Bone Mass Parameters Research Articles

Multiomics profiling reveals VDR as a central regulator of mesenchymal stem cell senescence with a known association with osteoporosis after high-fat diet exposure.

The consumption of a high-fat diet (HFD) has been linked to osteoporosis and an increased risk of fragility fractures. However, the specific mechanisms of HFD-induced osteoporosis are not fully understood. Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells (BMSCs), diminishing their proliferation and osteogenic capability, and thereby contributes to osteoporosis. Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor (VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice, suggesting that VDR is a key regulator of BMSC senescence. Notably, the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis, bone mass, and other bone parameters. Mechanistically, VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species (ROS) levels and preserving mitochondrial function. Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2 (SOD2)-ROS axis.

Catalpol attenuates osteoporosis in ovariectomized rats through promoting osteoclast apoptosis via the Sirt6-ERα-FasL axis

BackgroundCatalpol, a major active component of the Chinese herb Rehmannia glutinosa, possesses various pharmacological benefits, including anti-inflammatory, antidiabetic, and antitumor properties. Recent studies have reported that catalpol can attenuate bone loss and enhance bone formation. Nevertheless, the molecular mechanisms underlying its effects on osteoporosis pathogenesis remain unclear. PurposeWe investigated whether catalpol had a protective effect against postmenopausal osteoporosis (PMOP) and explored its exact mechanism of action. MethodsSeventy-two rats were randomly divided into six groups: sham, model, low-dose catalpol (5 mg/kg/day), medium-dose catalpol (10 mg/kg/day), high-dose catalpol (20 mg/kg/day), and positive control (alendronate, 2.5 mg/kg). In this experiment, a ovariectomy was performed to establish a female rat model of PMOP. After 12 weeks of gavage, micro-computed tomography (micro-CT) and histochemical staining were performed to evaluate bone mass, bone microstructure and histological parameters. Furthermore, RAW 264.7 cells were induced by RANKL to form mature osteoclasts to investigate the effect of catalpol on osteoclast differentiation and apoptosis in vitro. Additionally, the osteoclast apoptosis-related proteins of Sirt6, ERα, FasL, NFATc1, cleaved-caspase 8, cleaved-caspase 3, and Bax were assessed using western blotting. The expressions of NFATc1, Ctsk, Oscar, and Trap were quantified using RT-qPCR. The apoptotic rate of the osteoclasts was determined using flow cytometry. Sirt6 knockdown was performed using siRNA gene silencing in experiments to investigate its role in catalpol-mediated osteoclast apoptosis. The deacetylation of ERα in osteoclasts was tested via co-immunoprecipitation. ResultsCatalpol (10 and 20 mg/kg) and alendronate (2.5 mg/kg) could significantly improve bone mineral density (BMD) and microstructure and decrease osteoclast density in ovariectomized (OVX) rats. In addition, catalpol (10 and 20 mg/kg) upregulated the expression of Sirt6, ERα, FasL, cleaved-caspase 8, cleaved-caspase 3, Bax, and downregulated the expression of NFATc1, Ctsk, Oscar, Trap both in vivo and in vitro. Catalpol also promoted ERα deacetylation and stabilized ERα protein to enhance the expression of FasL. In addition, Sirt6 knockdown by siRNA prevented ERα deacetylation and eliminated catalpol-mediated osteoclast apoptosis. ConclusionsThe present study demonstrated that catalpol prevents estrogen deficiency-induced osteoporosis by promoting osteoclast apoptosis via the Sirt6-ERα-FasL axis. These findings revealed a novel molecular mechanism underpinning the impact of catalpol in the progression of osteoporosis and provided novel insights into the treatment of osteoporosis.

