Maternal vitamin A and D status in second and third trimester of pregnancy and bone mineral content in offspring at nine years of age.

Introduction: Maternal nutritional and vitamin status during pregnancy may have long-term effects on offspring health and disease. The aim of this study was to examine the associations between maternal vitamin A and D status in pregnancy and offspring bone mineral content (BMC) at nine years of age. Methods: This is a post-hoc study of a randomized control trial including 855 pregnant women from two Norwegian cities; Trondheim and Stavanger. The women were randomized into an exercise intervention or standard antenatal care. Mother and child pairs for the present study were recruited from those still living in Trondheim after 8-10 years. Serum vitamin A (retinol) and vitamin D (25(OH)D) were measured in the 2nd and 3rd trimesters of pregnancy, and active vitamin D (1,25(OH)2D) in serum was measured in a subgroup. Spine BMC and trabecular bone score were measured in the children at nine years of age. Associations were analyzed with linear regression models. Results: A total of 119 mother and child pairs were included in the analyses. Vitamin A insufficiency (retinol< 1.05 µmol/L) and vitamin D deficiency (25(OH)D< 50 mmol/L) increased from ~7% to ~43% and from ~28% to ~33%, respectively, from the 2nd to the 3rd trimester. An increase in serum 1,25(OH)2D from the 2nd to the 3rd trimester was observed in the subgroup. There was a negative association between serum retinol in the 2nd trimester and spine BMC in the boys, but not in the girls, when adjusted for maternal and child confounders. No other associations between maternal serum vitamin A or D and BMC in the children were found. Conclusion: We observed a high prevalence of vitamin A insufficiency and vitamin D deficiency during pregnancy. A negative association between mid-pregnancy vitamin A status and spine BMC was observed in boys, but not girls, while no associations were found between maternal vitamin D status and child BMC. The implications of optimal vitamin A and D status in pregnancy for offspring bone health, remains a subject for further investigations.

Bone Fragility in High Fat Diet-induced Obesity is Partially Independent of Type 2 Diabetes in Mice.

Obesity and type 2 diabetes (T2D) are risk factors for fragility fractures. It is unknown whether this elevated risk is due to a diet favoring obesity or the diabetes that often occurs with obesity. Therefore, we hypothesized that the fracture resistance of bone is lower in mice fed with a high fat diet (45% kcal; HFD) than in mice that fed on a similar, control diet (10% kcal; LFD), regardless of whether the mice developed overt T2D. Sixteen-week-old, male NON/ShiLtJ mice (resistant to T2D) and age-matched, male NONcNZO10/LtJ (prone to T2D) received a control LFD or HFD for 21 weeks. HFD increased the bodyweight to a greater extent in the ShiLtJ mice compared to the NZO10 mice, while blood glucose levels were significantly higher in NZO10 than in ShiLtJ mice. As such, the glycated hemoglobin A1c (HbA1c) levels exceeded 10% in NZO10 mice, but it remained below 6% in ShiLtJ mice. Diet did not affect HbA1c. HFD lowered trabecular number and bone volume fraction of the distal femur metaphysis (micro-computed tomography or µCT) in both strains. For the femur mid-diaphysis, HFD significantly reduced the yield moment (mechanical testing by three-point bending) in both strains but did not affect cross-sectional bone area, cortical thickness, nor cortical tissue mineral density (µCT). Furthermore, the effect of diet on yield moment was independent of the structural resistance of the femur mid-diaphysis suggesting a negative effect of HFD on characteristics of the bone matrix. However, neither Raman spectroscopy nor assays of advanced glycation end-products identified how HFD affected the matrix. HFD also lowered the resistance of cortical bone to crack growth in only the diabetic NZO10 mice (fracture toughness testing of other femur), while HFD reduced the ultimate force of the L6 vertebra in both strains (compression testing). In conclusion, the HFD-related decrease in bone strength can occur in mice resistant and prone to diabetes indicating that a diet high in fat deleteriously affects bone without necessarily causing hyperglycemia.

