Search Results (14)

Pediatric type 1 diabetes (T1D) disrupts musculoskeletal development during critical windows of growth, puberty, and peak bone mass accrual. Beyond classic micro- and macrovascular complications, accumulating evidence shows a dual burden of diabetic bone disease—reduced bone mineral density, microarchitectural deterioration, and higher fracture risk—and diabetic myopathy, characterized by loss of muscle mass, diminished strength, and metabolic dysfunction. Mechanistically, chronic hyperglycemia, absolute or functional insulin deficiency, and glycemic variability converge to suppress PI3K–AKT–mTOR signaling, activate FoxO-driven atrogenes (atrogin-1, MuRF1), and impair satellite-cell biology; advanced glycation end-products (AGEs) and RAGE signaling stiffen extracellular matrix and promote low-grade inflammation (IL-6, TNF-α/IKK/NF-κB), while oxidative stress and mitochondrial dysfunction further compromise the bone–muscle unit. In vitro, ex vivo, and human studies consistently link these pathways to lower BMD and trabecular/cortical quality, reduced muscle performance, and increased fractures—associations magnified by poor metabolic control and longer disease duration. Prevention prioritizes tight, stable glycemia, daily physical activity with weight-bearing and progressive resistance training, and optimized nutrition (adequate protein, calcium, vitamin D). Treatment is individualized: supervised exercise-based rehabilitation (including neuromuscular and flexibility training) is the cornerstone of skeletal muscle health. This review provides a comprehensive analysis of the mechanisms underlying the impact of type 1 diabetes on musculoskeletal system. It critically appraises evidence from in vitro studies, animal models, and clinical research in children, it also explores the effects of prevention and treatment. Full article

Background/Objectives: In children, an association exists between muscle and bone, as well as between physical activity and osteogenesis. Impact loading is a factor in increasing bone accrual during growth. In this work, we explored the muscle–bone association in girls exposed to long-term physical activity at different levels of impact loading. Methods: Four groups of girls aged 7–16 were considered. The curricular (C; n = 22) group only had curricular physical activity at school (2 h/w). In addition to curricular physical activity, the girls in the dance (D; n = 21), gymnastics at lower training (GL; n = 14), and gymnastics at higher training (GH; n = 20) groups had 2 h/w, 4 h/w, and 4 h/w < training ≤ 12 h/w additional physical activity, respectively, for at least one year. A visual analysis estimated the respective amounts of impact-loading activity. The bone mineral content (BMC), areal bone mineral density (aBMD), and fat-free soft tissue mass (FFSTM) were assessed with dual-energy X-ray absorptiometry. Results: The results showed that, after adjusting for several confounders, statistically significant correlations were present between muscle mass and several bone mineral variables. A regression analysis confirmed the correlation in the data, and showed the marginal role of other body composition variables and physical activity for predicting BMC and BMD. Conclusion: Skeletal muscle mass is a major determinant of the BMC and BMD of the TBLH, as well as of the Appendicular level, in girls exposed to different amounts of long-term impact-loading physical activity. Full article

Longitudinal measurements of Relative Energy Deficiency in Sport (REDs) among adolescent male elite athletes are lacking. We aimed to monitor REDs indicators and their possible impact on performance in elite high-school cross-country skiing and biathlon athletes (n = 13) (16.3 ± 0.4 years, 179.4 ± 7.6 cm, 63.6 ± 8.2 kg body mass (BM), and peak oxygen uptake (VO_2peak): 61.5 ± 5.3 mL/kg BM/min) every 6 months for 3 years. Protocols included assessments of energy availability (EA), body composition and bone mineral density (BMD), resting metabolic rate (RMR), disordered eating behavior, exercise addiction, VO_2peak, and muscle strength. Data were analyzed using a linear mixed model. At baseline, 38% had low lumbar BMD (Z-score ≤ −1), and overall, bone health increased only slightly. VO_2peak and muscle strength improved (p < 0.001), RMR decreased (p = 0.016), and no change was observed in EA or physiological or psychological REDs indicators. Conclusively, many of these young male athletes had poor bone health at baseline, and most either lost or did not achieve the expected pubertal bone mineral accrual, although no other indication of REDs was observed, while performance improved during the study period. Our findings highlight the importance of elite sports high schools focusing on screening for early detection of impaired bone health in male athletes. Full article

