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Diabetes, Obesity & Metabolism Jun 2024To evaluate the impact of denosumab on (i) the incidence of type 2 diabetes (T2D), and (ii) long-term health outcomes (microvascular [neuropathy, retinopathy,...
Denosumab, for osteoporosis, reduces the incidence of type 2 diabetes, risk of foot ulceration and all-cause mortality in adults, compared with bisphosphonates: An analysis of real-world, cohort data, with a systematic review and meta-analysis.
AIM
To evaluate the impact of denosumab on (i) the incidence of type 2 diabetes (T2D), and (ii) long-term health outcomes (microvascular [neuropathy, retinopathy, nephropathy] and macrovascular [cardiovascular disease, cerebrovascular accident] complications, and all-cause mortality) in patients with T2D, before (iii) combining results with prior studies using meta-analysis.
METHODS
A retrospective analysis of data in a large global federated database (TriNetX; Cambridge, MA) was conducted from 331 375 patients, without baseline T2D or cancer, prescribed either denosumab (treatment, n = 45 854) or bisphosphonates (control, n = 285 521), across 83 healthcare organizations. Propensity score matching (1:1) of confounders was undertaken that resulted in 45 851 in each cohort. Secondary analysis further evaluated the impact of denosumab on long-term health outcomes in patients with T2D. Additionally, we systematically searched prior literature that assessed the association between denosumab and T2D. Estimates were pooled using random-effects meta-analysis. Risk of bias and evidence quality were assessed using Cochrane-endorsed tools.
RESULTS
Denosumab (vs. bisphosphonates) was associated with a lower risk of incident T2D over 5 years (hazard ratio 0.83 [95% confidence interval {CI} 0.78-0.88]). Secondary analysis showed significant risk reduction in all-cause mortality (0.79 [0.72-0.87]) and foot ulceration (0.67 [0.53-0.86]). Also, pooled results from four studies (three observational, one randomized controlled trial) following meta-analysis showed a reduced relative risk (RR [95% CI]) for incident T2D in patients prescribed denosumab (0.83 [0.79-0.87]) (I = 10.76%).
CONCLUSIONS
This is the largest cohort study to show that denosumab treatment is associated with a reduced RR of incident T2D, as well as an associated reduced RR of all-cause mortality and microvascular complications, findings that may influence guideline development in the treatment of osteoporosis, particularly in patients who are at a high risk of T2D.
PubMed: 38899553
DOI: 10.1111/dom.15708 -
European Journal of Orthopaedic Surgery... Jun 2024Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with cancer, such as melanoma, renal cell carcinoma, head and neck cancer, non-small cell... (Review)
Review
PURPOSE
Immune checkpoint inhibitors (ICIs) have improved the prognosis of patients with cancer, such as melanoma, renal cell carcinoma, head and neck cancer, non-small cell lung cancer (NSCLC), and urothelial carcinoma. The extension of life expectancy has led to an increased incidence of bone metastases (BM) among patients with cancer. BM result in skeletal-related events, including severe pain, pathological fractures, and nerve palsy. Surgery is typically required for the treatment of BM in patients with an impending fracture; however, it may be avoided in those who respond to ICIs. We systematically reviewed studies analyzing BM responses to treatment with ICIs.
METHODS
This study was conducted in accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 statement and registered in the UMIN Clinical Trials Registry (ID: UMIN000053707). Studies reporting response rates based on the Response Evaluation Criteria in Solid Tumors (RECIST) or the MD Anderson Cancer Center (MDA) criteria specific for BM in patients treated with ICIs were included; reports of fewer than five cases and review articles were excluded. Studies involving humans, published in English and Japanese, were searched. The PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Ultimately, nine studies were analyzed. The Risk of Bias Assessment tool for Non-randomized Studies was used to assess the quality of studies.
RESULTS
Based on the MDA criteria, complete response (CR) or partial response (PR) was observed in 44-78% and 62% patients treated with ICIs plus denosumab for NSCLC and melanoma, respectively. According to the RECIST, CR or PR was recorded in 5% and 7-28% of patients treated with ICIs for renal cell carcinoma and urothelial carcinoma, respectively.