THU419 Comprehensive Evaluation Of Osteoporosis And Impaired Bone Micro Architecture In Patients With Transfusion Dependent Beta Thalassemia

Abstract Disclosure: P. Dutta: None. comprehensive evaluation of osteoporosis and impaired bone micro architecture in patients with transfusion dependent beta thalassemia Authors: Pinaki Dutta, Liza Das, Alka Khadwal, Pankaj Malhotra, Sanjay Kumar Bhadada, Vandana Dhiman, Vivek Sharma, Raman Introduction: Thalassemia-related bone disease is an entity that includes low bone mass, fractures and impaired bone microarchitecture. The current study was designed to evaluate the prevalence and determinants of low bone mass, osteoporosis and microarchitectural parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with transfusion-dependent thalassemia (TDT). Patients and Methods TDT patients (n=42) and age- and BMI-matched controls (n=40) were recruited. Demographic, biochemical and hormonal parameters were assessed. Bone mineral density (BMD), T- and Z- scores were measured by DEXA using the HOLOGIC Discovery A Viewer 6 machine. Bone microarchitecture was estimated by HR-pQCT (XtremeCT II, Scanco Medical AG, Switzerland). Results: The mean age of thalassemia patients at recruitment was 26.9 ± 6.5 years and that of controls was 28.9 ± 7.9 years. The mean age of transfusion initiation was 7 months (IQR 3-18) and the median number of transfusions required was 24 (15-25) annually. Serum calcium in cases (8.87 ± 0.67mg/dl) was significantly lower than the controls (9.40 ± 0.45mg/dl), with 9 patients having hypocalcemia and 7 of these having hypoparathyroidism. Hypogonadism was present in 40.4% patients. Bone turnover markers (P1NP, β-CTX) were not significantly different between cases and controls, except alkaline phosphatase (ALP) which was higher in the cases (102.6 ± 60.7 U/l) as opposed to controls (78.2 ± 32.1 U/l). There was a significant correlation between ALP and liver dysfunction (alanine transaminase exceeding the upper normal limit) (r = 0.36, p=0.01) and 63.6% of those with elevated ALP had liver dysfunction. Low bone mass (Z ≤−2) was present in significantly greater proportion of patients versus controls at femoral neck (29.3% vs 2.4%) and at lumbar spine (52.4% vs 14.7%). Total, cortical and trabecular volumetric bone mineral density were significantly lower in cases as compared to controls(p<0.05). The trabecular number was significantly lower (p<0.0001) and trabecular separation significantly higher at radius and tibia (p<0.001). Cortical thickness at radius and tibia were also significantly lower in cases than controls (p<0.0001). Conclusion: Patients with transfusion-dependent thalassemia have significantly lower areal and volumetric BMD (both cortical and trabecular). The bone microarchitecture is also significantly impaired in terms of lower number and wider spacing of trabeculae as well as lower cortical thickness at both radius and tibia. Presentation: Thursday, June 15, 2023

Association Among Complete Blood Count Parameters, Bone Mineral Density, and Cobb Angle in Cases of Adolescent Idiopathic Scoliosis.

BACKGROUND Improving the quality of life of scoliosis patients with appropriate preventive measures is critical. This study aimed to investigate the relationships among bone mass, Cobb angle, and complete blood count (CBC) parameters in patients with scoliosis. MATERIAL AND METHODS This joint study was conducted by the pediatric department and orthopedics clinics, which used the medical records of patients aged 10-18 years between 2018 and 2022. Patients were divided into 3 groups according to the Cobb angle. Patient blood count levels from medical records and bone mineral density (BMD) Z scores (g/cm²) were compared among groups. Notably, BMD Z scores were calculated using a (BMD) dataset from local Turkish children after adjusting for height and age. RESULTS A total of 184 individuals (120 females, 64 males) were included in the study. There were statistically significant differences among the groups in platelet-to-lymphocyte ratio (PLR). Significant differences in DXA Z scores among groups were found. There was a significantly strong and positive correlation between DXA Z scores and all CBC parameters in patients with severe scoliosis. CONCLUSIONS This study found that CBC parameters can predict BMD in adolescents. Furthermore, the association between vitamin D deficiency and low BMD may contribute to the follow-up of body adaptation in patients with scoliosis receiving conservative treatment.

METTL14 upregulates TCF1 through m6A mRNA methylation to stimulate osteogenic activity in osteoporosis.

