Establish and validate the reliability of predictive models in bone mineral density by deep learning as examination tool for women.

While FRAX with BMD could be more precise in estimating the fracture risk, DL-based models were validated to slightly reduce the number of under- and over-treated patients when no BMD measurements were available. The validated models could be used to screen for patients at a high risk of fracture and osteoporosis. PURPOSE: Fracture risk assessment tool (FRAX) is useful in classifying the fracture risk level, and precise prediction can be achieved by estimating both clinical risk factors and bone mineral density (BMD) using dual X-ray absorptiometry (DXA). However, DXA is not frequently feasible because of its cost and accessibility. This study aimed to establish the reliability of deep learning (DL)-based alternative tools for screening patients at a high risk of fracture and osteoporosis. METHODS: Participants were enrolled from the National Bone Health Screening Project of Taiwan in this cross-sectional study. First, DL-based models were built to predict the lowest T-score value in either the lumbar spine, total hip, or femoral neck and their respective BMD values. The Bland-Altman analysis was used to compare the agreement between the models and DXA. Second, the predictive model to classify patients with a high fracture risk was built according to the estimated BMD from the first step and the FRAX score without BMD. The performance of the model was compared with the classification based on FRAX with BMD. RESULTS: Approximately 10,827 women (mean age, 65.4 ± 9.4 years) were enrolled. In the prediction of the lumbar spine BMD, total hip BMD, femoral neck BMD, and lowest T-score, the root-mean-square error (RMSE) was 0.099, 0.089, 0.076, and 0.68, respectively. The Bland-Altman analysis revealed a nonsignificant difference between the predictive models and DXA. The FRAX score with femoral neck BMD for major osteoporotic fracture risk was 9.7% ± 6.7%, whereas the risk for hip fracture was 3.3% ± 4.6%. Comparison between the classification of FRAX with and without BMD revealed the accuracy rate, positive predictive value (PPV), and negative predictive value (NPV) of 78.8%, 64.6%, and 89.9%, respectively. The area under the receiver operating characteristic curve (AUROC), accuracy rate, PPV, and NPV of the classification model were 0.913 (95% confidence interval: 0.904-0.922), 83.5%, 71.2%, and 92.2%, respectively. CONCLUSION: While FRAX with BMD could be more precise in estimating the fracture risk, DL-based models were validated to slightly reduce the number of under- and over-treated patients when no BMD measurements were available. The validated models could be used to screen for patients at a high risk of fracture and osteoporosis.

Intraoperative physician assessment during total hip arthroplasty correlates with DXA parameters.

PURPOSE: Orthopedic surgeons can assess bone status intraoperatively and recommend skeletal health evaluation for patients with poor bone quality. Intraoperative physician assessment (IPA) at the time of total knee arthroplasty correlates with preoperative DXA-measured bone mineral density (BMD). This study evaluated IPA during total hip arthroplasty (THA) as a quantitative measure of bone status based on tactile assessment. METHODS: This retrospective analysis identified 60 patients (64 hips) undergoing primary THA who had IPA recorded in the operative report and a DXA within 2 years before surgery. Intraoperatively, two surgeons assessed bone quality on a 5-point scale (1 = excellent; 5 = poor). IPA score was compared to DXA BMD and T-score, 3D Shaper measurements, WHO classification, FRAX scores, radiographic Dorr classification, and cortical index. RESULTS: There was a strong correlation between the IPA score and lowest T-score, WHO classification, and FRAX major and hip fracture scores (r = ± 0.485-0.622, all p < 0.001). There was a moderate correlation between IPA score and total hip BMD and 3D Shaper measurements, including trabecular volumetric BMD, cortical surface BMD, and cortical thickness (r = ± 0.326-0.386, all p < 0.01). All patients with below-average IPA scores had osteopenia or osteoporosis by DXA. CONCLUSION: IPA during THA is a simple, valuable tool for quantifying bone status based on tactile feedback. This information can be used to identify patients with poor bone quality that may benefit from skeletal status evaluation and treatment and provide intraoperative guidance for implant selection. Orthopedic surgeons can assess bone health at the time of surgery. Intraoperative physician assessment (IPA) is a bone quality score based on surgeons' tactile assessment that correlates strongly with the lowest T-score, WHO classification, and FRAX fracture risk. IPA can guide surgical decision-making and future bone health treatment.

Prior fragility fractures are associated with a higher risk of 8-year complications following total shoulder arthroplasty.