Acquisition of peak bone mass in a Norwegian youth cohort: longitudinal findings from the Fit Futures study 2010-2022.

In a Norwegian youth cohort followed from adolescence to young adulthood, bone mineral density (BMD) levels declined at the femoral neck and total hip from 16 to 27 years but continued to increase at the total body indicating a site-specific attainment of peak bone mass. PURPOSE: To examine longitudinal trends in bone mineral density (BMD) levels in Norwegian adolescents into young adulthood. METHOD: In a prospective cohort design, we followed 980 adolescents (473 (48%) females) aged 16-19 years into adulthood (age of 26-29) on three occasions: 2010-2011 (Fit Futures 1 (FF1)), 2012-2013 (FF2), and 2021-2022 (FF3), measuring BMD (g/cm2) at the femoral neck, total hip, and total body with dual x-ray absorptiometry (DXA). We used linear mixed models to examine longitudinal BMD changes from FF1 to FF3. RESULTS: From the median age of 16 years (FF1), femoral neck BMD (mean g/cm2 (95% CI)) slightly increased in females from 1.070 (1.059-1.082) to 1.076 (1.065-1.088, p = 0.015) at the median age of 18 years (FF2) but declined to 1.041 (1.029-1.053, p < 0.001) at the median age of 27 years (FF3). Similar patterns were observed in males: 16 years, 1.104 (1.091-1.116); 27 years, 1.063 (1.050-1.077, p < 0.001); and for the total hip in both sexes (both p < 0.001). Total body BMD increased from age 16 to 27 years in both sexes (females: 16 years, 1.141 (1.133-1.148); 27 years, 1.204 (1.196-1.212), p < 0.001; males: 16 years, 1.179 (1.170-1.188); 27 years, 1.310 (1.296-1.315), p < 0.001). CONCLUSION: BMD levels increased from 16 to 18 years at the femoral and total hip sites in young Norwegian females and males, and a small decline was observed at the femoral sites when the participants were followed up to 27 years. Total body BMD continued to increase from adolescence to young adulthood.

The potential application of fermented tea as a drink for regulating bone mass.

Currently, there is evidence to suggest the benefits of drinking fermented tea for people with osteoporosis, and based on this, many studies have been conducted on the dosage, exact ingredients, mechanisms, and industrial applications of fermented tea for protecting against osteoporosis. A summary and analysis of studies on the regulation of bone mass by oolong tea, black tea, and their active ingredients (including 39 known catechin compounds) was conducted. It was found that the regulation of bone mass by fermented tea is backed by evidence from epidemiology, animal experiments, and cell experiments. The main active components of fermented tea are tea polyphenols, tea pigments, and trace amino acids. The specific mechanisms involved include regulating bone marrow mesenchymal stem cell osteogenesis, inhibiting osteoclast activity, promoting calcium and phosphorus absorption, reducing inflammation levels, regulating gut microbiota, regulating endocrine function, and inhibiting oxidative stress. In terms of its application, extraction, precipitation, biosynthesis and membrane separation method are mainly used to separate the active ingredients of anti osteoporosis from fermented tea. In conclusion, fermented tea has sufficient theoretical and practical support for regulating bone mass and preventing osteoporosis, and is suitable for development as a health supplement. At the same time, a large amount of epidemiological evidence is needed to prove the specific dosage of tea consumption.

Total Flavonoids Isolated from the Leaves of Eucommia ulmoides Augment Peak Bone Mass in Female Rats and Show no Side Effects in Other Organs.

