Changes In Bone Mineral Density Research Articles

Utilizing Generalized Linear Mixed Effects Models for Prediction of Bone Mineral Decrease After Lung Transplant - A Preliminary Study.

Recipients of lung transplants are at heightened risk of developing low bone mineral density (BMD). They also have increased risk of developing osteoporosis-related fractures. This rate of BMD decline is not well characterized. The aim of this manuscript is to characterize the rate of BMD decrease after lung transplant. This is a preliminary retrospective cohort study of 200 patients who received lung transplants. Each patient had pre-transplant dual energy X-ray absorptiometry (DXA) and post-transplant DXA scans on the same DXA scanner. The BMD at each lumbar vertebra, total hip, and femoral neck were recorded. Generalized linear mixed effects models with random intercepts and random slopes were used to model the rate of change of BMD after transplant, adjusting for time since transplant, sex, and sex*time interaction. We found that men had higher baseline BMD than women at all sites (P<0.05 for all). The rate of BMD decrease was fastest at the femoral neck (P<0.05). Men lost BMD at a faster rate (-5.23 x10-5 g/cm2/day) than women at the femoral neck (-2.22 x10-5 g/cm2 /day). BMD decreases after lung transplant and occurs faster in men than women.

Male-female spatio-temporal differences of age-related bone changes show faster bone deterioration in older women at femoral regions associated with incident hip fracture.

A better understanding of how age-related bone loss affects the fracture-prone regions of the proximal femur could lead to more informed fracture-prevention strategies. Therefore, the aim of this work was to assess the spatio-temporal distribution of bone deterioration in older men and women with aging. A subset of 305 men (74.87 ± 4.76years; mean ± SD) and 371 age-matched women (74.84 ± 4.71years) with no history of fracture was randomly selected from the Age, Gene/Environment Susceptibility-Reykjavik study. Quantitative computed tomography (QCT) scans of the left proximal femur obtained at baseline and at 5.2 ± 0.4years follow-up were processed to assess local changes in volumetric bone mineral density (vBMD), cortical bone thickness (Ct.Th), and internal bone structure using voxel-based morphometry (VBM), surface-based statistical parametric mapping (surf-SPM), and tensor-based morphometry (TBM). Local parametric changes within each sex and sex differences in these changes were statistically assessed using linear mixed effects models allowing for baseline and time-varying covariates, yielding Student's t-test and p-value statistical maps of the proximal femur. The statistical maps indicated regions with significant parametric changes in each sex and with significant different parametric changes between older men and older women with aging. Older women manifested significantly larger losses in vBMD, (Ct.Th), and structure than older men, and they did so in regions where deficiency in these parameters has been associated with incident hip fracture. Using longitudinal QCT scans of the proximal femur and Computational Anatomy, we provided new insights into the higher fracture rates of the proximal femur in older women compared with men of similar age providing new information on the pathophysiology of osteoporosis.

Effects of romosozumab combined with routine therapy on pain relief, disease progression and adverse reactions in patients with postmenopausal osteoporosis: a systematic review and meta-analysis.

Postmenopausal osteoporosis (PMOP) increases fracture risk in women. Though traditional treatments are slow to act, combining romosozumab with conventional therapy shows promise. Despite its growing use, studies on effectiveness are limited. This study aims to systematically evaluate the combined therapy's impact on pain relief, disease progression, and adverse reactions in PMOP patients. Databases including PubMed, EMBASE, ScienceDirect, and the Cochrane Library were searched from their inception to September 2023 to identify randomized controlled trials (RCTs) evaluating the role of romosozumab in PMOP. Random or fixed effect models were employed for statistical analysis. Two reviewers independently assessed the quality of the included studies and extracted the data. The meta-analysis was conducted using RevMan 5.4 software. Six RCTs with a total sample size of 17,985 cases were included. The incidence of vertebral fractures was compared and analyzed after 12 and 24 months of treatment. Romosozumab significantly reduced the incidence of vertebral fractures at 24 months (OR = 0.36; 95% CI: 0.35-0.52) but not at 12 months (OR = 0.39; 95% CI: 0.14-1.05). It was also associated with a decreased incidence of nonvertebral fractures (OR = 0.79; 95% CI: 0.66-0.94) and clinical fractures at 24 months (OR = 0.70; 95% CI: 0.59-0.82) compared to standard therapy. Romosozumab demonstrated a significant improvement in percentage change in bone mineral density (BMD) [mean difference (MD) = 10.38; 95% CI: 4.62-16.14] and in hip joint BMD (MD = 4.24; 95% CI: 2.92-5.56). There was no notable difference in adverse reactions compared to standard care (p > 0.05). Funnel plots displayed a predominantly symmetrical pattern, suggesting no evidence of publication bias in the selected literature. Combining romosozumab with conventional therapy effectively treats PMOP, significantly reducing vertebral, non-vertebral, and clinical fractures while increasing BMD in the hip, femoral neck, and lumbar spine. However, further high-quality studies are needed for validation.

