The aim of this randomized, double-blind, controlled trial was to examine the effects of infant formula on the growth, stool consistency, and bone strength of infants (n = 120) over a period of 4 months. The investigational group was fed an A2 β-casein cow\'s milk infant formula containing casein phosphopeptides (CPP) and high sn-2 palmitate (54% of total palmitate at sn-2). The control group was fed a standard cow\'s milk formula without CPP and with low sn-2 palmitate (29% of total palmitate at sn-2). The third group was fed human milk (HM) (n = 60). All three groups had similar baseline characteristics, and maintained similar BMI, sleep habits, and growth rates in body weight and length throughout the study. However, compared to the control group, infants in the investigational and human milk groups had significantly: (i) greater body length at 90, 120, and 150 days of age; (ii) greater growth rate in head circumference from 30 to 60 days of age, with larger head circumference at 60 days of age; (iii) larger daily stool frequency at 60, 90, and 120 days of age; (iv) softer stool at 60, 90, and 120 days of age; (v) higher bone quality index and bone speed of sound at 150 days of age; (vi) fewer hours of crying at 60 and 90 days of age; (vii) less abdominal distention, burp, and flatus at 60, 90, and 120 days of age; and (viii) less constipation at 90 days of age. At other time points, no significant differences were observed between the three groups. No serious adverse events (AEs) related to the study products were reported, and significantly fewer infants in the investigational and HM groups experienced at least one AE compared to the control group. The study suggests that the A2 β-casein formula with high sn-2 palmitate and CPP supports adequate growth, is well tolerated, and may have beneficial effects on stool consistency, gastrointestinal comfort, crying duration, and bone density, comparable to HM. Clinical trial registration: https://clinicaltrials.gov/, NCT04749290.

The present study sought to assess the effects of manganese complexes with lysine and glutamic acid (Mn-LG) as manganese (Mn) sources on growth performance, trace element deposition, antioxidant capacity, and metacarpal strength in weaned piglets. The study involved 288 healthy Duroc × Landrace × Yorkshire piglets that were weaned at 25 to 28 d of age and weighed 8.66 ± 0.96 kg. These piglets were randomly divided into six groups: a control group (Mn-LG-0, receiving a basal diet without Mn supplementation), a Mn sulfate group (basal diet supplemented with 40 mg·kg-1 diet of Mn, Mn-S-40 group), and four Mn-LG groups (Mn-LG-20, Mn-LG-40, Mn-LG-60, Mn-LG-80, supplemented with 20, 40, 60, and 80 mg·kg-1 Mn from Mn-LG in the basal diet). Grouping began at weaning on the 0th day of the experiment. The corn-soybean-based basal diet during the early (days 0 to 14) and late (days 15 to 42) phases of the experiment contained 20.88 and 30.12 mg·kg-1 Mn, respectively. Blood samples were collected on days 14 and 42, and pigs were sacrificed for sample collection on day 42. The results indicated no significant differences in average daily gain, average daily feed intake, or feed-to-gain ratio among the groups (P > 0.05). The diarrhea rates of all Mn-LG groups and the Mn-S-40 group were significantly lower in the 0 to 14 d and during the entire experimental period than in the Mn-LG-0 group (P < 0.001). The Mn-LG-40 group exhibited a significant increase in liver Mn concentration and serum Mn superoxide dismutase (Mn-SOD) activity on day 42 (P < 0.01), as well as a significant decrease in fecal Mn concentration (P < 0.05), compared to those of the Mn-S-40 group. Significant differences (P < 0.05) were detected in the serum, liver, and fecal Mn concentrations, as well as in the serum and liver Mn-SOD activity, across the different Mn-LG groups. The serum and fecal Mn concentrations and serum Mn-SOD activity increased linearly or quadratically (P < 0.01) with increasing Mn-LG supplementation. No significant differences (P > 0.05) were found in kidney, heart, or metacarpal bone Mn concentrations or in bone strength indices. In summary, compared with the Mn-LG-0 diet, dietary supplementation with Mn-LG enhanced serum Mn deposition and Mn-SOD activity and decreased the incidence of diarrhea. Additionally, the fecal Mn concentration was lower in the Mn-LG group than in the inorganic group at equivalent dosages.
This research explored the effects of a manganese complex containing lysine and glutamic acid (Mn-LG) on various health parameters in weaned piglets. Utilizing samples of 288 piglets, the study investigated how Mn-LG supplementation influences growth performance, Mn deposition and emission, antioxidant capacity, and metacarpal strength. Key findings include an increase in serum Mn levels and Mn superoxide dismutase (Mn-SOD) activity, a reduction in diarrhea incidence, and no significant effects in bone strength indices in piglets receiving Mn-LG. Additionally, the fecal Mn concentration was notably lower in the Mn-LG group than in the group receiving inorganic Mn at equivalent dosages.

