Search Results (946)

Peak bone mass gained in youth is crucial for preventing osteoporosis. Artistic gymnastics (AG) is highly osteogenic, yet its long-term effects on adults ≥ 45 years are not well documented. This case–control study compared bone mineral density (BMD) and the prevalence of osteopenia/osteoporosis in former gymnasts, age-matched controls, and reference populations from Brazil and Portugal. Participants included 65 former gymnasts (32 males, 33 females; 45–84 years), who trained for 12.6 ± 4.3 years and included 41 international competitors, and 91 controls (37 males; 45–87 years). Whole-body and femoral BMD were assessed by DXA. Physical activity during youth (10–20 years) (PA-Youth) and the past decade (PA-10) was recorded. Reference data were drawn from large cohorts in Brazil (FIBRA, n = 828) and Portugal (CIAFEL, n = 1089). Former gymnasts had substantially higher PA-Youth than controls, while PA-10 was similar. Gymnasts displayed 4–6 times higher femoral Z-scores (neck and total) and a markedly lower prevalence of osteopenia/osteoporosis (males: 3% vs. 16%; females: 36% vs. 52%, p < 0.05). These benefits remained after adjustment for age, PA-10, and hormonal/calcium therapy. Relative to reference populations, gymnasts showed greater whole-body and femoral mineralization, with no osteoporosis cases (vs. 6–12% overall; 9–13% among those ≥60 years). Age-stratified analysis (45–59 and ≥60 years) revealed a consistently lower osteopenia prevalence across age groups, except in females ≥ 60 years. In conclusion, early-life AG participation is associated with enduring skeletal benefits, including higher bone mineralization and reduced osteopenia/osteoporosis in adults ≥ 45 years. The protective effect appears diminished in older females, likely reflecting prolonged postmenopausal bone loss. Full article

Background: Vitamin D receptor (VDR) gene polymorphisms are linked to muscle and bone physiology, yet their influence on individual differences in resistance training adaptations, especially between sexes, is not well understood. Methods: In total, 191 healthy Chinese Han adults (94 men, 97 women) completed a 12-week, twice-weekly resistance training program (squat and bench press). Key indicators of strength, power, body composition, and muscle morphology were assessed before and after the intervention. Participants were genotyped for VDR polymorphisms (rs731236/TaqI, rs7975232/ApaI, rs1544410/BsmI, rs2228570/FokI). Data were analyzed to compare responses across genotype groups. Results: Training induced significant improvements in multiple outcomes. Overall, the AG genotype of rs731236 and the CT genotype of rs1544410 were associated with greater gains in bone mineral content. Sex-specific analyses revealed distinct patterns: in women, the rs731236-AA genotype correlated with better strength and power gains, while the AG genotype linked to greater body composition improvements. In men, the rs1544410-CC genotype was associated with superior lower-limb muscle growth. The rs7975232 showed no significant overall effect, and rs2228570 deviated from Hardy–Weinberg equilibrium. Conclusions: VDR gene polymorphisms, particularly rs731236 and rs1544410, are associated with inter-individual variability in resistance training responses among Chinese Han adults, demonstrating clear sex and phenotype specificity. These findings offer preliminary support for genotype-informed personalized training. Full article

Bone conduction hearing implant systems (BCHIs) are established treatments for patients with conductive or mixed hearing loss or single-sided deafness when conventional hearing aids are unsuitable. This study evaluated the cost-effectiveness of the active transcutaneous system Sentio versus a similar system, i.e., Osia in an Australian setting. Scenario analyses also compared Sentio to other systems, i.e., Ponto and Baha Attract. A Markov cohort model was adapted from a previously published source to reflect Australian practice, incorporating device acquisition, surgery, maintenance, battery replacement and adverse event management over a 15-year horizon from a healthcare perspective. Effectiveness inputs were derived from published evidence using a naïve indirect comparison. Extensive sensitivity analyses and external validation tested robustness. In the base case, Sentio was associated with lower costs and a small modelled incremental quality-adjusted life years (QALYs) gain versus Osia. Scenario analyses confirmed cost-effectiveness relative to Ponto and Baha Attract, with outcomes below the Australian willingness-to-pay threshold. Health state utility, device price and reimplantation assumptions were the most influential drivers, yet Sentio remained cost-effective in over 95% of simulations. These findings support Sentio as a clinically and economically efficient BCHI in Australia and highlight the need for direct utility and long-term durability data. Full article

