Impact of anti-fracture medications on bone material and strength properties: a systematic review and meta-analysis.

Background and aims: Reduced bone mineral density (BMD) and microarchitectural deterioration contribute to increased fracture risk. Although the effects of anti-fracture medications (AFMs) on BMD are well-documented, their impact on bone material properties (BMPs) remains poorly characterized. Accordingly, we conducted a systematic review and meta-analysis to evaluate the effects of AFMs on BMPs. Based on data availability, we further categorized AFMs into anti-resorptives, bisphosphonates alone, and strontium ranelate subgroups to perform additional analyses of BMPs in osteoporotic patients. Methods: We did a comprehensive search of three databases, namely, PubMed, Web of Science, and Google Scholar, using various permutation combinations, and used Comprehensive Meta-Analysis software to analyze the extracted data. Results: The 15 eligible studies (randomized and non-randomized) compared the following: (1) 301 AFM-treated patients with 225 on placebo; (2) 191 patients treated with anti-resorptives with 131 on placebo; (3) 86 bisphosphonate-treated patients with 66 on placebo; and (4) 84 strontium ranelate-treated patients with 70 on placebo. Pooled analysis showed that AFMs significantly decreased cortical bone crystallinity [standardized difference in means (SDM) -1.394] and collagen maturity [SDM -0.855], and collagen maturity in cancellous bone [SDM -0.631]. Additionally, anti-resorptives (bisphosphonates and denosumab) significantly increased crystallinity [SDM 0.387], mineral-matrix ratio [SDM 0.771], microhardness [SDM 0.858], and contact hardness [SDM 0.952] of cortical bone. Anti-resorptives increased mineral-matrix ratio [SDM 0.543] and microhardness [SDM 0.864] and decreased collagen maturity [SDM -0.539] in cancellous bone. Restricted analysis of only bisphosphonate-treated studies showed a significant decrease in collagen maturity [SDM -0.650] in cancellous bone and an increase in true hardness [SDM 1.277] in cortical bone. In strontium ranelate-treated patients, there was no difference in BMPs compared to placebo. Conclusion: Collectively, our study suggests that AFMs improve bone quality, which explains their anti-fracture ability that is not fully accounted for by increased BMD in osteoporosis patients.

The effect of salidroside on the bone and cartilage properties in broilers.

Leg disorders frequently occur in fast-growing broiler chickens, constituting severe health and welfare problems. Although salidroside (SAL) promotes osteogenesis and inhibits apoptosis of chondrocytes in rats, it remains to be determined whether SAL can effectively improve bone growth in broilers. The present study was designed to investigate the effects of dietary SAL supplementation on bone and cartilage characteristics in broiler chickens. Ninety-six Arbor Acres broiler chickens were randomly divided into 4 groups: control, low-dose SAL, medium-dose SAL, and high-dose SAL groups. The broiler chickens were raised until 42 d of age, with samples of bone and cartilage collected for biomechanical testing and bone metabolism index detection. The results showed that SAL significantly increased the vertical external diameter, cross-sectional moment of inertia, and cross-sectional area of the femur and tibia. Additionally, SAL enhanced bone mineral density and strength, as evidenced by significant increases in stiffness, Young's modulus, ultimate load, and fracture work of the femur and tibia. Furthermore, SAL influenced the relative content of phosphate, carbonate, and amide I in cortical bone. Moreover, SAL upregulated the expression of osteogenic genes (Collagen-1, RUNX2, BMP2, and ALP) in a dose-dependent manner and maintained the homeostasis of the extracellular matrix (ECM) of chondrocytes. These results indicated that SAL promoted leg health in broilers by improving bone and cartilage quality and enhancing chondrocyte activity.

Effect of advanced chelate technology-based trace minerals on growth performance, mineral digestibility, tibia properties, and antioxidant status in two broiler strains.

This research aimed to assess the impact of diet supplementation of Advanced Chelate Technology-based Mineral (ACTMS), on the Ross and Arian broilers performance. 520 broilers, of two strains, were allocated to 8 treatments (4 for each strain), 5 replicates, (13 chicks/replicate) and reared for 42 d. The treatments include 0 (CONT), 250 (SBC250), 1,000 (SBC1000), and 2,000 (SBC2000) of ACTMS. Feed intake, weight gain, and feed conversion ratio were recorded, and the European Production Efficiency Factor (EPEF) was also calculated. Serum antibody was measured in response to sheep red blood cell (SRBC) to evaluate humoral immune response. Blood sample and tibia were used to measure the bone composition of Ca and P. No significant difference was obtained in feed intake (P > 0.05), however, weight gain, feed conversion ratio, and EPEF showed significant differences (P ˂ 0.05). The results showed that the interaction effect of Ross× SBC250 had the highest average daily feed intake during 25 to 42 and 0 to 42 d of age, but Ross×CONT group provided the lowest average daily feed intake (P ˂ 0.05). Furthermore, the Ross×CONT group had the highest average daily gain during 0 to 10, 25 to 42, and 0 to 42 d of age (P < 0.05). The Ross×CONT group also provided the best feed conversion ratio during 0 to 10 d of rearing period compared to other treatments (P < 0.05). Various levels of ACTMS, significantly (P ˂ 0.05) enhanced the antioxidant activity of superoxide dismutase and glutathione peroxidase. No significant differences were obtained in blood parameter (P > 0.05), though, SBC2000 exhibited the greatest numerical phosphorus content. There was no significant impact of strain effects on blood metabolites, however, the Ross strain exhibited higher values. The results indicated that the Arian× SBC250 group had the largest tibia diameter which had a significant difference from the Arian×CONT group (P < 0.05). In conclusion, ACTMS inclusion in the ration (either replacement or on top) led to the significant improvement of FCR and ADWG (SBC250 as on top) and EPEF (SBC2000 replacement) in the Ross strain and some parameters in Arian strains (mostly numerically).

