Bone Microarchitecture and Strength in Long-Standing Type 1 Diabetes

Type 1 diabetes (T1DM) is associated with an increased fracture risk, specifically at nonvertebral sites. The influence of glycemic control and microvascular disease on skeletal health in long-standing T1DM remains largely unknown. We aimed to assess areal (aBMD) and volumetric bone mineral density (vBMD), bone microarchitecture, bone turnover, and estimated bone strength in patients with long-standing T1DM, defined as disease duration ≥25 years. We recruited 59 patients with T1DM (disease duration 37.7 ± 9.0 years; age 59.9 ± 9.9 years.; body mass index [BMI] 25.5 ± 3.7 kg/m²; 5-year median glycated hemoglobin [HbA1c] 7.1% [IQR 6.82–7.40]) and 77 nondiabetic controls. Dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT) at the ultradistal radius and tibia, and biochemical markers of bone turnover were assessed. Group comparisons were performed after adjustment for age, gender, and BMI. Patients with T1DM had lower aBMD at the hip (p < 0.001), distal radius (p = 0.01), lumbar spine (p = 0.04), and femoral neck (p = 0.05) as compared to controls. Cross-linked C-telopeptide (CTX), a marker of bone resorption, was significantly lower in T1DM (p = 0.005). At the distal radius there were no significant differences in vBMD and bone microarchitecture between both groups. In contrast, patients with T1DM had lower cortical thickness (estimate [95% confidence interval]: −0.14 [−0.24, −0.05], p < 0.01) and lower cortical vBMD (−28.66 [−54.38, −2.93], p = 0.03) at the ultradistal tibia. Bone strength and bone stiffness at the tibia, determined by homogenized finite element modeling, were significantly reduced in T1DM compared to controls. Both the altered cortical microarchitecture and decreased bone strength and stiffness were dependent on the presence of diabetic peripheral neuropathy. In addition to a reduced aBMD and decreased bone resorption, long-standing, well-controlled T1DM is associated with a cortical bone deficit at the ultradistal tibia with reduced bone strength and stiffness. Diabetic neuropathy was found to be a determinant of cortical bone structure and bone strength at the tibia, potentially contributing to the increased nonvertebral fracture risk. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Differing Effects of Zoledronic Acid on Bone Microarchitecture and Bone Mineral Density in Men Receiving Androgen Deprivation Therapy: A Randomized Controlled Trial

Androgen deprivation therapy (ADT) given to men with prostate cancer causes rapid and severe sex steroid deficiency, leading to increased bone remodeling and accelerated bone loss. To examine the effects of a single dose of zoledronic acid on bone microarchitecture, we conducted a 2-year randomized placebo controlled trial in 76 men, mean age (interquartile range [IQR]) 67.8 years (63.8 to 73.9) with non-metastatic prostate cancer commencing adjuvant ADT; 39 were randomized to zoledronic acid and 37 to matching placebo. Bone microarchitecture was measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). Using a mixed model, mean adjusted differences (MAD; 95% confidence interval [95% CI]) between the groups are reported as the treatment effect at several time points. Over 24 months, zoledronic acid showed no appreciable treatment effect on the primary outcomes for total volumetric bone mineral density (vBMD); radius (6.7 mg HA/cm³ [−2.0 to 15.4], p = 0.21) and tibia (1.9 mg HA/cm³ [−3.3 to 7.0], p = 0.87). Similarly, there were no between-group differences in other measures of microarchitecture, with the exception of a modest effect of zoledronic acid over placebo in total cortical vBMD at the radius over 12 months (17.3 mgHA/cm³ [5.1 to 29.5]). In contrast, zoledronic acid showed a treatment effect over 24 months on areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) at all sites, including lumbar spine (0.10 g/cm² [0.07 to 0.13]), p < 0.001), and total hip (0.04 g/cm² [0.03 to 0.05], p < 0.001). Bone remodeling markers were initially suppressed in the treatment group then increased but remained lower relative to placebo (MADs at 24 months CTX −176 ng/L [−275 to –76], p < 0.001; P1NP –18 mg/L [−32 to –5], p < 0.001). These findings suggest that a single dose of zoledronic acid over 2 years is ineffective in preventing the unbalanced bone remodeling and severe microstructural deterioration associated with ADT therapy. © 2020 American Society for Bone and Mineral Research.     

