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The Cochrane Database of Systematic... Apr 2024Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs... (Review)
Review
BACKGROUND
Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high).
OBJECTIVES
To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively.
SEARCH METHODS
We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023.
SELECTION CRITERIA
We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study.
MAIN RESULTS
Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies.
AUTHORS' CONCLUSIONS
This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention.
Topics: Humans; Female; Osteoporotic Fractures; Etidronic Acid; Wrist Fractures; Secondary Prevention; Calcium; Postmenopause; Osteoporosis; Spinal Fractures; Hip Fractures; Vitamin D; Wrist Injuries
PubMed: 38591743
DOI: 10.1002/14651858.CD003376.pub4 -
Global Spine Journal Jun 2024Systematic review and meta-analysis. (Review)
Review
Mechanical Vertebral Body Augmentation Versus Conventional Balloon Kyphoplasty for Osteoporotic Thoracolumbar Compression Fractures: A Systematic Review and Meta-Analysis of Outcomes.
STUDY DESIGN
Systematic review and meta-analysis.
OBJECTIVE
Surgical management of osteoporotic vertebral compression fractures (OVCFs) has traditionally consisted of vertebroplasty or kyphoplasty procedures. Mechanical percutaneous vertebral body augmentation (MPVA) systems have recently been introduced as alternatives to traditional methods. However, the effectiveness of MPVA systems vs conventional augmentation techniques for OVCFs remains unclear. This serves as the premise for this study.
METHODS
A systematic review and meta-analysis was conducted as per the guidelines. Studies of interest included randomized controlled trials (RCTs) which directly compared patient outcomes following kyphoplasty to patients treated with MPVA systems. Clinical and radiological findings were collated and compared for significance between cohorts.
RESULTS
6 RCTs were identified with 1024 patients total. The mean age of all patients was 73.5 years. 17% of the cohort were male, 83% were female. 515 patients underwent kyphoplasty and 509 underwent mechanical vertebral body augmentation using MPVA systems. MPVAs showed similar efficacy for restoration of vertebral body height ( = .18), total complications ( = .36), cement extravasation ( = .58) and device-related complications ( = .06). MPVAs also showed reduced rates of all new fractures (16.4% vs 22.2%; = .17) and adjacent fractures (14.7% vs 18.9%; = .23), with improved visual analogue scale (VAS) scores at 6-month ( = .13).
CONCLUSION
The results of this meta-analysis highlight no significant improvement in clinical or radiological outcomes for MPVA systems when compared to balloon kyphoplasty for vertebral body augmentation. Further research is needed to establish a true benefit over traditional operative methods.
PubMed: 38889443
DOI: 10.1177/21925682241261988 -
The Journal of Nutrition, Health & Aging Apr 2024Stroke survivors frequently encounter physical complications. This study aimed to evaluate the impact of stroke on bone mineral density (BMD) and assess the risk of... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Stroke survivors frequently encounter physical complications. This study aimed to evaluate the impact of stroke on bone mineral density (BMD) and assess the risk of post-stroke osteoporosis or osteoporotic fractures.
DESIGN
Systematic review and meta-analysis.
SETTING AND PARTICIPANTS
We systematically searched Medline, Embase, and the Cochrane Database of Systematic Reviews to identify longitudinal studies reporting the influence of stroke on BMD, osteoporosis, and osteoporotic fractures. Pooled analyses were performed utilizing random-effects models.
RESULTS
This study included 21 studies with 1,029,742 participants. The mean difference of BMD in the paretic femoral neck between follow-up and initial measurements was -0.07 g/cm (95% CI, -0.09 to -0.04), and -0.03 g/cm (95% CI, -0.05 to -0.01) in the non-paretic femoral neck. A follow-up length exceeding six months was associated with a more pronounced decrease compared to a follow-up of under six months (MD, -0.08; 95% CI, -0.11 to -0.05 vs MD, -0.04; 95% CI, -0.06 to -0.02; P = 0.03). No significant change in lumbar spine BMD was detected post-stroke (MD, -0.00; 95% CI, -0.03 to 0.02), nor was significant change observed in the non-paretic distal radius, proximal humerus, tibia, trochanter, and total hip. Stroke was not associated with an increased risk of osteoporosis or osteoporotic fractures (HR, 1.43; 95% CI, 0.95-2.13).
CONCLUSION
Stroke survivors undergo significant BMD loss in paralyzed limbs, most notably in the femoral neck. However, BMD in the lumbar spine does not exhibit a significant decrease post-stroke. The risk of post-stroke osteoporosis or osteoporotic fractures should be interpreted with caution and needs further investigation.