Bone Mineral Density Monitoring in Contiguous versus Non-Contiguous Lumbar Vertebrae: The Manitoba BMD Registry

Introduction: Only change in bone mineral density (BMD) on repeat DXA that exceeds the 95% least significant change (LSC) should be considered clinically meaningful. Frequently lumbar spine DXA must be reported after omitting vertebrae with localized structural artifact, which reduces measurement precision. Previous reports have raised concerns of higher least significant change (LSC) when spine BMD is based on non-contiguous rather than contiguous vertebrae. The current study was performed to compare lumbar spine LSC and BMD response to intervening anti-osteoporosis medication use from non-contiguous versus contiguous vertebrae.Methodology: LSCs for lumbar spine DXA based on L1-L4 and all combinations of non-contiguous and contiguous vertebrae were calculated using 879 scan-pairs from the Manitoba BMD Program. We compared BMD change from these regions, overall and in relation to intervening anti-osteoporosis medication use, in 11,722 patients who had 2 DXA examinations.Results: LSCs were slightly greater when calculated from combinations of fewer than 4 vertebrae, but there was no meaningful difference between contiguous versus non-contiguous vertebrae. There were consistently high correlations between lumbar spine BMD change from L1-L4 and all combinations of continuous and non-contiguous vertebrae (all Pearson r≥ 0.9, p<0.001). Percentage changes in spine BMD and the fraction with treatment-concordant change exceeding the LSC were similar using contiguous or non-contiguous vertebrae.Conclusions: Lumbar spine BMD change can be assessed from 2 or 3 non-contiguous vertebrae when clinically necessary, and precision in such cases is similar to using contiguous vertebrae. Non-contiguous vertebrae can detect treatment-concordant changes similar in spine BMD to contiguous vertebrae.

Effect of bisphosphonate and denosumab treatment on TBS in Japanese breast cancer patients with AIBL.

Bisphosphonates and denosumab increase bone mineral density (BMD) for osteoporosis treatment in patients with aromatase inhibitor-associated bone loss (AIBL). This study aimed to directly compare bisphosphonates with denosumab in treating patients with AIBL and to determine the effect of denosumab on the trabecular bone score (TBS). Thirty-nine patients with AIBL receiving osteoporosis treatment (21 in the bisphosphonates group and 18 in the denosumab group) were retrospectively evaluated for changes in lumbar spine and femoral BMD, lumbar spine bone quality (assessed by TBS), and blood bone metabolic markers. The Mann-Whitney and Wilcoxon tests were used for statistical evaluation. After 24months of treatment, the lumbar spine BMD change rate was 5.82 ± 1.10% with bisphosphonates and 10.49 ± 1.20% with denosumab, with the change rate of denosumab significantly increasing over that of bisphosphonates. The change rate in femoral BMD was 2.69 ± 1.16% with bisphosphonates and 2.95 ± 1.26% with denosumab, with no significant difference between the two groups. The rate of decrease in tartrate-resistant acid phosphatase isoform 5b was significantly higher in the denosumab group. The change rate in TBS at 24months of treatment was 0.53 ± 1.26% in the bisphosphonates group and 1.08 ± 1.33% in the denosumab group, with no significant difference between the two groups. After 24months, TBS remained stable. Both bisphosphonates and denosumab may increase BMD, improve bone metabolism, and inhibit bone quality loss in patients with AIBL.

One versus 2years of alendronate following denosumab: the CARD extension.

