Bone Mass Gain Research Articles

The role of osteopontin and osteocyte-derived factors in secondary hyperparathyroidism-induced myopathy.

Muscle weakness is a common symptom in CKD patients, and the pathway by which secondary hyperparathyroidism (SHPT) affects muscle function is unknown. Osteopontin (OPN), a bone matrix protein stimulated by PTH and phosphate, has been associated with inflammatory muscle diseases. In this observational and prospective cohort study, we evaluated 30 patients with severe SHPT (39 ± 12yr; 18 women), before and 6mo after parathyroidectomy (PTx). We examined the relationships among CKD-mineral and bone disorder parameters; myokine and inflammatory cytokine levels; and changes in resting energy expenditure (REE), muscle function, BMD, and muscle-related proteins. At baseline, the patients showed low gene expression of muscle turnover markers and irisin, as well as high protein expression of OPN, transforming growth factor beta (TGF-β), and fibroblast growth factor 21. Six months after PTx, REE and muscle mass had not changed, but physical performance, muscle strength, and bone mass improved, more so in patients undergoing total PTx. Also, there were reductions in the protein expression of OPN (11 vs 3%, p=.01) and TGF-β (21 vs 7%, p=.002) in muscle, together with a significant increase in irisin muscular levels (30 vs 35pg/mg, p=.02). The gain in bone mass and the increase in irisin levels correlated with a reduction in PTH. The levels of interleukin (IL)-1β, tumor necrosis factor alpha, and IL-17 (markers of myositis) were also lower after PTx. Our data suggest that SHPT plays a role in CKD-induced muscle dysfunction, indirectly, via release of bone-specific proteins, which is partially reverted with PTx.

An Additional Lrp4 High Bone Mass Mutation Mitigates the Sost-Knockout Phenotype in Mice by Increasing Bone Remodeling.

Pathogenic variants disrupting the binding between sclerostin (encoded by SOST) and its receptor LRP4 have previously been described to cause sclerosteosis, a rare high bone mass disorder. The sclerostin-LRP4 complex inhibits canonical WNT signaling, a key pathway regulating osteoblastic bone formation and a promising therapeutic target for common bone disorders, such as osteoporosis. In the current study, we crossed mice deficient for Sost (Sost-/-) with our p.Arg1170Gln Lrp4 knock-in (Lrp4KI/KI) mouse model to create double mutant Sost-/-;Lrp4KI/KI mice. We compared the phenotype of Sost-/- mice with that of Sost-/-;Lrp4KI/KI mice, to investigate a possible synergistic effect of the disease-causing p.Arg1170Trp variant in Lrp4 on Sost deficiency. Interestingly, presence of Lrp4KI alleles partially mitigated the Sost-/- phenotype. Cellular and dynamic histomorphometry did not reveal mechanistic insights into the observed phenotypic differences. We therefore determined the molecular effect of the Lrp4KI allele by performing bulk RNA sequencing on Lrp4KI/KI primary osteoblasts. Unexpectedly, mostly genes related to bone resorption or remodeling (Acp5, Rankl, Mmp9) were upregulated in Lrp4KI/KI primary osteoblasts. Verification of these markers in Lrp4KI/KI, Sost-/- and Sost-/-;Lrp4KI/KI mice revealed that sclerostin deficiency counteracts this Lrp4KI/KI effect in Sost-/-;Lrp4KI/KI mice. We therefore hypothesize that models with two inactivating Lrp4KI alleles rather activate bone remodeling, with a net gain in bone mass, whereas sclerostin deficiency has more robust anabolic effects on bone formation. Moreover, these effects of sclerostin and Lrp4 are stronger in female mice, contributing to a more severe phenotype than in males and more detectable phenotypic differences among different genotypes.

Medicarpin induces G1 arrest and mitochondria-mediated intrinsic apoptotic pathway in bladder cancer cells.