Background/Objectives: Limited residual bone height in the atrophic posterior maxilla complicates implant placement. Transcrestal sinus elevation can be used to correct bone shrinkage after sinus pneumatization or crestal bone loss. This study evaluated a minimally invasive, one-stage transcrestal sinus lift using a double-layer crosslinked collagen scaffold (MCCS) with autogenous bone from the implant osteotomy site in patients with RBH ≤ 6 mm. Methods: In this prospective series, 11 patients (48–64 years, mean RBH 4.75 mm, SD 0.95 mm) underwent one-stage transcrestal sinus floor elevation with simultaneous implants. After osteotomy, autogenous bone chips collected during drilling were compacted into the site, and two layers of MCCS were placed under the elevated Schneiderian membrane. Buccal and palatal bone heights were measured on CBCT before and after surgery to assess vertical bone gain (ΔRBH). Results: All implants achieved stable osseointegration. Mean ΔRBH was approximately 3.1 ± 0.9 mm (combined buccal–palatal). No postoperative complications occurred. Two small Schneiderian membrane perforations were sealed intraoperatively by MCCS placement, with uneventful healing. Follow-up imaging showed maintenance of the augmented bone around the implants. Conclusions: This double-layer MCCS plus autogenous bone approach is a safe, effective, and minimally invasive transcrestal sinus lift for atrophic maxillae. It yielded crestal bone gains even with minimal initial RBH, leveraging the palatal sinus wall’s osteogenic potential and the implant’s tent-pole effect. The MCCS scaffold maintained space for bone formation and enabled immediate sealing of any membrane perforations. This one-stage protocol is viable for implant placement in low-RBH sites. Full article

Background: Accurate microbiological diagnosis of bone and joint infections (BJIs) is frequently hampered by low bacterial load, biofilm formation, and suboptimal tissue processing. This study evaluated the diagnostic performance of mechanical bead-milling using the Ultra-Turrax^® Tube Drive system compared with standard vortex homogenization. Methods: In a prospective cohort of 116 patients undergoing surgery for suspected BJIs, 540 intraoperative samples were processed using both methods. Culture and 16S rRNA PCR results were analyzed using classical and Bayesian statistical approaches. Diagnostic performance was assessed globally and across specimen types and anatomical sites. Results: Ultra-Turrax^® significantly improved sensitivity across all sample types (87.1% vs. 75.2%, p < 0.0001), while maintaining comparable specificity (>99%). Culture positivity increased by 17%, with the greatest gains observed in bone samples and hip prosthesis infections. Quantitative cultures demonstrated a 1.5–2 log₁₀ CFU/mL increase in bacterial yield. In culture-negative specimens, 16S rRNA PCR detection doubled with Ultra-Turrax^® processing (26% vs. 13%, p = 0.04). No increase in contamination was observed. Time to positivity was similar between methods, although Ultra-Turrax^® provided earlier results in 17% of cases. Bayesian modeling confirmed superior sensitivity (posterior probability > 0.995). Conclusions: Ultra-Turrax^® bead-milling markedly enhances microbiological detection in BJIs, particularly in low-biomass and bone-derived specimens. Its simplicity, reproducibility, and compatibility with routine workflows support its integration into diagnostic pathways. This pre-analytical optimization may improve etiological identification and guide more targeted antimicrobial therapy. Full article