When denosumab is discontinued, antiresorptive therapy is critical to attenuate high-turnover bone loss. The ideal choice and duration of antiresorptive therapy are not yet defined, however. In the Comparison of Alendronate or Raloxifene following Denosumab (CARD) study, we demonstrated that 12months of alendronate was better able to maintain the bone mineral density (BMD) gains achieved with 12months of denosumab versus 12months of raloxifene. In this extension, we wished to determine if 12months of alendronate would be sufficient in maintaining these denosumab-induced BMD gains. In the CARD study, postmenopausal osteoporotic women aged 60-79 at high fracture risk received 12months of denosumab 60-mg SC every 6months followed by 12months of either alendronate 70mg weekly (N = 26) or raloxifene (N = 25). All subjects in the alendronate arm were then offered participation in a 1-year extension in which they were randomized to continue alendronate for an additional 12months (N = 10) or to receive calcium and vitamin D alone (N = 8). The primary outcome was change in spine BMD between months 24 and 36. Exploratory endpoints included changes in areal BMD (aBMD) at other anatomic sites as well as changes in serum bone turnover markers. The CARD study demonstrated the effectiveness of 12months alendronate in preserving denosumab-induced BMD gains. In the extension, aBMD was maintained at the spine, total hip, and femoral neck in both those randomized to an additional year of alendronate and those randomized to calcium/vitamin D alone. We did, however, observe a transient comparative decrease between months 24-30 in the calcium/vitamin D group at the total hip (P = 0.008) and femoral neck (P = 0.040). At the end of 24months of the CARD study, bone turnover markers serum c-telopeptide (CTX) and procollagen N-propeptide of type I collagen (PINP) were suppressed in both groups and then increased more between months 24-36 in the calcium/vitamin D group than the alendronate group (P = 0.051 for CTX, P = 0.030 for P1NP). Both CTX and PINP remained below the month 0 baseline in both groups (P < 0.05 for all comparisons). With the limitations of our small sample size, these data suggest that both 1 and 2years of alendronate effectively maintain BMD gains achieved with 1year of denosumab and prevented any rebound in bone turnover marker levels above pre-denosumab baseline. This is the first randomized trial to assess minimum duration of bisphosphonate after short-term denosumab and may be helpful to guide clinical care. Similar studies performed after longer durations of denosumab would be helpful to further define optimal management. ClinicalTrials.gov registration number: NCT03623633.

The potential effect of romosozumab on perioperative management for instrumentation surgery.

Age-related changes in bone health increase the risk for complications in elderly patients undergoing orthopedic surgery. Osteoporosis is a key therapeutic target that needs to be addressed to ensure successful instrumentation surgery. The effectiveness of pharmacological interventions in orthopedic surgery, particularly the new drug romosozumab, is still unknown. We aim to evaluate the effect of 3-month romosozumab treatment on biomechanical parameters related to spinal instrumentation surgery, using the Quantitative Computed Tomography (QCT)-based Finite Element Method (FEM). This open-labeled, prospective study included 81 patients aged 60 to 90 years, who met the osteoporosis criteria and were scheduled for either romosozumab or eldecalcitol treatment. Patients were assessed using blood samples, dual-energy absorptiometry (DXA), and QCT. Biomechanical parameters were evaluated using FEM at baseline and 3 months post-treatment. The primary endpoints were biomechanical parameters at 3 months, while secondary endpoints included changes in regional volumetric bone mineral density around the pedicle (P-vBMD) and vertebral body (V-vBMD). Romosozumab treatment led to significant gains in P-vBMD, and V-vBMD compared to eldecalcitol at 3 months. Notably, the romosozumab group showed greater improvements in all biomechanical parameters estimated by FEM at 3 months compared to the eldecalcitol group. Romosozumab significantly increased the regional vBMD as well as biomechanical parameters, potentially offering clinical benefits in reducing post-operative complications in patients with osteoporosis undergoing orthopedic instrumentation surgery. This study highlights the novel advantages of romosozumab treatment and advocates further research on its effectiveness in perioperative management.

Exploring Resveratrol Intervention in Managing Menopausal Symptoms: A Comprehensive Systematic Review of Clinical Trials

Introduction: Menopause, a significant event in a woman's reproductive lifespan, entails hormonal changes and a range of symptoms affecting various bodily systems. Conventional treatments like hormone replacement therapy (HRT) have limitations and associated risks, prompting interest in alternative therapies such as resveratrol. Materials/Methods: The literature search was conducted in six databases. The outcome of interest measures the mean changes in bone mineral density (BMD), Quality of Life (QoL), bone biomarkers, menopause symptoms, and cognitive and mood functions pre- and post-interventions. Resveratrol was administered in various forms and doses, including trans-resveratrol 75 mg twice or once daily, 250/500/1000 mg resveratrol tablets, and a combination of fermented soy containing 10 mg equol and 25 mg resveratrol. Quality appraisal was done using the Cochrane Risk of Bias Tool 2. Results: Resveratrol supplementation in post-menopausal women, involving 745 participants across various studies, has shown remarkable health benefits. These include improved cerebral vasoreactivity (CVR) to hypercapnia, a 10% decrease in overall pain, and enhanced quality of life. Additionally, resveratrol boosts flow-mediated dilation (FMD) by 23% and increases serum sex hormone-binding globulin (SHBG) concentrations by 10%, benefiting bone mineral density (BMD). Over the long term, it leads to a significant 35% increase in FMD and a substantial 33% enhancement in overall cognitive performance, highlighting its diverse benefits. Conclusion: For women in the post-menopausal stage, resveratrol supplementation shows potential for improving cardiovascular health, relieving pain, enhancing quality of life, supporting bone health, boosting cognitive function, and promoting overall mental well-being.