Bladder cancer (BC) is the tenth most commonly diagnosed cancer. High recurrence, chemoresistance, and low response rate hinder the effective treatment of BC. Hence, a novel therapeutic strategy in the clinical management of BC is urgently needed. Medicarpin (MED), an isoflavone from Dalbergia odorifera, can promote bone mass gain and kill tumor cells, but its anti-BC effect remains obscure. This study reve aled that MED effectively inhibited the proliferation and arrested the cell cycle at the G1 phase of BC cell lines T24 and EJ-1 in vitro. In addition, MED could significantly suppress the tumor growth of BC cells in vivo. Mechanically, MED induced cell apoptosis by upregulating pro-apoptotic proteins BAK1, Bcl2-L-11, and caspase-3. Our data suggest that MED suppresses BC cell growth in vitro and in vivo via regulating mitochondria-mediated intrinsic apoptotic pathways, which can serve as a promising candidate for BC therapy.

Rapid Transition from a High-Fat, High-Fructose to a Low-Fat, Low-Fructose Diet Reverses Gains in Bone Mass and Strength.

Obesity is thought to negatively impact bone quality and strength despite improving bone mineral density. We hypothesized that 1) continuous consumption of a high-fat, high-sugar (HFS) diet would impair bone quality and strength, and 2) a change from an HFS diet to a low-fat, low-sugar (LFS) would reverse HFS-induced impairments to bone quality and strength. Six-week-old male C57Bl/6 mice ( n = 10/group) with access to a running wheel were randomized to an LFS diet or an HFS diet with simulated sugar-sweetened beverages (20% fructose in place of regular drinking water) for 13 wk. HFS mice were subsequently randomized to continuing HFS feeding (HFS/HFS) or transition to the LFS diet (HFS/LFS) for four additional weeks. HFS/HFS mice exhibited superior femoral cancellous microarchitecture (i.e., greater BV/TV, Tb.N, Tb.Th, and decreased Tb.Sp) and cortical bone geometry (i.e., lower Ct.CSA and pMOI) compared with all other groups. At the femoral mid-diaphysis, structural, but not material, mechanical properties were greatest in HFS/HFS mice. However, HFS/HFS exhibited greater femoral neck strength only when compared with mice assigned to diet transition (HFS/LFS). Osteoclast surface and the percentage of osteocytes staining positive for interferon-gamma were greater in HFS/LFS mice, consistent with reduced cancellous microarchitecture postdiet transition. HFS feeding enhanced bone anabolism and structural, but not material, mechanical properties in exercising mice. A change from an HFS to LFS diet returned the bone structure to that of continuously LFS-fed mice while compromising strength. Our results indicate rapid weight loss from obese states should be performed with caution to prevent bone fragility. A deeper analysis into the altered bone phenotype in diet-induced obesity from a metabolic standpoint is needed.

Osteoporosis: Spotlight on current approaches to pharmacological treatment.

Despite the availability of safe and effective anti-osteoporosis treatments, osteoporosis continues to be undertreated. The increase in fragility fractures, which is the main clinical consequence of osteoporosis, is a major problem for healthcare systems of countries. A broad range of drugs including antiresorptive and anabolic agents are used in the pharmacological treatment of osteoporosis. Fracture risk assessment in drug selection is of utmost importance in terms of guiding treatment. The recommended thresholds for osteoporosis treatment decision making are based on major osteoporotic and hip fracture probabilities from the Fracture Risk Assessment Tool (FRAX®). Currently, antiresorptive agents are usually the first choice to increase bone mineral density (BMD) and reduce the fracture risk. Bisphosphonates and antiresorptive drugs such as denosumab, a nuclear factor kappa-B ligand (RANKL) inhibitor, are the most widely used drugs in the treatment of osteoporosis. Bisphosphonates alone are unlikely to provide long-term protection against fracture and restore BMD in patients with severe osteoporosis and high fracture risk. In such patients, treatment with an anabolic agent such as teriparatide, abaloparatide, or romosozumab should be ideally initiated to achieve maximal gain in bone mass and preserve the microarchitecture. Ideally, an antiresorptive drug should be continued to maintain gain in bone mass.