Patients who sustain fragility fractures prior to total shoulder arthroplasty have significantly higher risk for bone health-related complications within 8 years of procedure. Identification of these high-risk patients with an emphasis on preoperative, intraoperative, and postoperative bone health optimization may help minimize these preventable complications. PURPOSE: As the population ages, more patients with osteoporosis are undergoing total shoulder arthroplasty (TSA), including those who have sustained a prior fragility fracture. Sustaining a fragility fracture before TSA has been associated with increased risk of short-term revision rates, periprosthetic fracture (PPF), and secondary fragility fractures but long-term implant survivorship in this patient population is unknown. Therefore, the purpose of this study was to characterize the association of prior fragility fractures with 8-year risks of revision TSA, periprosthetic fracture, and secondary fragility fracture. METHODS: Patients aged 50 years and older who underwent TSA were identified in a large national database. Patients were stratified based on whether they sustained a fragility fracture within 3 years prior to TSA. Patients who had a prior fragility fracture (7631) were matched 1:1 to patients who did not based on age, gender, Charlson Comorbidity Index (CCI), smoking, obesity, diabetes mellitus, and alcohol use. Kaplan-Meier and Cox Proportional Hazards analyses were used to observe the cumulative incidences of all-cause revision, periprosthetic fracture, and secondary fragility fracture within 8 years of index surgery. RESULTS: The 8-year cumulative incidence of revision TSA (5.7% vs. 4.1%), periprosthetic fracture (3.8% vs. 1.4%), and secondary fragility fracture (46.5% vs. 10.1%) were significantly higher for those who had a prior fragility fracture when compared to those who did not. On multivariable analysis, a prior fragility fracture was associated with higher risks of revision (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.24-1.74; p < 0.001), periprosthetic fracture (HR, 2.98; 95% CI, 2.18-4.07; p < 0.001) and secondary fragility fracture (HR, 8.39; 95% CI, 7.62-9.24; p < 0.001). CONCLUSIONS: Prior fragility fracture was a significant risk factor for revision, periprosthetic fracture, and secondary fragility fracture within 8 years of primary TSA. Identification of these high-risk patients with an emphasis on preoperative and postoperative bone health optimization may help minimize these complications. LEVEL OF EVIDENCE: III.

Insulin resistance, bone health, and fracture risk.

Insulin resistance, defined as an impaired biological response to insulin stimulation in target tissues, arises most frequently in the presence of central obesity. Although obesity is generally associated with increased bone mass, recent data challenge this view and, if complicated by T2DM, obese patients are at high risk for fragility fractures. IR may play a key role in this increased fracture risk through effects on bone quality rather than bone quantity. Further understanding of the mechanisms and approaches to prevent osteoporotic fractures in IR-related diseases is needed. CLINICAL RELEVANCE: The dramatic increase in obesity and metabolic syndrome (MetS) over the last half-century has led to a worldwide epidemic of type 2 diabetes mellitus (T2DM) as well as in the incidence of insulin resistance (IR). IR is defined as an impaired biological response to insulin stimulation in target tissues and is primarily related to the liver, muscle, and adipose tissue. The most frequent underlying cause is central obesity, and it is known that excess abdominal adipose tissue secretes increased amounts of free fatty acids, which directly affects insulin signalling, reduces glucose uptake in muscle, and triggers excessive triglyceride synthesis and gluconeogenesis in the liver. When pancreatic ß cells are unable to secrete the higher levels of insulin needed, T2DM, the main complication of IR, occurs. OBSERVATIONS: Although obesity is generally associated with increased bone mass, recent data challenge this view and highlight the multifaceted nature of the obesity-bone relationship. Patients with T2DM are at significant risk for well-known complications of diabetes, including retinopathy, nephropathy, macrovascular disease, and neuropathy, but it is clear that they are also at high risk for fragility fractures. Moreover, recent data provide strong evidence that IR may key role in the increased fracture risk observed in both obesity and T2DM. CONCLUSIONS: In this concise review article, the role of IR in increased risk of osteoporotic fractures in MetS, obesity, and T2DM is discussed and summarised, including consideration of the need for fracture risk assessment as a 'preventive measure', especially in patients with T2DM and chronic MetS with abdominal obesity. Personalised and targeted diagnostic and therapeutic approaches to prevent osteoporotic fractures in IR-related diseases are needed and could make significant contributions to health outcomes.