Correlation study: Bone density and circulating inflammatory markers in postmenopausal patients.

This study aims to investigate the correlation between changes in bone mineral density (BMD) in postmenopausal women and circulating inflammatory markers. This retrospective study focused on postmenopausal women admitted to the orthopedic department of Suzhou Benq Medical Center from June 2022 to December 2023, following predetermined inclusion and exclusion criteria. We retrospectively collected data on initial blood routine test results and bone density measurements for all study subjects upon admission, including parameters such as white blood cell count (WBC), C-reactive protein, interleukin-6 (IL-6), and procalcitonin (PCT). Additionally, the systemic immune-inflammation index (SII) was calculated using neutrophil count, lymphocyte count, and platelet count. Statistical analyses using SPSS and GraphPad software were performed to assess the correlation between bone density and inflammatory markers. Patients were classified into three groups based on BMD results, including 60 individuals in the osteoporosis (OP) group, 127 individuals in the osteopenia group, and 37 individuals in the Normalgroup, respectively. Principal component analysis analysis suggested that WBC, SII, and postmenopausal OP(PMOP) held significant feature values. Correlation analysis indicated a correlation between WBC (p = 0.021), IL-6 (p = 0.044), SII (p = 0.034), and PMOP. One-way ANOVA analysis revealed significant differences in IL-6 (p = 0.0179), SII (p = 0.0210), and PCT (p = 0.0200) among the three groups. Finally, ROC curve analysis demonstrated that SII (area under the curve = 0.716) has predictive value for PMOP. This study identified a certain predictive value for PMOP through the assessment of inflammatory markers in peripheral blood using routine blood tests.

Does krill oil enhancing the new bone formation in orthopedically expanded median palatal suture in rat model? A micro-CT and immunohistochemical analysis

BackgroundThe purpose of this study was to assess the effects of systemically given krill oil (KO) on the development of new bone formation in the sutura palatina media following rapid maxillary expansion (RME).Methods28 4–5 week-old male Wistar albino rats were randomly divided into 4 groups: Control (C), Only Expansion (OE) (no supplement but undergoing expansion and retention), KE (supplemented during both the expansion and retention phases), Krill Oil Nursery Group (KN) (supplemented during the 40-day nursery phase as well as during the expansion and retention phases). A 5-day RME was followed by a 12-day retention period. All rats were euthanized simultaneously. Micro-computerized tomography (Micro-CT), hemotoxylen-eosin (H&E) staining, and immunohistochemical analysis were conducted. Kruskal-Wallis and Dunn tests with Bonferonni corrrection were applied (p < 0.05).ResultsExpansion and KO supplementation did not cause a statistically significant change in bone mineral density (BMD), bone volume fraction (BV/TV), spesific bone surface (BS/BV) and trabecular thickness (Tb.Th). While the expansion prosedure increased the trabecular seperation (Tb.Sp), KO supplemantation mitigated this effect. The KE group exhibited a statistically significantly increase in trabecular number (Tb.N) compared to the OE group. Although receptor activator of nuclear factor-kappa-Β ligand (RANKL)/osteoprotegerin (OPG) ratios did not show significant differences between groups, the KE and OE groups demonstrated the lowest and highest value, respectively. KE showed a reduced amount of tartrate-resistant acid phosphatase (TRAP) compared to the OE.ConclusionKO positively affected the architecture of the new bone formed in the mid-palatal suture. In this rat model of RME, results support the idea that administering of KO during the expansion period or beginning before the RME procedure may reduce relapse and enhance bone formation within the mid-palatal suture.