Alteration of N6-methyladenosine (m6A) is closely linked to spanning biological processes including osteoporosis (OP) development. This research focuses on the function of methyltransferase like 14 (METTL14) in bone turnover and its interaction with T cell factor 1 (TCF1). A mouse model of OP was established by ovariectomy (OVX). The bone mass parameters were evaluated by micro-CT analysis. Mouse MC3T3-E1 cells and mouse bone marrow macrophages (BMMs) were induced for osteogenic or osteoclastic differentiation, respectively, for in vitro experiments. The osteogenesis or osteoclasis activity was analyzed by measuring the biomarkers such as OPG, ALP, NFATC1, CTSK, RANKL, and TRAP. RT-qPCR and IHC assays identified reduced METTL14 expression in bone tissues of osteoporotic patients and ovariectomized mice. Artificial METTL14 overexpression increased bone mass of mice and promoted osteogenesis whereas suppressed osteoclasis both in vivo and in vitro. METTL14 promoted TCF1 expression through m6A mRNA methylation, and TCF1 increased the osteogenic activity by elevating the protein level of RUNX2, a key molecule linked to bone formation. In rescue experiments, TCF1 restored the RUNX2 level and osteogenic activity of cells suppressed by METTL14 silencing. In summary, this research demonstrates that METTL14 plays a protective role against OP by promoting the TCF1/RUNX2 axis.

Positive association of lean mass and negative association of protein intake on bone mass and bone geometry of adolescent soccer players

ObjectiveThe aim of this study was to evaluate the association of food consumption and body composition on bone parameters in adolescent soccer players. MethodsThere were 148 male soccer players 12 to 18 y who participated in the study. Body composition was assessed by dual energy x-ray absorptiometry, comprising bone mineral density (BMD) and bone mineral content (BMC) of total body without head (TBLH), lumbar spine (L1-L4), and right femoral neck (RFN). The bone geometry variables measured were femoral strength index (FSI), buckling ratio (BR), section modulus (Z), cross-sectional moment of inertia (CSMI), and cross-sectional area (CSA). Food intake was analyzed using the 24-h food recall. Somatic maturation was estimated by the peak height velocity equation. For the statistical analysis, the stepwise multiple linear regression was used, with P < 0.05. ResultsRegarding food consumption, there was a high protein intake and low calcium intake. Lean mass was a predictor of BMC of TBLH (R2 = 0.524), L1-L4 (R2 = 0.492), and RFN (R2 = 0.405); BMD of L1-L4 (R2 = 0.407) and RFN (R2 = 0.27); Z (R2 = 0.683), CSMI (R2 = 0.630), and CSA (R2 = 0.640). There was a negative correlation between protein intake with bone mass and bone geometry parameters. ConclusionIn adolescent soccer players, lean mass was a predictor of bone parameters, and high protein intake was negatively associated with bone mass and geometry.

Experimental Exposure to Bisphenol A Has Minimal Effects on Bone Tissue in Growing Rams-A Preliminary Study.

Simple SummaryBisphenol A (BPA) is a well-known synthetic compound that belongs to the group of chemicals that disrupt the endocrine system in humans and animals. Although bones represent a potential target for these compounds, studies investigating BPA-related effects in bones in large farm animals are limited. We exposed young rams aged 9–12 months to BPA through feed for 64 days and investigated the effects of BPA on bone length, mass, microscopic structure, mineral content, strength, and serum bone parameters. We discovered that BPA had no significant effects on most of the parameters studied. Only manganese was decreased, and copper increased in the femurs of the BPA-exposed rams. These results suggest that a 2-month, low-dose exposure to BPA in growing rams did not affect the macro- and microstructure, metabolism, and biomechanical behavior of femur bones; however, it did affect the composition of microelements in bone, which could affect the bone in the long term.Bisphenol A (BPA) is a well-known synthetic compound that belongs to the group of endocrine-disrupting chemicals. Although bone tissue is a target for these compounds, studies on BPA-related effects on bone morphology in farm animals are limited. In this preliminary study, we investigated the effects of short-term dietary BPA exposure on femoral morphology, metabolism, mineral content, and biomechanical behavior in rams aged 9–12 months. Fourteen rams of the Istrian Pramenka breed were randomly divided into a BPA group and a control group (seven rams/group) and exposed to 25 µg BPA/kg bw for 64 days in feed. Blood was collected for determination of bone turnover markers (procollagen N-terminal propeptide, C-terminal telopeptide), and femurs were assessed via computed tomography, histomorphometry, three-point bending test, and mineral analysis. BPA had no significant effects on most of the parameters studied. Only mineral analysis showed decreased manganese (50%; p ≤ 0.05) and increased copper content (25%; p ≤ 0.05) in the femurs of BPA-exposed rams. These results suggest that a 2-month, low-dose exposure to BPA in growing rams did not affect the histomorphology, metabolism, and biomechanical behavior of femurs; however, it affected the composition of microelements, which could affect the histometric and biophysical properties of bone in the long term.