[Translated article] Anatomical and biomechanical factors of osteoporotic vertebral fracture and the occurrence of cascade fractures. / [Artículo traducido] Factores anatómicos y biomecánicos de la fractura vertebral osteoporótica y la aparición de las fracturas en cascada.

Osteoporosis weakens the structural strength of bone to such an extent that normal daily activity may exceed the capacity of the vertebra to bear this load. Vertebral fracture and deformity is a hallmark of osteoporosis. The detriment of trabecular bone properties alone cannot explain the occurrence of osteoporotic vertebral fracture. The ability of the spine to bear and resist loads depends on the structural capacity of the vertebrae, but also on loading conditions arising from activities of daily living or low-energy trauma. This review describes the mechanical properties of the vertebral bone, the structural load-bearing capacity of the various elements forming the spine, the neuromuscular control of the trunk, as well as the biomechanics of the loads to which the spine is subjected in relation to the presence of osteoporosis and the risk of vertebral fracture. A better understanding of biomechanical factors may help to explain both the high incidence of osteoporotic vertebral fractures and their mechanism of production. Consideration of these issues may be important in the development of prevention and management strategies.

An A2 ß-casein infant formula with high sn-2 palmitate and casein phosphopeptides supports adequate growth, improved stool consistency, and bone strength in healthy, term Chinese infants: a randomized, double-blind, controlled clinical trial.

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 ß-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 ß-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.

Effects of two types of resistance training modalities (hypertrophy vs. contrast training) on bone parameters in a group of healthy elderly women.

The aim of the present study was to explore the effects of two types of resistance training modalities (hypertrophy training vs. contrast training) on bone health parameters in a group of healthy elderly women. Forty-nine healthy elderly women whose ages range between 60 and 70 years were included in this study. The study population was randomly divided into three groups: hypertrophy training group (HTG; n=16), contrast training group (CTG; n=16) and control group (CG; n=17). Bone mineral density (BMD) values at the whole body (WB), lumbar spine (L1-L4), total hip (TH) and femoral neck (FN) were measured by DXA before and after 12 months of resistance training. Composite indices of femoral neck strength were calculated. WB BMD, L1-L4 BMD, TH BMD and FN BMD increased in the contrast training group. WB BMD and L1-L4 BMD increased in the hypertrophy training group, while TH BMD and FN BMD remained unchanged. Significant decreases in WB BMD, L1-L4 BMD, TH BMD and FN BMD were observed in the control group. The contrast training group showed the highest improvements in BMD values compared to the two other groups. Both experimental groups (HTG and CTG) showed similar significant improvements in composite indices of femoral neck strength and muscular strength. In conclusion, contrast training and hypertrophy training can stimulate bone gain at clinically important sites of osteoporotic fractures in elderly women.

Bone Tissue Changes in Individuals Living with HIV/AIDS: The Importance of a Hierarchical Approach in Investigating Bone Fragility.

Skeletal alterations and their complications can significantly impact the quality of life and overall prognosis of patients living with HIV (PLWHIV). Considering skeletal alterations are often asymptomatic and unapparent during routine clinical evaluation, these conditions are frequently overlooked in the clinical management of PLWHIV. However, since the use of combined antiretroviral therapy (cART) has increased life expectancy in PLWHIV effectively, osteopenia, osteoporosis, and bone fragility are now considered to have a major health impact, with a substantial increase in healthcare costs. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to bone changes in PLWHIV, focusing on the importance of taking a multi-scale approach in the assessment of bone hierarchical organization. Even though a low bone mineral density is frequently reported in PLWHIV, numerous ambiguities still remain to be solved. Recent data suggest that assessment of other bone properties (on various levels of the bone structure) could contribute to our understanding of bone fragility determinants in these individuals. Special attention is needed for women living with HIV/AIDS since a postmenopausal status was described as an important factor that contributes to skeletal alterations in this population. Further research on complex etiopathogenetic mechanisms underlying bone alterations in PLWHIV may lead to the development of new therapeutic approaches specifically designed to reduce the health burden associated with skeletal disorders in this population. A major challenge in the clinical management of PLWHIV lies in the adverse skeletal effects of some frequently prescribed cART regimens (e.g., regimens containing tenofovir disoproxil fumarate), which may require a switch to other pharmacological approaches for maintained HIV infection (e.g., regimens containing tenofovir alafenamide). Taken together, the findings are indicative that the HIV/AIDS status should be taken into consideration when designing new guidelines and strategies for individualized prevention, diagnosis, and treatment of increased bone fragility.