Association Between Osteoporosis and Adiposity Index Reveals Nonlinearity Among Postmenopausal Women and Linearity Among Men Aged over 50 Years

PurposePrevious research shows conflicting views on the relationship between obesity and osteoporosis, partly due to variations in obesity classification and the nonlinear nature of these relationships. This study investigated the association between adiposity indices and osteoporosis, diagnosed using dual-energy X-ray absorptiometry (DXA), employing nonlinear models and offering optimal thresholds to prevent further bone mineral density decline.MethodsIn 2019, a prospective study enrolled males over 50 years and postmenopausal women. Anthropometric measurements, blood biochemistry, and osteoporosis measured by DXA were collected. Associations between adiposity indices and osteoporosis were analyzed using a generalized additive model and segmented regression model.ResultsThe study included 872 women and 1321 men. Indices such as abdominal volume index (AVI), visceral adiposity index (VAI), waist circumference (WC), hip circumference, body mass index (BMI), waist-to-hip ratio, and waist-to-height ratio (WHtR) were inversely associated with osteoporosis. In women, the relationship between the risk of osteoporosis and the adiposity indices was U-shaped, with thresholds of WC = 94 cm, AVI = 17.67 cm2, BMI = 25.74 kg/m2, VAI = 4.29, and WHtR = 0.61, considering changes in bone mineral density. Conversely, men exhibited a linear patterns for the inverse association.ConclusionThe impact of obesity and adiposity on osteoporosis varies significantly between women and men. In postmenopausal women, the relationship is nonlinear (U-shaped), with both very low and very high adiposity linked to higher osteoporosis risk. In men over 50, the relationship is linear, with higher adiposity associated with lower osteoporosis risk. The study suggests that maintaining specific levels of adiposity could help prevent osteoporosis in postmenopausal women.

Impact of dairy supplementation on bone acquisition in children's limbs: a 12-month cluster-randomized controlled trial and meta-analysis.

This study evaluated the impact of dairy supplementation on bone acquisition in children's limbs through a cluster-randomized controlled trial and a meta-analysis. The trial involved 315 children (4-6year) from Northwest China, randomized to receive either 390ml of milk daily (n = 215) or 20-30g of bread (n = 100) over 12months. We primarily assessed bone mineral density (BMD) and content (BMC) changes at the limbs, alongside bone-related biomarkers, measured at baseline, the 6th and 12th months. The meta-analysis aggregated BMD or BMC changes in the forearm/legs/calcaneus from published randomized trials involving children aged 3-18years supplemented with dairy foods (vs. control group). Of 278 completed the trial, intention-to-treat analysis revealed significant increases in BMD (4.05% and 7.31%) and BMC (4.69% and 7.34%) in the left forearm at the 6th and 12th months in the milk group compared to controls (P < 0.001). The calcaneus showed notable improvements in BMD (2.01%) and BMC (1.87%) at 6months but not at 12months. Additionally, milk supplementation was associated with beneficial changes in bone resorption markers, parathyroid hormone (- 12.70%), insulin-like growth factor 1 (6.69%), and the calcium-to-phosphorus ratio (2.22%) (all P < 0.05). The meta-analysis, encompassing 894 children, indicated that dairy supplementation significantly increased BMD (SMD, 0.629; 95%CI: 0.275, 0.983) and BMC (SMD, 0.616; 95%CI: 0.380, 0.851) (P < 0.05) in the arms, but not in the legs (P > 0.05). Milk supplementation significantly improves bone health in children's forearms, underscoring its potential as a strategic dietary intervention for bone development. Trial registration NCT05074836.

Romosozumab followed by denosumab versus denosumab only: a post hoc analysis of FRAME and FRAME extension.