Topics: Humans; Bone Density; Stroke; Osteoporosis; Osteoporotic Fractures; Femur Neck; Female; Male; Aged
PubMed: 38350301
DOI: 10.1016/j.jnha.2024.100189 -
Bone Reports Jun 2024Bone loss is a well-known phenomenon in the older population leading to increased bone fracture risk, morbidity, and mortality. Supplementation of eggshell membrane... (Review)
Review
Bone loss is a well-known phenomenon in the older population leading to increased bone fracture risk, morbidity, and mortality. Supplementation of eggshell membrane (ESM) is evaluated due to its possible application to prevent bone loss and usage in osteoporosis therapy. The similar organic chemical composition of ESM and human bone is described in detail as both mainly consist of collagen type I, chondroitin sulfate, dermatan sulfate, hyaluronic acid and elastan. ESM and its components are reported to improve mineralization in bone tissue. In many studies ESM intake reduced pain in patients with joint disorders and reduced inflammatory processes. Additionally, ESM improved calcium uptake in human cells. These findings in comparison with a clinical pilot study reporting pain reduction in osteoporotic patients and increased osteoblast activity in in vitro assays support ESM to be a beneficial supplement for bone health. In this systematic review we combined chemical structure analysis with clinical studies to give a more comprehensive picture with novel explanations.
PubMed: 38872992
DOI: 10.1016/j.bonr.2024.101776 -
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 -
World Neurosurgery Jan 2024Percutaneous curved vertebroplasty (PCVP), a modified traditional unilateral percutaneous vertebroplasty (UPVP) technique, is increasingly being used to treat... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Percutaneous curved vertebroplasty (PCVP), a modified traditional unilateral percutaneous vertebroplasty (UPVP) technique, is increasingly being used to treat osteoporotic vertebral compression fractures (OVCFs); however, its advantages remain controversial. This meta-analysis was conducted to determine whether PCVP is superior to traditional UPVP in treating OVCFs.
METHODS
Six databases were searched for studies comparing the clinical efficacy of PCVP and UPVP in treating patients with OVCFs published until March 2023. After study selection, data extraction, and risk of bias evaluation, a meta-analysis was conducted. The study protocol was registered in the PROSPERO platform (registration number: CRD42023417190).
RESULTS
Eight studies (6 randomized controlled trials and 2 cohort studies) were eligible for the final analysis. The pooled results revealed no between-group differences in operation time (P = 0.85), intraoperative fluoroscopy (P = 0.58), or postoperative short-term visual analog scale scores (P = 0.15). However, PCVP was associated with more injected cement (P = 0.003), a lower cement leakage rate (P = 0.006), and a lower final follow-up visual analog scale score (P < 0.0001).
CONCLUSIONS
PCVP was superior to UPVP in terms of reducing the bone cement leakage rate and providing long-term pain relief. Further trials with larger sample sizes and longer follow-up periods are required to verify these findings owing to the potential risk of bias.
Topics: Humans; Spinal Fractures; Fractures, Compression; Vertebroplasty; Spine; Kyphoplasty; Bone Cements; Treatment Outcome; Osteoporotic Fractures; Retrospective Studies
PubMed: 37839572
DOI: 10.1016/j.wneu.2023.10.035 -
European Journal of Orthopaedic Surgery... Dec 2023Distal femoral fractures account for 4-6% of fragility fractures. These may be managed using a combined nail-plate construct (NPC). The use of NPCs is gaining traction.... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Distal femoral fractures account for 4-6% of fragility fractures. These may be managed using a combined nail-plate construct (NPC). The use of NPCs is gaining traction. Whilst several theoretical advantages exist, there is little evidence reporting on binary or patient-reported outcomes. The aim of the current study was to perform a systematic review of the available literature pertaining to NPCs and their treatment of native distal femoral fractures, appraising the outcomes and focusing on the rationale for their increasing uptake in recent literature.
METHODS
A comprehensive search of MEDLINE, EMBASE, Clinical Key, PubMed and Cochrane library was performed from date of inception up to in August 9, 2022. All study languages were included initially. A further Google Scholar search review was performed to identify any other studies not identified in the database interrogation. Studies were eligible if they reported on the use of nail-plate constructs in managing distal femoral fractures. Any outcome metric was permitted. The study was conducted in accordance with PRISMA guidelines. Risk of bias was assessed using the Methodological Index for non-randomised Studies tool. Quantitative analysis was performed using a log odds ratio random effects model. The Knapp-Hartung adjustment was utilised if the total number of included studies was < 5. Study effect sizes and appropriate plots were constructed to illustrate the outcomes data.
RESULTS
A total of four studies were eligible for inclusion. Study data was extracted and summarised with their relevant outcomes presented. The literature review demonstrated that the use of NPCs led to significantly earlier full weight bearing (p < 0.001) and had reduced non-union rates over a single construct, without affecting infection rates (12.5% vs. 5.6%; p = 0.289) and significantly lower implant failure rates (10.5% vs. 0%; p = 0.011). A meta-analysis is performed of available studies and Forrest plots presented.