The present study aimed to evaluate the burden and management of fragility fractures in subjects with Rett syndrome. We searched all relevant medical literature from 1 January 1986 to 30 June 2023 for studies under the search term “Rett syndrome and fracture”. The fracture frequency ranges from a minimum of 13.9% to a maximum of 36.1%. The majority of such fractures occur in lower limb bones and are associated with low bone mineral density. Anticonvulsant use, joint contractures, immobilization, low physical activity, poor nutrition, the genotype, and lower calcium and vitamin D intakes all significantly impair skeletal maturation and bone mass accrual in Rett syndrome patients, making them more susceptible to fragility fractures. This review summarizes the knowledge on risk factors for fragility fracture in patients with Rett syndrome and suggests a possible diagnostic and therapeutic care pathway for improving low bone mineral density and reducing the risk of fragility fractures. The optimization of physical activity, along with adequate nutrition and the intake of calcium and vitamin D supplements, should be recommended. In addition, subjects with Rett syndrome and a history of fracture should consider using bisphosphonates. Full article

Hyperglycemia has various adverse health effects, some of which are due to chronic oxidative and inflammatory impairment of bone marrow (BM), hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs). Astaxanthin (ASTX) has been shown to ameliorate hyperglycemia-associated systemic complications and acute mortality, and this effect is partially associated with restoration of normal hematopoiesis. Here, the effects of ASTX on diabetes-induced complications in BM and BM stem cells were investigated, and the underlying molecular mechanisms were elucidated. Ten-week-old C57BL/6 mice received a single intraperitoneal injection of streptozotocin (STZ; 150 mg/kg) in combination with oral gavage of ASTX (12.5 mg/kg) for 30 or 60 consecutive days. Supplemental ASTX ameliorated acute mortality and restored the STZ-impaired bone mass accrual and BM microenvironment in STZ-injected mice. Oral gavage of ASTX suppressed osteoclast formation in the BM of STZ-injected mice. Specifically, supplementation with ASTX inhibited oxidative stress and senescence induction of BM HSCs and MSCs and ameliorated hematopoietic disorders in STZ-injected mice. These effects of ASTX were associated with BM restoration of angiopoietin 1, stromal cell-derived factor 1, β-catenin, and Nrf2. Long-term ASTX gavage also recovered the STZ-induced dysfunction in migration, colony formation, and mineralization of BM-derived stromal cells. Further, a direct addition of ASTX exhibited direct and dose-dependent inhibition of osteoclastic activation without cytotoxic effects. Collectively, these results indicate that ASTX protects against diabetes-induced damage in the BM microenvironment in BM, HSCs, and MSCs and restores normal hematopoiesis and bone accrual in STZ-injected mice. Full article

Aberrant subchondral bone architecture is a crucial driver of the pathological progression of osteoarthritis, coupled with increased sensory innervation. The sensory PGE2/EP4 pathway is involved in the regulation of bone mass accrual by the induction of differentiation of mesenchymal stromal cells. This study aimed to clarify whether the sensory PGE2/EP4 pathway induces aberrant structural alteration of subchondral bone in osteoarthritis. Destabilization of the medial meniscus (DMM) using a mouse model was combined with three approaches: the treatment of celecoxib, capsaicin, and sensory nerve-specific prostaglandin E2 receptor 4 (EP4)-knockout mice. Cartilage degeneration, subchondral bone architecture, PGE2 levels, distribution of sensory nerves, the number of osteoprogenitors, and pain-related behavior in DMM mice were assessed. Serum and tissue PGE2 levels and subchondral bone architecture in a human sample were measured. Increased PGE2 is closely related to subchondral bone’s abnormal microstructure in humans and mice. Elevated PGE2 concentration in subchondral bone that is mainly derived from osteoblasts occurs in early-stage osteoarthritis, preceding articular cartilage degeneration in mice. The decreased PGE2 levels by the celecoxib or sensory denervation by capsaicin attenuate the aberrant alteration of subchondral bone architecture, joint degeneration, and pain. Selective EP4 receptor knockout of the sensory nerve attenuates the aberrant formation of subchondral bone and facilitates the prevention of cartilage degeneration in DMM mice. Excessive PGE2 in subchondral bone caused a pathological alteration to subchondral bone in osteoarthritis and maintaining the physiological level of PGE2 could potentially be used as an osteoarthritis treatment. Full article