Consumption of Phytoestrogens Affects Bone Health by Regulating Estrogen Metabolism.

Osteoporosis is a significant concern in bone health, and understanding its pathomechanism is crucial for developing effective prevention and treatment strategies. This article delves into the relationship between estrogen metabolism and bone mineralization, shedding light on how phytoestrogens can influence this intricate process. Estrogen, a hormone primarily associated with reproductive health, plays a pivotal role in maintaining bone density and structure. The article explores the positive effects of estrogen on bone mineralization, highlighting its importance in preventing conditions like osteoporosis. Phytoestrogens, naturally occurring compounds found in certain plant-based foods, are the focal point of the discussion. These compounds have the remarkable ability to mimic estrogen's actions in the body. The article investigates how phytoestrogens can modulate the activity of estrogen, thereby impacting bone health. Furthermore, the article explores the direct effects of phytoestrogens on bone mineralization and structure. By regulating estrogen metabolism, phytoestrogens can contribute to enhanced bone density and reduced risk of osteoporosis. Finally, the article emphasizes the role of plant-based diets as a source of phytoestrogens. By incorporating foods rich in phytoestrogens into one's diet, individuals may potentially bolster their bone health, adding a valuable dimension to the ongoing discourse on osteoporosis prevention. In conclusion, this article offers a comprehensive overview of 137 positions of literature on the intricate interplay between phytoestrogens, estrogen metabolism, and bone health, shedding light on their potential significance in preventing osteoporosis and promoting overall well-being.

Adherence to the evidence-based recommendations in managing bone health, pain, and mobility of patients with multiple myeloma: a mixed method in the Palestinian healthcare system.

BACKGROUND: Consensus/evidence-based recommendations for assessing, managing, and monitoring bone health, pain, and mobility in patients with multiple myeloma were developed. This study was conducted to assess the adherence of the hematologists-oncologists to the consensus/evidence-based recommendations for assessing, managing, and monitoring bone health, pain, and mobility in patients with multiple myeloma who received care in the Palestinian healthcare system. METHODS: A mixed method was used in this study. The consensus/evidence-based recommendations were identified through a systematic search in Scopus, PubMed, SpringerLink, ScienceDirect, and Google Scholar. A panel of 5 researchers (3 hematologists-oncologists, 3 medical students, and 1 pharmacologist) sorted the consensus/evidence-based recommendations and developed the survey tool during 3 iterative meetings. The extent to which the hematologists-oncologists in the 5 centers caring for patients with multiple myeloma adhered to the consensus/evidence-based recommendations was assessed using a questionnaire. RESULTS: Responses were collected from 10 hematologists-oncologists in all 5 healthcare centers where patients with multiple myeloma receive healthcare in the West Bank of Palestine. The median number of years in the practice of the hematologists-oncologists was 7.5 [2.75, 14.0] years and the median number of patients with multiple myeloma care per month was 12.5 [7.5, 21.25]. The vast majority (90%) of the hematologists-oncologists reported inadequate adherence to screening for medication problems related to bone health, pain, cardiopulmonary fitness, healthy behaviors, nutritional deficits, and mental health. Of the hematologists-oncologists, 70% reported inadequate adherence to ordering and evaluating calcium, vitamin D, alkaline phosphatase, electrolytes, and phosphorus levels to monitor bone health and 60% reported inadequate adherence to prescribing calcium and vitamin D supplements whenever there was a need. CONCLUSION: The findings of this study suggested inadequate adherence to the consensus/evidence-based recommendations and highlighted areas for improvement to ensure that patients receive optimal care. The findings suggested a need for further education and training on the latest guidelines and recommendations. Decision-makers and policymakers might need to design measures and implement policies to improve adherence to the consensus/evidence-based recommendations. Addressing these gaps in adherence to the consensus/evidence-based recommendations may improve the care and outcomes of patients with multiple myeloma.

Sugar-Sweetened Beverage Consumption and Height Loss in Adults: A Longitudinal Analysis in the EPIC-Norfolk Study.