Beclin1- and Atg13-dependent autophagy activation and morroniside have synergistic effect on osteoblastogenesis.

Morroniside is known to improve osteoporosis by promoting osteoblastogenesis. The activation of PI3K/Akt/mTOR signaling is a significant mechanism in morroniside-promoted osteoblastogenesis. It is well known that protective autophagy is an important factor in osteoblastogenesis. However, the activation of mTOR signaling can inhibit autophagy. This study aimed to investigate the relationship between mTOR signaling and autophagy in morroniside-regulated osteoblastogenesis. In this study, we investigated the effect of morroniside on the autophagic activity (LC3 conversion rate, LC3-puncta formation, and autophagosome number) of differentiated osteoblast precursors (MC3T3-E1 cells). Then, we identified the roles of mTOR knockdown in morroniside-regulated alterations of autophagy and osteogenic parameters in MC3T3-E1 cells. Next, mTOR knockdown and overexpression were used to observe the roles of mTOR in morroniside-regulated alterations of autophagic molecules (Atg7, Atg13, and Beclin1). Subsequently, the additional value of the above autophagic molecules on morroniside-regulated osteogenic parameters in MC3T3-E1 cells was analyzed based on lentiviral transduction. Finally, combined with morroniside and TAT-Beclin1, the roles of Beclin1 upregulation in the in vivo effects of morroniside was investigated. Our experimental data showed that morroniside promoted both the mTOR activity and autophagy in MC3T3-E1 cells. Morroniside-upregulated autophagic activity and Atg13 or Beclin1 protein level in MC3T3-E1 cells were enhanced by mTOR knockdown. Furthermore, Morroniside-upregulated Atg13 and Beclin1 expression was reversed by mTOR overexpression. Importantly, autophagy upregulation with overexpression of the autophagic gene, Atg13 or BECN1 (gene form of Beclin1), significantly promoted osteoblastogenesis regulated by morroniside. The promotional effect of morroniside on bone microarchitecture, bone mass, and bone parameters (including trabecular bone area and OCN expression in trabecular bone) in ovariectomized (OVX) mice was enhanced by TAT-Beclin1 administration. In conclusion, the autophagy-enhancing drugs related to Beclin1 or Atg13 may be an effective adjuvant therapy in the treatment of osteoporosis with morroniside.

GPR109A gene deletion ameliorates gonadectomy-induced bone loss in mice.

Sex steroid deficiency plays critical roles in the pathophysiology of bone as the result of uncertain bone remodeling, i.e., increased bone resorption with equivocal bone formation. We have previously shown that GPR109A, a G protein coupled receptor, controls osteoclastogenesis and bone resorption, where global GPR109A deletion decreased osteoclast bone resorption and increased bone mass. Here, we used global GPR109A gene deletion, ovariectomized (OVX) and orchidectomized (ORX) mouse models to probe the role of GPR109A in gonadectomy-induced bone loss in female and male mice. Six months old GPR109A-/- mice and their wild type littermates were allocated to Sham or gonadectomized groups for six weeks. Using densitometric micro-CT confirmed by peripheral quantitative CT (pQCT) scans on tibia and spine, and three-point bending test on femur ex vivo, we found the bone volume, trabecular number, as well as bone mineral density and content in both trabecular and cortical sites were significantly decreased in wild type OVX and ORX compared with respective Sham groups. While bone mass in both male and female GPR109A-/- Sham groups were significantly higher compared with their respective wild type Sham groups, global GPR109A gene deletion ameliorated gonadectomy-induced bone loss. In GPR109A-/- females, most of bone mass and strength parameters measured by micro-CT, pQCT and three-point bending test were not different between Sham and OVX groups. In wild type but not in GPR109-/- mice, bone remodeling marker measurements indicated that both bone resorption (Cathepsin K) and bone formation (osteocalcin) markers were increased in gonadectomized mice compared to sham, with the exception of bone specific ALP, which was decreased in gonadectomized mice. Expression of bone resorption markers (Cathepsin K) were significantly lower, but β-catenin expression was higher in GPR109A-/- mice compared with their wild type littermates. Collectively, these data indicate that global GPR109A deletion ameliorates gonadectomy-induced bone loss through suppression of bone resorption.