While total body irradiation (TBI) is an everlasting curative therapy, the irradiation can cause long-term bone marrow (BM) injuries, along with senescence of hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) via reactive oxygen species (ROS)-induced oxidative damages. Thus, ameliorating or preventing ROS accumulation and oxidative stress is necessary for TBI-requiring clinical treatments. Here, we explored whether administration of ferulic acid, a dietary antioxidant, protects against TBI-mediated systemic damages, and examined the possible mechanisms therein. Sublethal TBI (5 Gy) decreased body growth, lifespan, and production of circulating blood cells in mice, together with ROS accumulation, and senescence induction of BM-conserved HSCs and MSCs. TBI also impaired BM microenvironment and bone mass accrual, which was accompanied by downregulated osteogenesis and by osteoclastogenic and adipogenic activation in BM. Long-term intraperitoneal injection of ferulic acid (50 mg/kg body weight, once per day for 37 consecutive days) protected mice from TBI-mediated mortality, stem cell senescence, and bone mass loss by restoring TBI-stimulated disorders in osteogenic, osteoclastic, and adipogenic activation in BM. In vitro experiments using BM stromal cells supported radioprotective effects of ferulic acid on TBI-mediated defects in proliferation and osteogenic differentiation. Overall, treatment with ferulic acid prevented TBI-mediated liver damage and enhanced endogenous antioxidant defense systems in the liver and BM. Collectively, these results support an efficient protection of TBI-mediated systemic defects by supplemental ferulic acid, indicating its clinical usefulness for TBI-required patients. Full article

The aim of this investigation was to determine the relationships of areal bone mineral density (aBMD) and content (BMC) with body composition, blood hormone and training load variables in adolescent female athletes with different loading patterns. The participants were 73 healthy adolescent females (14–18 years), who were divided into three groups: rhythmic gymnasts (RG; n = 33), swimmers (SW; n = 20) and untrained controls (UC; n = 20). Bone mineral and body compositional variables were measured by dual-energy X-ray absorptiometry, and insulin-like growth factor-1 (IGF-1), estradiol and leptin were analyzed from blood samples. In addition, aerobic performance was assessed by a peak oxygen consumption test. No differences (p > 0.05) in weekly training volume were observed between rhythmic gymnasts (17.6 ± 5.3 h/week) and swimmers (16.1 ± 6.9 h/week). Measured areal bone mineral density and bone mineral content values were higher in rhythmic gymnasts compared with other groups (p < 0.05), while no differences (p > 0.05) in measured bone mineral values were seen between swimmers and untrained control groups. Multiple regression models indicated that IGF-1 alone explained 14% of the total variance (R² × 100) in lumbar spine aBMD, while appendicular muscle mass and training volume together explained 37% of the total variance in femoral neck BMC in the rhythmic gymnast group only. In swimmers, age at menarche, estradiol and appendicular muscle mass together explained 68% of the total variance in lumbar spine BMC, while appendicular muscle mass was the only predictor and explained 19 to 53% of the total variance in measured bone mineral values in untrained controls. In conclusion, adolescent rhythmic gymnasts with specific weight-bearing athletic activity present higher areal bone mineral values in comparison with swimmers and untrained controls. Specific training volume together with appendicular muscle mass influenced cortical bone development at the femoral neck site of the skeleton in rhythmic gymnasts, while hormonal values influenced trabecular bone development at the lumbar spine site in both athletic groups with different loading patterns. Full article

Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased risk of fragility fractures and significant long-term disability. Although both anti-resorptive treatments and osteoanabolic drugs, such as parathyroid hormone analogues, are effective in fracture prevention, limitations exist due to lack of compliance or contraindications to these drugs. Thus, there is a need for novel potent therapies, especially for patients at high fracture risk. Romosozumab is a monoclonal antibody against sclerostin with a dual mode of action. It enhances bone formation and simultaneously suppresses bone resorption, resulting in a large anabolic window. In this opinion-based narrative review, we highlight the role of sclerostin as a critical regulator of bone mass and present human diseases of sclerostin deficiency as well as preclinical models of genetically modified sclerostin expression, which led to the development of anti-sclerostin antibodies. We review clinical studies of romosozumab in terms of bone mass accrual and anti-fracture activity in the setting of postmenopausal and male osteoporosis, present sequential treatment regimens, and discuss its safety profile and possible limitations in its use. Moreover, an outlook comprising future translational applications of anti-sclerostin antibodies in diseases other than osteoporosis is given, highlighting the clinical significance and future scopes of Wnt signaling in these settings. Full article

This study aimed to identify the interactional relationships between maturation (biological age (BA)) and lean mass on strength development in young athletes from different sports. Using a cross-sectional study design, a sample of 64 young athletes (rowers, swimmers, jiu-jitsu, volleyball, soccer and tennis players) of both sexes (13.6 ± 1.17 years) were recruited. Body composition was assessed using dual energy bone densitometry with X-ray source (DEXA). Strength of upper limbs (ULS), force hand grip (HG), vertical jump (VJ) and jump against movement (CMJ) were recorded. BA was estimated from anthropometrics. BA relationships were identified with upper limb strength in all athletes, and with the lower limb strength of tennis players, only (p < 0.05). An interaction effect between lean mass and BA was found (η²p = 0.753), as was a local effect within the regression models (ƒ² ≥ 0.33). Athletes with a higher concentration of lean mass had superior upper and lower limb strength (p < 0.05). Lean mass showed a local effect (ƒ²) greater than that associated with BA. Although maturation is related to strength development, the strength of the relationship is mitigated by the accrual of lean mass. Specifically, the local effect of lean mass on muscle strength is broader than that of maturation, especially for lower limb strength. Full article

This 7.5-year prospective controlled exercise intervention study assessed if daily school physical activity (PA), from before to after puberty, improved musculoskeletal traits. There were 63 boys and 34 girls in the intervention group (40 min PA/day), and 26 boys and 17 girls in the control group (60 min PA/week). We measured musculoskeletal traits at the start and end of the study. The overall musculoskeletal effect of PA was also estimated by a composite score (mean Z-score of the lumbar spine bone mineral content (BMC), bone area (BA), total body lean mass (TBLM), calcaneal ultrasound (speed of sound (SOS)), and muscle strength (knee flexion peak torque)). We used analyses of covariance (ANCOVA) for group comparisons. Compared to the gender-matched control group, intervention boys reached higher gains in BMC, BA, muscle strength, as well as in the composite score, and intervention girls higher gains in BMC, BA, SOS, as well as in the composite score (all p < 0.05, respectively). Our small sample study indicates that a daily school-based PA intervention program from Tanner stage 1 to 5 in both sexes is associated with greater bone mineral accrual, greater gain in bone size, and a greater gain in a musculoskeletal composite score for fractures. Full article

Young adulthood is an important stage in the accrual of bone mass. Young women are often unaware of the need, and how to optimize modifiable risk factors, particularly intake of nutrients associated with good bone health. In this study, an accessible way to estimate osteoporosis risk, quantitative ultrasound (QUS), is compared to the gold-standard technique dual X-ray absorptiometry (DXA) in a group of 54 healthy young women (18–26 years) from Manawatu, New Zealand, and the relationship with nutrient intake is investigated. Broadband ultrasound attenuation and speed of sound (BUA, SOS) were assessed by QUS calcaneal scans and bone mineral concentration/density (BMC/BMD) were determined by DXA scans of the lumbar spine and hip (total and femoral neck). Dietary intake of energy, protein, and calcium was estimated using three-day food diaries and questionnaires. DXA mean Z-scores (>−2.0) for the hip (0.19) and spine (0.2) and QUS mean Z-scores (>−1.0) (0.41) were within the expected ranges. DXA (BMD) and QUS (BUA, SOS) measurements were strongly correlated. Median intakes of protein and calcium were 83.7 g/day and 784 mg/day, respectively. Protein intake was adequate and, whilst median calcium intake was higher than national average, it was below the Estimated Average Requirement (EAR). No significant relationship was found between dietary intake of calcium or protein and BMD or BMC. To conclude, QUS may provide a reasonable indicator of osteoporosis risk in young women but may not be an appropriate diagnostic tool. Increased calcium intake is recommended for this group, regardless of BMD. Full article