Association between human papillomavirus infection and sperm quality: A systematic review and a meta-analysis

Human papillomavirus (HPV) has a high incidence rate in both males and females. HPV infection in women has been shown to affect fertility and lead to foetal death and pregnancy loss. However, research on HPV infection in men is limited. The aim of this study was to study the effect of HPV infection in semen on sperm quality and present the findings of previous studies through a meta-analysis. Databases including PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, WanFang data and China National Knowledge Infrastructure were searched for relevant studies. A systematic review and meta-analysis were performed, and 17 studies were included for analyses based on a set criterion. Meta-analyses indicated that HPV infection in semen significantly reduced sperm concentration (SMD = −0.12, 95% CI: −0.21 to −0.03, p = .009), sperm motility (SMD = −0.55, 95% CI: −0.780 to −0.33, p = .000), sperm viability (SMD = −0.55, 95% CI: −0.780 to −0.33, p = .000) and sperm morphology (SMD = −0.34, 95% CI: −0.61 to −0.07, p = .015). The high-risk HPV (HrHPV) infection could significantly reduce sperm count (SMD = −0.65, 95% CI: −1.11 to −0.18, p = .007) compared with high-risk HPV (LrHPV) infection. In conclusion, HPV infection in semen significantly reduced sperm quality, and the HrHPV infection could significantly reduce sperm count compared with LrHPV.     

Teriparatide Followed by Denosumab in Premenopausal Idiopathic Osteoporosis: Bone Microstructure and Strength by HR-pQCT

Premenopausal women with idiopathic osteoporosis (PreMenIOP) have marked deficits in skeletal microstructure. We have reported that sequential treatment with teriparatide and denosumab improves central skeletal bone mineral density (BMD) by dual-energy X-ray absorptiometry and central QCT in PreMenIOP. We conducted preplanned analyses of high-resolution peripheral quantitative computed tomography (HR-pQCT) scans from teriparatide and denosumab extension studies to measure effects on volumetric BMD (vBMD), microarchitecture, and estimated strength at the distal radius and tibia. Of 41 women enrolled in the parent teriparatide study (20 mcg daily), 34 enrolled in the HR-pQCT study. HR-pQCT participants initially received teriparatide (N = 24) or placebo (N = 10) for 6 months; all then received teriparatide for 24 months. After teriparatide, 26 enrolled in the phase 2B denosumab extension (60 mg q6M) for 24 months. Primary outcomes were percentage change in vBMD, microstructure, and stiffness after teriparatide and after denosumab. Changes after sequential teriparatide and denosumab were secondary outcomes. After teriparatide, significant improvements were seen in tibial trabecular number (3.3%, p = 0.01), cortical area and thickness (both 2.7%, p < 0.001), and radial trabecular microarchitecture (number: 6.8%, thickness: 2.2%, separation: −5.1%, all p < 0.02). Despite increases in cortical porosity and decreases in cortical density, whole-bone stiffness and failure load increased at both sites. After denosumab, increases in total (3.5%, p < 0.001 and 3.3%, p = 0.02) and cortical vBMD (1.7% and 3.2%; both p < 0.01), and failure load (1.1% and 3.6%; both p < 0.05) were seen at tibia and radius, respectively. Trabecular density (3.5%, p < 0.001) and number (2.4%, p = 0.03) increased at the tibia, while thickness (3.0%, p = 0.02) increased at the radius. After 48 months of sequential treatment, significant increases in total vBMD (tibia: p < 0.001; radius: p = 0.01), trabecular microstructure (p < 0.05), cortical thickness (tibia: p < 0.001; radius: p = 0.02), and whole bone strength (p < 0.02) were seen at both sites. Significant increases in total vBMD and bone strength parameters after sequential treatment with teriparatide followed by denosumab support the use of this regimen in PreMenIOP. © 2022 American Society for Bone and Mineral Research (ASBMR).     

A meta-analysis on the efficacy of vacuum sealing drainage combined with autologous platelet-rich plasma in the treatment of Grade 2 and Grade 3 diabetic foot ulcers

This meta-analysis aims to systemically evaluate the efficacy of vacuum sealing drainage (VSD) combined with autologous platelet-rich plasma (PRP) in the treatment of diabetic foot ulcers (DFU). The China HowNet, China Biomedical Literature, VIP periodical resource integration service platform, Wanfang, Embase, Cochrane Central, and PubMed databases were retrieved using the computer. The retrieval period was up to July 2021. Randomised controlled trials on VSD combined with PRP in the treatment of DFU were collected. Those trials that met the inclusion criteria were included for meta-analysis using RevMan 5.3 software. A total of 13 articles were included. In the trial group, 477 patients with DFU were treated with VSD combined with PRP, while in the control group, 482 patients with DFU were treated with conventional dressings and/or VSD. The meta-analysis showed that, compared with the control group, VSD combined with PRP has significant advantages in shortening healing time (standardised mean difference [SMD] = −0.87, 95% confidence interval [CI]: −1.07 to −0.67, P < .00001), improving ulcer healing rates (odds ratio = 4.01, 95% CI: 2.95 ~ 5.46, P < .00001), and reducing hospital stays (mean difference = −15.29, 95% CI: −16.05 to −14.54, P < .00001), but the differences in dressing change times (SMD = −1.27, 95% CI: −2.71 to 0.17, P = .08) and hospitalisation expenses (SMD = −0.16, 95% CI: −13.40 to 13.07, P = .98) were not statistically significant. VSD combined with autologous PRP has good curative efficacy in the treatment of DFU and is a better treatment option. However, this treatment is limited in patients with platelet dysfunction, thrombocytopenia, leukaemia, and poor general condition.     