The Combined Use of Platelet-Rich Plasma Clot Releasate and Allogeneic Human Umbilical Cord Mesenchymal Stem Cells Rescue Glucocorticoid-Induced Osteonecrosis of the Femoral Head.

Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is a refractory disease. The treatment options for ONFH, especially nonsurgical ones, merit further investigation. To evaluate the combinatorial therapeutic effects of platelet-rich plasma clot releasate (PRCR) and umbilical cord mesenchymal stem cells (UC-MSCs) on glucocorticoid-induced ONFH, a dexamethasone (DEX)-treated cell model and a high-dose methylprednisolone (MPS)-treated rat model were established. Cell counting kit-8 (CCK-8) assay was performed in vitro to determine the optimum dosage of PRCR for UC-MSC viability. The effects of PRCR, UC-MSCs, and PRCR + UC-MSCs on cell viability, apoptosis, migration, and differentiation capacities of DEX-treated bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cell (HUVECs) were explored via Transwell assays. Western blotting was conducted to evaluate the expression levels of RUNX2, VEGF, caspase-3, and Bcl-2 in the coculture systems. Ultrasound-guided intra-articular PRCR, UC-MSCs, and PRCR + UC-MSC injections were performed on the ONFH model rats. Microcomputed tomography, histological and immunohistochemical analyses, tartrate-resistant acid phosphatase (TRAP) staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess the therapeutic effects of PRCR and UC-MSCs on bone loss and necrosis induced by high-dose MPS. Results of this study revealed that the in vitro application of PRCR, UC-MSCs, and PRCR + UC-MSCs reversed the impaired proliferation and migration capacities and resisted apoptosis of BMSCs and HUVECs induced by DEX. Moreover, the PRCR and UC-MSC application significantly improved the alkaline phosphatase (ALP) and alizarin red (ALR) staining of BMSCs and tube formation capacity of HUVECs and promoted the protein expression of RUNX2 in BMSCs and VEGF in HUVECs. Similarly, in the ONFH rat model, the intra-articular injection of UC-MSCs and PRCR improved the subchondral bone mass parameters; promoted the expression of ALP, RUNX2, and VEGF; suppressed osteoclast overactivity; and resisted cell apoptosis. The combination of PRCR and UC-MSCs shows promising therapeutic effects in treating glucocorticoid-induced ONFH. The current study provides important information on intra-articular therapy, paving the way for the clinical management of ONFH in the future.

The relationship between circulating hormone levels, bone turnover markers and skeletal development in healthy boys differs according to maturation stage.

This study investigates peri-pubertal changes in bone turnover markers, Wnt-signalling markers, insulin-like growth factor-1 (IGF-1) and sex steroid levels, and how they reflect skeletal development in peri-pubertal boys. Population-based study in 118 peri-pubertal boys from the NINIOS cohort (age range at baseline 5.1-17.3years) with repeated measurements at baseline and after two years. Serum levels of the classical bone turnover markers (BTM) procollagen type 1N-terminal propeptide and carboxy-terminal collagen crosslinks, as well as sex-hormone binding globulin, IGF-1, osteoprotegerin, sclerostin and dickkopf-1 were measured using immunoassays. Sex steroids (estradiol, testosterone, and androstenedione) were measured using mass spectrometry and free fractions calculated. Dual energy x-ray absorptiometry was used for bone measurements at the lumbar spine and whole body. Volumetric bone parameters and bone geometry at the proximal and distal radius were assessed by peripheral QCT. Pubertal development was categorized based on Tanner staging. During puberty, sex steroid and IGF-1-levels along with most parameters of bone mass and bone size increased every next Tanner stage. In contrast, classical bone turnover markers and sclerostin peaked around mid-puberty, with subsequent declines towards adult values in late puberty. Especially classical BTM and sex steroid levels showed consistent associations with areal and volumetric bone parameters and bone geometry. However, observed associations differed markedly according to pubertal stage and skeletal site. Serum levels of sex steroids, IGF-1 and bone metabolism markers reflect skeletal development in peri-pubertal boys. However, skeletal development during puberty is nonlinear, and the relations between skeletal indices and hormonal parameters are nonlinear as well, and dependent on the respective maturation stage and skeletal site.

