Increase In Bone Mineral Content Research Articles

GSK3 inhibition improves skeletal muscle function and whole-body metabolism in male mouse models of Duchenne muscular dystrophy

Inhibiting glycogen synthase kinase 3 (GSK3) improves muscle function, metabolism, and bone health in many diseases and conditions; however, whether GSK3 should be targeted for Duchenne muscular dystrophy (DMD), a severe muscle wasting disorder with no cure, remains unknown. Here, we show the effects of GSK3 inhibition in male DBA/2J (D2) and C57BL/10 (C57) mdx mice. Treating D2 mdx mice with GSK3 inhibitors alone or in combination with aerobic exercise improves muscle strength, endurance, and morphology, attenuates the hypermetabolic phenotype, and enhances insulin sensitivity. GSK3 inhibition in C57 mdx mice also improves muscle fatigue resistance and increases cage ambulation. Moreover, muscle-specific GSK3 knockdown in mdx mice augments muscle force production and endurance. In both mdx strains, GSK3 inhibition increases bone mineral content and density. Overall, these improvements to muscle, metabolic, and bone health with GSK3 inhibition in mdx mice may have clinical implications for patients with DMD, where the current standard of care, glucocorticoids, delay the loss of ambulation but increase the risk for insulin resistance and osteoporosis. Along with our observation of lowered β-catenin content in DMD myoblasts, a known cellular target for GSK3, this study provides ample evidence in support of inhibiting GSK3 for this disease.

Examining the Influence of Season Phase, Age, and Anthropometrics on Body Composition Trends in National Basketball Association Athletes.

Russell, JL, Baker, BS, Mercer, RA, and McLean, BD. Examining the influence of season phase, age, and anthropometrics on body composition trends in NBA athletes. J Strength Cond Res XX(X): 000-000, 2024-This study aimed to describe seasonal body composition changes in NBA athletes using Dual-energy X-ray Absorptiometry (DXA) and to explore the relationship between these changes and factors such as age and anthropometrics. A retrospective analysis was conducted using 402 DXA scans from 62 professional male basketball players, obtained from one NBA team between 2012 and 2023. Seasonal phases were defined as preseason, pre all-star, post all-star, and offseason. A custom region of interest (ROI) method was used to ensure consistent scan areas for taller athletes who exceeded the DXA bed length. Linear mixed models analyzed the influence of seasonal phases, age, and height on lean mass (LM), fat mass (FM), and bone mineral content (BMC). In-season phases (pre all-star and post all-star) showed small increases in LM and decreases in FM compared with the preseason, with no significant BMC changes. Chronological age was associated with increases in LM but not FM. Taller athletes exhibited increases in LM, FM, and BMC. Significant random variance across players and seasons indicated that additional unmeasured factors might influence body composition. NBA athletes generally gain LM and lose FM during the season, with older players showing increased LM gain. The study's novel ROI method provide reliable data for athletes exceeding standard DXA limits, highlighting the importance of tailored body composition assessments in professional basketball. These findings can inform strength and conditioning, nutrition, and player development strategies across different seasonal phases and ages.

Enhancing Bone Formation Through bFGF-Loaded Mesenchymal Stromal Cell Spheroids During Fracture Healing in Mice.

This study aimed to evaluate the osteogenic potential of mesenchymal stromal cell (MSC) spheroids combined with the basic fibroblast growth factor (bFGF) in a mouse femur fracture model. To begin, MSC spheroids were generated, and the expression of key trophic factors (bFGF Bmp2, and Vegfa) was assessed using quantitative PCR (qPCR). A binding assay confirmed the interaction between the bFGF and the spheroids' extracellular matrix. The spheroid cultures significantly upregulated bFGF, Bmp2, and Vegfa expression compared to the monolayers (p < 0.001), and the binding assay demonstrated effective bFGF binding to the MSC spheroids. Following these in vitro assessments, the mice were divided into five groups for the in vivo study: (1) no treatment (control), (2) spheroids alone, (3) bFGF alone, (4) bFGF-loaded spheroids (bFGF-spheroids), and (5) non-viable (frozen) bFGF-loaded spheroids (bFGF-dSpheroids). Bone formation was analyzed by a micro-CT, measuring the bone volume (BV) and bone mineral content (BMC) of the mice four weeks post-fracture. A high dose of the bFGF (10 µg) significantly promoted bone formation regardless of the presence of spheroids, as evidenced by the increases in BV (bFGF, p = 0.010; bFGF-spheroids, p = 0.006; bFGF-dSpheroids, p = 0.032) and BMC (bFGF, p = 0.023; bFGF-spheroids, p = 0.004; bFGF-dSpheroids, p = 0.014), compared to the controls. In contrast, a low dose of the bFGF (1 µg) combined with the MSC spheroids significantly increased BV and BMC compared to the control (BV, p = 0.012; BMC, p = 0.015), bFGF alone (BV, p = 0.012; BMC, p = 0.008), and spheroid (BV, p < 0.001; BMC, p < 0.001) groups. A low dose of the bFGF alone did not significantly promote bone formation (p > 0.05). The non-viable (frozen) spheroids loaded with a low dose of the bFGF resulted in a higher BV and BMC compared to the spheroids alone (BV, p = 0.003; BMC, p = 0.017), though the effect was less pronounced than in the viable spheroids. These findings demonstrate the synergistic effect of the bFGF and MSC spheroids on bone regeneration. The increased expression of the BMP-2 and VEGF observed in the initial experiments, coupled with the enhanced bone formation in vivo, highlight the therapeutic potential of this combination. Future studies will aim to elucidate the underlying molecular mechanisms and assess the long-term outcomes for bone repair strategies.