Effects of a 12-Month Supervised,Community-Based,Multimodal Exercise Program Followed by a 6-Month Research-to-Practice Transition on Bone Mineral Density,Trabecular Microarchitecture,and Physical Function in Older Adults: A Randomized Controlled Trial

Multicomponent exercise programs are recommended to reduce fracture risk; however, their effectiveness in real-world community settings remain uncertain. This 18-month randomized controlled trial investigated the effects of a 12-month, community-based, supervised multicomponent exercise program followed by a 6-month “research-to-practice” transition on areal bone mineral density (BMD), trabecular bone microarchitecture, functional performance, and falls in older adults at increased fracture risk. One-hundred and sixty-two adults aged ≥60 years with osteopenia or at increased falls risk were randomized to the Osteo-cise: Strong Bones for Life multicomponent exercise program (n = 81) or a control group (n = 81). Exercise consisted of progressive resistance, weight-bearing impact, and balance training (3-days/week) performed at community leisure centers. Overall 148 (91%) participants completed the trial, and mean exercise adherence was 59% after 12 months and 45% during the final 6 months. After 12 months, there were significant net beneficial effects of exercise on lumbar spine and femoral neck BMD (1.0% to 1.1%, p < 0.05), muscle strength (10% to 13%, p < 0.05), and physical function (timed stair climb 5%; four-square step test 6%; sit-to-stand 16%, p ranging <0.05 to <0.001), which persisted after the 6-month transition. There were no significant effects of the 18-month intervention on distal femur or proximal tibia trabecular bone microarchitecture or falls incidence, but per protocol analysis (≥66% exercise adherence) revealed there was a significant net benefit of exercise (mean [95% confidence interval] 2.8% [0.2, 5,4]) on proximal tibia trabecular bone volume fraction (Osteo-cise 1.5% [−1.2, 4.2]; controls −1.3% [−2.6, 0.1]) after 18 months due to changes in trabecular number (Osteo-cise 1.7% [−0.9, 4.3]; controls −1.1% [−2.4, 0.2]) but not trabecular thickness (Osteo-cise − 0.2% [−0.5, 0.2]; controls −0.2% [−0.4, 0.0]). In conclusion, this study supports the effectiveness of the Osteo-cise: Strong Bones for Life program as a real-world, pragmatic, evidence-based community exercise program to improve multiple musculoskeletal health outcomes in older adults at increased fracture risk. © 2019 American Society for Bone and Mineral Research.     

Causal Associations of Anthropometric Measurements With Fracture Risk and Bone Mineral Density: A Mendelian Randomization Study

Uncovering additional causal clinical traits and exposure variables is important when studying osteoporosis mechanisms and for the prevention of osteoporosis. Until recently, the causal relationship between anthropometric measurements and osteoporosis had not been fully revealed. In the present study, we utilized several state-of-the-art Mendelian randomization (MR) methods to investigate whether height, body mass index (BMI), waist-to-hip ratio (WHR), hip circumference (HC), and waist circumference (WC) are causally associated with two major characteristics of osteoporosis, bone mineral density (BMD) and fractures. Genomewide significant (p ≤ 5 × 10⁻⁸) single-nucleotide polymorphisms (SNPs) associated with the five anthropometric variables were obtained from previous large-scale genomewide association studies (GWAS) and were utilized as instrumental variables. Summary-level data of estimated bone mineral density (eBMD) and fractures were obtained from a large-scale UK Biobank GWAS. Of the MR methods utilized, the inverse-variance weighted method was the primary method used for analysis, and the weighted-median, MR-Egger, mode-based estimate, and MR pleiotropy residual sum and outlier methods were utilized for sensitivity analyses. The results of the present study indicated that each increase in height equal to a single standard deviation (SD) was associated with a 9.9% increase in risk of fracture (odds ratio [OR] = 1.099; 95% confidence interval [CI] 1.067–1.133; p = 8.793 × 10⁻¹⁰) and a 0.080 SD decrease of estimated bone mineral density (95% CI −0.106–(−0.054); p = 2.322 × 10⁻⁹). We also found that BMI was causally associated with eBMD (beta = 0.129, 95% CI 0.065–0.194; p = 8.113 × 10⁻⁵) but not associated with fracture. The WHR adjusted for BMI, HC adjusted for BMI, and WC adjusted for BMI were not found to be related to fracture occurrence or eBMD. In conclusion, the present study provided genetic evidence for certain causal relationships between anthropometric measurements and bone mineral density or fracture risk. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Associations Between Late Pregnancy Dietary Inflammatory Index (DII) and Offspring Bone Mass: A Meta-Analysis of the Southampton Women's Survey (SWS) and the Avon Longitudinal Study of Parents and Children (ALSPAC)