Bone phenotypes in multiple endocrine neoplasia type 1: survey on the MEN1 Florentine database.

Multiple endocrine neoplasia type 1 (MEN1) is a rare, inherited cancer syndrome characterized by the development of multiple endocrine and non-endocrine tumors. MEN1 patients show a reduction of bone mass and a higher prevalence of early onset osteoporosis, compared to healthy population of the same age, gender, and ethnicity. During the monitoring and follow-up of MEN1 patients, the attention of clinicians is primarily focused on the diagnosis and therapy of tumors, while the assessment of bone health and mineral metabolism is, in many cases, marginally considered. In this study, we retrospectively analyzed bone and mineral metabolism features in a series of MEN1 patients from the MEN1 Florentine database. Biochemical markers of bone and mineral metabolism and densitometric parameters of bone mass were retrieved from the database and were analyzed based on age ranges and genders of patients and presence/absence of the three main MEN1-related endocrine tumor types. Our evaluation confirmed that patients with a MEN1 diagnosis have a high prevalence of earlyonset osteopenia and osteoporosis, in association with levels of serum and urinary markers of bone turnover higher than the normal reference values, regardless of their different MEN1 tumors. Fifty percent of patients younger than 26 years manifested osteopenia and 8.3% had osteoporosis, in at least one of the measured bone sites. These data suggest the importance of including biochemical and instrumental monitoring of bone metabolism and bone mass in the routine medical evaluation and follow-up of MEN1 patients and MEN1 carriers as important clinical aspects in the management of the syndrome.

Bone density and body composition in small for gestational age children with adequate catch up growth: A preliminary retrospective case control study

Fetal growth patterns and birth weight (BW) have been associated with bone mineral density (BMD) and content (BMC) throughout infancy and childhood up to early adulthood. We hypothesized that in small for gestational age (SGA) children, compensatory infant catch-up growth to normal height centiles counteracts the adverse consequences of low BW on bone accrual. To evaluate BMD and BMC of SGA children born at term who experienced a normal catch-up growth as compared to children born appropriate for gestational age (AGA). We recruited 53 SGA (26 females) and 60 AGA children (27 females), aged 6 to 18years, matched for sex and body mass index (BMI). Fat mass (FM); Free fat mass (FFM); Lumbar spine and Total body less head (TBLH) BMD; BMC and BMD standard deviation scores corrected for body size (BMAD, BMAD z-score and TBLH BMD/Height) and TBLH BMC for FFM (TBLHBMC/FFM) were derived from Dual Energy X-ray absorptiometry (DXA) scans. SGA and AGA children did not differ in any auxological, body composition and bone parameters appropriately adjusted for height and FFM. BMI, FM and, remarkably, FFM were significantly correlated with bone mass parameters in both groups while no correlation was found between FM and FFM with the BW SDS in the univariate analysis. Our preliminary data demonstrate that SGA children born at term who recover from their growth deficiency through catch-up growth achieve bone mass and body composition not different from children born AGA.

Associations between nutrition, energy expenditure and energy availability with bone mass acquisition in dance students: a 3-year longitudinal study.