BACKGROUND: Height loss in aging has been recognized to reflect a decline in musculoskeletal health but not investigated in relation to dietary factors, such as sugar-sweetened beverages (SSBs), the consumption of which may deteriorate musculoskeletal health. OBJECTIVES: This study aimed to evaluate the longitudinal association of habitual consumption of total SSBs and its subtypes with height loss and examine effect-modification by age, sex, and anthropometry. METHODS: We evaluated 16,230 adults aged 40-79 y in the European Prospective Investigation into Cancer and Nutrition-Norfolk cohort. At baseline (1993-1997), SSB consumption (soft drinks, squashes, sweetened milk beverages, sweetened coffee/tea, and sweetened alcoholic beverages) was assessed using 7-d food diaries. Height was objectively measured at the baseline, second (1997-2000), and third (2004-2011) health checks. Multivariable linear regression was used to examine baseline SSB consumption and the rate of height change over the follow-up. RESULTS: The median (IQR) height change was -1.07 (-2.09 to -0.28) cm/10 y. Adjusted for potential confounders including behavioral factors, medications, and baseline body mass index (BMI), total SSB consumption was associated with height loss (ß: -0.024; 95% CI: -0.046, -0.001 cm/10 y per 250 g/d of SSB), and similar results were seen for the individual beverages, except for sweetened milk beverages (ß: +0.07; 95% CI: -0.16, 0.30), with wide CIs. No effect-modification by prespecified factors was evident, except for baseline BMI (P-interaction = 0.037). Total SSB consumption was associated with height loss (-0.038; 95% CI: -0.073, -0.004) in participants with BMI ≤ 25 kg/m2 but not apparently in those with BMI > 25 kg/m2. CONCLUSIONS: SSB consumption was modestly associated with height loss, particularly in adults with normal weight status.

Influence of Menstrual Cycle and Oral Contraceptive Phases on Bone (re)modelling Markers in Response to Interval Running.

To explore how sex hormone fluctuations may affect bone metabolism, this study aimed to examine P1NP and ß-CTX-1 concentrations across the menstrual and oral contraceptive (OC) cycle phases in response to running. 17ß-oestradiol, progesterone, P1NP and ß-CTX-1 were analysed pre- and post-exercise in eight eumenorrheic females in the early-follicular, late-follicular, and mid-luteal phases, while 8 OC users were evaluated during the withdrawal and active pill-taking phases. The running protocol consisted of 8 × 3min treadmill runs at 85% of maximal aerobic speed. 17ß-oestradiol concentrations (pg·ml-1) were lower in early-follicular (47.22 ± 39.75) compared to late-follicular (304.95 ± 235.85;p = < 0.001) and mid-luteal phase (165.56 ± 80.6;p = 0.003) and higher in withdrawal (46.51 ± 44.09) compared to active pill-taking phase (10.88 ± 11.24;p < 0.001). Progesterone (ng·ml-1) was higher in mid-luteal (13.214 ± 4.926) compared to early-follicular (0.521 ± 0.365; p < 0.001) and late-follicular phase (1.677 ± 2.586;p < 0.001). In eumenorrheic females, P1NP concentrations (ng·ml-1) were higher in late-follicular (69.97 ± 17.84) compared to early-follicular (60.96 ± 16.64;p = 0.006;) and mid-luteal phase (59.122 ± 11.77;p = 0.002). ß-CTX-1 concentrations (ng·ml-1) were lower in mid-luteal (0.376 ± 0.098) compared to late-follicular (0.496 ± 0.166; p = 0.001) and early-follicular phase (0.452 ± 0.148; p = 0.039). OC users showed higher post-exercise P1NP concentrations in withdrawal phase (61.75 ± 8.32) compared to post-exercise in active pill-taking phase (45.45 ± 6;p < 0.001). Comparing hormonal profiles, post-exercise P1NP concentrations were higher in early-follicular (66.91 ± 16.26;p < 0.001), late-follicular (80.66 ± 16.35;p < 0.001) and mid-luteal phases (64.57 ± 9.68;p = 0.002) to active pill-taking phase. These findings underscore the importance of studying exercising females with different ovarian hormone profiles, as changes in sex hormone concentrations affect bone metabolism in response to running, showing a higher post-exercise P1NP concentrations in all menstrual cycle phases compared with active pill-taking phase of the OC cycle.

Identifying Gut Microbiome Features that Predict Responsiveness Toward a Prebiotic Capable of Increasing Calcium Absorption: A Pilot Study.