Background and Clinical Significance: Prader–Willi syndrome (PWS) is an imprinting disorder not typically associated with severe congenital sensorineural hearing loss (SNHL). When profound SNHL is present in an infant with a known syndrome, an independent monogenic etiology should be considered. We report the first molecularly confirmed case of PWS co-occurring with biallelic pathogenic TMC1 variants causing congenital SNHL, outlining diagnostic challenges, cochlear implant (CI) outcomes, and implications for blended phenotypes. Case Presentation: A male infant with PWS due to a paternal 15q11.2–q13 deletion failed newborn hearing screening. Diagnostic auditory brainstem response and auditory steady-state response confirmed bilateral severe-to-profound SNHL. Temporal bone CT/MRI were normal. Comprehensive genetic testing identified compound heterozygous TMC1 variants consistent with autosomal recessive DFNB7/11 hearing loss, plus two variants of uncertain significance in SERPINB6 and EPS8L2. Sequential bilateral cochlear implantation was performed (left ear at 14 months, right at 20 months), followed by auditory–verbal therapy. Over four years, the child showed steady improvements in hearing and early-speech development. Conclusions: Early genomic evaluation is essential when clinical features appear atypical for a known syndrome. Identifying TMC1-related deafness enabled timely cochlear implantation and measurable gains. This case highlights that severe congenital SNHL in a syndromic infant may reflect a distinct monogenic disorder rather than phenotypic expansion of the primary syndrome, emphasizing the importance of recognizing blended phenotypes to guide precision-care strategies in rare disorders. Full article

Obesity is a major global health concern, being associated with insulin resistance and multiple metabolic disorders. Gremlin 1 (GREM1), a bone morphogenetic protein (BMP) antagonist, is increasingly recognized as a key regulator of adipose tissue dysfunction and impaired thermogenesis in obesity. Orlistat, a lipase inhibitor that reduces dietary fat absorption, is one of the most commonly used pharmacological agents for obesity management. White tea has demonstrated antioxidant and anti-obesity properties in experimental models. The aim of this study was to evaluate the effects of white tea on metabolic parameters (HOMA-IR, BMP4, Gremlin1) and GREM1 expression in rats made obese by a high-fat diet (HFD). A total of 40 male Sprague-Dawley rats were randomized into five groups: a standard diet group (STD); a high-fat diet group (HFD); an HFD + orlistat group (ORL); an HFD + 50 mg/kg white tea group (WT50); and an HFD + 150 mg/kg white tea group (WT150). Obesity was induced by feeding the rats a 45% high-fat diet for 3 weeks. Serum insulin, glucose and HOMA-IR levels were measured. Levels of GREM1 and BMP4 in serum and retroperitoneal adipose tissue were assessed. White tea supplementation significantly reduced weight gain and HOMA-IR compared to the HFD group. GREM1 mRNA expression in visceral adipose tissue decreased markedly in the WT50 and WT150 groups (p = 0.002 and p = 0.017, respectively). Serum GREM1 levels were significantly lower in the white tea-treated groups than in the HFD group (p = 0.011). Tissue BMP4 levels were only significantly reduced in the WT50 group (p = 0.005), indicating a non-linear dose–response pattern. There was a negative correlation between serum BMP4 levels and weight gain (rho = −0.440, p = 0.015). White tea was associated with improvements in metabolic parameters in an HFD-induced obesity model. These observations suggest a potential association between white tea bioactives and adipose tissue-related molecular pathways implicated in obesity. Given the short intervention duration and the exploratory design of this animal study, the findings should be interpreted with caution. Full article

The two-parameter Birnbaum–Saunders (B-S) distribution is widely applied across various fields due to its favorable statistical properties. This study aims to enhance the efficiency of modified moment estimators for the B-S distribution by systematically incorporating auxiliary non-sample information. To this end, we developed and analyzed a suite of estimation strategies, including restricted estimators, preliminary test estimators, and Stein-type shrinkage estimators. A pretest procedure was formulated to guide the decision on whether to integrate the non-sample information. The relative performance of these estimators was rigorously evaluated through an asymptotic distributional analysis, comparing their asymptotic distributional bias and risk under a sequence of local alternatives. The finite-sample properties were assessed via Monte Carlo simulation studies. The practical utility of the proposed methods is demonstrated through applications to two real-world datasets: failure times for mechanical valves and bone mineral density measurements. Both numerical results and theoretical analysis confirm that the proposed shrinkage-based techniques deliver substantial efficiency gains over conventional estimators. Full article