EVALUATION OF THE EFFECTIVENESS OF DIFFERENT METHODS SINUS FLOOR ELEVATION THE LATERAL APPROACH

Background: The posterior maxillary area sometimes has insufficient bone mass for dental implants. The augmentation of the sinus floor allows the implant to be placed in the posterior of the upper jaw. Purpose: The aim of this study was to compare the effectiveness antral balloon- assisted maxillary sinus elevation and traditional sinus floor elevation followed by bone graft and delayed implant placement the posterior maxillary area. Material and methods: A total of 68 patients, (aged 27 to 56 years, 32 women and 36 men), without any systemic diseases with unilateral/bilateral missing teeth and atrophy of the posterior maxillary area, who required an enlargement of the sinus prior to implant placement, whom the location of the sinus floor from the crest was 3-5mm, width ≥5 mm were included in the study between 2018 and 2021. Patients underwent a thorough clinical examination according to the generally accepted scheme. All patients were selected after meticulous evaluation of their medical histories and dental examinations, including OPG and dental Computed Tomography (CT) scans. Results: The sinus lift using balloon technique was performed successfully in patients 1 group, with no complications. In 9 patients 2 group, perforation of the sinus membrane occurred during the operation, sinusitis in 4 patients, graft failure in 3 patients. Regardless of the approach used, both approaches showed significant increases in bone mass gain. Though not statistically significant difference, balloon-assisted procedure showed more mean bone gain (8.4 mm) compared to osteotome -assisted procedure (8.1 mm). The mean amount of Marginal Bone Loss (MBL) in patients 1 group 3 years follow-up was 0.86 mm in patients 2 group showed significantly less marginal bone loss 1,16mm. The implant survival rate 3 years follow-up was in patients 1 group was 97.62%, in patients 2 groups was 95.2%. Conclusions: Research has shown that the balloon sinus lifting offers predictable, safe and effective results, and eliminates the complications associated with traditional side window techniques. However, further controlled clinical trials are needed to evaluate the efficacy and safety of these technique for their appropriate implementation in the field of oral implanotology.

In vitro effects of the myokine irisin on human adipose tissue-derived mesenchymal stem cells during proliferation and osteogenic differentiation

Purpose: Irisin is a hormone-like molecule secreted from skeletal muscle in response to exercise both in mice and in humans and identified as an important effector in the crosstalk between muscle and bone. Although a number of studies report that irisin increased osteoblast differentiation in vitro and cortical bone mass in vivo, the models used are exclusively rodent ones. Due to the lack of reports on human cell models, the aim of our work was to investigate the in vitro effects of irisin on the proliferation and the osteogenic differentiation processes in human adipose tissue-derived mesenchymal stem cells (hAMSCs). Methods: hAMSCs were obtained by enzymatic digestion and mechanical dispersion, and cultured in growth medium. Cells were exposed to 10 and 100 ng/ml irisin for the entire experimental period and refreshed every two days. The proliferation was performed in growth medium containing 2.5% fetal bovine serum, and measured by cell counting at 24-48-72 hours. Alkaline phosphatase (ALP) activity and Ca2+ depositions were quantified by fluorometric assay during up to 35 days of osteogenic induction. Results: Cell proliferation assay showed that 100 ng/ml irisin significantly increased the proliferation process (p<0.01) vs control, with a decrease of cell doubling time from 88 to 63 hours. Osteodifferentiation with 10 and 100 ng/ml irisin showed significant increases in ALP activity vs control (p<0.01) after 14 days. Moreover, both tested concentrations of irisin were able to accelerate the deposition of mineralized matrix, resulting in significant increments in the production of Ca2+ nodules vs control after 35 days (p<0.01). Conclusions: This work showed the in vitro effects of irisin on a human cell model of AMSCs. The preliminary results show this myokine to be an important effector on cell proliferation and during osteo-differentiation of hAMSCs, supporting the hypothesis that irisin could represent a potent new anabolic treatment to bring about gain of bone mass.