Osteoanabolic-first treatment sequences are superior to oral bisphosphonates for fracture reduction and bone mineral density (BMD) gain. However, data comparing osteoanabolic medications, with the more potent antiresorptive, denosumab (DMAb), are limited. We analyzed FRAME and FRAME Extension data to assess BMD and fracture incidence in patients treated with romosozumab (Romo) followed by DMAb (Romo/DMAb) versus DMAb (DMAb/DMAb) for 24months. In FRAME, women aged ≥55years (total hip [TH] or femoral neck [FN] T-score: -2.5 to -3.5) were randomized to Romo or placebo for 12months followed by DMAb for 12months. In FRAME Extension, both cohorts received DMAb for another 12months. This post hoc analysis compared BMD change and fracture incidence in patients on Romo/DMAb (months 0-24) versus DMAb/DMAb (months 12-36). Patient characteristics were balanced by propensity score weighting (PSW) and sensitivity analyses were conducted using PSW with multiple imputation (PSW-MI) and propensity score matching (PSM). Unmeasured confounding was addressed using E-values. After PSW, over 24months, compared with DMAb/DMAb, treatment with Romo/DMAb produced significantly greater BMD increases at the lumbar spine [LS], TH, and FN (mean differences: 9.3%, 4.4%, and 4.1%, respectively; all p<0.001). At month 24, in women with a baseline T-score of -3.0, the probability of achieving a T-score > -2.5 was higher with Romo/DMAb versus DMAb/DMAb (LS: 92% versus 47%; TH: 50% versus 5%). In the Romo/DMAb versus DMAb/DMAb cohorts, new vertebral fractures were significantly reduced (0.62% versus 1.26% [odds ratio = 0.45; p=0.003]) and rates of clinical, nonvertebral, and hip fractures were lower (differences not significant). Similar BMD and fracture outcomes were observed with PSW-MI and PSM sensitivity analyses. The sequence of Romo/DMAb resulted in greater BMD gains and higher probability of achieving T-scores > -2.5, significantly reduced new vertebral fracture incidence, and numerically lowered the incidence (not significant) of clinical, nonvertebral, and hip fractures versus DMAb only through 24months.

Impact of Different Anti-Hyperglycaemic Treatments on Bone Turnover Markers and Bone Mineral Density in Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-Analysis.

Diabetic bone disease (DBD) is a frequent complication in patients with type 2 diabetes mellitus (T2DM), characterised by altered bone mineral density (BMD) and bone turnover marker (BTMs) levels. The impact of different anti-diabetic medications on the skeleton remains unclear, and studies have reported conflicting results; thus, the need for a comprehensive systematic review is of paramount importance. A systematic search was conducted in PubMed and the Cochrane Library. The primary outcomes assessed were changes in BMD in relation to different anatomical sites and BTMs, including mainly P1NP and CTX as well as OPG, OCN, B-ALP and RANK-L. Risk of bias was evaluated using the JADAD score. The meta-analysis of 19 randomised controlled trials comprising 4914 patients showed that anti-diabetic medications overall increased BMD at the lumbar spine (SMD: 0.93, 95% CI [0.13, 1.73], p = 0.02), femoral neck (SMD: 1.10, 95% CI [0.47, 1.74], p = 0.0007) and in total hip (SMD: 0.33, 95% CI [-0.25, 0.92], p = 0.27) in comparison with placebo, but when compared with metformin, the overall effect favoured metformin over other treatments (SMD: -0.23, 95% CI [-0.39, -0.07], p = 0.004). GLP-1 receptor agonists and insulin analogues seem to improve BMD compared to placebo, while SGLT2 inhibitors and thiazolidinediones (TZDs) showed no significant effect, although studies' number cannot lead to safe conclusions. For BTMs, TZDs significantly increased P1NP levels compared to placebo. However, no significant differences were observed for CTX, B-ALP, OCN, OPG, and RANK-L between anti-diabetic drugs and metformin or placebo. High heterogeneity and diverse follow-up durations among studies were evident, which obscures the validity of the results. This review highlights the variable effects of anti-diabetic drugs on DBD in T2DM patients, emphasising the need for long-term trials with robust designs to better understand these relationships and inform clinical decisions.

Effects of romosozumab on bone mineral density and fractures in postmenopausal women: a meta-analysis

Purpose: Romosozumab, a mono-clonal antibody has been approved for the treatment of postmenopausal women with osteoporosis and high fracture risk. This meta-analysis evaluated the effect of romosozumab on Bone Mineral Density (BMD) and fracture occurrence in postmenopausal women with osteoporosis.Methods: A systematic search was done adhered to the PRISMA guidelines in PubMed, Ovid and Clinicaltrials.gov and eligible studies were selected. The details related to study participants, changes in BMD at the lumber spine (LS), total hip (TH) and femoral neck (FN) and the occurrence of fractures during the period were extracted. The mean differences of BMDs between the two groups and odds ratios (OR) of fractures were considered as the outcome of the studies.Results: Of the 11 potentially eligible articles, only four studies fulfilled the selection criteria and they were included in the final analysis. Romosozumab therapy for 12 months increased mean BMD at the LS by 12.7% (95% CI, 9.7, 15.6), TH by 4.8% (95% CI, 3.3,6.3) and FN by 4.1% (95% CI, 3.1, 5.2). Treatment with romosozumab decreased the odds of new vertebral fractures and vertebral fractures by 58% (OR=0.42, CI, 0.23,0.91) and 25% (OR=0.75, CI, 0.53,1.06) respectively at the end of 12 months.Conclusion: Romosozumab significantly increases BMD at LS, TH and FN and reduces the risk of new vertebral and non-vertebral fractures in postmenopausal women with osteoporosis.