CONCLUSION
Although response rates to ICIs for BM are poor, patients treated with ICI plus denosumab for bone metastases with impending fractures from NSCLC and melanoma are likely to avoid surgery to prevent fractures.
PubMed: 38836904
DOI: 10.1007/s00590-024-04018-1 -
Journal of Clinical Medicine Apr 2024This systematic review aimed to evaluate the impact of antiresorptive drug therapy on osseointegrated dental implants and the association with medication-related... (Review)
Review
This systematic review aimed to evaluate the impact of antiresorptive drug therapy on osseointegrated dental implants and the association with medication-related osteonecrosis of the jaw (MRONJ). A systematic search, including a computer search of several databases with specific keywords, a reference search, and a manual search of four key maxillofacial journals were performed. Relevant articles were then evaluated and those that fulfilled the five predetermined criteria were chosen to enter the final review. A total of 445 implants in 135 subjects were included in the eight studies analyzed in the final review. The failure rate of dental implants after antiresorptive medication in the included studies was 23%, with 83% of failures attributed to MRONJ. The average time from antiresorptive drug initiation to MRONJ development was approximately 34 months, ranging from 3 months to 16 years. The majority of MRONJ cases were classified as stage 2, and all sites showed either complete healing or substantial mucosal coverage after treatment. This review highlights the significant impact of antiresorptive drugs on osseo- integrated implants, with MRONJ identified as a leading cause of implant failure. The potential role of peri-implantitis as a trigger for MRONJ is emphasized. Regular monitoring and maintaining good periodontal health, especially within the first three years of antiresorptive drug therapy initiation, are crucial for implant success. Physicians and dentists should provide comprehensive information to patients prescribed with antiresorptive drugs, emphasizing the need for an awareness of the risks of MRONJ in the context of osseointegrated implants. A longer term of follow-up is recommended to identify and manage MRONJ around dental implants in an early manner.
PubMed: 38610856
DOI: 10.3390/jcm13072091 -
Osteoporosis International : a Journal... Jul 2024To determine and appraise the certainty of fracture liaison service (FLS) in reducing the risk of secondary fragility fractures in older adults aged ≥ 50 years... (Meta-Analysis)
Meta-Analysis Review
To determine and appraise the certainty of fracture liaison service (FLS) in reducing the risk of secondary fragility fractures in older adults aged ≥ 50 years and to examine the nature of the FLS and the roles of various disciplines involved in the delivery of the FLS. Medline, EMBASE, PubMed, CINAHL, SCOPUS, and The Cochrane Library were searched from January 1st, 2010, to May 31st, 2022. Two reviewers independently extracted data. The risk of bias was evaluated using the Newcastle-Ottawa Scale for cohort studies and the PEDro scale for randomized trials, while the GRADE approach established the certainty of the evidence. Thirty-seven studies were identified of which 34 (91.9%) were rated as having a low risk of bias and 22 (59.5%) were meta-analyzed. Clinically important low certainty evidence at 1 year (RR 0.26, CI 0.13 to 0.52, 6 pooled studies) and moderate certainty evidence at ≥ 2 years (RR 0.68, CI 0.55 to 0.83, 13 pooled studies) indicate that the risk of secondary fragility fracture was lower in the FLS intervention compared to the non-FLS intervention. Sensitivity analyses with no observed heterogeneity confirmed these findings. This review found clinically important moderate certainty evidence showing that the risk of secondary fragility fracture was lower in the FLS intervention at ≥ 2 years. More high-quality studies in this field could improve the certainty of the evidence. Review registration: PROSPERO-CRD42021266408.
Topics: Humans; Osteoporotic Fractures; Aged; Secondary Prevention; Middle Aged; Osteoporosis
PubMed: 38536447
DOI: 10.1007/s00198-024-07052-1 -
Journal of Orthopaedic Science :... Feb 2024Periprosthetic bone loss following total hip arthroplasty (THA) threatens prosthesis stability. This systematic review and network meta-analysis aimed to compare the...
BACKGROUND
Periprosthetic bone loss following total hip arthroplasty (THA) threatens prosthesis stability. This systematic review and network meta-analysis aimed to compare the efficacy of anti-osteoporotic drugs for measures of hip function according to functional outcomes, periprosthetic femoral bone mineral density loss in each Gruen zone, and revision surgery after THA.
