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Brazilian Oral Research 2024The aim of this systematic review was to answer the following question: "Does alendronate, a nitrogen-containing bisphosphonate, improve or impair alveolar socket...
The aim of this systematic review was to answer the following question: "Does alendronate, a nitrogen-containing bisphosphonate, improve or impair alveolar socket healing after tooth extraction in animal models"? To this end, a systematic review of the literature was carried out in PubMed, Scopus, LILACS, Web of Science, as well as in the gray literature up to May 2023. Preclinical studies that evaluated alveolar healing after tooth extraction and the intake of sodium alendronate compared with placebo were included. Two investigators were responsible for screening the articles independently, extracting the data, and assessing their quality through the SYRCLE's RoB tool for randomized trials in animal studies. The study selection process, study characteristics, risk of bias in studies, impact of alendronate on bone healing, and certainty of evidence were described in text and table formats. Methodological differences among the studies were restricted to the synthesis methods. The synthesis of qualitative results followed the Synthesis Without Meta-analysis (SWiM) reporting guideline. From the 19 included studies, five were considered to have low risk, three were of unclear risk, and eleven presented a high risk of bias. The studies were considered heterogeneous regarding alendronate posology, including its dosage and route of administration. Furthermore, a variety of animal species, different age ranges, diverse teeth extracted, and exposure or not to ovariectomy contributed to the lack of parity of the selected studies. Our results indicated that alendronate monotherapy negatively affects the early phase of wound healing after tooth extraction in preclinical studies, suggesting that the bone resorption process after tooth extraction in animals treated with alendronate might impair the bone healing process of the extraction socket. In conclusion, alendronate administration restrains bone resorption, thereby delaying alveolar socket healing . Future studies should be conducted to validate these findings and to better understand the effects of alendronate therapy on oral tissues.
Topics: Alendronate; Tooth Extraction; Animals; Wound Healing; Tooth Socket; Bone Density Conservation Agents
PubMed: 38747825
DOI: 10.1590/1807-3107bor-2024.vol38.0038 -
Neurospine May 2024We investigated the clinical efficacy of anabolic agents compared with bisphosphonates (BPs) for the incidence of new osteoporotic vertebral fracture (OVF) and fracture...
Comparison of the Clinical Efficacy of Anabolic Agents and Bisphosphonates in the Patients With Osteoporotic Vertebral Fracture: Systematic Review and Meta-analysis of Randomized Controlled Trials.
OBJECTIVE
We investigated the clinical efficacy of anabolic agents compared with bisphosphonates (BPs) for the incidence of new osteoporotic vertebral fracture (OVF) and fracture healing of OVF in the patients with OVF via meta-analyses of randomized controlled trials (RCTs).
METHODS
Electronic databases, including PubMed, Embase, and Cochrane Library were searched for published RCTs till December 2022. The RCTs that recruited participants with osteoporosis at high-/very high-risk of fracture (a history of osteoporotic vertebral or hip fracture) or fresh OVF were included in this study. We assessed the risk of bias on every included RCTs, estimated relative risk (RR) for the incidence of new OVF and fracture healing of OVF, and overall certainty of evidence. Meta-analyses were performed by Cochrane review manager (RevMan) version 5.3. Cochrane risk of bias 2.0 and GRADEpro/GDT were applied for evaluating methodological quality and overall certainty of evidence, respectively.
RESULTS
Five hundred eighteen studies were screened, and finally 6 eligible RCTs were included in the analysis. In the patients with prevalent OVF, anabolic agents significantly reduced the incidence of new OVF (teriparatide and romosozumab vs alendronate and risedronate [RR = 0.57, 95% CI 0.45 - 0.71; p < 0.00001; high-certainty of evidence]; teriparatide vs risedronate [RR = 0.50, 95% CI 0.37 - 0.68; p < 0.0001; high-certainty of evidence]. However, there was no evidence of teriparatide compared to alendronate in fracture healing of OVF (RR = 1.23, 95% CI 0.95 - 1.60; p = 0.12; low-certainty of evidence).