Previously, we demonstrated that prebiotics may provide a complementary strategy for increasing calcium (Ca) absorption in adolescents which may improve long-term bone health. However, not all children responded to prebiotic intervention. We determine if certain baseline characteristics of gut microbiome composition predict prebiotic responsiveness. In this secondary analysis, we compared differences in relative microbiota taxa abundance between responders (greater than or equal to 3% increase in Ca absorption) and non-responders (less than 3% increase). Dual stable isotope methodologies were used to assess fractional Ca absorption at the end of crossover treatments with placebo, 10, and 20 g/day of soluble corn fiber (SCF). Microbial DNA was obtained from stool samples collected before and after each intervention. Sequencing of the 16S rRNA gene was used to taxonomically characterize the gut microbiome. Machine learning techniques were used to build a predictive model for identifying responders based on baseline relative taxa abundances. Model output was used to infer which features contributed most to prediction accuracy. We identified 19 microbial features out of the 221 observed that predicted responsiveness with 96.0% average accuracy. The results suggest a simplified prescreening can be performed to determine if a subject's bone health may benefit from a prebiotic. Additionally, the findings provide insight and prompt further investigation into the metabolic and genetic underpinnings affecting calcium absorption during pubertal bone development.

Hormonal contraception and medical readiness for female service members.

Many female military service members choose to use hormonal contraception to prevent pregnancy and/or to control or suppress menses. Hormonal contraception, which comes in many different forms based on dose, estrogen/progestin type, and route of administration (oral, vaginal, transdermal, implant, intrauterine device, injectable), may cause side effects, some of which can influence military medical readiness, or the health status necessary to perform assigned missions. This expert review summarizes the evidence around common military-relevant side effects of hormonal contraception that could impact readiness, including effects on weight and body composition, bone health, psychological health, and physical performance, and serves as a tool for uniformed and civilian clinicians counseling female service members about hormonal contraception. Current evidence suggests some hormonal contraception can lead to weight and fat gain, may modulate susceptibility to mood or mental health disorders, and could impact bone mineral density and stress fracture risk; more research is needed on physical performance effects. Clinicians must be familiar with readiness considerations of each type of hormonal contraception to provide comprehensive patient education and allow for optimal shared decision-making about hormonal contraception use among female Service members. Considering the relative lack of data on the effects of nonoral hormonal contraception routes on readiness outcomes and the growing interest in long-acting reversible contraceptives among female service members, future research should continue to investigate effects of all hormonal contraception methods available to service members.

Metabolic Complications Associated with Use of Integrase Strand Transfer Inhibitors (InSTI) for the Treatment of HIV-1 Infection: Focus on Weight Changes, Lipids, Glucose and Bone Metabolism.

PURPOSE OF REVIEW: This review aims to summarize recently published peer reviewed papers on the influence of treatment with Integrase Strand Transfer Inhibitors (InSTI) in people with HIV (HIV) on metabolic health, including weight gain, lipid parameters, glucose homeostasis, and bone health. RECENT FINDINGS: InSTI have a mild/moderate effect on weight gain in both antiretroviral (ART) naïve and ART experienced PWH, which is more pronounced in certain groups (i.e. women, people of Black African ethnicity, those with lower socioeconomic status, and older people). The effect on weight is also driven by other components of the ART regimen as well as previous exposure to certain ART. InSTI have a relatively safe profile in terms of lipid parameters and bone health, compared to other ART classes, although some studies suggest a greater risk of insulin resistance and diabetes in PWH using InSTI, especially 2nd generation InSTI. While there is some evidence suggesting a negative impact of InSTI on some aspects of metabolic health (weight gain and glucose homeostasis), they remain the preferred treatment option for most PWH, due to their high efficacy and tolerability. However, an individualised approach to ART choice in PWH should be used in order to avoid negative outcomes in populations at higher risks of metabolic complications.

Tea consumption and risk of bone health: an updated systematic review and meta-analysis.