METHODS
The systematic search of six literature databases was conducted in December 2021 in accordance with PRISMA guidelines. Adult participants who underwent primary THA were included. A random-effects network meta-analysis was performed within a frequentist framework, and the confidence in the evidence for each outcome was evaluated using the CINeMA tool, which assessed the credibility of results from the network meta-analysis. We included 22 randomized controlled trials (1243 participants) comparing the efficacy and safety of bisphosphonates (including etidronate, clodronate, alendronate, risedronate, pamidronate, and zoledronate), denosumab, selective estrogen receptor modulator, teriparatide, calcium + vitamin D, calcium, and vitamin D. We defined the period for revision surgery as the final follow-up period.
RESULTS
Raloxifene, bisphosphonate, calcium + vitamin D, and denosumab for prosthetic hip function might have minimal differences when compared with placebos. The magnitude of the anti-osteoporotic drug effect on periprosthetic femoral bone loss varied across different Gruen zones. Bisphosphonate, denosumab, teriparatide might be more effective than placebo in Gruen zone 1 at 12 months after THA. Additionally, bisphosphonate might be more effective than placebo in Gruen zones 2, 5, 6, and 7 at 12 months after THA. Denosumab was efficacious in preventing bone loss in Gruen zones 6 and 7 at 12 months after THA. Teriparatide was likely to be efficacious in preventing bone loss in Gruen zone 7 at 12 months after THA. Raloxifene was slightly efficacious in preventing bone loss in Gruen zones 2 and 3 at 12 months after THA. Calcium was slightly efficacious in preventing bone loss in Gruen zone 5 at 12 months after THA. None of the studies reported revision surgery.
CONCLUSIONS
Bisphosphonate and denosumab may be effective anti-osteoporotic drugs for preventing periprosthetic proximal femoral bone loss due to stress shielding after THA, particularly in cementless proximal fixation stems, which are the most commonly used prostheses worldwide.
PubMed: 38342711
DOI: 10.1016/j.jos.2024.01.011 -
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 -
Journal of Oral & Maxillofacial Research 2023The objective of this systematic review is to evaluate the current knowledge on the effectiveness of conservative and surgical treatment of medication-related... (Review)
Review
OBJECTIVES
The objective of this systematic review is to evaluate the current knowledge on the effectiveness of conservative and surgical treatment of medication-related osteonecrosis of the jaw.
MATERIAL AND METHODS
MEDLINE (PubMed), ScienceDirect and Cochrane Library search in combination with hand-search of relevant journals was conducted including human studies published in English between January 2017 and February 2023. Studies assessing treatment strategies for medication-related osteonecrosis of the jaw (MRONJ) were included. Quality and risk-of-bias assessment were evaluated by Joanna Briggs Institute (JBI) Risk of Bias tool.
RESULTS
A total of 4227 articles were screened from which 9 studies (7 cohort studies and 2 randomized controlled trials) met the inclusion criteria and were included in the final data synthesis. Two studies evaluate effectiveness of conservative approaches for treating MRONJ, 5 studies evaluate surgical approaches effectiveness, and 2 studies compare between those approaches. The follow-up period ranged from 6 months to 60 months. According to bias assessment, the mean JDI score of the included studies was > 9 ("low risk of bias"). The stage of the disease, the procedure performed on the patient and the results of the treatment were presented.
CONCLUSIONS
Surgical therapy seems to be superior to conservative therapy for the management of adverse stages medication-related osteonecrosis of the jaws, while conservative treatment appears to yield good outcomes at asymptomatic patients with early stages of the disease.
PubMed: 38222882
DOI: 10.5037/jomr.2023.14401 -
Annals of Geriatric Medicine and... Dec 2023
PubMed: 38185872
DOI: 10.4235/agmr.22.0139.r1 -
Maturitas Jan 2024Nocebo is a concept of therapeutics referring to unpleasant symptoms attributed by a patient to a drug, due to negative anticipation. Patients receiving oral... (Meta-Analysis)
Meta-Analysis Review
Nocebo-associated treatment discontinuation with subcutaneous anti-osteoporotic drugs. A systematic review and meta-analysis of placebo-arm dropouts in randomized-controlled trials.