Effect of recombinant irisin on recombinant human bone morphogenetic protein-2 induced osteogenesis and osteoblast differentiation

Osteoporotic fragility fractures substantially impact aging societies, necessitating long-term care and increasing healthcare costs. Myokine irisin, secreted by skeletal muscle, influences bone metabolism; however, a comprehensive understanding of the mechanisms by which irisin affects bone metabolism is still lacking. Therefore, this study aimed to explore the effects of irisin on osteogenesis and osteoblast differentiation triggered by bone morphogenetic protein-2 (BMP-2). We used 4-week-old male ICR mice and implanted polyethylene glycol pellets containing recombinant human BMP-2 (rh-BMP-2) into the left dorsal muscle pouch. Mice received weekly intraperitoneal injections of either phosphate-buffered saline or recombinant irisin (re-irisin). Ectopic bone formation was evaluated 3 weeks post-surgery using micro-computed tomography (μ-CT) and histological analysis. In vitro experiments, C2C12 cells were treated with or without rh-BMP-2 and re-irisin, and we assessed osteoblast differentiation markers, e.g., runt-related transcription factor 2, alkaline phosphatase, osteocalcin, and osteopontin, using real-time reverse transcription-polymerase chain reaction. The μ-CT analyses showed that re-irisin significantly increased bone mineral content and bone volume of ectopic bones newly formed by rh-BMP-2. The gene expressions of the osteoblast markers were significantly increased by rh-BMP-2 and further upregulated by re-irisin. The treatment of cyclic AMP response element-binding protein (CREB) small interfering RNA attenuated these effects, suggesting that CREB signaling pathway was involved in rh-BMP-2/re-irisin-induced osteoblastic differentiation. This study demonstrates the potential of irisin to enhance osteogenesis through BMP signaling, offering insights for osteoporosis treatment and highlighting irisin as a promising therapeutic target for improving bone health and extending a healthy lifespan.

Combined application of mesenchymal stem cells and different glucocorticoid dosing alleviates osteoporosis in SLE murine models.

Bone mesenchymal stem cells (BMSCs) have been tentatively applied in the treatment of glucocorticoid-induced osteoporosis (GIOP) and systemic lupus erythematosus (SLE). However, the effects of BMSCs on osteoporosis within the context of glucocorticoid (GC) application in SLE remain unclear. Our aim was to explore the roles of BMSCs and different doses of GC interventions on osteoporosis in SLE murine models. MRL/MpJ-Faslpr mice were divided into eight groups with BMSC treatment and different dose of GC intervention. Three-dimensional imaging analysis and hematoxylin and eosin (H&E) staining were performed to observe morphological changes. The concentrations of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in serum were measured by enzyme-linked immunosorbent assay (ELISA). The subpopulation of B cells and T cells in bone marrows and spleens were analyzed by flow cytometry. Serum cytokines and chemokines were assessed using Luminex magnetic bead technology. BMSCs ameliorated osteoporosis in murine SLE models by enhancing bone mass, improving bone structure, and promoting bone formation through increased bone mineral content and optimization of trabecular morphology. BMSC and GC treatments reduced the number of B cells in bone marrows, but the effect was not significant in spleens. BMSCs significantly promoted the expression of IL-10 while reducing IL-18. Moreover, BMSCs exert immunomodulatory effects by reducing Th17 expression and rectifying the Th17/Treg imbalance. BMSCs effectively alleviate osteoporosis induced by SLE itself, as well as osteoporosis resulting from SLE combined with various doses of GC therapy. The therapeutic effects of BMSCs appear to be mediated by their influence on bone marrow B cells, T cell subsets, and associated cytokines. High-dose GC treatment exerts a potent anti-inflammatory effect but may hinder the immunotherapeutic potential of BMSCs. Our research may offer valuable guidance to clinicians regarding the use of BMSC treatment in SLE and provide insights into the judicious use of GCs in clinical practice.