Fragility fractures, which are more prevalent in women, may be significantly influenced by autophagy due to altered bone turnover. As an essential mediator of autophagy, Beclin-1 modulates bone homeostasis by regulating osteoclast and chondrocyte differentiation, however, the alteration in the local bone mechanical environment in female Beclin-1+/- mice remains unclear. In this study, our aim is to investigate the biomechanical behavior of femurs from seven-month-old female wild-type (WT) and Beclin-1+/- mice under peak physiological load, using finite element analysis on micro-CT images. Micro-CT imaging analyses revealed femoral cortical thickening in Beclin-1+/- female mice compared to WT. Three-point bending test demonstrated a 63.94% increase in whole-bone strength and a 61.18% increase in stiffness for female Beclin-1+/- murine femurs, indicating improved biomechanical integrity. After conducting finite element analysis, Beclin-1+/- mice exhibited a 26.99% reduction in von Mises stress and a 31.62% reduction in maximum principal strain in the femoral midshaft, as well as a 36.64% decrease of von Mises stress in the distal femurs, compared to WT mice. Subsequently, the strength-safety factor was determined using an empirical formula, revealing that Beclin-1+/- mice exhibited significantly higher minimum safety factors in both the midshaft and distal regions compared to WT mice. In summary, considering the increased response of bone adaptation to mechanical loading in female Beclin-1+/- mice, our findings indicate that increasing cortical bone thickness significantly improves bone biomechanical behavior by effectively reducing stress and strain within the femoral shaft.

Functional adaptation refers to the active modification of bone structure according to the mechanical loads applied daily to maintain its mechanical integrity and adapt to the environment. Functional adaptation relates to bone mass, bone mineral density (BMD), and bone morphology (e.g., trabecular bone architecture). In this study, we discovered for the first time that another form of bone functional adaptation of a cortical bone involves a change in bone quality determined by the preferential orientation of apatite nano-crystallite, a key component of the bone. An in vivo rat ulnar axial loading model was adopted, to which a 3-15 N compressive load was applied, resulting in approximately 440-3200 μɛ of compression in the bone surface. In the loaded ulnae, the degree of preferential apatite c-axis orientation along the ulnar long axis increased in a dose-dependent manner up to 13 N, whereas the increase in BMD was not dose-dependent. The Young\'s modulus along the same direction was enhanced as a function of the degree of apatite orientation. This finding indicates that bone has a mechanism that modifies the directionality (anisotropy) of its microstructure, strengthening itself specifically in the loaded direction. BMD, a scalar quantity, does not allow for load-direction-specific strengthening. Functional adaptation through changes in apatite orientation is an excellent strategy for bones to efficiently change their strength in response to external loading, which is mostly anisotropic.

BACKGROUND: The relationship between the components of particulate matter with an aerodynamic diameter of 2.5 or less (PM2.5) and bone strength remains unclear.
OBJECTIVE: Based on a large-scale epidemiologic survey, we investigated the individual and combined associations of PM2.5 and its components with bone strength.
METHODS: A total of 65 906 individuals aged 30 to 79 years were derived from the China Multi-Ethnic Cohort Annual average concentrations of PM2.5 and its components were estimated using satellite remote sensing and chemical transport models. Bone strength was expressed by the calcaneus quantitative ultrasound index (QUI) measured by quantitative ultrasound. The logistic regression model and weighted quantile sum method were used to estimate the associations of single and joint exposure to PM2.5 and its components with QUI, respectively.
RESULTS: Our analysis shows that per-SD increase (μg/m3) in 3-year average concentrations of PM2.5 (mean difference [MD] -7.38; 95% CI, -8.35 to -6.41), black carbon (-7.91; -8.90 to -6.92), ammonium (-8.35; -9.37 to -7.34), nitrate (-8.73; -9.80 to -7.66), organic matter (-4.70; -5.77 to -3.64), and soil particles (-5.12; -6.10 to -4.15) were negatively associated with QUI. In addition, these associations were more pronounced in men, and people older than 65 years with a history of smoking and chronic alcohol consumption.
CONCLUSIONS: We found that long-term exposure to PM2.5 and its components may lead to reduced bone strength, suggesting that PM2.5 and its components may potentially increase the risk of osteoporosis and even fracture. Nitrate may be responsible for increasing its risk to a greater extent.