To determine whether risk factors normally associated with low bone mass in athletic populations (i.e. nutrition intake, energy expenditure and energy availability) are significant predictors of bone mass changes in vocational dance students. The total of 101 vocational dancers (63 females, 12.8 ± 2.2years; 38 males, 12.7 ± 2.2years) and 115 age-matched controls (68 females, 13.0 ± 2.1years; 47 males, 13.0 ± 1.8years) were monitored for 3 consecutive years. Bone mass parameters were measured annually at impact sites (femoral neck, FN; lumber spine, LS) and non-impact site (forearm) using DXA. Nutrition (3-day record), energy expenditure (accelerometer), energy availability and IGF-1 serum concentration (immunoradiometric assays) were also assessed. Female and male vocational dancers had consistently reduced bone mass at all anatomical sites (p < 0.001) than controls. IGF-1 did not differ between male vocational dancers and controls, but female dancers showed it higher than controls. At baseline, calcium intake was significantly greater in female vocational dancers than controls (p < 0.05). Male vocational dancers' fat and carbohydrate intakes were significantly lower than matched controls (p < 0.001 and p < 0.05, respectively). Energy availability of both female and male vocational dancers was within the normal range. A significant group effect was found at the FN regarding energy intake (p < 0.05) in female dancers. No significant predictors were found to explain bone mass differences in males. Our 3-year study revealed that both female and male vocational dancers displayed lower bone mass compared to controls, at both impact and non-impact sites. The aetiology of these findings may be grounded on factors different than those usually considered in athletic populations.

Influencia de la composición corporal y la masa ósea en la velocidad máxima obtenida durante un partido de fútbol en futbolistas jóvenes

Objective: The purpose of this study was to establish associations between the maximum speed obtained during a soccer match with body composition and bone mass in young soccer players from different maturational groups. Methodology: Cross-sectional study with 175 male soccer players. The velocity was measured by the global positioning system (Polar Team2 -USA). Bone mass (bone mineral density and content) and body composition parameters were obtained by the double-energy x-ray absorptiometry (iDXA-GE Healthcare Lunar, Madison, WI, USA) of the whole body and legs (lower limbs), the mass of (n = 42), During (n = 57) and Post (n = 76) the peak of growth was evaluated by means of this instrument, and somatic maturation was evaluated by the peak of growth velocity. growth rate. Results: Showed significant differences between groups for all variables studied. No significant correlations were found between the variables of bone mass and body composition with speed performance. Although not significant, we observed low coefficients of determination in the different groups: pre (23, 12% for bone density), during (27, 25% for the total lean tissue) and post (24,61% for the percentage of fat and total fat tissue). Conclusions: The results indicate a weak capacity of prediction of bone mass and body composition for the performance of the maximum velocity obtained during a soccer match in maturational groups. However, differences in bone mass behavior and body composition on maximal velocity were observed as the main component for each group.

Aged skeletal stem cells generate an inflammatory degenerative niche.

Loss of skeletal integrity during ageing and disease is associated with an imbalance in the opposing actions of osteoblasts and osteoclasts1. Here we show that intrinsic ageing of skeletal stem cells (SSCs)2 in mice alters signalling in the bone marrow niche and skews the differentiation of bone and blood lineages, leading to fragile bones that regenerate poorly. Functionally, aged SSCs have a decreased bone- and cartilage-forming potential but produce more stromal lineages that express high levels of pro-inflammatory and pro-resorptive cytokines. Single-cell RNA-sequencing studies link the functional loss to a diminished transcriptomic diversity of SSCs in aged mice, which thereby contributes to the transformation of the bone marrow niche. Exposure to a youthful circulation through heterochronic parabiosis or systemic reconstitution with young haematopoietic stem cells did not reverse the diminished osteochondrogenic activity of aged SSCs, or improve bone mass or skeletal healing parameters in aged mice. Conversely, the aged SSC lineage promoted osteoclastic activity and myeloid skewing by haematopoietic stem and progenitor cells, suggesting that the ageing of SSCs is a driver of haematopoietic ageing. Deficient bone regeneration in aged mice could only be returned to youthful levels by applying a combinatorial treatment of BMP2 and a CSF1 antagonist locally to fractures, which reactivated aged SSCs and simultaneously ablated the inflammatory, pro-osteoclastic milieu. Our findings provide mechanistic insights into the complex, multifactorial mechanisms that underlie skeletal ageing and offer prospects for rejuvenating the aged skeletal system.

Commentaries on Viewpoint: Fragile bones of elite cyclists: to treat or not to treat?