Linear growth and relative weight gain in childhood and bone mass in adolescence: findings from the Pelotas (Brazil) 2004 birth cohort.

To investigate independent relationships of linear growth and relative weight gain during defined periods of infancy, childhood, and early adolescence with areal bone mineral density (aBMD) of three sites at 11years. Data on weight and length/height were obtained at birth, 3, 12, and 24months, and the ages of 4, 6, and 11. The outcome was whole body, femoral neck, and lumbar spine aBMD (g/cm2) measured at 11years using dual-energy X-ray absorptiometry. The effects of weight gain and linear growth were analyzed using conditional relative weight and conditional length/height. Associations between conditional growth and outcomes were analyzed using linear regression, adjusted for multiple confounders. Individuals with data available for exposures and bone outcomes were 2875 and comprised the sample. For boys, the greatest magnitude of increase for whole body and height gain was at 48months (β 0.014, 95% CI 0.010; 0.018). For girls, higher aBMD was observed for those with greater height gain at 11years, representing for lumbar spine an increase of 0.056g/cm2 (95% CI 0.050; 0.062). For body weight, among boys, the greatest magnitude in the whole body was also associated with weight gain at 48months (β 0.014, 95% CI 0.010; 0.018). For girls, the highest coefficient was at 24months, representing for lumbar spine an increase of 0.028g/cm2, (95% CI 0.021; 0.035). Positive associations were demonstrated between length/height and weight gain and aBMD in both sexes, with emphasis on girls' aBMD in response to the linear growth achieved mainly at 11years.

Zoledronic acid for osteoporosis and associated low-energy fractures

Zoledronic acid is a third-generation amino-containing BF that has been used to treat patients with osteoporosis for more than 15 years. Over the years, numerous experimental and clinical studies have proven the high efficacy of the drug in osteoporosis, both in women of various age groups, and in men, with primary and secondary osteoporosis, in patients with varying degrees of bone loss and risk of fractures. Intravenous infusions of zoledronic acid have been shown to result in a rapid gain of bone mass, a significant reduction in the risk of low-energy fractures of the vertebrae (spine), proximal femoral and nonvertebral fractures on the whole. However, in recent years, the use of the drug has significantly decreased, which is associated both with the lack of awareness of primary care physicians about the possibilities of this drug, and the fear of such complications of its use as atypical fractures and osteonecrosis of the jaw bones. The presented review aims to increase the knowledge of physicians regarding the mechanism of action of zoledronic acid, the regimens for prescribing the drug in various forms of osteoporosis and fractures against its background. The given clinical example shows the ability of zoledronic acid (osteostatics) to increase the mass of not only cancellous, but also the cortical bone of the proximal femur, which increases the role of zoledronic acid in the prevention of recurrent fractures. On top of that, the prolonged effect of the drug allows, when the desired therapeutic effect is achieved, to reduce the frequency of prescribing according to the ‘drug holiday’ principal, decreasing economic expenditures and medical and social burden.

ISPAD Clinical Practice Consensus Guidelines 2022: Diabetes in adolescence.

ISPAD Clinical Practice Consensus Guidelines 2022: Diabetes in adolescence.

Associations between Dietary Antioxidant Vitamin Intake and the Changes in Bone Mass in Chinese Adolescents: A 2.5-Year Longitudinal Study.