CONCLUSION
The use of NPC in the management of native osteoporotic DFFs is gaining traction but the available evidence is of low grade with significant heterogeneity in small cohorts of patients. We suggest that a large-scale, multicentre prospective study should be performed, with agreed functional and radiological outcome metrics, to provide a more robust evidence base.
Topics: Humans; Femoral Fractures, Distal; Femoral Fractures; Prospective Studies; Fracture Fixation, Internal; Fracture Fixation, Intramedullary
PubMed: 37106139
DOI: 10.1007/s00590-023-03552-8 -
Medicine Nov 2023To investigate the effect of Vertebral augmentation (VA) in the treatment of single-level osteoporotic vertebral compression fractures (OVCFs) on new vertebral fractures. (Meta-Analysis)
Meta-Analysis
The risk of new vertebral fracture after percutaneous vertebral augmentation in patients suffering from single-level osteoporotic vertebral compression fractures: A meta-analysis and systematic review.
BACKGROUND
To investigate the effect of Vertebral augmentation (VA) in the treatment of single-level osteoporotic vertebral compression fractures (OVCFs) on new vertebral fractures.
METHODS
Electronic databases Pubmed, Embase, and the Cochrane Central Register of Controlled Trials were searched from database creation to 5 September 2022. Eligible studies had to use VA as an intervention and conservative treatment as a control group. Studies had to explicitly report whether new vertebral fractures occurred during follow-up. Data were extracted by multiple investigators. Data were pooled using random or fixed effects models depending on the degree of heterogeneity.
RESULTS
Of the 682 articles screened, 7 met the inclusion criteria and were included in the analysis, giving a total of 1240 patients. Meta-analysis showed that VA (OR = 2.10, 95% CI: 1.35-3.28, P = .001) increased the risk of new postoperative vertebral fractures compared with conservative treatment. Subgroup analyses showed that the risk was greater in the group with a follow-up time greater than 1 year (OR = 2.57, 95% CI: 1.06-6.26, P = .001). Compared with conservative treatment, VA (OR = 2.17, 95% CI: 1.23-3.82, P = .007) increased the risk of postoperative adjacent vertebral fracture.
CONCLUSION SUBSECTIONS
VA is associated with an increased risk of new vertebral fractures and adjacent vertebral fractures following single-level OVCFs. With longer follow-ups, new vertebral fractures may be more significant. Clinical surgeons should pay attention to long-term postoperative complications and choose treatment carefully.
Topics: Humans; Spinal Fractures; Fractures, Compression; Kyphoplasty; Vertebroplasty; Osteoporotic Fractures; Treatment Outcome
PubMed: 37986316
DOI: 10.1097/MD.0000000000035749 -
Zeitschrift Fur Orthopadie Und... Dec 2023To summarize the literature and compare the advantages and disadvantages of the unilateral transverse process-pedicle approach (UTPA) and conventional transpedicular... (Meta-Analysis)
Meta-Analysis
PURPOSE
To summarize the literature and compare the advantages and disadvantages of the unilateral transverse process-pedicle approach (UTPA) and conventional transpedicular approach (CTPA) vertebral augmentation in the treatment of osteoporotic vertebral compression fractures (OVCF).
METHODS
A single researcher performed a systematic literature review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Online scientific databases were searched in September 2021 for English- and Chinese-language publications. A series of comparative studies were included, with UTPA as the main intervention and CTPA as the comparison indicator. A meta-analysis was performed for studies that reported clinical outcome indicators. The χ was used to study heterogeneity between trials, and the I statistic was calculated to estimate variation across studies.
RESULTS
A total of eight studies were included for meta-analysis, all of which were observational studies with mixed bias risk. There were 613 subjects in the UTPA group and 488 subjects in the CTPA group. The results of the meta-analysis showed that there was no difference between the UTPA group and the CTPA group in terms of visual analogue scale scores (p = 0.31), Oswestry Disability Index scores (p = 0.50), correction of kyphosis angle (p = 0.65), and the amount of bone cement (p = 0.13), but the UTPA group had a shorter operative time (p < 0.001), bone cement leakage rates (p = 0.02), and fluoroscopy times than the CTPA group (p < 0.001). Partial analysis results had a high risk of bias, and the most common source of bias was that there was high heterogeneity between studies, and the sensitivity can only be reduced by a random effect model, and some studies (four items) did not clearly describe the confounders that they controlled.
CONCLUSION
The limited evidence obtained in this study proves that the new puncture method does not have more advantages than the traditional technique, so it is no longer meaningful to continue to obsess over the impact of the puncture method on surgical outcome.
Topics: Humans; Kyphoplasty; Spinal Fractures; Fractures, Compression; Bone Cements; Spine; Vertebroplasty; Osteoporotic Fractures; Treatment Outcome; Retrospective Studies
PubMed: 35378564
DOI: 10.1055/a-1785-5698 -
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