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Calcified Tissue International Aug 2023Osteoporosis and hyperlipidemia are closely correlated and statins might be associated with a decreased risk of fracture. We aimed to investigate the association between... (Meta-Analysis)
Meta-Analysis
Osteoporosis and hyperlipidemia are closely correlated and statins might be associated with a decreased risk of fracture. We aimed to investigate the association between proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) therapy and the risk of fracture. The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to October 22, 2022. Randomized clinical trials (RCTs) that addressed to fracture events of participants using alirocumab, evolocumab, bococizumab or inclisiran, with a follow-up of ≥ 24 weeks were included. Meta-analyses were conducted to calculate the odds ratio (OR) with 95% confidence intervals (CIs) for major osteoporotic fracture, hip fracture, osteoporotic non-vertebral fracture, and total fracture. 30 trials assessing PCSK9i among 95, 911 adults were included. There were no significant associations between PCSK9i therapy and the risk of major osteoporotic fracture [OR 1.08 (95% Cl 0.87-1.34), p = 0.49], hip fracture [OR 1.05 (95% Cl 0.73-1.53), p = 0.79], osteoporotic non-vertebral fracture [OR 1.03 (95% Cl 0.80-1.32), p = 0.83], and total fracture [OR 1.03 (95% Cl 0.88-1.19), p = 0.74] over a period of 6-64 months. No significant associations were detected in any of the sensitivity analyses and subgroup analyses stratified by the type of PCSK9i, follow-up duration, age, sex, sample size, and patient profile. Pooled results of our meta-analysis showed that exposure to PCSK9i was not associated with reduced risks of fracture in the short term.
Topics: Adult; Humans; Osteoporotic Fractures; PCSK9 Inhibitors; Proprotein Convertases; Randomized Controlled Trials as Topic; Subtilisins
PubMed: 37099141
DOI: 10.1007/s00223-023-01085-0 -
Journal of Endocrinological... Nov 2023Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral...
PURPOSE
Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral density have been developed to better estimate fracture risk and possible treatment thresholds. This systematic review supported panel members of the Italian Fragility Fracture Guidelines in recommending the use of best-performant tool. The clinical performance of the three most used fracture risk assessment tools (DeFRA, FRAX, and FRA-HS) was assessed in at-risk patients.
METHODS
PubMed, Embase, and Cochrane Library were searched till December 2020 for studies investigating risk assessment tools for predicting major osteoporotic or hip fractures in patients with osteoporosis or fragility fractures. Sensitivity (Sn), specificity (Sp), and areas under the curve (AUCs) were evaluated for all tools at different thresholds. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2; certainty of evidence (CoE) was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach.
RESULTS
Forty-three articles were considered (40, 1, and 2 for FRAX, FRA-HS, and DeFRA, respectively), with the CoE ranging from very low to high quality. A reduction of Sn and increase of Sp for major osteoporotic fractures were observed among women and the entire population with cut-off augmentation. No significant differences were found on comparing FRAX to DeFRA in women (AUC 59-88% vs. 74%) and diabetics (AUC 73% vs. 89%). FRAX demonstrated non-significantly better discriminatory power than FRA-HS among men.
CONCLUSION
The task force formulated appropriate recommendations on the use of any fracture risk assessment tools in patients with or at risk of fragility fractures, since no statistically significant differences emerged across different prediction tools.
Topics: Male; Humans; Female; Osteoporosis; Osteoporotic Fractures; Bone Density; Risk Factors; Risk Assessment
PubMed: 37031450
DOI: 10.1007/s40618-023-02082-8 -
Neurospine Dec 2023We aimed to comprehensively compare surgical methods for osteoporotic vertebral compression fracture (OVCF) using systematic review and network meta-analysis to...
OBJECTIVE
We aimed to comprehensively compare surgical methods for osteoporotic vertebral compression fracture (OVCF) using systematic review and network meta-analysis to understand their effectiveness and outcomes, as current research provides limited overviews.
METHODS
We followed PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, preregistering our protocol with PROSPERO. We analyzed Englishpublished randomized controlled trials (RCTs) on adults with OVCFs that evaluated pain intensity or functionality using tools like visual analogue scale (VAS) or Oswestry Disability Index (ODI). Exclusions included non-RCTs, malignancy-related fractures, and certain interventions. Using the RoB 2 tool, we assessed bias and visualized results with Robvis. Our primary outcome was pain intensity, with secondary outcomes including disability, new fractures, and cement leakage. Results were synthesized using Stata/MP.