(1) Background: Optimal bone mass accumulation during adolescence is crucial for maximising peak bone mass during adulthood. Dietary antioxidant vitamins may contribute to bone mass accumulation. This 2.5-year-long longitudinal study aimed to evaluate the relationships between dietary vitamin A, C, and E intakes and the annual changes in bone parameters among Chinese adolescents. (2) Method: Subjects aged 10–18 years (n = 1418) were recruited from a secondary school in Jiangmen, China. Dietary vitamin A, C, and E intakes were assessed using 24 h dietary records over 3 consecutive days. The Sahara Clinical Bone Sonometer was used to measure the broadband ultrasound attenuation (BUA) and the speed of sound (SOS). Their annual changes were then calculated (i.e., BUA%/year, SOS%/year). The associations were detected after adjusting for the baseline bone phenotype; age; sex; weight; height; pubertal stage; physical activity; and dietary intakes of vitamin D, calcium and energy. (3) Results: A curvilinear relationship was found between the dietary intake of vitamin C and BUA%/year (p = 0.026); further analyses in the subgroups revealed that this relationship was observed in male adolescents (p = 0.012). A positive association was observed only in boys with a dietary vitamin C intake of ≥159.01 mg/day (β = 0.395, p = 0.036). Moreover, a linear positive association was shown between the dietary intake of vitamin E and BUA%/year in female adolescents (β = 0.082, p = 0.033). (4) Conclusion: Our findings indicated that dietary vitamin C intake has a threshold effect on bone mass gain in male adolescents and that dietary vitamin E intake could be a positive predictor of bone mass gain in female adolescents.

Antagonizing microRNA‐19a/b augments PTH anabolic action and restores bone mass in osteoporosis in mice

Postmenopausal bone loss often leads to osteoporosis and fragility fractures. Bone mass can be increased by the first 34 amino acids of human parathyroid hormone (PTH), parathyroid hormone‐related protein (PTHrP), or by a monoclonal antibody against sclerostin (Scl‐Ab). Here, we show that PTH and Scl‐Ab reduce the expression of microRNA‐19a and microRNA‐19b (miR‐19a/b) in bone. In bones from patients with lower bone mass and from osteoporotic mice, miR‐19a/b expression is elevated, suggesting an inhibitory function in bone remodeling. Indeed, antagonizing miR‐19a/b in vivo increased bone mass without overt cytotoxic effects. We identified TG‐interacting factor 1 (Tgif1) as the target of miR‐19a/b in osteoblasts and essential for the increase in bone mass following miR‐19a/b inhibition. Furthermore, antagonizing miR‐19a/b augments the gain in bone mass by PTH and restores bone loss in mouse models of osteoporosis in a dual mode of action by supporting bone formation and decreasing receptor activator of NF‐κB ligand (RANKL)‐dependent bone resorption. Thus, this study identifies novel mechanisms regulating bone remodeling, which opens opportunities for new therapeutic concepts to treat bone fragility.

PERFORMANCE OF THE ANTI-SCLEROSTIN ANTIBODY IN DENTISTRY

<h3>Objectives</h3> Metabolic disorders can interfere with the balance of bone tissue that is maintained during the remodeling process. The use of anti-sclerostin antibody (Scl-Ab) is a promising treatment that has been suggested for this condition. The aim was to approach the vast and important role of the Scl-Ab in dentistry and highlight the importance of studies to obtain worldwide approval for the therapeutic agent, which can offer improved quality of life to several patients through bone mass gain. <h3>Study Design</h3> This article presents a narrative review approach using the keywords "dentistry" and "sclerostin" from the previous 5 years, including experimental and clinical studies that have evaluated the effect of Scl-Ab on the jaws. <h3>Results</h3> Scl-Ab has a potent anabolic effect on bone therapy, contributing both to increased bone formation and reduced resorption in patients who have certain deficiencies in bone metabolism. In dentistry, it can play an important role in several specialties because bone balance is fundamental to enable different treatments, such as surgery and maintenance of oral health. <h3>Conclusions</h3> The regulation of sclerostin through the Scl-Ab is a current strategy in dentistry that aims at therapeutic bone regulation, with excellent results achieved so far that require validation for large-scale use.

Spaceflight-Associated Vascular Remodeling and Gene Expression in Mouse Calvaria.