INTRODUCTION: Eucommia ulmoides is a unique monophyletic and tertiary relict in China and is listed as a national second-class precious protected tree species. Eucommia ulmoides, recognized as a traditional Chinese medicine, can tonify the liver and kidneys and strengthen bones and muscles. Modern pharmacological research has proved that Eucommia ulmoides has multiple osteoprotective effects, including prohibiting the occurrence of osteoporosis and arthritis and enhancing the healing of bone fractures and bone defects. AIM: To check its osteotropic effects, which may provide ideas for its potential use for the development of novel drugs to treat osteoporosis, this study evaluated the effect of total flavonoids from Eucommia ulmoides leaves (TFEL) on the acquisition of Peak Bone Mass (PBM) in young female rats. MATERIALS AND METHODS: TFEL was isolated, and its purity was confirmed by using a UV spectrophotometer. TFEL with a purity of 85.09% was administered to 6-week-old female rats by oral gavage at a low (50), mid (100), or high (200 mg/kg/d) dose, and the control group was administrated only with the same volume of water. After 13 weeks of treatment, the rats were sacrificed, and serum, different organs, and limb bones (femurs and tibias) were harvested, and the bone turnover markers, organ index, Bone Mineral Density (BMD), biomechanical property, and microstructure parameters were assayed. Furthermore, molecular targets were screened, and network pharmacology analyses were conducted to reveal the potential mechanisms of action of TFEL. RESULTS: Oral administration of TFEL for 13 weeks decreased the serum level of bone resorption marker TRACP-5b. As revealed by micro-computer tomography analysis, it elevated BMD even at a low dose (50 mg/kg/d) and improved the microstructural parameters, which were also confirmed by H&E histological staining. However, TFEL showed no effects on body weights, organ index, and micromorphology in the uterus. In our network pharmacology study, an intersection analysis screened out 64 shared targets, with quercetin, kaempferol, naringenin, and apigenin regulating the greatest number of targets associated with osteoporosis. Flavonoids in Eucommia ulmoides inhibited the occurrence of osteoporosis potentially through targeting signaling pathways for calcium, VEGF, IL-17, and NF-κB. Furthermore, AKT1, EGFR, PTGS2, VEGFA, and CALM were found to be potentially important target genes for the osteoprotective effects of flavonoids in Eucommia ulmoides. CONCLUSION: The above results suggested that TFEL can be used to elevate the peak bone mass in adolescence in female individuals, which may prevent the occurrence of postmenopausal osteoporosis, and the good safety of TFEL also suggests that it can be used as a food additive for daily life to improve the bone health.

Cold exposure-induced plasma exosomes impair bone mass by inhibiting autophagy.

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.

The high-bone-mass phenotype of novel transgenic mice with LRP5 A241T mutation.

Gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) can cause high-bone-mass (HBM) phenotype, with 19 identified mutations so far. The A242T mutation in LRP5 has been found in 9 families, making it one of the most prevalent mutations. However, the correlation between the A242T mutation and HBM phenotype remains unverified in animal models. This study aimed to investigate the bone properties in a new transgenic mouse model carrying the LRP5 A241T missense mutation, equivalent to A242T in humans. Heterozygous Lrp5A241T mice were generated using CRISPR/Cas9 genome editing. Body weight increased with age from 4 to 16 weeks, higher in males than females, with no difference between Lrp5A241T mice and wild-type control. Micro-CT showed slightly longer femur and notably elevated trabecular bone mass of the femur and fifth lumbar spine with higher bone mineral density, bone volume fraction, and trabecular thickness in Lrp5A241T mice compared to wild-type mice. Additionally, increased cortical bone thickness and volume of the femur shaft and skull were observed in Lrp5A241T mice. Three-point bending tests of the tibia demonstrated enhanced bone strength properties in Lrp5A241T mice. Histomorphometry confirmed that the A241T mutation increased bone formation without affecting osteoblast number and reduced resorption activities in vivo. In vitro experiments indicated that the LRP5 A241T mutation enhanced osteogenic capacity of osteoblasts with upregulation of the Wnt signaling pathway, with no significant impact on the resorptive activity of osteoclasts. In summary, mice carrying the LRP5 A241T mutation displayed high bone mass and quality due to enhanced bone formation and reduced bone resorption in vivo, potentially mediated by the augmented osteogenic potential of osteoblasts. Continued investigation into the regulatory mechanisms of its bone metabolism and homeostasis may contribute to the advancement of novel therapeutic strategies for bone disorders.