CONCLUSION
In the patients with prevalent OVF, anabolic agents showed a significant superiority for preventing new OVF than BPs, with no significant evidence for promoting fracture healing of OVF. However, considering small number of RCTs in this study, additional studies with large-scale data are required to obtain more robust evidences.
PubMed: 38697911
DOI: 10.14245/ns.2347256.628 -
Health Technology Assessment... Apr 2024Bisphosphonates are a class of medication commonly used to treat osteoporosis. Alendronate is recommended as the first-line treatment; however, long-term adherence (both...
BACKGROUND
Bisphosphonates are a class of medication commonly used to treat osteoporosis. Alendronate is recommended as the first-line treatment; however, long-term adherence (both treatment compliance and persistence) is poor. Alternative bisphosphonates are available, which can be given intravenously and have been shown to improve long-term adherence. However, the most clinically effective and cost-effective alternative bisphosphonate regimen remains unclear. What is the most cost-effective bisphosphonate in clinical trials may not be the most cost-effective or acceptable to patients in everyday clinical practice.
OBJECTIVES
1. Explore patient, clinician and stakeholder views, experiences and preferences of alendronate compared to alternative bisphosphonates. 2. Update and refine the 2016 systematic review and cost-effectiveness analysis of bisphosphonates, and estimate the value of further research into their benefits. 3. Undertake stakeholder/consensus engagement to identify important research questions and further rank research priorities.
METHODS
The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: • Stage 1A - we elicited patient and healthcare experiences to understand their preferences of bisphosphonates for the treatment of osteoporosis. This was undertaken by performing a systematic review and framework synthesis of qualitative studies, followed by semistructured qualitative interviews with participants. • Stage 1B - we updated and expanded the existing Health Technology Assessment systematic review and clinical and cost-effectiveness model, incorporating a more comprehensive review of treatment efficacy, safety, side effects, compliance and long-term persistence. • Stage 2 - we identified and ranked further research questions that need to be answered about the effectiveness and acceptability of bisphosphonates.
RESULTS
Patients and healthcare professionals identified a number of challenges in adhering to bisphosphonate medication, balancing the potential for long-term risk reduction against the work involved in adhering to oral alendronate. Intravenous zoledronate treatment was generally more acceptable, with such regimens perceived to be more straightforward to engage in, although a portion of patients taking alendronate were satisfied with their current treatment. Intravenous zoledronate was found to be the most effective, with higher adherence rates compared to the other bisphosphonates, for reducing the risk of fragility fracture. However, oral bisphosphonates are more cost-effective than intravenous zoledronate due to the high cost of zoledronate administration in hospital. The importance of including patients and healthcare professionals when setting research priorities is recognised. Important areas for research were related to patient factors influencing treatment selection and effectiveness, how to optimise long-term care and the cost-effectiveness of delivering zoledronate in an alternative, non-hospital setting.
CONCLUSIONS
Intravenous zoledronate treatment was generally more acceptable to patients and found to be the most effective bisphosphonate and with greater adherence; however, the cost-effectiveness relative to oral alendronate is limited by its higher zoledronate hospital administration costs.
FUTURE WORK
Further research is needed to support people to make decisions influencing treatment selection, effectiveness and optimal long-term care, together with the clinical and cost-effectiveness of intravenous zoledronate administered in a non-hospital (community) setting.
LIMITATIONS
Lack of clarity and limitations in the many studies included in the systematic review may have under-interpreted some of the findings relating to effects of bisphosphonates.
TRIAL REGISTRATION
This trial is registered as ISRCTN10491361.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127550) and is published in full in ; Vol. 28, No. 21. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Diphosphonates; Alendronate; Zoledronic Acid; Osteoporotic Fractures; Osteoporosis
PubMed: 38634483
DOI: 10.3310/WYPF0472 -
Frontiers in Pharmacology 2024Several medications have been used for glucocorticoids-induced osteoporosis (GIO). However, the best therapeutic option for GIO is still controversial. A Bayesian...