RESULTS
Thirty-four RCTs from 10 countries, totaling 4,384 patients, were analyzed. Shortterm VAS indicated kyphoplasty with facet joint injection (KIJ) as the top treatment at 87.7%, while unipedicular kyphoplasty (UKP) led to long-term at 74.9%. Short-term ODI favored vertebroplasty with facet joint injection (VIJ) at 98.4%, with kyphoplasty (KP) leading longterm at 66.0%. All surgical techniques were superior to conservative treatment. Vertebral augmentation devices reported the fewest new fractures and curved vertebroplasty had the least cement leakage. SUCRA (surface under the cumulative ranking) analyses suggested UKP and VIJ as top choices for postoperative pain relief, with VIJ excelling in postoperative disability improvement.
CONCLUSION
Our analysis evaluates 12 OVCF interventions, underscoring KIJ for short-term pain relief and VIJ and UKP for long-term efficacy. Notably, VIJ stands out in disability outcomes, emphasizing the need for comprehensive OVCF management.
PubMed: 38171285
DOI: 10.14245/ns.2346996.498 -
Journal of Cachexia, Sarcopenia and... Apr 2024Half of osteoporotic fractures occur in patients with normal/osteopenic bone density or at intermediate or low estimated risk. Muscle measures have been shown to... (Review)
Review
Half of osteoporotic fractures occur in patients with normal/osteopenic bone density or at intermediate or low estimated risk. Muscle measures have been shown to contribute to fracture risk independently of bone mineral density. The objectives were to review the measurements of muscle health (muscle mass/quantity/quality, strength and function) and their association with incident fragility fractures and to summarize their use in clinical practice. This scoping review follows the PRISMA-ScR guidelines for reporting. Our search strategy covered the three overreaching concepts of 'fragility fractures', 'muscle health assessment' and 'risk'. We retrieved 14 745 references from Medline Ovid SP, EMBASE, Web of Science Core Collection and Google Scholar. We included original and prospective studies on community-dwelling adults aged over 50 years that analysed an association between at least one muscle parameter and incident fragility fractures. We systematically extracted 17 items from each study, including methodology, general characteristics and results. Data were summarized in tables and graphically presented in adjusted forest plots. Sixty-seven articles fulfilled the inclusion criteria. In total, we studied 60 muscle parameters or indexes and 322 fracture risk ratios over 2.8 million person-years (MPY). The median (interquartile range) sample size was 1642 (921-5756), age 69.2 (63.5-73.6) years, follow-up 10.0 (4.4-12.0) years and number of incident fragility fractures 166 (88-277). A lower muscle mass was positively/not/negatively associated with incident fragility fracture in 28 (2.0), 64 (2.5) and 10 (0.2 MPY) analyses. A lower muscle strength was positively/not/negatively associated with fractures in 53 (1.3), 57 (1.7 MPY) and 0 analyses. A lower muscle function was positively/not/negatively associated in 63 (1.9), 45 (1.0 MPY) and 0 analyses. An in-depth analysis shows how each single muscle parameter was associated with each fragility fractures subtype. This review summarizes markers of muscle health and their association with fragility fractures. Measures of muscle strength and function appeared to perform better for fracture risk prediction. Of these, hand grip strength and gait speed are likely to be the most practical measures for inclusion in clinical practice, as in the evaluation of sarcopenia or in further fracture risk assessment scores. Measures of muscle mass did not appear to predict fragility fractures and might benefit from further research, on D3-creatine dilution test, lean mass indexes and artificial intelligence methods.