Optimal Body Weights for Adults with Severe Motor and Intellectual Disabilities.

Determining the optimal body weight for individuals with severe motor and intellectual disabilities (SMID) lacks a standardized approach. In this study, we aimed to develop a formula to estimate the ideal body weight for each SMID patient, considering factors such as reduced muscle and bone mass. We analyzed data from 111 SMID patients (56 male, 55 female; age range 20 to 73 y) who underwent blood tests measuring creatinine (Cr) and cystatin C (cysC) for clinical reasons between Feb. 2018 and Feb. 2023. To create the optimal body weight formula, we utilized three variables: height, estimated glomerular filtration (eGFR)-Cr, and eGFR-cysC. The validity of the formula was assessed by comparing the measured triceps subcutaneous fat thickness (TSF) to the reference TSF (%TSF), evaluating how accurately it reflects the appropriate physique. The derived optimal body weight formula is as follows: Optimal body weight=(height)2×(18.5-25.0)×{1-0.41×(1-eGFR-cysC/eGFR-Cr)}×0.93. Our formula demonstrated validity when using %TSF as an indicator. Establishing a method to determine optimal body weight in SMID patients, considering their low muscle and bone mass, is crucial for accurate nutritional assessment and subsequent nutritional management.

The association between computed tomography-based osteosarcopenia and osteoporotic vertebral fractures: a longitudinal study.

PURPOSE: Osteoporosis and sarcopenia usually coexist in older population. The concept of osteosarcopenia has been proposed in recent years. However, studies on the relationship between osteosarcopenia and the risk of fracture are rare, and the association is unclear at present. This study aimed to investigate the association between osteosarcopenia evaluated based on chest computed tomography (CT) and osteoporotic vertebral fracture (OVF). METHODS: This study recruited 7906 individuals aged 50 years and older who did not have OVFs and underwent chest CT for physical examination between July 2016 and September 2019. Subjects were followed up annually until June 2023. Osteosarcopenia was defined by a low muscle area of the erector spinae (< 25.4 cm2) and the bone attenuation (Hounsfield unit, HU < 135). Genant's grades were used to define OVFs. Control subjects were selected by Propensity Score Matching at a ratio 20:1. Cox proportional hazards models were used to assess the associations between osteosarcopenia and OVFs. RESULTS: Of the 7906 participants included, 95 had a new OVF within a median follow-up of 3 years. A total of 1900 control subjects were matched. Individuals in the osteosarcopenia group had a higher prevalence of spinal fractures than those in normal group (16.4% vs. 0.4%, P < 0.001). Osteosarcopenia was independently associated with OVF (adjusted hazard ratio (aHR): 12.67, 95% confidence interval (CI) 3.79-42.40) and severe OVF (aHR = 14.07, 95% CI 1.84-107.66). Similar trends were observed in males, females and those subjects aged older than 60 years. Osteosarcopenia had good predictive efficacy for OVF (area under the curve = 0.836). A nomogram was also developed for clinical application. CONCLUSION: Osteosarcopenia assessed based on chest CT was associated with OVF, and osteosarcopenia has good performance for vertebral fracture prediction.