The Effects of Tai Chi Rouli Ball Exercise on Bone Mineral Content and Bone Metabolism Indicators in Perimenopausal Women

Background Perimenopause is associated with a decline in estrogen levels, leading to decreased bone mineral density (BMD) and altered bone metabolism, increasing the risk of osteoporosis. Tai Chi Rouli Ball, a traditional Chinese sport, is thought to have beneficial effects on physical health, but its impact on bone health in perimenopausal women is not well understood.Methods This study involved a randomized controlled trial with 52 perimenopausal women aged 45–55 years from community senior centers. Participants were divided into two groups: the Tai Chi Rouli Ball group and the control group. Baseline assessments of bone density, bone mineral content (BMC), and bone metabolism markers, including estrogen levels, were conducted. The Tai Chi Rouli Ball group underwent regular training for a specific period, while the control group did not receive any intervention. Post-experiment assessments were then compared to the baseline.Results Post-intervention, the Tai Chi Rouli Ball group showed a significant increase in spine bone density and BMC in various body parts, including the whole body, trunk/torso, and spine, compared to the control group. Bone metabolism indicators also improved, with increased levels of estrogen and a decrease in follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Calcium levels showed a significant increase, while other markers like alkaline phosphatase (ALP), phosphorus (P), and magnesium (Mg) had non-significant changes.Conclusions Tai Chi Rouli Ball exercise may positively influence bone health by improving bone density, BMC, and altering bone metabolism markers in perimenopausal women. These findings suggest that Tai Chi Rouli Ball could be a viable non-pharmacological approach to prevent osteoporosis in this demographic.

Development of Upper-Extremity Morphological Asymmetries in Male and Female Elite Youth Tennis Players: A Longitudinal Study.

This 2-year longitudinal study examined the development of upper-extremity bone mineral density (BMD), bone mineral content (BMC), and lean mass (LM) asymmetry magnitudes in male and female youth tennis players. Dominant and nondominant upper-extremity BMD, BMC, and LM values of 49 male and 31 female players were measured yearly using dual X-ray absorptiometry. From these values, asymmetry magnitudes were calculated and expressed as a percentage. Maturity offset was estimated using anthropometric measurements. Linear mixed effect models examined the development of BMD, BMC, and LM asymmetry magnitudes according to players' maturity offset, sex, and training volume. Adjusted for sex and training volume, a 1-year increment in maturity offset was associated with a significant increase in BMD (1.3% [2.2%]; P < .001) and BMC (0.6% [2.4%]; P = .011) asymmetry magnitudes. Male players displayed significantly higher LM asymmetry magnitudes (Δ3.2% [8.4%]; P = .002) compared with their female counterparts. Training volume was not significantly associated with asymmetry magnitude development. In contrast to LM, male and female youth tennis players' upper-extremity bones are still responsive to mechanical loading with a significant increase in BMD and BMC asymmetry magnitudes according to maturity offset.

Calcium-fortified fresh milk ameliorates postmenopausal osteoporosis via regulation of bone metabolism and gut microbiota in ovariectomized rats

The aging of the global population has made postmenopausal osteoporosis prevention essential; however, pharmacological treatments are limited. Herein, we evaluate the effect of calcium-fortified fresh milk (FM) in ameliorating postmenopausal osteoporosis in a rat model established using bilateral ovariectomy. After 3 months of FM (containing vitamin D, and casein phosphopeptides, 1000 mg Ca/100 g) or control milk (110 mg Ca/100 g milk) supplementation, bone changes were assessed using dual-energy X-ray absorptiometry, microcomputed tomography, and bone biomechanical testing. The results revealed that FM can regulate bone metabolism and gut microbiota composition, which act on bone metabolism through pathways associated with steroid hormone biosynthesis, relaxin signaling, serotonergic synapse, and unsaturated fatty acid biosynthesis. Furthermore, FM administration significantly increased bone mineral content and density in the lumbar spine and femur, as well as femoral compressive strength, while improving femoral trabecular bone parameters and microarchitecture. Mechanistically, we found that the effects may be due to increased levels of estrogen, bone formation marker osteocalcin, and procollagen type I N-propeptide, and decreased expression of the bone resorption marker C-telopeptide and tartrate-resistant acid phosphatase 5b. Overall, the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.