Astronauts suffer from a loss of bone mass at a rate of 1.5% per month from lower regions of the body during the course of long-duration (>30 days) spaceflight, a phenomenon that poses important risks for returning crew. Conversely, a gain in bone mass may occur in non-load bearing regions of the body as related to microgravity-induced cephalad fluid shift. Representing non-load bearing regions with mouse calvaria and leveraging the STS-131 (15-day) and BION-M1 (30-day) flights, we examined spatial and temporal calvarial vascular remodeling and gene expression related to microgravity exposure compared between spaceflight (SF) and ground control (GC) cohorts. We examined parasagittal capillary numbers and structures in calvaria from 16 to 23 week-old C57BL/6 female mice (GC, n = 4; SF, n = 5) from STS-131 and 19–20 week-old C57BL/6 male mice (GC, n = 6; SF, n = 6) from BION-M1 using a robust isolectin-IB4 vessel marker. We found that the vessel diameter reduces significantly in mice exposed to 15 days of spaceflight relative to control. Capillarization increases by 30% (SF vs. GC, p = 0.054) in SF mice compared to GC mice. The vessel numbers and diameter remain unchanged in BION-M1 mice calvarial section. We next analyzed the parietal pro-angiogenic (VEGFA) and pro-osteogenic gene (BMP-2, DMP1, RUNX2 and OCN) expression in BION-M1 mice using quantitative RT-PCR. VEGFA gene expression increased 15-fold while BMP-2 gene expression increased 11-fold in flight mice compared to GC. The linkage between vascular morphology and gene expression in the SF conditions suggests that angiogenesis may be important in the regulation of pathological bone growth in non-weight bearing regions of the body. Short-duration microgravity-mediated bone restructuring has implications in planning effective countermeasures for long-duration flights and extraterrestrial human habitation.

Bone mineral density and body composition in normal weight, overweight and obese children.

BackgroundThere is a possibility that excess body fat affects bone mass gain and may compromise skeletal health in obese children. The purpose of the study was to identify the relationship between bone mineral density (BMD) and body composition in normal weight, overweight and obese children.MethodsThis was a cross-sectional study of 6- to 11-year-old children who attended the hospital's outpatient clinic. They were apparently healthy and had no history of prematurity, low birth weight, or chronic diseases. Body mass index (BMI) was used to identify subjects as normal weight, overweight or obese. BMD and body composition were assessed by dual energy X–ray absorptiometry. The BMD values (total and lumbar spine) were compared between normal weight, overweight and obese children. Correlation coefficients were calculated, and multivariate models were performed.ResultsForty-nine children were included: 16 with normal weight, 15 that were overweight and 18 with obesity; the mean age was 8.4 ± 1.7 years. All the participants had a normal BMD (> – 2 SD). BMD was higher in obese children and had a positive correlation with total and trunk lean mass in the three study groups (p < 0.001). In obese children, an inverse correlation of lumbar spine BMD (Z score) with total and trunk fat mass (p < 0.05) was identified. In the multivariate models (with the whole group), the total lean mass was the only significant variable that explained BMD variability.ConclusionsBMD in obese children was higher than that in normal weight children, which is explained by their greater lean mass and not by excess body fat. In obese children, a higher fat mass was related to a lower lumbar spine BMD. Lean mass had a direct correlation with BMD in the three study groups and was the most important predictor of BMD, reflecting the importance of strengthening the muscular system through performing physical activity and practicing a healthy lifestyle.

Does environmental enrichment improve performance, morphometry, yield and weight of broiler parts at different ages?

ABSTRACT The inclusion of environmental enrichment in conventional broiler rearing can increase mobility, bone mass and muscle. This research aimed to evaluate the use of environmental enrichment in the rearing of broilers at different ages and its influence on performance, morphometry, yield and weight of the parts. It was used the completely randomized design in split-plot scheme, being the plots the treatments presence (T1) and absence (T2) of environmental enrichment and the subplots the broiler ages (1, 7, 14, 21, 28, 35 and 42 days), with 56 chicks in each treatment (T1 and T2). Data obtained were analyzed by the linear effect model of fixed effects and compared by Tukey’s test of means. The animals were raised in a controlled environment, divided into four boxes with dimensions: 1.5 × 1.0 × 0.7 m, containing rice straw bed. In T1 a ladder with a perch on top was used, distributed every 1.5 m2. Environmental enrichment used did not influence broiler’s zootechnical performance. Broilers’ morphometric properties, parts weight and body weight increased due to environmental enrichment and, improvement was observed in chicks rearing’s final phase. The environmental enrichment was beneficial for muscle and bone mass gain in the main commercial parts of the chicken carcass, in addition to reducing the allometric coefficient of the breasts in chickens.