Upper and lower limb bone mass accrual in adolescent footballers across a short period of training and competition

Abstract Objectives: To analyze bone mineral content (BMC) and area bone mineral density (aBMD) accrual in adolescent male footballers who started their first football season. Methods: 17 athletes (14.8 ± 0.4 years) were monitored across 15 weeks of football training. Participants were evaluated for somatic maturation (HPHV), BMC, and aBMD at three time points: before (M1) and after (M2) a preparatory phase, and at the end of the competitive phase (M3). BMC and aBMD were measured using DXA scans. Participants were divided into groups according to maturation status (circa-PHV and post-PHV), and the amount of accumulated training load (median split). Results: A significant effect (12.1 g/week, standard error (SE) = 2.6 g/week) was observed for lower limbs BMC across the three time points. There were no significant effects of time for upper limbs BMC. There was a significant effect of time for total body aBMD (0.007, SE = 0.003 g/cm2/week) across the three time points. Adolescents at post-PHV had a significant 245.6 g (SE = 56.1 g) higher BMC compared to adolescents at circa-PHV. No significant effects were observed for the accumulated training load. Conclusion: Systematic football training, even during the growth spurt, has a positive impact on adolescent bone markers despite the accumulated training load and maturation.

Frailty, Sarcopenia and Osteoporosis. / Fragilidad, sarcopenia y osteoporosis.

Frailty, sarcopenia and osteoporosis are entities specific to the elderly, who share some risk factors. For this reason, their relationship has been studied in different works, which have provided disparate results, probably because these studies have not always focused on the same aspects. This article reviews the relationship of frailty and sarcopenia with osteoporosis.

Long-term Musculoskeletal Consequences of Chemotherapy in Pediatric Mice.

Thanks to recent progress in cancer research, most children treated for cancer survive into adulthood. Nevertheless, the long-term consequences of anticancer agents are understudied, especially in the pediatric population. We and others have shown that routinely administered chemotherapeutics drive musculoskeletal alterations, which contribute to increased treatment-related toxicity and long-term morbidity. Yet, the nature and scope of these enduring musculoskeletal defects following anticancer treatments and whether they can potentially impact growth and quality of life in young individuals remain to be elucidated. Here, we aimed at investigating the persistent musculoskeletal consequences of chemotherapy in young (pediatric) mice. Four-week-old male mice were administered a combination of 5-FU, leucovorin, irinotecan (a.k.a., Folfiri) or the vehicle for up to 5 wk. At time of sacrifice, skeletal muscle, bones, and other tissues were collected, processed, and stored for further analyses. In another set of experiments, chemotherapy-treated mice were monitored for up to 4 wk after cessation of treatment. Overall, the growth rate was significantly slower in the chemotherapy-treated animals, resulting in diminished lean and fat mass, as well as significantly smaller skeletal muscles. Interestingly, 4 wk after cessation of the treatment, the animals exposed to chemotherapy showed persistent musculoskeletal defects, including muscle innervation deficits and abnormal mitochondrial homeostasis. Altogether, our data support that anticancer treatments may lead to long-lasting musculoskeletal complications in actively growing pediatric mice and support the need for further studies to determine the mechanisms responsible for these complications, so that new therapies to prevent or diminish chemotherapy-related toxicities can be identified.

SIRT1 maintains bone homeostasis by regulating osteoblast glycolysis through GOT1.

The silent information regulator T1 (SIRT1) is linked to longevity and is a crucial mediator of osteoblast function. We investigated the direct role of Sirt1 during bone modeling and remodeling stages in vivo using Tamoxifen-inducible osteoblast-specific Sirt1 conditional knockout (cKO) mice. cKO mice exhibited lower trabecular and cortical bone mass in the distal femur. These phenotypes were coupled with lower bone formation and bone resorption. Metabolomics analysis revealed that the metabolites involved in glycolysis were significantly decreased in cKO mice. Further analysis of the quantitative acetylome revealed 11 proteins with upregulated acetylation levels in both the femur and calvaria of cKO mice. Cross-analysis identified four proteins with the same upregulated lysine acetylation site in both the femur and calvaria of cKO mice. A combined analysis of the metabolome and acetylome, as well as immunoprecipitation, gene knockout, and site-mutation experiments, revealed that Sirt1 deletion inhibited glycolysis by directly binding to and increasing the acetylation level of Glutamine oxaloacetic transaminase 1 (GOT1). In conclusion, our study suggested that Sirt1 played a crucial role in regulating osteoblast metabolism to maintain bone homeostasis through its deacetylase activity on GOT1. These findings provided a novel insight into the potential targeting of osteoblast metabolism for the treatment of bone-related diseases.