Objective: To investigate the effects of adding whole body vibration (WBV) to routine exercise regimen of pulmonary rehabilitation (PR) on bone strength, lung function and exercise ability of elderly patients with stable chronic obstructive pulmonary disease (COPD) complicated with osteoporosis (OP). Methods: Thirty seven elderly patients with stable COPD were randomly divided into control group (group C, n=12, age: 64.6±3.8 years), conventional PR group (PR group, n=12, age: 66.1±4.9 years), and whole body vibration combined PR group (WP group, n=13, age: 65.5±3.3 years). Before intervention, X-ray and computerized tomography bone scan, bone metabolic markers, pulmonary function, cardiopulmonary exercise, 6-minute walking and isokinetic muscle strength were performed, and then intervened for 36 weeks, three times/week, among which group C subjects were given routine treatment, PR group added aerobic running and static weight resistance on the basis of routine treatment, and WP group added WBV on the basis of PR group intervention. After the intervention, the same indicators were detected. Results: Compared with before the intervention, the pulmonary function indexes of each group were significantly improved after the intervention (P＜0.05), and the bone mineral density and bone microstructure indexes of the patients in the WP group were also significantly improved (P＜0.05). Compared with group C and group PR, the bone mineral density, bone microstructure, parathyroid hormone (PTH), insulin-like growth factor-1 (IGF-1), interleukin-6 (IL-6), osteocalcin (OCN) and other bone metabolism indexes, knee flexion, peak extension torque, fatigue index and muscle strength of patients in WP group were significantly improved (P＜0.05). Conclusion: Adding WBV to the conventional PR regimen can improve the bone strength, lung function and exercise capacity of elderly patients with COPD complicated with OP, and may be able to make up for the deficiency of the current conventional PR regimen for insufficient muscle and bone stimulation.
目的: 探讨在肺康复(PR)常规运动方案中加入全身振动(WBV)对稳定期慢性阻塞性肺疾病(COPD)合并骨质疏松(OP)老年患者的骨强度、肺功能、运动能力的干预效果。方法: 将37例稳定期COPD老年患者随机分为对照组(C组,n=12,年龄:64.6±3.8岁)、常规PR组(PR组,n=12,年龄:66.1±4.9岁)、全身振动联合PR组(WP组,n=13,年龄:65.5±3.3岁),干预前进行X射线和电子计算机断层骨扫、骨代谢标志物、肺功能、心肺运动、6 min步行和等速肌力的测试,然后进行36周、3次/周的干预,其中C组受试者给予常规治疗,PR组在常规治疗的基础上加入有氧跑和静态自重抗阻动作,WP组在PR组干预的基础上加入WBV。干预完成后,检测干预前相同的指标。结果: 与干预前比较,干预后各组肺功能指标均显著提升(P＜0.05),WP组患者骨密度、骨微结构指标也显著提升(P＜0.05);与C组和PR组比较,WP组患者骨密度、骨微结构指标和甲状旁腺激素(PTH)、胰岛素样生长因子-1(IGF-1)、白介素-6(IL-6)、骨钙素(OCN)等骨代谢指标以及膝屈曲、伸展峰值力矩、疲劳指数肌力指标改善效果明显(P＜0.05)。结论: 将WBV加入常规PR常规运动方案中可改善COPD并发OP老年患者的骨强度、肺功能和运动能力,可弥补现行常规运动方案对肌肉和骨骼刺激不足的缺陷。.

Vertebral fracture is one of the most serious consequences of osteoporosis. Estimation of vertebral strength from magnetic resonance imaging (MRI) scans may provide a new approach for the prediction of vertebral fractures. To that end, we sought to establish a biomechanical MRI (BMRI) method to compute vertebral strength and test its ability to distinguish fracture from non-fracture subjects. This case-control study included 30 subjects without vertebral fractures and 15 subjects with vertebral fractures. All subjects underwent MRI with a mDIXON-Quant sequence and quantitative computed tomography (QCT), from which proton fat fraction-based bone marrow adipose tissue (BMAT) content and volumetric bone mineral density (vBMD) were measured, respectively. Nonlinear finite element analysis was applied to MRI and QCT scans of L2 vertebrae to compute vertebral strength (BMRI- and BCT-strength). The differences in BMAT content, vBMD, BMRI-strength and BCT-strength between the two groups were examined by t-tests. Receiver operating characteristic (ROC) analysis was performed to assess the ability of each measured parameter to distinguish fracture from non-fracture subjects. Results showed that the fracture group had 23 % lower BMRI-strength (P < .001) and 19 % higher BMAT content (P < .001) than the non-fracture group, whereas no significant difference in vBMD was detected between the two groups. A poor correlation was found between vBMD and BMRI-strength (R2 = 0.33). Compared to vBMD and BMAT content, BMRI- and BCT-strength had the larger area under the curve (0.82 and 0.84, respectively) and provided better sensitivity and specificity in separating fracture from non-fracture subjects. In conclusion, BMRI is capable of detecting reduced bone strength in patients with vertebral fracture, and may serve as a new approach for risk assessment of vertebral fracture.