Topics: Humans; Aged; Middle Aged; Hand Strength; Prospective Studies; Artificial Intelligence; Risk Factors; Osteoporotic Fractures; Muscle, Skeletal
PubMed: 38284511
DOI: 10.1002/jcsm.13418 -
Orthopaedic Surgery Oct 2023This systematic review and meta-analysis is aimed to provide higher quality evidence regarding the efficacy and safety between PCVP and PVP/KP in OVCFs. We searched the... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis is aimed to provide higher quality evidence regarding the efficacy and safety between PCVP and PVP/KP in OVCFs. We searched the Cochrane Library, PubMed, Web of Science, and Embase databases for all randomized controlled trials (RCTs) and observational studies (cohort or case-control studies) that compare PCVP to PVP/KP for OVCFs. The Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of the RCTs and non-RCTs, respectively. Meta-analysis was performed using RevMan 5.4 software. A total of seven articles consisting of 562 patients with 593 diseased vertebral bodies were included. Statistically significant differences were found in the postoperative visual analog scale (VAS) at 1 day (MD = -0.11; 95% CI: [-0.21 to -0.01], p = 0.03), but not at 3 months (MD = -0.21; 95% CI: [-0.41-0.00], p = 0.05) or 6 months (MD = 0.03; 95% CI: [-0.13-0.20], p = 0.70). There was no statistically significant difference in postoperative Oswestry disability index (ODI) at 1 day (MD = -0.28; 95% CI: [-0.62-0.05], p = 0.10), 3 months (MD = -1.52; 95% CI: [-3.11-0.07], p = 0.06), or 6 months (MD = 0.18; 95% CI: [-0.13-0.48], p = 0.25). Additionally, there were no statistically significant differences in Cobb angle (MD = 0.30; 95% CI: [-1.69-2.30], p = 0.77) or anterior vertebral body height (SMD = -0.01; 95% CI: [-0.26-0.23], p = 0.92) after surgery. Statistically significant differences were found in surgical time (MD = -8.60; 95% CI: [-13.75 to -3.45], p = 0.001), cement infusion volume (MD = -0.82; 95% CI: [-1.50 to -0.14], P = 0.02), and dose of fluoroscopy (SMD = -1.22; 95% CI: [-1.84 to -0.60], p = 0.0001) between curved and noncurved techniques, especially compared to bilateral PVP. Moreover, cement leakage showed statistically significant difference (OR = 0.40; 95% CI: [0.27-0.60], p < 0.0001). Compared with PVP/KP, PCVP is superior for pain relief at short-term follow-up. Additionally, PCVP has the advantages of significantly lower surgical time, radiation exposure, bone cement infusion volume, and cement leakage incidence compared to bilateral PVP, while no statistically significant difference is found when compared with unilateral PVP or PKP. In terms of quality of life and radiologic outcomes, the effects of PCVP and PVP/KP are not significantly different. Overall, this meta-analysis reveals that PCVP was an effective and safe therapy for patients with OVCFs.
Topics: Humans; Fractures, Compression; Vertebroplasty; Kyphoplasty; Osteoporotic Fractures; Spinal Fractures; Bone Cements; Treatment Outcome
PubMed: 37497571
DOI: 10.1111/os.13800 -
Sleep Medicine Reviews Feb 2024We reviewed and meta-analyzed 20 observational studies to examine the relationship between sedative-hypnotic use and osteoporotic fractures. We searched PubMed, Embase,... (Meta-Analysis)
Meta-Analysis Review
We reviewed and meta-analyzed 20 observational studies to examine the relationship between sedative-hypnotic use and osteoporotic fractures. We searched PubMed, Embase, APA PsycINFO, and Web of Science™ for studies that used cohort, case-control, case-crossover, and self-controlled case series designs. We further assessed the quality of each study and performed meta-analyses of association estimates, e.g., odds ratios (ORs). The analysis included 6,084,083 participants and found a slight association between the use of sedative-hypnotics and osteoporotic fractures, with differing strength of associations between different classes of drugs and greater sedative-hypnotics exposure. The pooled estimates ORs for case-control studies were 1.33 (95% CI 0.98-1.80) with benzodiazepines (BZD) and any fractures, 1.32 (95% CI 1.05-1.66) with BZDs and hip fractures, and case-crossover studies were 1.15 (95% CI 0.95-1.41) with BZDs and any fractures, 1.41 (95% CI 1.08-1.85) with Z-drugs and any fractures. The study suggests that more research is needed to aid medical professionals in balancing this potential risk of osteoporotic fractures associated with sedative-hypnotic use against other reported adverse events and anticipated therapy outcomes.
Topics: Humans; Benzodiazepines; Case-Control Studies; Hypnotics and Sedatives; Osteoporotic Fractures
PubMed: 37926010
DOI: 10.1016/j.smrv.2023.101866 -
Osteoporosis International : a Journal... May 2024Patients with myasthenia gravis (MG), because of their muscle weakness and exposure to corticosteroids treatment, are generally considered to be at increased risk for... (Review)
Review
Patients with myasthenia gravis (MG), because of their muscle weakness and exposure to corticosteroids treatment, are generally considered to be at increased risk for osteoporosis or fracture. However, clinical evidence of this issue is lacking. In this review, we systematically searched databases, including Cochrane Library, PubMed, Embase, and Airiti library from inception to the end of November 2023 for cohort studies that compared participants with MG and participants without MG for incidence of osteoporosis or fracture. We used the Newcastle-Ottawa Scale for quality assessment. In total, we included 3 studies with 34,865 participants. The pooled meta-analysis using the random effect model demonstrated no significant difference in risk of fracture in the MG group (odds ratio = 1.52; 95% confidence interval = 0.74 to 3.12; I = 93%; between-study variance [τ] = 0.32) compared with that for the non-MG group. Due to limited studies, we could not perform a quantitative analysis for risk of osteoporosis. In conclusion, we found no robust evidence to support the proposition that patients with MG are at higher risk for fracture than general comparators. The explanations and underlying mechanisms of this finding remain unclear, we therefore conclude that additional studies are warranted.