INTRODUCTION: Current research evaluating the association between tea consumption and bone health still has inconsistent findings. MATERIALS AND METHODS: The electronic databases of Embase, PubMed, Scopus, and Web of Science were systematically searched from inception until December 2022 to identify eligible studies. The calculation of summary relative risks (RRs) and 95% confidence intervals (CIs) was carried out using random-effects models. I2 statistics and Forest plots were used to assess the heterogeneity of RR values across studies. RESULTS: The pooled relative risks for bone health-related outcomes of interest among tea drinkers, compared to non-drinkers, were 0.910 (95% confidence interval 0.845 to 0.980) for fractures, based on 20 studies, 0.332 (0.207-0.457) for BMD (13 studies), 0.800 (0.674-0.950) for osteoporosis (10 studies), and 1.006 (0.876-1.156) for osteopenia (5 studies). Subgroup analysis of locations showed that the pooled relative risks were 0.903 (0.844-0.966) for the hip, 0.735 (0.586-0.922) for the femur, 0.776 (0.610-0.988) for the lumbar, 0.980 (0.942-1.021) for the forearm and wrist, 0.804 (0.567-1.139) for the phalanges, and 0.612 (0.468-0.800) for Ward's triangle. One-stage dose-response analysis revealed that individuals who consumed less than 4.5 cups of tea per day had a lower risk of bone health-related outcomes than those who did not consume tea, with statistically significant results. CONCLUSION: There is an association between tea consumption and a reduced risk of fractures, osteoporosis, hip, femur, and lumbar, as well as increased BMD.

Linear and non-linear relationships between body fat mass distribution and bone mineral density in adults: The NHANES, 2011-2018.

OBJECTIVE: The relationship between body fat mass and bone mineral density (BMD) remains controversial. This research aimed to explore the linear or non-linear relationship between body fat mass and BMD among adults in the United States. METHODS: This cross-sectional study identified adults aged 18 years or older in the National Health and Nutrition Examination Survey from 2011 to 2018. After adjusting for covariates, linear relationships between body fat mass and BMD in different genders were tested by generalized linear models, and potential non-linear relationships were explored by generalized additive models and piecewise linear regression models. RESULTS: The research included 4691 (57.9% of the total sample) males and 3417 (42.1% the of total sample) females. In both males and females, we found a negative association between android or total body fat mass and lumbar spine BMD and a positive association between appendicular, android, gynoid, or total body fat mass and whole body BMD (all P < 0.05). The relationships between body fat mass in all regions and lumbar spine BMD were U-shaped in males and inverted U-shaped in females (all Pnon-linear < 0.05). Inverted U-shaped relationships existed between body fat mass in all regions and whole body BMD in females (all Pnon-linear < 0.05). CONCLUSIONS: Body fat mass was negatively and linearly associated with lumbar spine BMD, but positively associated with whole body BMD. Body fat mass had a U-shaped relationship with lumbar spine BMD in males and an inverted U-shaped association with lumbar spine and whole body BMD in females.

From tradition to science: Possible mechanisms of ghee in supporting bone and joint health.

Ghee, a traditional form of clarified butter, has been used for centuries in Ayurvedic medicine for its numerous health benefits. Recent scientific studies have begun to elucidate the molecular mechanisms by which ghee may support bone and joint health. This review explores the bioactive components of ghee, including short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), and fat-soluble vitamins (A, D, E, K2), and their potential therapeutic effects on bone density, joint lubrication, and inflammation. SCFAs in ghee can potentially improve joint lubrication and reduce inflammation. MCFAs and conjugated linoleic acid (CLA) exhibit anti-inflammatory properties, modulating cytokine production and oxidative stress pathways. Vitamins D and K2 in ghee can play potentially crucial roles in calcium metabolism and bone mineralization, while vitamin A supports immune regulation and cartilage health. This review integrates traditional knowledge with contemporary scientific research, highlighting the potential of ghee as a complementary therapy for conditions such as osteoporosis and arthritis. By understanding the molecular mechanisms involved, future studies can focus on this field to shed a light on different effects of ghee on bone and joint health.

Effect of probiotics on postmenopausal bone health: a preclinical meta-analysis.

Postmenopausal osteoporosis is a major concern for women worldwide due to increased risk of fractures and diminished bone quality. Recent research on gut microbiota has suggested that probiotics can combat various diseases, including postmenopausal bone loss. Although several preclinical studies have explored the potential of probiotics in improving postmenopausal bone loss, the results have been inconsistent and the mechanism of action remains unclear. To address this, a meta-analysis was conducted to determine the effect of probiotics on animal models of postmenopausal osteoporosis. The bone parameters studied were bone mineral density (BMD), bone volume fractions (BV/TV), and hallmarks of bone formation and resorption. Pooled analysis showed that probiotic treatment significantly improves BMD and BV/TV of the ovariectomised animals. Probiotics, while not statistically significant, exhibited a tendency towards enhancing bone formation and reducing bone resorption. Next, we compared the effects of Lactobacillus sp. and Bifidobacterium sp. on osteoporotic bone. Both probiotics improved BMD and BV/TV compared with control, but Lactobacillus sp. had a larger effect size. In conclusion, our findings suggest that probiotics have the potential to improve bone health and prevent postmenopausal osteoporosis. However, further studies are required to investigate the effect of probiotics on postmenopausal bone health in humans.