BACKGROUND: Femoral neck fractures are serious consequence of osteoporosis (OP), numbers of people are working on the micro-mechanisms of femoral neck fractures. This study aims to investigate the role and weight of microscopic properties on femoral neck maximum load (Lmax), funding the indicator which effects Lmax most.
METHODS: A total of 115 patients were recruited from January 2018 to December 2020. Femoral neck samples were collected during the total hip replacement surgery. Femoral neck Lmax, micro-structure, micro-mechanical properties, micro-chemical composition were all measured and analyzed. Multiple linear regression analyses were performed to identify significant factors that affected the femoral neck Lmax.
RESULTS: The Lmax, cortical bone mineral density (cBMD), cortical bone thickness (Ct. Th), elastic modulus, hardness and collagen cross-linking ratio were all significantly decreased, whereas other parameters were significantly increased during the progression of OP (P < 0.05). In micro-mechanical properties, elastic modulus has the strongest correlation with Lmax (P < 0.05). The cBMD has the strongest association with Lmax in micro-structure (P < 0.05). In micro-chemical composition, crystal size has the strongest correlation with Lmax (P < 0.05). Multiple linear regression analysis showed that elastic modulus was most strongly related to Lmax (β = 0.920, P = 0.000).
CONCLUSIONS: Compared with other parameters, elastic modulus has the greatest influence on Lmax. Evaluation of microscopic parameters on femoral neck cortical bone can clarify the effects of microscopic properties on Lmax, providing a theoretical basis for the femoral neck OP and fragility fractures.

BACKGROUND: This study aims to develop nomogram models based on the speed of sound (SOS) measurements results along with demographic information to predict the risk of low bone strength (LBS) of radius appropriate to the Chinese population of a broad age spectrum.
METHODS: A population-based cross-sectional study was conducted in 5 outpatient clinics located in Zhejiang, the southern part of China. A total of 38,699 participants from 2013 to 2017 were included. Baseline measurements included SOS of the distal radius and clinical risk factor evaluation. Logistic regression models were used to evaluate prognosis and identify independent predictive factors, which were then utilized to establish nomograms for predicting the low bone strength of radius. The discrimination and calibration of nomograms were validated using the calibration plots, the decision curve analysis (DCA), and the receiver operating characteristics curve (ROC).
RESULTS: A total of 19,845 of the 38,904 participants ranged in age from 10 to 88 years were selected in this process. LBP nomogram model 1 was constructed based on age, weight, height, BMI, and gender. LBP nomogram model 2 was constructed based on age, height, BMI, and gender. The AUCs for model 1 and model 2 were 0.838 (95% CI: 0.832-0.844) and 0.837 (95% CI: 0.831-0.843), respectively. High-quality calibration plots and DCA in nomogram models were noticed, indicated that the constructed nomogram models were clinically useful.
CONCLUSIONS: Our study demonstrates that the nomograms established in this study could effectively evaluate the high-risk population groups of distal radius fracture in China.

We investigated the effects of high- vs. standard-dose vitamin D supplementation on kidney function and bone metabolism in children with chronic kidney disease (CKD). Children were randomized to receive one of two formulations: 75 participants received 2,000 IU/D of oral supplementation of vitamin D, while 75 participants received 400 IU/d for a minimum of 4 months. We investigated the effects of vitamin D supplementation on kidney-related indicators and bone metabolism-related indicators at different doses. A total of 158 participants were screened, among whom 150 met the inclusion criteria. The indicators of chronic kidney disease such as eGFR and serum uric acid were negatively correlated with the 25(OH)D level and BMD. Serum 25(OH)D and osteocalcin levels were positively correlated with spine BMD. The standard dose of vitamin D can improve the serum uric acid level, but high doses of vitamin D supplementation had no significant effect on the serum uric acid level. High doses of vitamin D supplementation can also improve the alkaline phosphatase level. When comparing the results of different doses of vitamin D supplementation, it was found that high-dose vitamin D supplementation did not improve bone density in the spine and femur neck relative to the standard dose of vitamin D but improved hypocalcemia and N-terminal propeptide of the human procollagen type I (PINP) level. Among the children with clinical kidney disease, high-dose vitamin D treatment for 4 months resulted in statistically significant improvement in kidney function but no significant difference in bone metabolism compared with the standard-dose vitamin D treatment.