Commentaries on Viewpoint: Fragile bones of elite cyclists: to treat or not to treat?

Association between handgrip strength and bone mass parameters in HIV-infected children and adolescents. A cross-sectional study.

Low bone mineral content (BMC) and bone mineral density (BMD) have been identified in human immunodeficiency virus (HIV)-infected children and adolescents. The direct adverse effects of HIV infection and combined antiretroviral therapy (ART) negatively contribute to bone metabolism. A direct relationship between muscle strength levels and BMD in HIV-infected adults and older adults has been described. However, it is unknown whether handgrip strength (HGS) is associated with bone mass in pediatric populations diagnosed with HIV. To ascertain whether HGS levels are associated with BMC and BMD in HIV-infected children and adolescents. Cross-sectional study conducted in Florianãpolis, Brazil, in 2016. The subjects were 65 children and adolescents (8-15 years) diagnosed with vertically-transmitted HIV. Subtotal and lumbar-spine BMC and BMD were obtained via dual-emission X-ray absorptiometry (DXA). HGS was measured using manual dynamometers. The covariates of sex, ART, CD4+ T lymphocytes and viral load were obtained through questionnaires and medical records. Sexual maturation was self-reported and physical activity was measured using accelerometers. Simple and multiple linear regression were used, with P < 0.05. HGS was directly associated with subtotal BMD (β = 0.002; R² = 0.670; P < 0.001), subtotal BMC (β = 0.090; R² = 0.734; P = 0.005) and lumbar-spine BMC (β = 1.004; R² = 0.656; P = 0.010) in the adjusted analyses. However, no significant association was found between HGS and lumbar-spine BMD (β = 0.001; R² = 0.464; P = 0.299). HGS was directly associated with BMD and BMC in HIV-infected children and adolescents.

Age-Related Effects on Right Femoral Bone of Male Wistar Rats: A Morphometric and Biomechanical Study

Abstract Introduction Study of the variations of bone characteristics with age in different animal models is important to design musculoskeletal studies. Thus, this study aimed to evaluate the bone mass, dimensions, and biomechanical parameters of the femur in young, middle-aged, and aged Wistar rats. Materials and Methods Thirty male rats (Rattus norvegicus) were divided in three groups (n = 10 per group)—3-month-old young rats, 12-month-old middle-aged rats, and 18-months-old aged rats. The right femurs were subjected sequentially to morphometric study (bone weight, cortical thickness) and biomechanical tests (maximum resistance strength and bone stiffness). Results We observed a significant increase in femur histological (cortical thickness) and biomechanical (maximum strength and bone stiffness) parameters with aging when compared with young animals. Conclusions With the advancing age, the right femoral bone of middle-aged and old animals had greater variations when compared with young animals. However, further studies with the aid of a comparison between right and left femur and other long bones in both male and female rats are needed to corroborate with our findings.

IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation

The IL-23 receptor (IL-23R) signaling pathway has pleiotropic effects on the differentiation of osteoclasts and osteoblasts, since it can inhibit or stimulate these processes via different pathways. However, the potential role of this pathway in the regulation of bone homeostasis remains elusive. Therefore, we studied the role of IL-23R signaling in physiological bone remodeling using IL-23R deficient mice. Using µCT, we demonstrate that 7-week-old IL-23R−/− mice have similar bone mass as age matched littermate control mice. In contrast, 12-week-old IL-23R−/− mice have significantly lower trabecular and cortical bone mass, shorter femurs and more fragile bones. At the age of 26 weeks, there were no differences in trabecular bone mass and femur length, but most of cortical bone mass parameters remain significantly lower in IL-23R−/− mice. In vitro osteoclast differentiation and resorption capacity of 7- and 12-week-old IL-23R−/− mice are similar to WT. However, serum levels of the bone formation marker, PINP, are significantly lower in 12-week-old IL-23R−/− mice, but similar to WT at 7 and 26 weeks. Interestingly, Il23r gene expression was not detected in in vitro cultured osteoblasts, suggesting an indirect effect of IL-23R. In conclusion, IL-23R deficiency results in temporal and long-term changes in bone growth via regulation of bone formation.