Off- to in-season body composition adaptations in elite male and female endurance and power event athletics competitors: an observational study

BackgroundMonitoring elite athletes’ body composition (BC) is vital for health and optimizing performance in sports emphasizing leanness, such as athletics. This study aims to investigate and compare sex- and event-specific off-to in-season BC changes in endurance and power event athletics competitors.MethodsElite male and female endurance athletes (> 800 m runners; n = 21) and power event athletes (sprinters, jumpers; n = 32) underwent dual-energy X-ray absorptiometry (DXA) scans for whole and regional lean mass (LM), fat mass (FM), bone mineral content (BMC), and density (BMD) during off-season (September-October) and in-season (April-May). Linear mixed models tested between-group off-season differences in BC, within-group off-season to in-season changes, and between-group differences in change. To assess meaningful or least significant changes (LSC) in BC, DXA precision errors were determined from two consecutive total body scans in a subsample of athletes (n = 30).ResultsMale athletes (n = 26) gained significantly (p < 0.05) more body mass (BM; mean difference 1.5 [95% confidence interval (CI):0.5–2.4] kg), LM (843 [95% CI:-253:1459] g), and trunk LM (756 [-502:1156] g) than female athletes (n = 27). The proportion of changes in athlete’s BC exceeding the LSC threshold for LM and trunk LM were 70% and 65% in males, and 48% and 26% in females. Significant (p < 0.05) within-group off-season to in-season increases in LM were found for male endurance and power athletes, and female power athletes. All groups significantly increased BMD (p < 0.05). Only male and female power athletes had significant in- to-off-season increases in BMC. 80% of all athletes who had a meaningful increase in BMC belonged to the power event group. No significant within- or between group change in FM was observed.ConclusionsThe present study found that male athletes gained more BM, LM and trunk LM than females. Within-group increases in regional and whole-body LM and BMC were predominantly found among power event competitors. Incorporating individual meaningful changes alongside traditional statistics provided additional insights into sex and event-group differences. Future research on elite athletic event groups should include DXA measurements closer to major outdoor-season competitions, coupled with site-specific measures (ultrasound, MRI) for better detection of subtle changes in LM and FM.

Polysacharide of Agaricusblazei gel mitigates bone necrosis in model of the jaws related to bisphosphonate via Wnt signaling

To investigate de effect of PAb gel on the bone tissue of rats submitted to Bisphosphonate-related osteonecrosis of the jaws (BRONJ). Initially, 54 animals were submitted to BRONJ model by Zoledronic Acid (ZA) (0.1 mg/kg 3x/wk for 9 wk, ip), followed by the 1st upper left molar extraction at the 8th wk. After tooth removal, the animals were divided into 3 groups, ZA that received placebo gel or PAb gel that received 1% PAb gel, inside the dental alveolus. The control Group (CONTROL) received 0.1 mg/kg of 0.9% saline and then placebo gel. Three weeks after tooth extraction, the animals were euthanized, and maxillae were colleted for macroscopic, radiographic, histological and Raman spectomery assays. Additionally, GSK3b, beta-catenin, and Runx2 mRNA expressions were determined. Blood samples were collected for the analysis of Bone-specific alkaline phosphatase (BALP) levels. PAb gel improved mucosal healing, increased the number of viable osteocytes, while it reduced the number of empty lacunae, as well as the amount of bone sequestration. Furthermore, PAb gel positively influenced the number and functionality of osteoblasts by stimulating Wnt signaling, thereby inducing bone remodeling. Additionally, PAb gel contributed to improved bone quality, as evidenced by an increase in bone mineral content, a decrease in bone solubility, and an enhancement in the quality of collagen, particularly type I collagen. PAb gel mitigated bone necrosis by stimulating of bone remodeling through Wnt signaling and concurrently improved bone quality. PAb gel emerges as a promising pharmacological tool for aiding in BRONJ therapy or potentially preventing the development of BRONJ.

