69; low certainty evidence). Anti-osteoporotic drugs probably makes little or no difference to the risk of clinical fracture (RR 0.91, 95% CI 0.79 to 1.05; moderate certainty evidence) and adverse events (RR 0.99, 95% CI 0.98 to 1.00; moderate certainty evidence). We were unable to incorporate studies into the meta-analyses for BMD at the femoral neck, lumbar spine and total hip as they only reported the percentage change in the BMD in the intervention group. Among patients with severe CKD stages 5 or 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture (RR 0.33, 95% CI 0.01 to 7.87; very low certainty evidence). It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low (MD 0.01, 95% CI 0.00 to 0.02). Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine (MD 0.03, 95% CI 0.03 to 0.04, low certainty evidence). No adverse events were reported in the included studies. It is uncertain whether anti-osteoporotic drug reduces the risk of death (RR 1.00, 95% CI 0.22 to 4.56; very low certainty evidence).
AUTHORS' CONCLUSIONS
Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture in low certainty evidence. Anti-osteoporotic drugs make little or no difference to the risk of clinical fracture and adverse events in moderate certainty evidence. Among patients with CKD stages 5 and 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture and death because the certainty of this evidence is very low. Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine in low certainty evidence. It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low. Larger studies including men, paediatric patients or individuals with unstable CKD-mineral and bone disorder are required to assess the effect of each anti-osteoporotic drug at each stage of CKD.
Topics: Antibodies, Monoclonal; Bias; Bone Density; Bone Density Conservation Agents; Denosumab; Female; Femur Neck; Fractures, Spontaneous; Hip; Humans; Indoles; Lumbar Vertebrae; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Spinal Fractures; Teriparatide; Thiophenes; Watchful Waiting
PubMed: 34231877
DOI: 10.1002/14651858.CD013424.pub2 -
Current Molecular Medicine 2022Osteoporosis is the most prevalent metabolic bone disorder worldwide. This review was undertaken to compare the efficacies of bisphosphonates therapies for patient...
OBJECTIVES
Osteoporosis is the most prevalent metabolic bone disorder worldwide. This review was undertaken to compare the efficacies of bisphosphonates therapies for patient persistence and compliance for the treatment of osteoporosis.
METHODS
A systematic review was performed in accordance with the available reporting items. MEDLINE and Cochrane library databases were applied for literature searched up to January 2020. All major studies such as prospective, retrospective and review articles that examined patient persistence or compliance to bisphosphonates for osteoporosis were included.
RESULTS
The literature search found 656 relevant published reports, out of which 87 were included. The 10, 712, 176 osteoporotic patients were studied for patient persistence and 5, 875, 718 patients were studied for patient compliances. Analysis of all studied bisphosphonates showed almost similar patterns for patient persistence rates as it was decreased over the time following initial prescription, but persistence length was found to be significantly higher for alendronate therapy as compared to the other studied bisphosphonates (p<0.001), whereas the length of persistence of all other bisphosphonates (other than alendronate) were almost same (p>0.05). Analysis of patient compliances with etidronate therapy showed the highest percent medication possession ratio (MRP) at 12 months, followed by the MRPs of ibandronate, alendronate, risedronate, and clodronate.
CONCLUSION
This is the first systematic review that shows the comparison of the efficiencies of bisphosphonates for patient persistence and compliance for the treatment of osteoporosis. The data showed that the length of patient persistence was highest for alendronate therapy, whereas patient compliance was highest for etidronate therapy for the treatment of osteoporosis.
Topics: Alendronate; Bone Density Conservation Agents; Diphosphonates; Etidronic Acid; Humans; Osteoporosis; Patient Compliance; Prospective Studies; Retrospective Studies
PubMed: 33855941
DOI: 10.2174/1566524021666210414100227 -
PloS One 2021Bisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bisphosphonate drugs can be used to improve the outcomes of women with breast cancer. Whilst many meta-analyses have quantified their potential benefits for patients, attempts at comprehensive quantification of potential adverse effects have been limited. We undertook a meta-analysis with novel methodology to identify and quantify these adverse effects.
METHODS
We systematically reviewed randomised controlled trials in breast cancer where at least one of the treatments was a bisphosphonate (zoledronic acid, ibandronate, pamidronate, alendronate or clodronate). Neoadjuvant, adjuvant and metastatic settings were examined. Primary outcomes were adverse events of any type or severity (excluding death). We carried out pairwise and network meta-analyses to estimate the size of any adverse effects potentially related to bisphosphonates. In order to ascertain whether adverse effects differed by individual factors such as age, or interacted with other common adjuvant breast cancer treatments, we examined individual-level patient data for one large trial, AZURE.
FINDINGS
We identified 56 trials that reported adverse data, which included a total of 29,248 patients (18,301 receiving bisphosphonate drugs versus 10,947 not). 24 out of the 103 different adverse outcomes analysed showed a statistically and practically significant increase in patients receiving a bisphosphonate drug compared with those not (2 additional outcomes that appeared statistically significant came only from small studies with low event counts and no clinical suspicion so are likely artifacts). Most of these 24 are already clinically recognised: 'flu-like symptoms, fever, headache and chills; increased bone pain, arthralgia, myalgia, back pain; cardiac events, thromboembolic events; hypocalcaemia and osteonecrosis of the jaw; as well as possibly stiffness and nausea. Oral clodronate appeared to increase the risk of vomiting and diarrhoea (which may also be increased by other bisphosphonates), and there may be some hepatotoxicity. Four additional potential adverse effects emerged for bisphosphonate drugs in this analysis which have not classically be recognised: fatigue, neurosensory problems, hypertonia/muscle spasms and possibly dysgeusia. Several symptoms previously reported as potential side effects in the literature were not significantly increased in this analysis: constipation, insomnia, respiratory problems, oedema or thirst/dry mouth. Individual patient-level data and subgroup analysis revealed little variation in side effects between women of different ages or menopausal status, those with metastatic versus non-metastatic cancer, or between women receiving different concurrent breast cancer therapies.
CONCLUSIONS
This meta-analysis has produced estimates for the absolute frequencies of a range of side effects significantly associated with bisphosphonate drugs when used by breast cancer patients. These results show good agreement with previous literature on the subject but are the first systematic quantification of side effects and their severities. However, the analysis is limited by the availability and quality of data on adverse events, and the potential for bias introduced by a lack of standards for reporting of such events. We therefore present a table of adverse effects for bisphosphonates, identified and quantified to the best of our ability from a large number of trials, which we hope can be used to improve the communication of the potential harms of these drugs to patients and their healthcare providers.
Topics: Adult; Aged; Aged, 80 and over; Bone Density Conservation Agents; Breast Neoplasms; Diphosphonates; Female; Humans; Middle Aged; Network Meta-Analysis; Randomized Controlled Trials as Topic; Young Adult
PubMed: 33544765
DOI: 10.1371/journal.pone.0246441