PubMed: 38748216
DOI: 10.1007/s00198-024-07097-2 -
Osteoporosis International : a Journal... Jun 2024Fracture liaison services (FLS) have been proven clinically effective and cost-effective in preventing subsequent fractures among patients with an existing fragility... (Review)
Review
Fracture liaison services (FLS) have been proven clinically effective and cost-effective in preventing subsequent fractures among patients with an existing fragility fracture. Little is known about their monetary benefits such as their return on investment (ROI). This systematic review aimed to investigate the ROI of FLS and identify the FLS characteristics with better ROI. Studies on the cost-effectiveness of FLS published between January 2000 and December 2022 were searched from MEDLINE, EMBASE, PubMed, and Cochrane Central. Two independent reviewers conducted study selection and data extraction. ROI was calculated based on the difference between monetary benefits and FLS costs divided by the FLS costs. Subgroup analysis of ROI was performed across FLS types and FLS design details. A total of 23 FLS were included in this review. The majority of them were targeting patients aged over 50 years having fractures without identified sites. The mean ROI of these FLS was 10.49 (with a median ROI of 7.57), and 86.96% of FLS had positive ROI. FLS making treatment recommendations yielded the highest ROI (with a mean ROI of 18.39 and a median of 13.60). Incorporating primary care providers (with a mean ROI of 16.04 and a median of 13.20) or having them as program leaders (with a mean ROI of 12.07 and a median of 12.07) has demonstrated a high ROI. FLS for specific fracture sites had great monetary return. Intensive FLS such as type A and B FLS programs had higher ROI than non-intensive type C and D FLS. This review revealed a 10.49-fold monetary return of FLS. Identified characteristics contributing to greater economic return informed value-for-money FLS designs. Findings highlight the importance of FLS and the feasibility of expanding their contribution in mitigating the economic burden of osteoporotic fracture and are conducive to the promotion of FLS internationally.
Topics: Humans; Osteoporotic Fractures; Cost-Benefit Analysis; Health Care Costs; Secondary Prevention
PubMed: 38300316
DOI: 10.1007/s00198-024-07027-2 -
Current Osteoporosis Reports Apr 2024Recently, the American Diabetes Association updated the 2024 guidelines for Standards of Care in Diabetes and recommend that a T-score of - 2.0 in patients with diabetes... (Review)
Review
PURPOSE OF REVIEW
Recently, the American Diabetes Association updated the 2024 guidelines for Standards of Care in Diabetes and recommend that a T-score of - 2.0 in patients with diabetes should be interpreted as equivalent to - 2.5 in people without diabetes. We aimed to evaluate the most recent findings concerning the bone mineral density (BMD)-derived T-score and risk of fractures related to osteoporosis in subjects with diabetes.
RECENT FINDINGS
The dual-energy X-ray absorptiometry (DXA) scan is the golden standard for evaluating BMD. The BMD-derived T-score is central to fracture prediction and signifies both diagnosis and treatment for osteoporosis. However, the increased fracture risk in diabetes is not sufficiently explained by the T-score, complicating the identification and management of fracture risk in these patients. Recent findings agree that subjects with type 2 diabetes (T2D) have a higher T-score and higher fracture risk compared with subjects without diabetes. However, the actual number of studies evaluating the direct association of higher fracture risk at higher T-score levels is scant. Some studies support the adjustment based on the 0.5 BMD T-score difference between subjects with T2D and subjects without diabetes. However, further data from longitudinal studies is warranted to validate if the T-score treatment threshold necessitates modification to prevent fractures in subjects with diabetes.
Topics: Humans; Bone Density; Osteoporosis; Absorptiometry, Photon; Diabetes Mellitus, Type 2; Osteoporotic Fractures; Risk Factors
PubMed: 38509440
DOI: 10.1007/s11914-024-00867-1 -
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