Osteoblastic erythropoietin is not required for bone mass accrual.

Erythropoietin (EPO), primarily produced by interstitial fibroblasts in the kidney during adulthood, and its receptor are well-known for their crucial role in regulating erythropoiesis. Recent research has unveiled an additional function of circulating EPO in the control of bone mass accrual and homeostasis through its receptor, which is expressed in both osteoblasts and osteoclasts. Notably, cells of the osteoblast lineage can produce and secrete functional EPO upon activation of the hypoxia signaling pathway. However, the physiological relevance of osteoblastic EPO remains to be fully elucidated. This study aimed to investigate the potential role of osteoblastic EPO in regulating bone mass accrual and erythropoiesis in young adult mice. To accomplish this, we employed a mutant mouse model lacking EPO specifically in mesenchymal progenitors and their descendants. Our findings indicate that in vivo loss of EPO in the osteoblast lineage does not significantly affect either bone mass accrual or erythropoiesis in young adult mice. Further investigations are necessary to comprehensively understand the potential contribution of EPO produced and secreted by osteoblast cells during aging, repair, and under pathological conditions.

Diagnostic performance of radiomics for predicting osteoporosis in adults: a systematic review and meta-analysis.

This study aimed to assess the diagnostic accuracy of radiomics for predicting osteoporosis and the quality of radiomic studies. The study protocol was prospectively registered on PROSPERO (CRD42023425058). We searched PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to June 1, 2023, for eligible articles that applied radiomic techniques to diagnosing osteoporosis or abnormal bone mass. Quality and risk of bias of the included studies were evaluated with radiomics quality score (RQS), METhodological RadiomICs Score (METRICS), and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tools. The data analysis utilized the R program with mada, metafor, and meta packages. Ten retrospective studies with 5926 participants were included in the systematic review and meta-analysis. The overall risk of bias and applicability concerns for each domain of the studies were rated as low, except for one study which was considered to have a high risk of flow and time bias. The mean METRICS score was 70.1% (range 49.6-83.2%). There was moderate heterogeneity across studies and meta-regression identified sources of heterogeneity in the data, including imaging modality, feature selection method, and classifier. The pooled diagnostic odds ratio (DOR) under the bivariate random effects model across the studies was 57.22 (95% CI 27.62-118.52). The pooled sensitivity and specificity were 87% (95% CI 81-92%) and 87% (95% CI 77-93%), respectively. The area under the summary receiver operating characteristic curve (AUC) of the radiomic models was 0.94 (range 0.8 to 0.98). The results supported that the radiomic techniques had good accuracy in diagnosing osteoporosis or abnormal bone mass. The application of radiomics in osteoporosis diagnosis needs to be further confirmed by more prospective studies with rigorous adherence to existing guidelines and multicenter validation.

Osteopetrosis and related osteoclast disorders in adults: A review and knowledge gaps On behalf of the European calcified tissue society and ERN BOND.