Predictors of low and very low bone mineral density in long-term childhood acute lymphoblastic leukemia survivors: Toward personalized risk prediction.

BACKGROUND: Cohorts of childhood acute lymphoblastic leukemia (cALL) survivors reaching adulthood are increasing. Approximately 30% of survivors meet criteria for low bone mineral density (BMD) 10 years after diagnosis. We investigated risk factors for low BMD in long-term cALL survivors. METHODS: We recruited 245 cALL survivors from the PETALE (Prévenir les effets tardifs des traitements de la leucémie aiguë lymphoblastique chez l'enfant) cohort, who were treated with the Dana Farber Cancer Institute protocols, did not experience disease relapse or hematopoietic stem cell transplants, and presented with more than 5 years of event-free survival. Median time since diagnosis was 15.1 years. RESULTS: Prevalence of low DXA-derived BMD (Z-score ≤-1) ranged between 21.9% and 25.3%, depending on site (lumbar spine (LS-BMD), femoral neck (FN-BMD), and total body (TB-BMD), and between 3.7% and 5.8% for very low BMD (Z-score ≤-2). Males had a higher prevalence of low BMD than females for all three outcomes (26%-32% vs. 18%-21%), and male sex acted as a significant risk factor for low BMD in all models. Treatment-related factors such as cumulative glucocorticoid (GC) doses and cranial radiation therapy (CRT) were associated with lower BMDs in the full cohort and in females at the FN-BMD site. CONCLUSION: Low and very low BMD is more prevalent in male cALL survivors. Male sex, high cumulative GC doses, CRT, risk group, and low body mass index (BMI) were identified as risk factors for low BMD. A longer follow-up of BMD through time in these survivors is needed to establish if low BMD will translate into a higher risk for fragility fractures through adulthood.

Dietary inflammatory index is not associated with bone mineral density in functionally able community-dwelling older adults.

BACKGROUND: Osteoporosis poses a significant health and quality-of-life burden on older adults, particularly with associated fractures after a fall. A notable increase in pro-inflammatory cytokines associated with aging contributes to a decline in bone mineral density (BMD). Certain food components have been shown to influence an individual's inflammatory state and may contribute to optimal bone health as a modifiable risk factor, particularly later in life. This study aims to explore the relationship between the dietary inflammatory index (DII) and dietary intake with BMD in community-dwelling older adults. METHODS: Heathy community-dwelling older adults aged 65-85 years. DII scores were calculated using 24-h dietary recalls, and lumbar spine (L1-L4) and femoral neck (ward's triangle) BMD was assessed via dual-energy x-ray absorptiometry. RESULTS: A total of 94 participants were recruited (72.9 ± 4.9 years, 76.6% female) with 61.7% identified having an anti-inflammatory diet (average DII = - 0.50 ± 1.6), 88.3% were physically active, 47.8% were osteopenic and 27.7% osteoporotic. There was no significant difference between DII scores, nutrient or food group intake in groups stratified by BMD T-Score except for lean meats and alternatives food group (p = 0.027). Multiple regression analysis found no associations between DII and lumbar spine (unadjusted model ß = 0.020, p = 0.155) or femoral neck BMD (unadjusted model ß = - 0.001, p = 0.866). CONCLUSION: Most of this cohort of functionally able community-dwelling older adults followed an anti-inflammatory diet. DII and dietary intake were not associated with BMD. This research underlines the complex interplay between modifiable and non-modifiable risk factors on the BMD of older, physically active adults.

Predictors for pathological bone fractures in children undergoing liver transplantation: A retrospective cohort study.