Background: Gout is an inflammatory arthritis associated with increased bone anabolism and a higher risk of ectopic bone formation. Colchicine, used to prevent and treat acute gouty flares, inhibits microtubule polymerization and has been described to promote osteoblastogenesis. In bone disorders such as osteoporosis, disruption of the osteoblast–adipocyte balance contributes to pathology, yet no therapies directly target bone marrow adiposity. Thus, we decided to investigate the impact of colchicine on the osteoblast-adipocyte balance. Methods: C3H10T1/2 mesenchymal stem cells were differentiated to both cell fates in the presence or absence of colchicine. Differentiation was assessed by studying differentiation phenotypes as well as adipocytic and osteoblastic marker genes. Disrupting microtubule homeostasis through stathmin (STMN1) silencing was employed to mimic colchicine effects on differentiation. Proteomic analysis was performed to gain further insight into colchicine’s effects on adipogenesis. Results: Colchicine promoted transcriptional changes consistent with osteoblastogenic commitment and inhibited adipogenesis, as evidenced by reduced intracellular lipid accumulation and downregulation of adipogenic marker genes. These effects were observed following both continuous and transient exposure (median fold change across adipogenic markers 0.41 and 0.59, respectively). Consistent with colchicine-induced microtubule destabilisation, microtubule disruption by STMN1 silencing also suppressed adipogenic differentiation (median fold change = 0.66), suggesting that colchicine’s anti-adipogenic effect may be due to its impact on the cytoskeleton. Conclusions: These findings indicate that colchicine can suppress adipogenic differentiation while favouring osteoblast commitment in mesenchymal stem cells. Although further validation in relevant preclinical models is required, its efficacy following transient exposure supports the exploration of site-specific strategies that limit systemic toxicity. Full article

Background and Objectives: People living with HIV (PLWH) have excess osteoporosis and fractures not fully captured by dual-energy X-ray absorptiometry (DXA). We evaluated whether trabecular bone score (TBS), calcaneal quantitative ultrasound (QUS) and bone turnover markers improve vertebral fracture risk assessment beyond areal bone mineral density (BMD) in PLWH. Methods: In this cross-sectional study, 87 antiretroviral-treated adults undergoing DXA had lumbar spine TBS and calcaneal QUS. Morphometric vertebral fractures were identified, correlates of degraded TBS were analyzed using multivariable regression, and sequential logistic models quantified the incremental contribution of TBS and CTX to discriminate for prevalent morphometric vertebral fractures. Results: Low BMD (osteopenia/osteoporosis) was present in 62% of participants, degraded TBS in 37% and morphometric vertebral fractures in 17%. Degraded versus normal TBS was associated with older age (49.1 vs. 39.7 years), longer HIV duration and lower nadir CD4+ count, as well as more frequent tenofovir disoproxil fumarate exposure (66% vs. 52%; all p ≤ 0.04). In multivariable analysis, age (per 10-year increase; adjusted odds ratio [aOR] 1.78; 95% CI 1.13–2.83) and nadir CD4+ < 200 cells/mm³ (aOR 2.29; 95% CI 1.06–4.97) independently predicted degraded TBS. In sequential cross-sectional models for prevalent morphometric vertebral fractures, the area under the curve increased from 0.71 (clinical variables) to 0.79 after adding lumbar spine T-score and to 0.85 after adding TBS; adding CTX yielded 0.87 without a statistically significant incremental gain. Conclusions: In PLWH, TBS captures bone quality deficits and improves vertebral fracture risk discrimination beyond BMD, supporting its integration alongside DXA in routine HIV care. Full article