Several medications have been used for glucocorticoids-induced osteoporosis (GIO). However, the best therapeutic option for GIO is still controversial. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of denosumab, teriparatide and bisphosphonates for patients with GIO. Relevant randomized controlled trials published in PubMed, Embase, Cochrane Library and ClinicalTrials.gov up to August 2023 were searched. The following efficiency and safety outcomes were extracted for comparison: bone mineral density (BMD) percentage changes in lumbar spine, femur neck and total hip, and incidences of adverse events (AEs), serious adverse events (SAEs), vertebrae and non-vertebrae fracture. Bayesian random effects models were used for multiple treatment comparisons. 11 eligible RCTs involving 2,877 patients were identified. All the six medications including alendronate, risedronate, etidronate, zoledronate, teriparatide, and denosumab and were effective in increasing BMD. Teriparatide and denosumab were more effective in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. Alendronate and denosumab were more effective in improving total hip BMD. Alendronate and teriparatide had the lowest incidences of AEs and SAEs. Teriparatide denosumab and the bisphosphonates are all effective in improving BMD for GIO patients. Based on this network meta-analysis, teriparatide and denosumab have higher efficiency in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. 10.17605/OSF.IO/2G8YA, identifier CRD42023456305.
PubMed: 38313307
DOI: 10.3389/fphar.2024.1336075 -
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 -
International Journal of Clinical... Apr 2024Ibandronate is effective in reducing the risk of vertebral fractures, but experimental evidence offers conflicting results regarding nonvertebral fractures. Real-world... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ibandronate is effective in reducing the risk of vertebral fractures, but experimental evidence offers conflicting results regarding nonvertebral fractures. Real-world evidence has been published evaluating the anti-nonvertebral fracture effect of ibandronate.
AIM
This meta-analysis of observational studies assessed the effectiveness of ibandronate in reducing the risk of nonvertebral fractures in women with osteoporosis.
METHOD
Pubmed/Embase databases were searched for observational studies. Risks of nonvertebral fractures and hip fractures were the outcomes. Meta-analyses were performed pooling rate ratios (RRs), using random-effects models. Data were reanalysed in sensitivity analyses considering Knapp-Hartung method and Bayesian random-effects.
RESULTS
Six cohort studies were included. Overall, once-monthly 150 mg oral ibandronate reduced the risk of nonvertebral fractures (RR 0.84; 95% CI 0.76-0.94). Similar results were obtained when the comparison was restricted to once-monthly 150 mg risedronate, but no differences were found when the comparator was other oral bisphosphonates (weekly alendronate/risedronate). Ibandronate didn't significantly change the risk of hip fractures (RR 1.25; 95% CI 0.89-1.76). The risk of hip fracture was comparable between once monthly, 150 mg oral ibandronate and other oral bisphosphonates. Intravenous ibandronate was not effective in reducing hip fractures comparing to intravenous zoledronate. The low number of studies diminished the robustness of sensitivity analyses.
CONCLUSION
Results suggest that once-monthly 150 mg oral ibandronate may be as effective as other oral bisphosphonates in reducing the risk of nonvertebral fractures. However, uncertainty associated to the small number of included studies, which are characterized by heterogeneous demographics and methodologies, precluded definitive conclusions.
Topics: Female; Humans; Ibandronic Acid; Risedronic Acid; Bone Density Conservation Agents; Diphosphonates; Bayes Theorem; Osteoporosis; Hip Fractures; Osteoporosis, Postmenopausal; Observational Studies as Topic
PubMed: 38112890
DOI: 10.1007/s11096-023-01666-x -
Journal of Pharmacy & Bioallied Sciences Jul 2023Class II mandibular furcation defect is a periodontal condition characterized by a cul-de-sac lesion, a definite parallel constituent with only a portion of alveolar...