OBJECTIVE
Nocebo is a concept of therapeutics referring to unpleasant symptoms attributed by a patient to a drug, due to negative anticipation. Patients receiving oral anti-osteoporotic drugs in randomized controlled trials (RCT) can experience adverse events leading to dropout, implying that nocebo contributes to treatment discontinuation for these drugs. In this study we aim to investigate the nocebo effect of subcutaneous anti-osteoporotic drugs with a higher compliance rate than orally administered drugs.
STUDY DESIGN
We searched MEDLINE, EMBASE, SCOPUS, and Cochrane databases for double-blind trials investigating subcutaneous anti-osteoporotic drugs for osteoporosis (namely, denosumab, teriparatide, abaloparatide and romosozumab) published up to May 2023.
MAIN OUTCOME MEASURE
Dropouts due to reported adverse events in the placebo arms ("nocebo dropouts").
RESULTS
Data from 17 trials were extracted. Among 10,529 placebo-treated patients the pooled nocebo-dropout percentage was 3 % for denosumab (average: 0.03; 95 % CI: 0.01-0.05), 1 % for romosozumab (average: 0.01; 95 % CI: 0.00-0.03) and 6 % for teriparatide and abaloparatide (average: 0.06; 95 % CI: 0.05-0.07). Nocebo-dropouts were significantly higher in men than women (6 % vs. 3 %, respectively, p = 0.012), in older (mean age >68 years) than in younger patients (5 % vs. 1 %, respectively, p = 0.017) and in those with more severe osteoporosis (based on the percentage of participants with prior fragility-related fractures in the study cohort) compared with patients with no prior fracture history (4 % vs. 1 %, respectively, p = 0.046).
CONCLUSION
Nocebo responses may contribute to treatment discontinuation with subcutaneous anti-osteoporotic drugs in clinical practice. Higher nocebo-related dropout rates in the higher-risk RCT population (older patients, males, those with prior fractures) show that nocebo mechanisms have the potential to hinder therapeutic efforts to specific populations who would benefit most. Prospero registration number CRD42020212843.
Topics: Male; Female; Humans; Aged; Teriparatide; Nocebo Effect; Denosumab; Osteoporosis; Fractures, Bone; Bone Density Conservation Agents; Randomized Controlled Trials as Topic
PubMed: 37976923
DOI: 10.1016/j.maturitas.2023.107874 -
Alternative Therapies in Health and... Nov 2023This meta-analysis aims to assess the clinical effectiveness of the combination therapy involving Teriparatide (TPTD) and Denosumab (DEN) in managing postmenopausal...
OBJECTIVE
This meta-analysis aims to assess the clinical effectiveness of the combination therapy involving Teriparatide (TPTD) and Denosumab (DEN) in managing postmenopausal osteoporosis (PMO). The findings provide valuable insights into clinical treatment decisions.
METHODS
We conducted a comprehensive search of PubMed, the Cochrane Library, Embase, and other relevant databases to gather literature concerning the treatment of PMO with TPTD and DEN. After a thorough screening, we selected and analyzed the final literature set. Information relevant to the study was extracted, and a quality assessment was carried out. The meta-analysis utilized RevMan 5.3 software to evaluate the impact of DEN combined with TPTD on parameters such as bone mineral density (BMD), tartrate-resistant acid phosphatase-5b (TRACP-5b), fracture incidence, and adverse reactions in PMO patients.
RESULTS
After the screening process, a total of 513 patients were studied across 8 studies. Among these, 259 patients received treatment involving DEN combined with TPTD (the research group), while 254 patients were subjected to different treatment regimens (the control group). As per the Cochrane Handbook's quality assessment, all included literature exhibited high overall quality. The meta-analysis demonstrated that the research group exhibited significantly higher BMD than the control group, lower TRACP-5b levels and fracture incidence (P < .05). However, the two groups had no evident difference in adverse reaction incidence (P > .05).
CONCLUSIONS
The combined treatment of DEN and TPTD exhibits notable efficacy in managing PMO, warranting its promotion and use in clinical practice.
PubMed: 37944971
DOI: No ID Found