Background: Osteosarcoma (OSA) is the most common type of bone cancer in canines. Novel therapies are required to prevent the growth, survival, and metastatic progression of this cancer, to increase life expectancy of patients. Immunohistochemical (IHC) studies and RNA sequencing help us gain a deeper understanding into the molecular mechanisms of the disease. Methods: We previously compared canine OSA tissues with patient matched non-tumour tissues, revealing 442 overexpressed genes within the samples. The present research used IHC staining for four of these genes in OSA tissues: G protein-coupled receptor 64 (GPR64), TOX High Mobility Group Box Family Member 3 (TOX3), Matrix Metallopeptidase 12 (MMP-12), and Forkhead Box F1 (FOXF1). H-scoring was performed to quantitatively assess protein expression and qualitatively contextualise staining locations. Additional analyses addressed whether gender or anatomical location of lesions (axial or appendicular tumours) affected protein expression. cBioPortal was employed to analyse expression and genetic alterations in patients. Results: GPR64, TOX3, MMP-12, and FOXF1 showed high mRNA expression and genetic alterations in people with OSA. GPR64, TOX3, MMP-12, and FOXF1 were all expressed in canine OSA with novel findings regarding cellular expression. Additionally, differential sex expression was revealed for GPR64 and TOX3. Potential biomarkers or therapeutic targets were identified. Conclusions: These studies, and subsequent analysis, have provided insights into the molecular mechanisms associated with OSA progression and revealed potential biomarkers for diagnostic and prognostic purposes. A deeper understanding of genetic and protein interactions will support and progress novel pathways towards diagnostic, prognostic, and treatment interventions for OSA in both veterinary and human medicine. Full article

Background/Objectives: Abaloparatide is an osteoanabolic therapy used in patients at high risk of fracture; however, the breadth of evidence across routes, comparators, and sequential strategies has not yet been comprehensively summarized. This study aimed to evaluate the efficacy and safety of abaloparatide for reducing fractures and improving bone mineral density (BMD) in adults with osteoporosis. Methods: Following PRISMA 2020, we searched PubMed, Embase, CENTRAL, and Web of Science (2016–2024) for randomized controlled trials and comparative real-world studies. Additional meta-analyses and network meta-analyses were included as contextual evidence but not pooled to avoid double-counting. Primary outcomes were vertebral, non-vertebral, and hip fractures; secondary outcomes included percentage change in BMD and safety endpoints. Random-effects models were used; heterogeneity, influence analyses, and prediction intervals were examined. Risk of bias was assessed using RoB 2 and AMSTAR 2. Results: Nine quantitative evidence sources met the criteria. Abaloparatide reduced vertebral fractures (RR 0.13–0.21) and showed moderate reductions in non-vertebral fractures. Lumbar spine BMD increased substantially, while hip and femoral neck gains were smaller and heterogeneous. Hypercalcemia risk was consistently lower compared to teriparatide. Transdermal delivery was less effective, and sequential abaloparatide → antiresorptive therapy further reduced fractures. Serious adverse events were not increased. Conclusions: Abaloparatide provides strong vertebral protection, significant BMD improvement, and shows a favorable calcemic profile, with moderate certainty for non-vertebral effects. Evidence in men and long-term safety remains limited. Full article

Background/Objectives: Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine with multifactorial etiology. Its treatment is conservative and/or surgical. The most commonly used conservative method is a full-time brace. However, nighttime braces have recently gained prominence, offering improved tolerance and a positive impact on health-related quality of life. The main objective of this study was to conduct a narrative review of published articles comparing the effectiveness of Providence nighttime versus full-time brace use to determine whether nighttime use is an effective option for improving therapeutic adherence, health-related quality of life, and psychosocial impact. Methods: A scientific literature search was conducted using the Scopus and PubMed databases. We searched for randomized controlled trials (RCTs), meta-analyses, systematic reviews and retrospective comparative studies reported in English from 2019 to 2024. The literature search was conducted from October to April 2024. Different combinations of the terms and MeSH terms “adolescent”, “idiopathic”, “scoliosis”, “Providence”, “full-time” and “brace” connected with various Boolean operators were included. Results: Overall, 70 articles were reviewed from the selected database. After removing duplicated papers and title/abstract screening, 10 studies were included in our review. The results showed that nighttime brace use has similar results in terms of effectiveness to full-time brace use in mild to moderate curves. However, nighttime brace use improves therapeutic adherence, health-related quality of life and psychosocial impact. Nevertheless, the effectiveness of night braces depends on factors such as curve type, magnitude, and bone maturity. So, in patients with moderate-severe curves and high growth velocity, it is important to reconsider the type of brace, as in these cases night braces alone may be ineffective in slowing the progression of the curve. Conclusions: Providence nighttime brace could be an effective treatment and better tolerated alternative to full-time brace in specific cases. This approach could improve therapeutic adherence. Nevertheless, more controlled and homogeneous studies are needed to establish definitive recommendations. Full article