Microstructure of axial bones of lithostrotian titanosaurs (Neosauropoda: Sauropodomorpha) shows extended fast-growing phase

Titanosaurs reached extremes in size and diversity, but many paleobiological aspects of these sauropod dinosaurs are still unknown. Here we infer life history traits based on the microstructure of axial bones of three lithostrotian titanosaur species: Austroposeidon magnificus, Gondwanatitan faustoi and Maxakalisaurus topai — Campanian–Maastrichtian of Bauru Group, Brazil. The present study is the first wide characterization of the microstructure of axial bones comparing distinct lithostrotian lineages with different body sizes. We analyzed the cross sections of cervical ribs, dorsal ribs and haemal arches. The medullary cavity in samples of A. magnificus are pneumatic, with the primary bone rich in fibrolamellar bone, with scarce growth marks, which is different from the Lines of Arrested Growth (LAGs)-dominated pattern of G. faustoi and M. topai, with parallel fibered bone. In general, the inner cortex exhibits fibrolamellar bone with longitudinal canals. The outer cortex is rich in parallel fibered bone rows of longitudinal canals and growth marks. Based on dense remodeling, decrease of LAGs distances and presence of an External Fundamental System in some samples; we concluded that all individuals reached at least the sexual maturity. These titanosaurs shared with basal neosauropods two main growth phases: modular (inner cortex) and LAG-dominated (outer cortex). Distinct from basal neosauropods, titanosaurs presented extended fast modular period (rather than LAG-dominated). This pattern supported that titanosaurs adopted a distinct strategy of bone mass gain in dorsal ribs, alternating the timing in rib growth.

Short-Term Analysis of the Changes in the Bone Mineral Density of the Proximal Femur After Uncemented Total Hip Arthroplasty: A Prospective Study of 110 Patients.

IntroductionMechanical loading continuously exposes the bone to remodeling processes. Increased load leads to a gain in bone mass, and reduced load results in a loss. After inserting a prosthesis, the proximal femur is bypassed in loading as the bodyweight shifts distally. This lack of load induces bone resorption according to Wolff’s law. To avoid this bone resorption, the implant's bending stiffness should be less than the femoral bone. Dual-energy X-ray absorptiometry (DEXA) is a well-accepted method to measure periprosthetic bone mineral density (BMD) after total hip arthroplasty (THA). Since the strength and durability of the fixation of a femoral prosthesis in cementless hip arthroplasty depend largely on the quantity and quality of the surrounding bone, preoperative and postoperative evaluation of the quantity and quality of the femoral bone is very important in the long-term prognosis of hip arthroplasty.Materials and methodsA prospective study of 110 patients in the age group of 25-60 years who underwent uncemented total hip arthroplasty in our tertiary healthcare institution was performed. An uncemented, fully hydroxyapatite-coated implant from a single manufacturer was used in all the patients. All the patients were mobilized on the first post-operative day. The BMD was measured at the proximal femur and the distal tip using a DEXA scan. Gruen zones were used for calculating BMD at different anatomical locations in the femur, with particular importance to zones 1, 4, and 7.ResultsThe pre-operative BMD in all zones measured, viz. zones 1, 4, and zone 7 of the affected side, was found to be significantly lower as compared to the BMD values on the control side (P< 0.05). The mean change in the mean BMD was calculated for all the zones and compared with each other using an unpaired t-test. The mean BMD changes were found to be significantly higher in zone 7 in comparison to both zones 1 and 4 (p<0.05).ConclusionSignificant periprosthetic bone loss after uncemented THA in the femur was noted in Gruen zones 1, 4, and 7 during the first six months after THA, with the greatest bone loss in the femoral calcar area (zone 7). The lower the preoperative BMD of the patient, the greater the postoperative bone loss.