Class II mandibular furcation defect is a periodontal condition characterized by a cul-de-sac lesion, a definite parallel constituent with only a portion of alveolar bone remaining intact. There may be involvement of vertical bone loss. Local drug deliveries such as Boric acid, alendronate gel, and other drugs exhibited anti-inflammatory, antibacterial & osteoblastic differentiation activity. The present systematic review compares the drugs based on their outcomes and pharmacological action. To analzse & compare various forms of local drug delivery systems on a class II furcation. A search was conducted using PubMed, Google scholar, science direct, and Pub Med central using MeSH terms - local drug delivery in periodontics, boric acid in the management of class II mandibular furcation, simvastatin in the treatment of furcation. A total of 560 articles were screened; 58 out of 560 were full-text articles accessed for eligibility, and five articles were included in the systematic review. PRISMA guidelines were used for reporting this review. In addition, five randomized controlled trials were enclosed and used in this systematic review. The various local drugs used in treating class II mandibular furcation defects are effective in the prevention of bleeding on probing, bone resorption, gingival bleeding index and increase in the bone fill, and microbial deposit removal. The managing of class II mandibular furcation defect with the drugs mentioned in this review can be effective by reducing several clinical parameters such as bleeding on probing, gingival indices, osteoblastic differentiation, bone fill, etc., Considering the results of the studies, it can be concluded that it can be used as a therapeutic therapy against class II furcation defects with positive outcomes.
PubMed: 37654351
DOI: 10.4103/jpbs.jpbs_572_22 -
Journal of Pharmacy & Bioallied Sciences Jul 2023The chief aim in managing periodontal diseases is the elimination of causative factors that may vary from pathogens to physical parameters. In the current systematic...
INTRODUCTION
The chief aim in managing periodontal diseases is the elimination of causative factors that may vary from pathogens to physical parameters. In the current systematic review, the effectiveness of "" as a supplement to ")" in the management of periodontitis is calibrated from the previous studies.
MATERIALS AND METHODS
An extensive online search in the various databanks of EMBASE, Medline, Pubmed, and Scopus was conducted. The keywords searched were "Probing depth (PD)" which was the main endpoint, and variations in " (CAL)" and/or " (BD) fill" were the secondary variants that were searched for in the current study. The data collected were tabulated and compared using the means and the standard deviations. Using the random effect method the mean variations and the confidence intervals (95%) of the parameters were assessed.
RESULTS
Eight studies were finalized. Alendronate was utilized as a supplement to SRP in seven studies, four of which employed topical administration and three of which used oral alendronate. A substantial grade of heterogeneity for Probing depth ( < 0.0001), Clinical Attachment Level ( = 0.007), and Bone Defect fill ( < 0.0001) was observed amongst groups when comparing the properties of adjunctive BT to SRP alone. In comparison to SRP alone, SRP with bisphosphonate treatment significantly reduced PD ( = 0.002), increased CAL ( = 0.008), and filled BD ( < 0.001).
CONCLUSIONS
Although BT as an adjunct appears to be successful in treating periodontitis, its practical applicability is questionable due to the possibility of developing jaw osteonecrosis and the short-range follow-up of the research.
PubMed: 37654331
DOI: 10.4103/jpbs.jpbs_504_22 -
JBMR Plus Jun 2023Most women do not qualify for pharmacologic osteoporosis treatment until more than a decade after menopause, by which time they will have lost up to 30% of their bone...