BACKGROUND: Hepatic osteodystrophy refers to bone disorders associated with chronic liver disease, including children undergoing liver transplantation (LT). The aim of this study was to quantify the prevalence of pathological fractures (PF) in children before and after LT and to identify associated factors for their occurrence. METHODS: Children aged 0-18 years who underwent LT from 1/2005 to 12/2020 were included in this retrospective study. Data on patient demographics, types and anatomical locations of fracture and biological workups were extracted. Variables were assessed at 3 time points: T - 1 at the moment of listing for LT; T0 at the moment of LT and T + 1 at 1-year post-LT. RESULTS: A total of 105 children (49 [47%] females) were included in this study. Median age at LT was 19 months (range 0-203). Twenty-two patients (21%) experienced 65 PF, 11 children before LT, 10 after LT, and 1 before and after LT. The following variables were observed as associated with PF: At T - 1, low weight and height z-scores, and delayed bone age; at T0, low weight and height z-scores, high total and conjugated bilirubin; at T + 1, persistent low height z-score. Patients in the PF-group were significantly more under calcium supplementation and/or nutritional support at T - 1, T0 and T + 1. CONCLUSION: More than one in five children needing LT sustain a PF before or after LT. Patients with low weight and height z-scores and delayed bone age are at increased risk for PF. Nutritional support remains important, even if to date it cannot fully counteract the risks of PF.

Development and validation of a frailty index for use in the osteoarthritis initiative.

BACKGROUND: The Osteoarthritis Initiative (OAI) evaluates the development and progression of osteoarthritis. Frailty captures the heterogeneity in aging. Use of this resource-intensive dataset to answer aging-related research questions could be enhanced by a frailty measure. OBJECTIVE: To: (i) develop a deficit accumulation frailty index (FI) for the OAI; (ii) examine its relationship with age and compare between sexes, (iii) validate the FI versus all-cause mortality and (iv) compare this association with mortality with a modified frailty phenotype. DESIGN: OAI cohort study. SETTING: North America. SUBJECTS: An FI was determined for 4,755/4,796 and 4,149/4,796 who had a valid FI and frailty phenotype. METHODS: Fifty-nine-variables were screened for inclusion. Multivariate Cox regression evaluated the impact of FI or phenotype on all-cause mortality at follow-up (up to 146 months), controlling for age and sex. RESULTS: Thirty-one items were included. FI scores (0.16 ± 0.09) were higher in older adults and among females (both, P < 0.001). By follow-up, 264 people had died (6.4%). Older age, being male, and greater FI were associated with a higher risk of all-cause mortality (all, P < 0.001). The model including FI was a better fit than the model including the phenotype (AIC: 4,167 vs. 4,178) and was a better predictor of all-cause mortality than the phenotype with an area under receiver operating characteristic curve: 0.652 vs. 0.581. CONCLUSION: We developed an FI using the OAI and validated it in relation to all-cause mortality. The FI may be used to study aging on clinical, functional and structural aspects of osteoarthritis included in the OAI.

Bone health in children with Angelman syndrome at the ENCORE Expertise Center.

Angelman syndrome (AS) is a rare genetic disorder due to lack of UBE3A function on chromosome 15q11.2q13 caused by a deletion, uniparental paternal disomy (UPD), imprinting center disorder (ICD), or pathological variant of the UBE3A gene. AS is characterized by developmental delay, epilepsy, and lack of speech. Although fractures are observed frequently in our clinical practice, there are few studies on bone health in AS. The aim of this study is to investigate bone health in children with AS. In this prospective cohort study, we describe bone health in 91 children with AS visiting the ENCORE Expertise Center for AS between April 2010 and December 2021. Bone health was assessed with the bone health index (BHI) in standard deviation score (SDS) measured by digital radiogrammetry of the left hand using BoneXpert software. Risk factors analyzed were age, sex, genetic subtype, epilepsy, anti-seizure medication use, mobility, body mass index (BMI), and onset of puberty. Children with AS had a mean BHI of -1.77 SDS (SD 1.4). A significantly lower BHI was found in children with a deletion (-2.24 SDS) versus non-deletion (-1.02 SDS). Other factors associated with reduced BHI-SDS were inability to walk and late onset of puberty. Children with a history of one or more fractures (22%) had a significantly lower BHI than children without fractures (-2.60 vs -1.56 SDS). Longitudinal analysis showed a significant decrease in BHI-SDS with age in all genetic subtypes.  Conclusions: Children with AS have a reduced bone health. Risk factors are deletion genotype, no independent walking, and late onset of puberty. Bone health decreased significantly with age. What is Known: • Children with neurological disorders often have a low bone health and higher risk of fractures. • Little is known about bone health in children with Angelman syndrome (AS). What is New: • Children with AS showed a reduced bone health and this was significantly associated with having a deletion, not being able to walk independently, and late onset of puberty. • Longitudinal analysis showed a significant decrease in bone health as children got older.