Systemic inflammation is associated with reduced bone mineral density and may be influenced by pro-inflammatory diets. We undertook an observational analysis of associations between late pregnancy energy-adjusted dietary inflammatory index (E-DII) scores and offspring bone outcomes in childhood. E-DII scores (higher scores indicating pro-inflammatory diets) were derived from food frequency questionnaires in late pregnancy in two prospective mother-offspring cohorts: the Southampton Women's Survey (SWS) and the Avon Longitudinal Study of Parents and Children (ALSPAC). The mean (SD) offspring age at dual-energy X-ray absorptiometry (DXA) scanning was 9.2 (0.2) years. Linear regression was used to assess associations between E-DII and bone outcomes, adjusting for offspring sex and age at DXA and maternal age at childbirth, educational level, pre-pregnancy body mass index (BMI), parity, physical activity level, and smoking in pregnancy. Associations were synthesized using fixed-effect meta-analysis. Beta coefficients represent the association per unit E-DII increment. In fully adjusted models (total n = 5910) late pregnancy E-DII was negatively associated with offspring whole body minus head bone area (BA: β = −3.68 [95% confidence interval −6.09, −1.27] cm²/unit), bone mineral content (BMC: β = −4.16 [95% CI −6.70, −1.62] g/unit), and areal bone mineral density (aBMD: β = −0.0012 [95% CI −0.0020, −0.0004] g.cm⁻²/unit), but there was only a weak association with BMC adjusted for BA (β = −0.48 [95% CI −1.11, 0.15] g/unit) at 9 years. Adjustment for child height partly or, for weight, fully attenuated the associations. Higher late pregnancy E-DII scores (representing a more pro-inflammatory diet) are negatively associated with offspring bone measures, supporting the importance of maternal and childhood diet on longitudinal offspring bone health. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Positive emotion in posttraumatic stress disorder: A global or context-specific problem?

Problems with positive emotion are an important component of posttraumatic stress disorder (PTSD), with competing perspectives as to why. The global model suggests that people with PTSD experience a relatively permanent shift in their capacity for positive emotion regardless of context, whereas the context-specific model posits access to the full repertoire of positive emotion that only becomes reduced during exposure to trauma reminders. We tested the global versus context-specific models using ecological momentary assessment (EMA). Trauma-exposed adult community members (N = 80) with (n = 39) and without diagnosed PTSD completed 3 days of EMA (n = 2,158 observations). Participants with PTSD reported lower average momentary levels of positive emotion, B = −0.947, 95% CI [−1.35, −0.54], p < .001, and positive situations, B = −0.607, 95% CI [−1.16, −0.05], p = .032, and more thinking about trauma reminders, B = 0.360, 95% CI [0.21, 0.51], p < .001. There was no between-group difference in positive emotion reactivity (degree of positive emotion derived from positive situations), B = 0.03, 95% CI [−0.09, 0.14], p = .635. Increased thinking about trauma reminders predicted lower momentary levels of positive emotion, B = −0.55, 95% CI [−0.83, −0.26], p < .001, but not reactivity, B = 0.02, 95% CI [−0.35, 0.40], p = .906, irrespective of PTSD status. Findings supported the global model and were inconsistent with the context-specific model. This study helps clarify positive emotional functioning in trauma-exposed adults and highlights future directions to better understand problems with positive emotion in PTSD.     

Bone Mass,Bone Microstructure and Biomechanics in Patients with Hand Osteoarthritis

The impact of primary hand osteoarthritis (HOA) on bone mass, microstructure, and biomechanics in the affected skeletal regions is largely unknown. HOA patients and healthy controls (HCs) underwent high-resolution peripheral quantitative computed tomography (HR-pQCT). We measured total, trabecular, and cortical volumetric bone mineral densities (vBMDs), microstructural attributes, and performed micro–finite element analysis for bone strength. Failure load and scaled multivariate outcome matrices from distal radius and second metacarpal (MCP2) head measurements were analyzed using multiple linear regression adjusting for age, sex, and functional status and reported as adjusted Z-score differences for total and direct effects. A total of 105 subjects were included (76 HC: 46 women, 30 men; 29 HOA: 23 women, six men). After adjustment, HOA was associated with significant changes in the multivariate outcome matrix from the MCP2 head (p < .001) (explained by an increase in cortical vBMD (Δz = 1.07, p = .02) and reduction in the trabecular vBMD (Δz = −0.07, p = .09). Distal radius analysis did not show an overall effect of HOA; however, there was a gender-study group interaction (p = .044) explained by reduced trabecular vBMD in males (Δz = −1.23, p = .02). HOA was associated with lower failure load (−514 N; 95%CI, −1018 to −9; p = 0.05) apparent in males after adjustment for functional status. HOA is associated with reduced trabecular and increased cortical vBMD in the MCP2 head and a reduction in radial trabecular vBMD and bone strength in males. Further investigations of gender-specific changes of bone architecture in HOA are warranted. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Heterogeneity and Spatial Distribution of Intravertebral Trabecular Bone Mineral Density in the Lumbar Spine Is Associated With Prevalent Vertebral Fracture