Background: Ewing’s sarcoma (EwS) is a pediatric bone and soft tissue cancer driven by the oncogenic fusion protein EWS::FLI1. Currently, EwS lacks targeted therapies, necessitating the identification of novel regulatory mechanisms. While the role of microRNAs and long non-coding RNAs has been explored in EwS, the presence and functional significance of circular RNAs (circRNAs) in EwS is not reported. This is the first study to report the presence and role of oncogenic circRNA, circZNF609 in EwS tumor progression. Methods: Expression of circZNF609 was validated in 5 different EwS cell lines using qPCR. Cellular localization of circZNF609 was identified using circFISH. Functional assays for proliferation, migration and apoptosis were performed in wild type and circZNF609 knocked down (KD) cell lines to confirm its oncogenic role. The impact of circZNF609 on EWS::FLI1 protein levels was confirmed using western blots, immunofluorescence, and polysome fractionation. Mechanistic insights were gained utilizing bioinformatic, dual-luciferase reporter assays, rescue experiments, and microscopy to identify and validate the circRNA-miRNA-mRNA regulatory axis. Results: We report the first identification of circZNF609 in EwS, demonstrating that its expression is EWS::FLI1-dependent. Functional analysis reveals that circZNF609 promotes cell proliferation and metastasis while inhibiting apoptosis. Mechanistically, circZNF609 acts as a molecular sponge for miR-145-5p. By sequestering this miRNA, circZNF609 prevents the translational repression of EWS::FLI1, thereby sustaining oncogenic signaling. Conclusions: These findings identify circZNF609 as a novel post-transcriptional regulator of EWS::FLI1 and establish its critical role in EwS pathogenesis. Our results suggest that targeting the circZNF609/miR-145-5p/EWS::FLI1 axis may offer a promising therapeutic strategy for EwS. Full article

Improving phosphorus (P) utilization in broilers is crucial for reducing feed costs and environmental pollution. Bone mineralization trait is strongly associated with P utilization in poultry and is thus often used as an alternative trait for evaluating P utilization. Dentin matrix protein 1 (DMP1), an essential matrix protein for bone mineralization and P deposition, has been shown to be actively involved in P utilization in broilers, but the underlying mechanisms remain unclear. The current study aimed to investigate the possible mechanisms whereby DMP1 regulates P utilization of poultry by using gene silencing and overexpression technologies, combined with an in vitro model of primary broiler osteoblasts. The results showed that DMP1 overexpression augmented the P utilization of broiler osteoblasts, characterized by significant increases (p < 0.001) in P utilization rate, mineralization formation, alkaline phosphatase activity, and bone gla protein content. Meanwhile, DMP1 overexpression effectively (p < 0.05) activated the focal adhesion kinase (FAK) signaling, along with obvious (p < 0.01) decreases in fibroblast growth factor 23 (FGF23) expression and production. In contrast, DMP1 silencing reversed (p < 0.05) the above effects. Consistently, FAK activation promoted (p < 0.05) P utilization accompanied by remarkable (p < 0.05) decreases in FGF23 expression and production. Furthermore, gain- and loss-of-function assays demonstrated that a high level of FGF23 contributed to impaired P utilization, while a low level was beneficial. Interestingly, blocking FAK signaling not only recovered (p < 0.05) the FGF23 expression and production in DMP1 overexpressed cells but also obviously (p < 0.05) weakened their P utilization. These findings indicate that DMP1 inhibits FGF23 expression by activating FAK, thereby contributing to P utilization in broiler osteoblasts. They reveal a novel DMP1-FAK-FGF23 regulatory axis in broiler osteoblasts and provide a potential target for improving P efficiency in poultry. Full article