The Notch pathway regulates the bone gain induced by PTH anabolic signaling.

Parathyroid hormone (PTH) signaling downstream of the PTH 1 receptor (Pth1r) results in both bone anabolic and catabolic actions by mechanisms not yet fully understood. In this study, we show that Pth1r signaling upregulates the expression of several components of the Notch pathway and that Notch signals contribute to the catabolic actions of PTH in bone. We found that constitutive genetic activation of PTH receptor signaling in osteocytes (caPth1rOt ) or treatment with PTH daily increased the expression of several Notch ligands/receptors in bone. In contrast, sustained elevation of endogenous PTH did not change Notch components expression. Deletion of the PTH receptor or sclerostin overexpression in osteocytes abolished Notch increases by PTH. Further, deleting the canonical Notch transcription factor Rbpjk in osteocytes decreased bone mass and increased resorption and Rankl expression in caPth1rOt mice. Moreover, pharmacological bone-targeted Notch inhibition potentiated the bone mass gain induced by intermittent PTH by reducing bone resorption and preserving bone formation. Thus, Notch activation lies downstream of anabolic signaling driven by PTH actions in osteocytes, and Notch pharmacological inhibition maximizes the bone anabolic effects of PTH.

Adolescent female handball players present greater bone mass content than soccer players: A cross-sectional study.

Osteoporosis is a systemic disease affecting half of women over the age of 50years. Considering that almost 90% of peak of bone mass is achieved until the second decade of life, ensuring a maximal bone mineral content acquisition may compensate for age-associated bone loss. Among several other factors, physical activity has been recommended to improve bone mass acquisition. However, it is unknown whether athletes involved with sports with different impact loading characteristics differ in regards to bone mass measurements. To compare the bone mass content, bone mass density and lean mass of young female soccer players (odd-impact loading exercise), handball players (high-impact loading exercises) and non-athletes. A total of 115 female handball players (15.5±1.3years, 165.2±5.6cm and 61.9±9.3kg) and 142 soccer players (15.5±1.5years, 163.7±6.6cm and 56.5±7.7kg) were evaluated for body composition using a dual-emission X-ray absorptiometry system, and 136 female non-athletes (data from NHANES) (15.1±1.32years, 163.5±5.8cm and 67.2±19.4kg) were considered as the control. Handball players presented higher bone mass content values than soccer players for upper limbs (294.8±40.2g and 270.7±45.7g, p<0.001), lower limbs (1011.6±145.5g and 967.7±144.3g, p=0.035), trunk (911.1±182.5g and 841.6±163.7g, p=0.001), ribs (312.4±69.9g and 272.9±58.0g, p<0.001), spine (245.1±46.8g and 222.0±45.1g, p<0.001) and total bone mass (2708.7±384.1g and 2534.8±386.0g, p<0.001). Moreover, non-athletes presented lower bone mass content for lower limbs (740.6±132.3g, p<0.001), trunk (539.7±98.6g, p<0.001), ribs (138.2±29.9g, p<0.001), pelvis (238.9±54.6g, p<0.001), spine (152.8±26.4g, p<0.001) and total bone mass (1987.5±311.3g, p<0.001) than both handball and soccer players. Handball players also presented higher bone mass density values than soccer players for trunk, ribs and spine (p<0.05) and handball and soccer players presented higher bone mass density than non-athletes for all measurements (p<0.005). Finally, the non-athletes' lower limb lean mass was lower than soccer and handball players values (p<0.05). Adolescent females engaged in handball training for at least one year present higher bone mass contents than those who are engaged in soccer training, which, in turn, present higher bone mass contents than non-athletes. These results might be used by physicians and healthcare providers to justify the choice of a particular sport to enhance bone mass gain in female adolescents.