The spatial heterogeneity in trabecular bone density within the vertebral centrum is associated with vertebral strength and could explain why volumetric bone mineral density (vBMD) exhibits low sensitivity in identifying fracture risk. This study evaluated whether the heterogeneity and spatial distribution of trabecular vBMD are associated with prevalent vertebral fracture. We examined the volumetric quantitative computed tomography (QCT) scans of the L₃ vertebra in 148 participants in the Framingham Heart Study Multidetector CT study. Of these individuals, 37 were identified as cases of prevalent fracture, and 111 were controls, matched on sex and age with three controls per case. vBMD was calculated within 5-mm contiguous cubic regions of the centrum. Two measures of heterogeneity were calculated: (i) interquartile range (IQR); and (ii) quartile coefficient of variation (QCV). Ratios in the spatial distributions of the trabecular vBMD were also calculated: anterior/posterior, central/outer, superior/mid-transverse, and inferior/mid-transverse. Heterogeneity and spatial distributions were compared between cases and controls using Wilcoxon rank sum tests and t tests and tested for association with prevalent fractures with conditional logistic regressions independent of integral vBMD. Prevalent fracture cases had lower mean ± SD integral vBMD (134 ± 38 versus165 ± 42 mg/cm³, p < .001), higher QCV (0.22 ± 0.13 versus 0.17 ± 0.09, p = .003), and lower anterior/posterior rBMD (0.65 ± 0.13 versus 0.78 ± 0.16, p < .001) than controls. QCV was positively associated with increased odds of prevalent fracture (OR 1.61; 95% CI, 1.04 to 2.49; p = .034), but this association was not independent of integral vBMD (p = .598). Increased anterior/posterior trabecular vBMD ratio was associated with decreased odds of prevalent fracture independent of integral vBMD (OR 0.38; 95% CI, 0.20 to 0.71; p = .003). In conclusion, increased trabecular vBMD in the anterior versus posterior centrum, but not trabecular vBMD heterogeneity, was associated with decreased risk of prevalent fracture independent of integral vBMD. Regional measurements of trabecular vBMD could aid in determining the risk and underlying mechanisms of vertebral fracture. © 2019 American Society for Bone and Mineral Research.     

Therapeutic Efficacy and Safety of Percutaneous Curved Vertebroplasty in Osteoporotic Vertebral Compression Fractures: A Systematic Review and Meta‐Analysis

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.     

Application of controlled low central venous pressure during hepatectomy: A systematic review and meta-analysis

Study objectivePrevious studies reported that controlled low central venous pressure (CVP) can reduce blood loss during liver resection. This systematic review and meta-analysis sought to explore the efficacy and safety of low CVP in patients undergoing hepatectomy.DesignA systematic review and meta-analysis of randomized controlled trials (RCTs).Review methodsRCTs were searched in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese BioMedical database, Chinese Scientific Journals Database, and Wanfang database from inception to April 30, 2021. Subgroup analyses were performed based on different surgical methods (open hepatectomy vs laparoscopic hepatectomy) and published countries (China vs other countries). The quality of evidence was assessed by Grading of Recommendations, Assessment, Development, and Evaluation.Main resultsEighteen RCTs containing 1285 participants (626 patients in the low CVP group and 659 patients in the control group) were included in this study. The forest plot showed that low CVP effectively reduced blood loss during liver resection compared with the control group (MD = −311.92 mL, 95% CI [−429.03, −194.81]; P < 0.001, I² = 96%). Furthermore, blood transfusion volume (MD = −158.85 mL, 95% CI [−218.30, −99.40]; P < 0.001, I² = 55%) and the number of patients requiring transfusion (RR 0.41, 95% CI 0.27–0.65, P < 0.001, I² = 0%) were decreased in the low CVP group. Subgroup analyses showed similar results. Notably, the alanine transaminase level was significantly lower in the low CVP group during the first five postoperative days. However, no significant differences were observed for other postoperative liver function indicators (aspartate aminotransferase, total bilirubin, serum albumin, and prothrombin time), renal function indicators (blood urea nitrogen and serum creatinine) and perfusion parameters (heart rate, mean arterial pressure, and urine volume). The incidence of complications was similar between the two groups.ConclusionThe findings of this study showed that low CVP is effective and safe during hepatectomy. Therefore, this technique is recommended to reduce blood loss during hepatectomy.PROSPERO registration number: CRD42021232829.     