Abaloparatide promotes bone repair of vertebral defects in ovariectomized rats by increasing bone formation

Osteoporotic vertebral fracture (OVF) is the most common type of osteoporotic fracture and is associated with immobility and mortality. Bone anabolic agents, such as abaloparatide (ABL), are usually administered to patients with OVF to prevent subsequent fractures. Although several studies have shown that bone anabolic agents promote healing of long bone fractures, there is little evidence of their healing effect on vertebral bone fractures. In the present study, we investigated the effect of ABL on vertebral bone defects using ovariectomized (OVX) rats with vertebral body drill-hole defects, an animal model of OVF. Eight-week-old female Sprague-Dawley rats were subjected to OVX, followed by the 32–36 days of bone depletion period, once-daily subcutaneous ABL was administered to OVX rats at a dose of 30 μg/kg for a maximum of 6 weeks from the day of the vertebral defect surgery. We found that ABL significantly increased bone mineral content and improved trabecular structural parameters at the vertebral defect site. Moreover, ABL significantly increased bone strength of the defected vertebrae. Bone histochemical analysis revealed formation of thick trabecular bone networks at the defect site after ABL administration, consistent with an improvement in trabecular structural parameters by ABL. ABL increased ALPase- and PHOSPHO1-positive osteoblastic cells and ALPase/PCNA double-positive cells, indicating enhanced preosteoblast proliferation as well as bone formation at the defect site. On the other hand, ABL did not affect the number of cathepsin K-positive osteoclasts per bone surface, suggesting that ABL did not promote excessive bone resorption. Our findings suggest that ABL is useful not only for preventing secondary vertebral fractures but also for promoting bone healing in OVF.

Insufficient Bone Mineralization to Sustain Mechanical Load of Weight in Obese Boys: A Cross-Sectional Study.

The increase in bone mineral content (BMC) and density (BMD) measured by dual-energy x-ray absorptiometry (DXA) in obese children may not sustain the mechanical load associated with weight, and the factors influencing bone mineralization are not well known. We described bone mineralization in boys with overweight/obesity and leanness in relation to body composition. Cross-sectional study in the Pediatric Endocrinology Unit of Angers University Hospital with 249 overweight/obese boys aged 8-18 who underwent DXA and insulin, testosterone, and IGF-1 measurements. Bone mineralization was compared with data from 301 lean boys of similar age and height from NHANES 2011-2015, using the same DXA model. Path analyses were performed to evaluate factors associated with total body less head (TBLH) BMC. The mean age- and height-adjusted difference in TBLH BMC between obese and lean boys was 241 ± 20 g/cm2. Each 1 kg/m2 increase in BMI was associated with +39 ± 6 g of TBLH BMC in lean subjects vs + 25 ± 3 g in obese subjects (P < .05). Each 1 kg/m2 increase in lean BMI (LBMI) was associated with +78 ± 5 g of TBLH BMC in lean and obese boys, and each 1 kg/m2 increase in fat mass index (FMI) was associated with a decrease of 9 ± 3 g of TBLH BMC. The TBLH BMC was directly positively influenced by LBMI and indirectly and positively influenced by IGF-1, testosterone, and insulin (mediated through height and LBMI). FMI indirectly influenced TBLH BMC, both positively through LBMI and negatively through its negative impact on IGF-1 and testosterone. The increase in bone mineralization in obese children does not adapt to the increase in body mass.

256 Evaluation Calcium and Phosphorus Ratios in the Presence of Phytase on Performance and Whole-Body Bone Mineralization in Growing Pigs