Osteopetrosis refers to a group of related rare bone diseases characterized by a high bone mass due to impaired bone resorption by osteoclasts. Despite the high bone mass, skeletal strength is compromised and the risk of fracture is high, particularly in the long bones. Osteopetrosis was classically categorized by inheritance pattern into autosomal recessive forms (ARO), which are severe and diagnosed within the first years of life, an intermediate form and an autosomal dominant (ADO) form; the latter with variable clinical severity and typically diagnosed during adolescence or in young adulthood. Subsequently, the AD form was shown to be a result of mutations in the gene CLCN7 encoding for the ClC-7 chloride channel). Traditionally, the diagnosis of osteopetrosis was made on radiograph appearance alone, but recent molecular and genetic advances have enabled a greater fidelity in classification of osteopetrosis subtypes. In the more severe ARO forms (e.g., malignant infantile osteopetrosis MIOP) typical clinical features have severe consequences and often result in death in early childhood. Major complications of ADO are atypical fractures with delay or failure of repair and challenge in orthopedic management. Bone marrow failure, dental abscess, deafness and visual loss are often underestimated and neglected in relation with lack of awareness and expertise. Accordingly, the care of adult patients with osteopetrosis requires a multidisciplinary approach ideally in specialized centers. Apart from hematopoietic stem cell transplantation in certain infantile forms, the treatment of patients with osteopetrosis, has not been standardized and remains supportive. Further clinical studies are needed to improve our knowledge of the natural history, optimum management and impact of osteopetrosis on the lives of patients living with the disorder.

Genetic Evaluation for Monogenic Disorders of Low Bone Mass and Increased Bone Fragility: What Clinicians Need to Know.

PURPOSE OF REVIEW: The purpose of this review is to outline the principles of clinical genetic testing and to provide practical guidance to clinicians in navigating genetic testing for patients with suspected monogenic forms of osteoporosis. RECENT FINDINGS: Heritability assessments and genome-wide association studies have clearly shown the significant contributions of genetic variations to the pathogenesis of osteoporosis. Currently, over 50 monogenic disorders that present primarily with low bone mass and increased risk of fractures have been described. The widespread availability of clinical genetic testing offers a valuable opportunity to correctly diagnose individuals with monogenic forms of osteoporosis, thus instituting appropriate surveillance and treatment. Clinical genetic testing may identify the appropriate diagnosis in a subset of patients with low bone mass, multiple or unusual fractures, and severe or early-onset osteoporosis, and thus clinicians should be aware of how to incorporate such testing into their clinical practices.

Sarcopenic obesity and reduced BMD in young men living with HIV: body composition and sex steroids interplay.

PURPOSE: Sex steroids play a key role on male bone homeostasis and body composition (BC), their role in men living with HIV (MLWH) is less recognized. This study aimed at investigating the prevalence of low BMD, sarcopenia, and sarcopenic obesity (SO) and their relationship with sex steroids in MLWH aged < 50. METHODS: Prospective, cross-sectional, observational study on MLWH younger than 50 (median age 47.0 years). BC and BMD were evaluated with DXA. Two different definitions of sarcopenia were applied: appendicular lean mass/height2 (ALMI) < 7.26 kg/m2 or appendicular lean mass/body weight (ALM/W) < 28.27%. Low BMD was defined for Z-score < -2.0. Sarcopenia coupled with obesity identified SO. Serum total testosterone (T) and estradiol (E2) were measured by LC-MS/MS; free testosterone (cFT) was calculated by Vermeulen equation. RESULTS: Sarcopenia was detected in 107 (34.9%) and 44 (14.3%) out of 307 MLWH according to ALMI and ALM/W, respectively. The prevalence of SO was similar by using both ALMI (11.4%) and ALM/W (12.4%). Sarcopenic and SO MLWH had lower total T and cFT in both the definition for sarcopenia. BMD was reduced in 43/307 (14.0%). Serum E2 < 18 pg/mL was an independent contributing factor for sarcopenia, SO, and low BMD. CONCLUSIONS: T and E2 are important determinants of BC even in MLWH. This is among the first studies investigating the distribution of obesity phenotypes and the prevalence of SO among MLWH showing that SO is present in 11-12% of enrolled MLWH regardless of the definition used. However, deep differences emerged using two different diagnostic definitions.

Knowledge, Attitude, and Practices Towards Osteoporosis Among Adults in the United Arab Emirates (UAE) in 2023.