Bone Microarchitecture in Transgender Adults: A Cross-Sectional Study

Gender-affirming hormone therapy aligns physical characteristics with an individual's gender identity, but sex hormones regulate bone remodeling and influence bone morphology. We hypothesized that trans men receiving testosterone have compromised bone morphology because of suppression of ovarian estradiol production, whereas trans women receiving estradiol, with or without anti-androgen therapy, have preserved bone microarchitecture. We compared distal radial and tibial microarchitecture using high-resolution peripheral quantitative computed tomography images in a cross-sectional study of 41 trans men with 71 cis female controls, and 40 trans women with 51 cis male controls. Between-group differences were expressed as standardized deviations (SD) from the mean in age-matched cisgender controls with 98% confidence intervals adjusted for cross-sectional area (CSA) and multiple comparisons. Relative to cis women, trans men had 0.63 SD higher total volumetric bone mineral density (vBMD; both p = 0.01). Cortical vBMD and cortical porosity did not differ, but cortices were 1.11 SD thicker (p < 0.01). Trabeculae were 0.38 SD thicker (p = 0.05) but otherwise no different. Compared with cis men, trans women had 0.68 SD lower total vBMD (p = 0.01). Cortical vBMD was 0.70 SD lower (p < 0.01), cortical thickness was 0.51 SD lower (p = 0.04), and cortical porosity was 0.70 SD higher (p < 0.01). Trabecular bone volume (BV/TV) was 0.77 SD lower (p < 0.01), with 0.57 SD fewer (p < 0.01) and 0.30 SD thicker trabeculae (p = 0.02). There was 0.56 SD greater trabecular separation (p = 0.01). Findings at the distal radius were similar. Contrary to each hypothesis, bone microarchitecture was not compromised in trans men, perhaps because aromatization of administered testosterone prevented bone loss. Trans women had deteriorated bone microarchitecture either because of deficits in microstructure before treatment or because the estradiol dosage was insufficient to offset reduced aromatizable testosterone. Prospective studies are needed to confirm these findings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Distribution of bone density in the proximal femur and its association with hip fracture risk in older men: The osteoporotic fractures in men (MrOS) study

This prospective case‐cohort study aimed to map the distribution of bone density in the proximal femur and examine its association with hip fracture. We analyzed baseline quantitative computed tomography (QCT) scans in 250 men aged 65 years or older, which comprised a randomly‐selected subcohort of 210 men and 40 cases of first hip fracture during a mean follow‐up period of 5.5 years. We quantified cortical, trabecular, and integral volumetric bone mineral density (vBMD), and cortical thickness (CtTh) in four quadrants of cross‐sections along the length of the femoral neck (FN), intertrochanter (IT), and trochanter (TR). In most quadrants, vBMDs and CtTh were significantly (p < 0.05) lower in cases compared to the subcohort and these deficits were present across the entire proximal femur. To examine the association of QCT measurements with hip fracture, we merged the two quadrants in the medial and lateral aspects of the FN, IT, and TR. At most sites, QCT measurements were associated significantly (p < 0.001) with hip fracture, the hazard ratio (HR) adjusted for age, body mass index (BMI), and clinical site for a 1‐SD decrease ranged between 2.28 (95% confidence interval [CI], 1.44–3.63) to 6.91 (95% CI, 3.11–15.53). After additional adjustment for total hip (TH) areal BMD (aBMD), trabecular vBMDs at the FN, TR, and TH were still associated with hip fracture significantly (p < 0.001), the HRs ranged from 3.21 (95% CI, 1.65–6.24) for the superolateral FN to 6.20 (95% CI, 2.71–14.18) for medial TR. QCT measurements alone or in combination did not predict fracture significantly (p > 0.05) better than TH aBMD. With an area under the receiver operating characteristic curve (AUC) of 0.901 (95% CI, 0.852–0.950), the regression model combining TH aBMD, age, and trabecular vBMD predicted hip fracture significantly (p < 0.05) better than TH aBMD alone or TH aBMD plus age. These findings confirm that both cortical and trabecular bone contribute to hip fracture risk and highlight trabecular vBMD at the FN and TR as an independent risk factor. © 2012 American Society for Bone and Mineral Research.     