Abstract The objective of this study was to evaluate the effects of dietary calcium and phosphorus ratios in the presence of super dose phytase on grower pigs growth performance and bone mineral density. In two replicates, a total of 48 mixed sex pigs (26.7 kg BW) were allotted by BW and sex into individual pens across 3 dietary treatments (16 pigs/treatment) for 28 days. All diets contain phytase at 1,500 FTU/kg of complete feed and the three diet treatments were formulated with differing levels of Ca to achieve 0.7, 1.1 and 1.5 total Ca:total P. All diets were formulated to be isocaloric and isonitrogenous and ratios were achieved by vary limestone and sand. Pig BW and feed disappearance were recorded at the start (d 0) and end (d 28) of the study to calculate ADG, ADFI and G:F. On day 28, all pigs were euthanized to determine whole body bone, foot, rib, femur and tibia bone mineral density via dual x-ray absorptiometry. Data were analyzed with pen as the experimental unit, fixed effect of dietary treatment, sex and their interaction, and initial BW block and repartition as random effects. Differences were determined significant at P ≤ 0.05. Pig ADG was increased in the 1.1 verses 0.7 and 1.5 Ca:P diets (1.01, 0.95 and 0.95 kg/d, respectively, P = 0.046). End body weight was not different in the 0.7, 1.12 and 1.5 Ca:P treatments (53.5, 54.8 and 53.1 kg, respectively, P = 0.106). Diet Ca:P ratio did not alter ADFI or G:F. Whole body, tibia and femur bone mineral density was increased by 110% in 1.5 verses 0.7 Ca:P fed pigs, with bone mineral density being intermediated in the 1.1 Ca:P diets. Whole body (0.740, 0.752, 0.797, g/cm2, for 0.7, 1.1 and 1.5 Ca:P respectively, P = 0.033). For 0.7, 1.1 and 1.5 Ca:P femurs, bone mineral density was 0.463, 0.498 and 0.516, respectively, P = 0.034). Dietary treatment did not alter whole foot or 10th rib bone mineral densities (P &amp;gt; 0.05). Sex did not affect pig performance, but gilts had a 9% increase in bone mineral content. In conclusion, formulating dietary Ca:P in the presence of super dosing phytase at 1.1:1 total Ca:P resulted in the best ADG, but a ratio of 1.5:1 had the greatest bone mineral density.

SAT644 Gender Affirming Hormone Therapy (GHAT) In Adult Male-to-female Mice Increases Cortical And Trabecular Bone, Resulting In An Increase In Bone Strength

Abstract Disclosure: J.D. Zajac: None. T. Nie: None. V. Venkatesh: None. S. Golub: None. K. Stok: None. R. Desai: None. D.J. Handelsman: None. R.A. Davey: None. There are conflicting reports of the effects of GAHT on bone health and fracture risk in adult transgender women, and the underlying changes are poorly understood. We aimed to determine the effects of GAHT administered during adulthood on bone microarchitecture and strength in a mouse model of male-to-female transition. To model male-to-female transition in adults, C57BL/6 male mice aged 16 weeks that had reached peak bone mass were administered an estradiol-filled silastic implant (∼1.3mg) intraperitoneally for 12 weeks. Controls included vehicle treated intact males and females, n=9-10/group. At study end, serum sex steroids were determined by LCMS/MS, femoral bone microarchitecture by μ-CT, and strength by 3-point bending. Mean serum estradiol was 4.7-fold higher in males treated with estradiol (91.8±10.4 pg/mL) than the peak estradiol levels observed during the proestrus stage of the estrus cycle in adult female mice (19.4±13.5 pg/mL, Handelsman, 2020). Estradiol treatment in males increased the endocortical deposition of bone evidenced by an increase in cortical thickness (mm)(P&amp;lt;0.05) and a decrease in medullary volume (mm3)(P&amp;lt;0.05) compared to male and female controls. Periosteal circumference was not effected by estradiol treatment in males compared to controls. Trabecular bone volume/tissue volume (%) was 4-fold higher in estradiol treated males compared to male controls and 12-fold higher than female controls due to an increase in trabecular number (μm)(P&amp;lt;0.0001). The increase in both cortical and trabecular bone contributed to increased bone strength, as the maximum force (N) the bone could withstand prior to fracture was 2-fold higher in males treated with estradiol compared to both male and female controls (P&amp;lt;0.0001). Measurement of the material properties of the femur showed an increase in ultimate stress (MPa)(P&amp;lt;0.001) and elastic modulus (MPa)(P&amp;lt;0.01) in males following estradiol treatment compared to male controls, indicative of increased rigidity. In this model of adult male-to-female transition, supraphysiological levels of estradiol in male mice increases cortical and trabecular bone mass leading to increased bone strength. The increased rigidity of the femur following estradiol treatment suggests increased bone mineral content. It may be possible therefore, to preserve bone health and prevent fractures in trans women treated with GAHT, however a dose of estradiol that protects the bone without adverse side effects needs to be identified. Presentation: Saturday, June 17, 2023

Repurposing sarecycline for osteoinductive therapies: an in vitro and ex vivo assessment.