Background and objectives: Studies indicate that genetic and lifestyle factors influence optimal bone development. Adaptations in bone mineral characteristics related to physical activity (PA) are most often observed in pre- and peri-puberty. Longitudinal associations between bone mineral accrual and objectively measured PA in puberty are poorly understood. The present study aims to investigate whether pubertal PA at different intensities is related to bone mineral characteristics in individuals at 18 years of age. Materials and Methods: Anthropometrics, pubertal stage, bone age and PA by accelerometer were measured in 88 boys at the mean age of 12.1 (T1), 13.1 (T2), 14.0 (T3) and 18.0 years (T4). Different bone mineral parameters were measured by dual-energy X-ray at T4. Stepwise multiple regression analysis was performed to determine the effect of bone age, body mass and PA characteristics on measured bone mineral parameters at 18 years of age. Results: Total PA in puberty together with mean pubertal body mass predicted 35.5% of total body (TB) bone mineral density (BMD), 43.0% of TB less head (LH) bone mineral content (BMC) and 48.1% of BMC/height in individuals at 18 years of age. Vigorous PA and body mass in puberty predicted 43.2% of femoral neck (FN) BMD; bone age at T1, vigorous PA and body mass in puberty predicted 47.3% of FN BMC at 18 years of age. No associations between pubertal PA levels and lumbar spine bone mineral characteristics in individuals at 18 years of age were found. Conclusions: Physical activity in puberty has a significant impact on bone mineral characteristics in individuals at 18 years of age, with total PA being a significant predictor of TB BMD and TB LH BMC as well as BMC/height, whereas vigorous PA is a significant predictor of FN BMD and FN BMC. Full article

Adequate vitamin D and calcium are essential for optimal adolescent skeletal development. Adolescent vitamin D insufficiency/deficiency and poor calcium intake have been reported worldwide. Heavy alcohol use impacts negatively on skeletal health, which is concerning since heavy adolescent drinking is a rising public health problem. This study aimed to examine biochemical vitamin D status and dietary intakes of calcium and vitamin D in 12–16 year-old adolescents with alcohol use disorders (AUD), but without co-morbid substance use disorders, compared to adolescents without AUD. Substance use, serum 25-hydroxyvitamin D (s-25(OH)D) concentrations, energy, calcium and vitamin D intakes were assessed in heavy drinkers (meeting DSM-IV criteria for AUD) (n = 81) and in light/non-drinkers without AUD (non-AUD) (n = 81), matched for age, gender, language, socio-economic status and education. Lifetime alcohol dose was orders of magnitude higher in AUD adolescents compared to non-AUD adolescents. AUD adolescents had a binge drinking pattern and “weekends-only” style of alcohol consumption. Significantly lower (p = 0.038) s-25(OH)D (adjusted for gender, smoking, vitamin D intake) were evident in AUD adolescents compared to non-AUD adolescents. High levels of vitamin D insufficiency/deficiency (s-25(OH)D < 29.9 ng/mL) were prevalent in both groups, but was significantly higher (p = 0.013) in the AUD group (90%) compared to the non-AUD group (70%). All participants were at risk of inadequate calcium and vitamin D intakes (Estimated Average Requirement cut-point method). Both groups were at risk of inadequate calcium intake and had poor biochemical vitamin D status, with binge drinking potentially increasing the risk of the latter. This may have negative implications for peak bone mass accrual and future osteoporosis risk, particularly with protracted binge drinking. Full article