Analgesic efficacy of PECS and serratus plane blocks after breast surgery: A systematic review,meta-analysis and trial sequential analysis

Study objectiveTo determine whether pectoral nerves (PECS) blocks provide effective postoperative analgesia when compared with no regional technique in patients undergoing breast surgery.DesignSystematic review, meta-analysis and trial sequential analysis.SettingOperating room, postoperative recovery area and ward, up to 24 postoperative hours.PatientsPatients undergoing breast surgery under general anaesthesia with either PECS block or no regional technique.InterventionsWe searched five electronic databases for randomized controlled trials comparing PECS block with no block or sham injection.MeasurementsThe primary outcome was rest pain scores (analogue scale, 0–10) at 2 h, analysed according to surgery (mastectomy vs other breast surgery) and regional technique (PECS 2 vs other blocks), among others. Secondary outcomes included morphine equivalent consumption, and rate of postoperative nausea and vomiting at 24 h.Main resultsSixteen trials including 1026 patients were identified. Rest pain scores at 2 h were decreased in the PECS blocks group, with a mean (95%CI) difference of −1.5 (−2.0, −1.0); I2 = 93%; p < 0.001, with no differences between surgery (mastectomy, mean difference [95%CI]: −1.8 [−2.4, −1.2], I² = 91%, p < 0.001; other breast surgery, mean difference [95%CI]: −1.1 [−2.1, −0.1], I² = 94%, p = 0.03; p for subgroup difference = 0.25), and regional technique (PECS 2, mean differences [95%CI]: −1.6 [−2.3, −1.0], I² = 94%, p < 0.001; other blocks, mean differences [95%CI]: −1.3 [−2.4, −0.1], I² = 74%, p = 0.04; p for subgroup difference = 0.57). The rate of postoperative nausea and vomiting was reduced from 30.8% (95%CI: 25.7%, 36.3%) to 18.7% (95%CI, 14.4%, 23.5%; p = 0.01). Similarly, secondary outcomes were significantly improved in the PECS blocks group. The overall quality of evidence was moderate-to-high.ConclusionsThere is moderate-to-high level evidence that PECS blocks provide postoperative analgesia after breast surgery when compared with no regional technique and reduce rate of PONV. This might provide the most benefit to those at high-risk of postoperative pain.     

Recombinant human bone morphogenetic protein is a valid alternative to autologous bone graft for long bone non-unions: a systematic review and meta-analysis

ObjectiveTo compare the efficacy of recombinant human bone morphogenetic proteins (rhBMPs) and autologous bone graft (ABG) on the healing of long bone non-union.MethodsA systematic literature search was conducted on PubMed, Web of Science, Cochrane Library, and CNKI up to December 2021. Two authors independently screened the studies, extracted data, and assessed the quality of the trials. A Meta-analysis was performed using state software (version 12.0).ResultsA total of 14 studies were included in this meta-analysis. Overall, there was no significant difference between the rhBMPs group and the ABG group in terms of healing rate (RR = 1.04, 95% CI = 0.96–1.12, p = 0.365) and healing time (SMD = −0.31, 95% CI = −0.76–0.14, p = 0.175). Subgroup analysis showed rhBMPs lead to higher healing rates (RR = 1.35, 95% CI = 1.17–1.56, p < 0.001), and shorter healing time (SMD = −0.65, 95% CI = −1.08 to −0.22, p = 0.003) in the subgroup of moderate-quality studies. Sensitivity analysis proved that our conclusions were relatively robust. No significant publication bias was recognized in all studies (Begg’s test, p = 0.193; Egger's test, p = 0.307).ConclusionsRhBMPs or combined with allografts bone, inorganic bone was a valid alternative to ABG for the treatment of long bone non-union.     

Bone Geometry,Volumetric Density,Microarchitecture, and Estimated Bone Strength Assessed by HR‐pQCT in Adult Patients With Hypophosphatemic Rickets

Hypophosphatemic rickets (HR) is characterized by a generalized mineralization defect. Although densitometric studies have found the patients to have an elevated bone mineral density (BMD), data on bone geometry and microstructure are scarce. The aim of this cross‐sectional in vivo study was to assess bone geometry, volumetric BMD (vBMD), microarchitecture, and estimated bone strength in adult patients with HR using high‐resolution peripheral quantitative computed tomography (HR‐pQCT). Twenty‐nine patients (aged 19 to 79 years; 21 female, 8 male patients), 26 of whom had genetically proven X‐linked HR, were matched with respect to age and sex with 29 healthy subjects. Eleven patients were currently receiving therapy with calcitriol and phosphate for a median duration of 29.1 years (12.0 to 43.0 years). Because of the disproportionate short stature in HR, the region of interest in HR‐pQCT images at the distal radius and tibia were placed in a constant proportion to the entire length of the bone in both patients and healthy volunteers. In age‐ and weight‐adjusted models, HR patients had significantly higher total bone cross‐sectional areas (radius 36%, tibia 20%; both p < 0.001) with significantly higher trabecular bone areas (radius 49%, tibia 14%; both p < 0.001) compared with controls. In addition, HR patients had lower total vBMD (radius ?20%, tibia ?14%; both p < 0.01), cortical vBMD (radius ?5%, p < 0.001), trabecular number (radius ?13%, tibia ?14%; both p < 0.01), and cortical thickness (radius ?19%; p < 0.01) compared with controls, whereas trabecular spacing (radius 18%, tibia 23%; p < 0.01) and trabecular network inhomogeneity (radius 29%, tibia 40%; both p < 0.01) were higher. Estimated bone strength was similar between the groups. In conclusion, in patients with HR, the negative impact of lower vBMD and trabecular number on bone strength seems to be compensated by an increase in bone diameter, resulting in HR patients having normal estimates of bone strength. © 2014 American Society for Bone and Mineral Research.     