Tetracyclines (TCs) embrace a class of broad-spectrum antibiotics with unrelated effects at sub-antimicrobial levels, including an effective anti-inflammatory activity and stimulation of osteogenesis, allowing their repurposing for different clinical applications. Recently, sarecycline (SA)-a new-generation molecule with a narrower antimicrobial spectrum-was clinically approved due to its anti-inflammatory profile and reduced adverse effects verified with prolonged use. Notwithstanding, little is known about its osteogenic potential, previously verified for early generation TCs. Accordingly, the present study is focused on the assessment of the response of human bone marrow-derived mesenchymal stromal cells (hBMSCs) to a concentration range of SA, addressing the metabolic activity, morphology and osteoblastic differentiation capability, further detailing the modulation of Wnt, Hedgehog, and Notch signaling pathways. In addition, an ex vivo organotypic bone development system was established in the presence of SA and characterized by microtomographic and histochemical analysis. hBMSCs cultured with SA presented a significantly increased metabolic activity compared to control, with an indistinguishable cell morphology. Moreover, RUNX2 expression was upregulated 2.5-fold, and ALP expression was increased around sevenfold in the presence of SA. Further, GLI2 expression was significantly upregulated, while HEY1 and HNF1A were downregulated, substantiating Hedgehog and Notch signaling pathways' modulation. The ex vivo model developed in the presence of SA presented a significantly enhanced collagen deposition, extended migration areas of osteogenesis, and an increased bone mineral content, substantiating an increased osteogenic development. Summarizing, SA is a promising candidate for drug repurposing within therapies envisaging the enhancement of bone healing/regeneration.

Effects of resistance exercise training on bone physical and mineral properties in rats submitted to growth hormone intervention

PurposeTo investigate the effects of applying growth hormone (GH) and performing a strength training protocol on mineralization, rigidity, and crystallinity on the bone tissue of Wistar rats. MethodIn total, 40 male animals, 60 days old, of the Wistar lineage were used, distributed into four groups: control (C) [n = 10], control and application of GH (GHC) [n = 10], resistance training (T) [n = 10], and resistance training and application of GH (GHT) [n = 10]. The training period lasted four weeks and consisted of four sets of 10 jumps in a liquid medium. The amount of 0.2 IU per kilogram of body mass (0.2 IU/Kg) of GH was administered in the GHC and GHT groups. After the experimental period, samples of the tibia were collected and analyzed using Raman Spectroscopy (633 nm), Bone Densitometry - dual-energy x-ray absorptiometry (DXA), and Mechanical Assay (F-max). ResultsThe GHT group presented an increase for the variable Amide II (1544 cm-1) and decrease for the variable Proline (727 cm-1) from the Raman Spectroscopy analysis (p < 0.05). In addition, an increase was observed for the variables bone mineral density (BMD) and bone mineral content (BMC) (p < 0.05). Finally, no statistically significant differences were observed for the variables mineralization, crystallinity, phosphate carbonate types A and B, and bone rigidity (p > 0.05). ConclusionIt is concluded that GH added to RT resulted in an increase in the mineral Amide II (1544 cm-1) and a decrease in Proline (727 cm-1). Furthermore, an increase in BMD and BMC was observed only in the GHT group. Finally, no alterations were observed in crystallinity and rigidity in the different groups of animals.

THE ROLE OF PPARδ-DRIVEN β-OXIDATION IN BONE HEALTH DURING AGING

Abstract Musculoskeletal disorders are a significant complication of aging, leading to increased morbidity and mortality. However, current understanding of the mechanisms by which aging affects skeletal health is limited. Osteocytes are the most numerous and long-lived bone cells and play key roles in maintaining bone mass by responding to anabolic signals such as mechanical loading. Energy metabolism is dysregulated in many cells with aging, however regulation of energy metabolism in osteocytes and how this is affected during aging and by mechanical loading remains undefined. To investigate this, we first used IDG-SW3 osteocyte cells to determine the effects of mechanical loading on osteocytes in vitro by applying fluid flow shear stress (FFSS). FFSS increased Pparδ and Cpt1 expression, key promoters of fatty acid β-oxidation (FAO). Pharmacological antagonism of PPARδ or CPT1 resulted in dysregulated expression of key bone remodeling genes and impaired ATP release in response to FFSS. In vivo, mechanical loading significantly increased FAO in tibia cortical bone. However, FAO was impaired in the bones from aged mice. To further elucidate the role of osteocyte FAO, we deleted PPARδ specifically in osteocytes (PPARδ cKO), which resulted in decreased FAO and bone volume in female PPARδ cKO mice. Lastly, treatment of aging mice with the PPARδ activator GW0742 resulted in significantly increased bone mineral content, density and trabecular bone volume. These findings suggest important functions of osteocyte energy metabolism during aging and with mechanical loading on bone and identify PPARδ-driven FAO as a novel therapeutic target for improving skeletal health with aging.