Setrusumab for the treatment of osteogenesis imperfecta: 12-month results from the phase 2b asteroid study.

Osteogenesis imperfecta (OI) is a rare genetic disorder commonly caused by variants of the type I collagen genes COL1A1 and COL1A2. OI is associated with increased bone fragility, bone deformities, bone pain, and reduced growth. Setrusumab, a neutralizing antibody to sclerostin, increased areal bone mineral density (aBMD) in a 21-week phase 2a dose escalation study. The phase 2b Asteroid (NCT03118570) study evaluated the efficacy and safety of setrusumab in adults. Adults with a clinical diagnosis of OI type I, III, or IV, a pathogenic variant in COL1A1/A2, and a recent fragility fracture were randomized 1:1:1:1 to receive 2, 8, or 20mg/kg setrusumab doses or placebo by monthly intravenous infusion during a 12-mo treatment period. Participants initially randomized to the placebo group were subsequently reassigned to receive setrusumab 20mg/kg open label. Therefore, only results from the 2, 8, and 20mg/kg double-blind groups are presented herein. The primary endpoint of Asteroid was change in distal radial trabecular volumetric bone mineral density (vBMD) from baseline at month 12, supported by changes in high-resolution peripheral quantitative computed tomography micro-finite element (microFE)-derived bone strength. A total of 110 adults were enrolled with similar baseline characteristics across treatment groups. At 12mo, there was a significant increase in mean (SE) failure load in the 20mg/kg group (3.17% [1.26%]) and stiffness in the 8 (3.06% [1.70%]) and 20mg/kg (3.19% [1.29%]) groups from baseline. There were no changes in radial trabecula vBMD (p>05). Gains in failure load and stiffness were similar across OI types. There were no significant differences in annualized fracture rates between doses. Two adults in the 20mg/kg group experienced related serious adverse reactions. Asteroid demonstrated a beneficial effect of setrusumab on estimates of bone strength across the different types of OI and provides the basis for additional phase 3 evaluation.

Blackcurrants shape gut microbiota profile and reduce risk of postmenopausal osteoporosis via the gut-bone axis: Evidence from a pilot randomized controlled trial

This study aimed to investigate the effects of blackcurrant (BC) on gut microbiota abundance and composition, inflammatory and immune responses, and their relationship with bone mass changes. The effects of BC on bone mineral density (BMD), gut microbiota, and blood inflammatory and immune biomarkers were evaluated using DXA, stool and fasting blood collected from a pilot three-arm, randomized, double-blind, placebo-controlled clinical trial. Fifty-one peri- and early postmenopausal women aged 45–60 years were randomly assigned into one of three treatment groups for 6 months: control, low BC (392 mg/day) and high BC (784 mg/day); and 40 women completed the trial. BC supplementation for 6 months effectively mitigated the loss of whole-body BMD (P<.05). Six-month changes (%) in peripheral IL-1β (P=.056) and RANKL (P=.052) for the high BC group were marginally significantly lower than the control group. Six-month changes in whole-body BMD were inversely correlated with changes in RANKL (P<.01). In proteome analysis, four plasma proteins showed increased expression in the high BC group: IGFBP4, tetranectin, fetuin-B, and vitamin K-dependent protein S. BC dose-dependently increased the relative abundance of Ruminococcus 2 (P<.05), one of six bacteria correlated with BMD changes in the high BC group (P<.05), suggesting it might be the key bacteria that drove bone protective effects. Daily BC consumption for 6 months mitigated bone loss in this population potentially through modulating the gut microbiota composition and suppressing osteoclastogenic cytokines. Larger-scale clinical trials on the potential benefits of BC and connection of Ruminococcus 2 with BMD maintenance in postmenopausal women are warranted.Trial Registration: NCT04431960, https://classic.clinicaltrials.gov/ct2/show/NCT04431960.

Influence of broach surface design of a fully hydroxyapatite coated, double tapered stem on periprosthetic bone mineral density after total hip arthroplasty: a study based on the morphology of the proximal femur.