Is Patient-Specific Instrumentation Accurate and Necessary for Open-Wedge High Tibial Osteotomy? A Meta-Analysis

The purpose of this meta-analysis was to identify if patient-specific instrumentation (PSI) could increase the accuracy of the correction in high tibial osteotomy (HTO) and to explore the assessment indices and the necessity of using a PSI in HTO. A systematic search was carried out using online databases. A total of 466 patients were included in 11 papers that matched the inclusion criteria. To evaluate the accuracy of PSI-assisted HTO, the weight bearing line ratio (WBL%), hip-knee-ankle angle (HKA), mechanical medial proximal tibial angle (mMPTA), and posterior tibial slope angle (PTSA) were measured preoperatively and postoperatively and compared to the designed target values. Statistical analysis was performed after strict data extraction with Review Manager (version 5.4). Significant differences were detected in WBL% (MD = −36.41; 95% CI: −42.30 to −30.53; p < 0.00001), HKA (MD = −9.95; 95% CI: –11.65 to –8.25; p < 0.00001), and mMPTA (MD = –8.40; 95% CI:−10.27 to −6.53; p < 0.00001) but not in PTSA (MD = 0.34; 95% CI: −0.59 to 1.27; p = 0.47) between preoperative and postoperative measurements. There was no significant difference between the designed target values and the postoperative correction values of HKA (MD = 0.14; 95% CI: −0.19 to 0.47; p = 0.41) or mMPTA (MD = 0.11; 95% CI −0.34 to 0.55; p = 0.64). The data show that 3D-based planning of PSI for HTO is both accurate and safe. WBL%, HKA, and mMPTA were the optimal evaluation indicators of coronal plane correction. Sagittal correction is best evaluated by the PTSA. The present study reports that PSI is accurate but not necessary in typical HTO.     

Effects of non-pharmacological interventions on pain intensity of children with burns: A systematic review and meta-analysis

Pain is one of the complications associated with burns, which can lead to anxiety and sleeplessness in children. Various studies evaluated the effects of non-pharmacological interventions on burn wound care. The present study was conducted to determine the effects of non-pharmacological interventions on pain intensity of children with burns. A comprehensive systematic search was conducted in various international electronic databases, such as Scopus, PubMed, Web of Science, and Persian electronic databases such as Iranmedex, and Scientific Information Database using keywords extracted from Medical Subject Headings such as ‘Non-pharmacological’, ‘Virtual reality’, ‘Pain’, ‘Burn’, ‘Wound’ and ‘Child’ from the earliest to December 1, 2022. The risk of bias in the final articles was also assessed with the Version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2). Finally, a total of 1005 burn patients were included in 19 studies. The age range of the patients was from 0.5 to 19 years. Of the participants, 50.05% were in the intervention group. All studies had a randomised clinical trial design. The results found that non-pharmacological interventions significantly reduced pain intensity in children (ES: −0.73, 95% CI: −1.08 to −0.38, Z = 4.09, I²:79.8, P < .001). Virtual reality (VR) (ES: −0.54, 95% CI: −1.19 to −0.18, Z = 2.90, I²:72.9%, P = .004) and non-VR (ES: -0.86, 95% CI: −1.45 to −0.27, Z = 2.86, I²:91.4%, P = .04) interventions decreased pain intensity significantly in children based sub-group analysis. Non-pharmacological interventions significantly reduced the pain intensity of dressing removal (ES: −0.77, 95% CI: −1.34 to −0.20, Z = 66.3, I²:91.8%, P = .008), dressing application (ES: −0.53, 95% CI: −0.97 to −0.09, Z = 2.37, I²:60.8%, P = .02), and physical therapy (ES: −1.18, 95% CI: −2.10 to −0.26, Z = 2.51, I²:88.0%, P = .01). Also, interventions reduced the pain of burn wound care (ES: −0.29, 95% CI: −1.01 to 0.44, Z = 0.78, I²:72.6%, P = .43), but it was statistically insignificant. In sum, the result of the present study indicated that using non-pharmacological interventions significantly reduced pain intensity in children. The reduction of pain intensity was greater in non-VR than in VR interventions. Future studies should focus on comparing VR interventions with non-VR and single versus multi-modal distraction to clarify the effectiveness of each.