Four hundred IU vs One thousand IU of vitamin D supplementation in first episode of nephrotic syndrome

Use of steroids in nephrotic children may lead to changes in bone mineral density and osteoporosis eventually affecting growth on a long term basis. We compared the proportionate changes in bone mineral content (BMC) and density(BMD), Vitamin D levels, Serum Calcium, phosphate and alkaline phosphatase levels in nephrotic children with the aim of giving high Vs low vitamin D doses (1000 IU Vs 400 IU) to two groups; group 1 (n=20) vs group 2 (n=20) respectively. The median BMC in group 1 increased from 11.53±3.48 g to 11.61±3.54 g after 1000 IU Vitamin D supplement and was statistically significant. However group 2 showed insignificant increases in BMC from 11.24±2.71 g to 11.25±2.67 g following 400IU Vitamin D. The change in BMD observed in group 1 from a mean of 0.426 to 0.429g/cm2 whereas in group 2 with 400 IU of vitamin D it didn’t show any significant change. The median vitamin D increased significantly in both groups; from 16.62±7.20 ng/ml to 27.45±6.47 ng/ml in group 1 while in group 2 from 18.72±8.07 ng/ml to 26.18±7.61 ng/ml which was statistically significant. The serum calcium levels normalized irrespective of 1000 IU or 400 IU of vitamin D supplementation. Changes in serum phosphate levels (decline from initial) were statistically significant however the changes in serum ALP were insignificant. We concluded that children supplemented with 1000 IU /day of vitamin D had better osteoprotection as compared to the other group.

Effects of whole body vibration on bone properties in growing rats

ABSTRACT This study aimed to examine the continuous effects of whole body vibration (WBV) on bone properties, in growing rats. Fifty 5-week-old male rats were divided into control and experimental groups. Each experimental group underwent WBV at 50 Hz (0.5 g, 15 min/day, 5 days/week) for 5 or 10 weeks. Bone size, muscle weight and bone mechanical strength of the right tibia were measured. Trabecular bone microstructure, cortical bone geometry and bone mass of the left tibia were analyzed by micro-CT. Serum levels of bone formation/resorption markers were also measured. In rats that underwent 5-week WBV, tibial cortical bone mineral content and cortical bone area significantly increased (p < 0.05), and tibial cortical bone volume, thickness, maximum load, break point and stiffness tended to be increased (p = 0.05–0.09), compared with control rats. In rats that underwent 10-week WBV, stiffness tended to be increased (p = 0.07), and the serum level of osteocalcin decreased, compared with control rats. These findings suggest that 5-week WBV had beneficial effects on bone properties, and that increased bone mineral content and cortical bone geometry may lead to higher bone mechanical strength. Further studies will be needed to determine the optimal conditions of WBV for improving bone properties in the growth stage.

Association between bone mineral density and content and physical growth parameters among children and adolescents diagnosed with HIV: a cross-sectional study.

ABSTRACTBACKGROUND:During childhood and adolescence, there are significant increases in bone mineral content (BMC) and bone mineral density (BMD).OBJECTIVE:To investigate physical growth parameters associated with BMD and BMC among children and adolescents diagnosed with human immunodeficiency virus (HIV).DESIGN AND SETTING:Cross-sectional study conducted in Florianópolis, Brazil, among 63 children and adolescents (aged 8-15 years) diagnosed with HIV.METHOD:BMD, BMC and fat percentage z score were evaluated using dual X-ray absorptiometry. Age/height z score and body mass index (BMI)/age z score were obtained in accordance with international recommendations, and bone age was obtained through hand-wrist radiography. Sex, family income, information on HIV infection (T CD4+ lymphocyte count, viral load and type of antiretroviral therapy, moderate-vigorous physical activity and sedentary behavior) were used as adjustment variables in the analyses. Simple and multiple linear regression analyses were performed, with a significance level of P ≤ 0.05.RESULTS:Subtotal BMD (without the head region) was directly associated with bone age, BMI/age z score and fat percentage z score, even after adjusting for covariates. Subtotal BMC/height was directly associated with bone age, height/age z score, BMI/age z score and fat percentage z score, even after adjusting for covariates.CONCLUSION:Subtotal BMD and subtotal BMC/height were directly associated with physical growth indicators among children and adolescents diagnosed with HIV.