274th ENMC international workshop: recommendations for optimizing bone strength in neuromuscular disorders. Hoofddorp, The Netherlands, 19-21 January 2024.

The 274th ENMC workshop for optimizing bone strength in neuromuscular disorders (NMDs) was held on January 19-21, 2024. The group of participants included experts in the fields of bone health and neuromuscular medicine along with the patient voice. Bone strength represents a crucial aspect of the management of pediatric and adult patients with NMDs. Bone strength may be compromised due to different pathophysiologic mechanisms, including disrupted bone-muscle "cross-talk", loss of biomechanical loading, nutritional insufficiency, inadequate weight-bearing physical activity, muscle weakness and/or immobility, and drug treatment. While for Duchenne muscular dystrophy recommendations for evaluation and treatment of bone strength have been published, evidence on bone strength in other hereditary and acquired NMDs is scarce. Enhanced knowledge is needed to understand the development and maintenance of bone strength in patients with NMDs. This workshop aimed to develop a strategy to improve bone strength and thus prevent fractures in patients with NMDs.

Association between physical function and parameters of hip structural analysis in patients with hip fracture.

OBJECTIVES: The current study sought to investigate whether physical function and activity were associated with hip structural analysis (HSA) parameters on the non-fracture side of patients with hip fractures. METHODS: Participants were patients with unilateral hip fracture treated by surgery. HSA of the proximal femur was conducted based on dual-energy x-ray absorptiometry data. HSA parameters in the narrow neck region included cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (SM), and buckling ratio (BR). Hierarchical multiple regression analysis was conducted to identify predictors of HSA. RESULTS: Except for the adjustment variables, age, gender and BMI, other variables were extracted. Hierarchical multiple regression analysis (standardised partial regression coefficients) identified movement control during one-leg standing on the non-fractured side (0.15) as factors associated with CSA. Hierarchical multiple regression analysis (standardised partial regression coefficients) identified hand grip (0.12, 0.23) as factors associated with CSMI and SM, respectively. Hierarchical multiple regression analysis (standardised partial regression coefficients) identified presence of steroid (0.23) and cerebrovascular disease (0.19) as factors associated with BR. The coefficients of determination adjusted for degrees of freedom (R2) were 0.545, 0.331, 0.401, and 0.148 for CSA, CSMI, SM, and BR, respectively. CONCLUSIONS: Our results indicate that movement control during 1-leg standing and muscle strength may be important for maintaining and improving bone strength.

Osteogenic effect of an adiponectin-derived short peptide that rebalances bone remodeling: a potential disease-modifying approach for postmenopausal osteoporosis therapy.

Adiponectin, an adipokine, regulates metabolic processes, including glucose flux, lipid breakdown, and insulin response, by activating adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2). We have previously shown that globular adiponectin (gAd), an endogenous form of adiponectin, has osteoanabolic and anti-catabolic effects in rodent models of postmenopausal osteopenia. Moreover, we reported the identification of a 13-mer peptide (ADP-1) from the collagen domain of adiponectin, which exhibited significant adiponectin-mimetic properties. Since the clinical development of gAd is constrained by its large size, here, we investigated the osteogenic property of ADP-1. ADP-1 induced osteoblast differentiation more potently than gAd. ADP-1 elicited osteoblast differentiation through two downstream pathways that involved the participation of adiponectin receptors. Firstly, it enhanced mitochondrial biogenesis and OxPhos, leading to osteoblast differentiation. Secondly, it activated the Akt-glycogen synthase kinase 3ß-Wnt pathway, thereby increasing osteoblast differentiation. Additionally, ADP-1 suppressed the production of receptor-activator of nuclear kappa B ligand from osteoblasts, enabling it to act as a dual-action molecule (suppressing osteoclast function besides promoting osteoblast function). In osteopenic ovariectomized rats, ADP-1 increased bone mass and strength and improved trabecular integrity by stimulating bone formation and inhibiting bone resorption. Furthermore, by increasing ATP-producing intermediates within the tricarboxylic acid cycle in bones, ADP-1 likely fueled osteoblast function. Given its dual-action mechanism and high potency, ADP-1 offers a unique opportunity to address the unmet clinical need to reset the aberrant bone remodeling in osteoporosis to normalcy, potentially offering a disease-modifying impact.