This study aimed to compare the impact of different broach surface designs on post-operative clinical outcomes, bone reactions and changes in bone mineral density (BMD) in patients who underwent total hip arthroplasty (THA) using a fully hydroxyapatite coated and double tapered stem with either compaction shape (COM) or hybrid shape (HYB) broaches. A retrospective analysis was conducted on 76 patients (100 hips) who underwent primary THA using the Avenir complete stem®. Patients were divided into two groups: the COM broach group (50 hips) and HYB broach group (50 hips). We evaluated clinical outcomes using the Japanese Orthopaedic Association hip scores one month before the surgery, and 12 and 24months after the surgery. Radiographic findings, including stem alignment angles, radiolucent lines, spot welds, and cortical hypertrophy, were assessed. BMD around the stem in Gruen zones 1-7 was evaluated using dual-energy X-ray absorptiometry (DEXA) at 7days, 12, and 24months post-operatively. The Dorr classification was used to assess femoral morphology. There were no significant differences in clinical outcomes, radiographic findings, or BMD changes between the COM and HYB broach groups in the overall patient cohort. However, in Dorr type A femurs, the COM broach group demonstrated superior BMD superior preservation in zones 1 and 7 after 12months and in zones 1, 6 and 7 after 24months. Additionally, in Dorr type B femurs, significant BMD preservation was observed in zone 3 at 24months in the COM broach group. This study suggests that the broach surface design of fully hydroxyapatite coated stems may influence periprosthetic BMD changes, especially in Dorr type A and B femurs. Surgeons should consider broach selection based on patient-specific femoral morphology to optimize BMD preservation in THA procedures using fully hydroxyapatite coated stems.

Efficacy and safety of romosozumab: a meta-analysis of placebo-controlled trials.

We aimed to comprehensively compile placebo-controlled trials on the efficacy and safety of romosozumab (210mg, subcutaneously, once monthly) in postmenopausal women and men with osteoporosis. PubMed, Google Scholar, and ClinicalTrials.gov were searched for relevant placebo-controlled trials (as of January 1, 2024). Percent change in bone mineral density (BMD), falls, fractures, and adverse events (AEs) after drug administration were collected. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Six trials (7990 patients; follow-up period, 6-12months) were included. Compared with placebo, romosozumab significantly increased lumbar spine BMD (MD = 12.69; 95% CI 11.10-14.29), total hip BMD (MD = 4.42; 95% CI 3.03-5.80), and femoral neck BMD (MD = 3.99; 95% CI 2.42-5.57) at 12months. Romosozumab significantly decreased falls (RR = 0.80; 95% CI 0.68-0.93) and major osteoporotic fractures (RR = 0.37; 95% CI 0.25-0.54), but increased injection-site reactions (RR = 1.83; 95% CI 1.46-2.30) within 12months. No significant differences were observed in other AEs (including cardiovascular AEs) within 12months. Romosozumab treatment resulted in a significant BMD gain, reduced falls and major osteoporotic fractures. It was generally well-tolerated, including the cardiovascular aspects. However, clinicians should consider the occurrence of minor AEs (e.g., injection-site reactions).

Modelling future bone mineral density: Simplicity or complexity?

BackgroundOsteoporotic fractures are a major global public health issue, leading to patient suffering and death, and considerable healthcare costs. Bone mineral density (BMD) measurement is important to identify those with osteoporosis and assess their risk of fracture. Both the absolute BMD and the change in BMD over time contribute to fracture risk. Predicting future fracture in individual patients is challenging and impacts clinical decisions such as when to intervene or repeat BMD measurement. Although the importance of BMD change is recognised, an effective way to incorporate this marginal effect into clinical algorithms is lacking. MethodsWe compared two methods using longitudinal DXA data generated from subjects with two or more hip DXA scans on the same machine between 2000 and 2018. A simpler statistical method (ZBM) was used to predict an individual's future BMD based on the mean BMD and the standard deviation of the reference group and their BMD measured in the latest scan. A more complex deep learning (DL)-based method was developed to cope with multidimensional longitudinal data, variables extracted from patients' historical DXA scan(s), as well as features drawn from the ZBM method. Sensitivity analyses of several subgroups was conducted to evaluate the performance of the derived models. Results2948 white adults aged 40–90 years met our study inclusion: 2652 (90 %) females and 296 (10 %) males. Our DL-based models performed significantly better than the ZBM models in women, particularly our Hybrid-DL model. In contrast, the ZBM-based models performed as well or better than DL-based models in men. ConclusionsDeep learning-based and statistical models have potential to forecast future BMD using longitudinal clinical data. These methods have the potential to augment clinical decisions regarding when to repeat BMD testing in the assessment of osteoporosis.