BACKGROUND: Osteoporosis, the silent epidemic, is defined as a systemic skeletal disease characterized by low mineral bone mass and micro-architectural deterioration of bone tissue. Osteoporosis is considered a burden to global economic, social, and health development. Osteoporosis exerts a substantial global influence, markedly influencing rates of illness and death on a broad scale. Clinical features of osteoporosis can include chronic back pain, loss of height, and a stooped posture, as well as an increased risk of fractures in the spine, hip, and wrist. Accurate identification and monitoring of these clinical features are essential for effective management and treatment of osteoporosis. This study aims to identify the knowledge, attitudes, and practices (KAP) of adults (over 18 years) about osteoporosis and identify relations between knowledge, attitudes, and practices with demographic data. Furthermore, to assess the risk factors and preventive measures for osteoporosis. METHODOLOGY: Data from 446 responders were collected using a Google Forms questionnaire, including questions to assess knowledge, attitudes, and practice levels among adults 18 years and above in the United Arab Emirates (UAE). The collected data and statistical analysis were done through the IBM® SPSS® Statistics. Chi-Square was used in SPSS Statistics; the chi-square test was used for the relation between categorical variables, and P less than 0.05 was the cut-off level of significance. RESULTS: The research revealed that 41.9% of the participants had good knowledge, 38.8% had a positive attitude, and 45.3% had poor practices. The results also showed that there is a statistically significant correlation between gender and knowledge, attitudes, and practices. CONCLUSION: Our research demonstrates that there's a statistically significant correlation between gender variables with knowledge, attitudes, and practices. These findings have important implications in assessing the correlation between variables in our research that could be used to prevent osteoporosis further, target the specific demographic group, and provide the required education. Overall, our research contributes to a better understanding of the knowledge, attitude, and practices towards Osteoporosis among adults in the UAE and underscores the importance of further awareness in this area.

Clinical features, treatment, and follow-up of OPPG and high-bone-mass disorders: LRP5 is a key regulator of bone mass.

Osteoporosis-pseudoglioma syndrome (OPPG) and LRP5 high bone mass (LRP5-HBM) are two rare bone diseases with opposite clinical symptoms caused by loss-of-function and gain-of-function mutations in LRP5. Bisphosphonates are an effective treatment for OPPG patients. LRP5-HBM has a benign course, and age-related bone loss is found in one LRP5-HBM patient. PURPOSE: Low-density lipoprotein receptor-related protein 5 (LRP5) is involved in the canonical Wnt signaling pathway. The gain-of-function mutation leads to high bone mass (LRP5-HBM), while the loss-of-function mutation leads to osteoporosis-pseudoglioma syndrome (OPPG). In this study, the clinical manifestations, disease-causing mutations, treatment, and follow-up were summarized to improve the understanding of these two diseases. METHODS: Two OPPG patients and four LRP5-HBM patients were included in this study. The clinical characteristics, biochemical and radiological examinations, pathogenic mutations, and structural analysis were summarized. Furthermore, several patients were followed up to observe the treatment effect and disease progress. RESULTS: Congenital blindness, persistent bone pain, low bone mineral density (BMD), and multiple brittle fractures were the main clinical manifestations of OPPG. Complex heterozygous mutations were detected in two OPPG patients. The c.1455G > T mutation in exon 7 was first reported. During the follow-up, BMD of two patients was significantly improved after bisphosphonate treatment. On the contrary, typical clinical features of LRP5-HBM included extremely high BMD without fractures, torus palatinus and normal vision. X-ray showed diffuse osteosclerosis. Two heterozygous missense mutations were detected in four patients. In addition, age-related bone loss was found in one LRP5-HBM patient after 12-year of follow-up. CONCLUSION: This study deepened the understanding of the clinical characteristics, treatment, and follow-up of OPPG and LRP5-HBM; expanded the pathogenic gene spectrum of OPPG; and confirmed that bisphosphonates were effective for OPPG. Additionally, it was found that Ala242Thr mutation could not protect LRP5-HBM patients from age-related bone loss. This phenomenon deserves further study.