Most women do not qualify for pharmacologic osteoporosis treatment until more than a decade after menopause, by which time they will have lost up to 30% of their bone mass and may have already sustained fractures. Short or intermittent courses of bisphosphonate therapy, initiated around the time of menopause, might prevent excessive bone loss and lower long-term fracture risk. We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effects of nitrogen-containing bisphosphonates on fracture incidence, bone mineral density (BMD), and bone turnover markers in early menopausal women (ie, perimenopausal or <5 years postmenopausal) over ≥12 months. Medline, Embase, CENTRAL, and CINAHL were searched in July 2022. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Random effect meta-analysis was undertaken using RevMan v5.3. In total, 12 trials were included ( = 1722 women); five evaluated alendronate, three risedronate, three ibandronate, and one zoledronate. Four were at low risk of bias; eight raised some concerns. Fractures were infrequent in the three studies that reported them. Compared with placebo, bisphosphonates improved BMD over 12 months (mean percentage difference, 95% confidence interval [CI]) at the spine (4.32%, 95% CI, 3.10%-5.54%, < 0.0001, = 8 studies), the femoral neck (2.56%, 95% CI, 1.85%-3.27%, = 0.001, = 6 studies), and the total hip (1.22%, 95% CI 0.16%-2.28%, = 0.002, = 4 studies). Over treatment durations of 24 to 72 months, bisphosphonates improved BMD at the spine (5.81%, 95% CI 4.71%-6.91%, < 0.0001, = 8 studies), femoral neck (3.89%, 95% CI 2.73%-5.05%, = 0.0001, = 5 studies) and total hip (4.09%, 95% CI 2.81%-5.37%, < 0.0001, = 4 studies). Bisphosphonates reduced urinary N-telopeptide (-52.2%, 95% CI -60.3% to -44.2%, < 0.00001, = 3 studies) and bone-specific alkaline phosphatase (-34.2%, 95% CI -42.6% to -25.8%, < 0.00001, = 4 studies) more than placebo at 12 months. This systematic review and meta-analysis shows that bisphosphonates improve BMD and lower bone turnover markers in early menopause, warranting further investigation of these agents for osteoporosis prevention. © 2023 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PubMed: 37283657
DOI: 10.1002/jbm4.10748 -
Sao Paulo Medical Journal = Revista... 2023Osteoporosis compromises bone strength and increases the risk of fractures. Zoledronate prevents loss of bone mass and reduces the risk of fractures. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osteoporosis compromises bone strength and increases the risk of fractures. Zoledronate prevents loss of bone mass and reduces the risk of fractures.
OBJECTIVES
To determine the efficacy and safety of zoledronate in postmenopausal women with osteopenia and osteoporosis.
DESIGN AND SETTINGS
A systematic review and meta-analysis was conducted within the evidence-based health program at the Universidade Federal de São Paulo.
METHODS
An electronic search of the CENTRAL, MEDLINE, Embase, and LILACS databases was performed until February 2022. Randomized controlled trials comparing zoledronate with placebo or other bisphosphonates were included. Standard methodological procedures were performed according to the Cochrane Handbook and the certainty of evidence for the Grading of Recommendations Assessment, Development, and Evaluation Working Group. Two authors assessed the risk of bias and extracted data on fractures, adverse events, bone turnover markers (BTM), and bone mineral density (BMD).
RESULTS
Twelve trials from 6,652 records were included: nine compared zoledronate with placebo, two trials compared zoledronate with alendronate, and one trial compared zoledronate with ibandronate. Zoledronate reduced the incidence of fractures in osteoporotic [three years: morphometric vertebral fractures (relative risk, RR = 0.30 (95% confidence interval, CI: 0.24-0.38))] and osteopenic women [six years: morphometric vertebral fractures (RR = 0.39 (95%CI: 0.25-0.61))], increased incidence of post-dose symptoms [RR = 2.56 (95%CI: 1.80-3.65)], but not serious adverse events [RR = 0.97 (95%CI: 0.91-1.04)]. Zoledronate reduced BTM and increased BMD in osteoporotic and osteopenic women.
CONCLUSION
This review supports the efficacy and safety of zoledronate in postmenopausal women with osteopenia for six years and osteoporosis for three years.
PROSPERO REGISTRATION NUMBER
CRD42022309708, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=309708.
Topics: Female; Humans; Zoledronic Acid; Bone Density Conservation Agents; Postmenopause; Brazil; Osteoporosis; Fractures, Bone; Bone Density; Osteoporosis, Postmenopausal
PubMed: 37255065
DOI: 10.1590/1516-3180.2022.0480.R1.27032023