Ganoderic Acid A (GAA) has demonstrated beneficial effects in anti-inflammatory and anti-oxidative stress studies. However, it remains unknown whether GAA exerts positive impacts on bone loss induced by lipopolysaccharide (LPS). This study aims to investigate the influence of GAA on bone loss in LPS-treated rats. The study assesses changes in the viability and osteogenic potential of MC3T3-E1 cells, as well as osteoclast differentiation in RAW264.7 cells in the presence of LPS using CCK-8, ALP staining, AR staining, and Tartrate-resistant acid phosphatase (TRAP) staining. In vitro experiments indicate that LPS-induced inhibition of osteoclasts (OC) and Superoxide Dismutase 2 (SOD2) correlates with heightened levels of inflammation and oxidative stress. Furthermore, GAA has displayed the ability to alleviate oxidative stress and inflammation, enhance osteogenic differentiation, and suppress osteoclast differentiation. Animal experiment also proves that GAA notably upregulates SOD2 expression and downregulates TNF-α expression, leading to the restoration of impaired bone metabolism, improved bone strength, and increased bone mineral density. The collective experimental findings strongly suggest that GAA can enhance osteogenic activity in the presence of LPS by reducing inflammation and oxidative stress, hindering osteoclast differentiation, and mitigating bone loss in LPS-treated rat models.

UNASSIGNED: Previous studies have reported a close relationship between body mass index (BMI) and bone mineral density (BMD). However, the effects of fat on bone mass remain controversial, particularly for fat tissue distribution. The aim of this study was to evaluate the association between regional fat percentage and BMD using a population-based database.
UNASSIGNED: This study included participants who were referred to the Department of Radio Diagnosis for dual-energy X-ray absorptiometry (DEXA) scan from January 2018 to December 2020. The relationships between BMI and regional fat percentage with BMD were assessed using multiple linear regression and generalized additive models. The risk of low bone mass was determined using logistic regression.
UNASSIGNED: There was a negative relationship between the regional fat percentage and femoral neck BMD (FN BMD) or lumbar spine BMD (LS BMD) in both genders (p < 0.05). In females, an inverted U-shaped relationship was observed between regional fat percentage and BMD at both the femoral neck and lumbar spine. The impact of trunk fat percentage on LS BMD was associated with the highest OR of low bone mass in females (OR 3.1, 95% CI 2.6 to 3.7, p for trend <0.001), while the impact of abdomen fat percentage on FN BMD was associated with the highest OR of low bone mass in males (OR 2.2, 95% CI 1.8 to 2.7, p for trend <0.001).
UNASSIGNED: There was an inverted U-shaped relationship between regional fat percentage and BMD. Excessive regional fat percentage may be harmful to bone health in both genders. To promote bone health, males should restrict their abdomen circumference and avoid abdominal adiposity, while females should control their trunk circumference.

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 3β-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.

Background Osteoporosis is a chronic bone disease associated with a reduction in bone mass and an increased risk of fractures. The prevalence of osteoporosis is rising globally, including in Saudi Arabia, where there is a lack of information regarding the uptake of osteoporosis screening services. This study aims to examine self-efficacy and barriers toward osteoporosis screening in older women and men in Al-Madina Munawara, Saudi Arabia. Methods A cross-sectional study was conducted among adults aged 60 and above who attended primary healthcare centers. Convenience sampling was used to recruit participants, and a self-administered questionnaire was used to assess sociodemographic characteristics, osteoporosis status, general health-related characteristics, and screening self-efficacy. Analyses included multivariable regression analyses to evaluate the association between osteoporosis screening self-efficacy and potential explanatory variables. Data were collected in the last quarter of 2023. Results In a study involving 342 completed questionnaires, the mean age of participants was 66.2 years (SD = 4.3), with a range from 60 to 79 years, and the majority were male (230, 67.3%), having chronic diseases (226, 66.3%). Regarding osteoporosis risk factors and screening behaviors, the majority did not use prednisolone (252, 74.1%), did not have a family history of osteoporosis (216, 63.2%), had not experienced falls in the past five years (223, 65.2%), and had not undergone osteoporosis screening (299, 87.4%). The mean self-efficacy score for osteoporosis screening was 37.7 (SD = 4.7), ranging from 10 to 50, which indicated a moderate level of screening self-efficacy. In multivariate analysis, smokers were more likely to have higher scores in self-efficacy for osteoporosis screening compared to non-smokers (RR = 1.10; 95% CI = 1.01, 1.21). Participants who did osteoporosis screening (RR = 1.12; 95% CI = 1.01, 1.24) and those who were planning to do osteoporosis screening (RR = 1.10; 95% CI = 1.03, 1.19) were more likely to have higher score in self-efficacy for osteoporosis screening compared to their counterparts. Conclusion The participants had a fair level of screening self-efficacy. The smokers and those who had undergone or planned to undertake osteoporosis screening demonstrated higher self-efficacy scores than others. A lot of progress could be made in decreasing the burden of osteoporosis and enhancing the overall health and well-being of the older population by addressing these issues using specific interventions and policy measures.

BACKGROUND: Female bone health is influenced by familial resemblance, health parameters and maturational periods (puberty and menopause); this combination has been researched using familial multi-generational cross-sectional studies.
OBJECTIVE: This scoping review aimed to compile bone health research which uses sexually mature (grandmother-) mother-daughter pairs (and triads) and to determine the trends in its methodologies and familial comparisons.
METHODS: The Joanna Briggs Institute methodology for scoping reviews was used. Extraction included study and population characteristics, methodology (with an emphasis on imaging) and family-based results.
RESULTS: Twenty-nine studies were included, and their generations were categorized into four developmental categories: late adolescent to young adult, pre-menopause, mixed-menopause, and post-menopause. Eleven different pair/triad combinations were observed; the most common was pre-menopausal daughters and post-menopausal mothers. Dual-energy X-ray absorptiometry (DXA) was the most utilized imaging modality, and the hip was the most imaged region of interest (ROI). Regardless of pairing, imaging modality and ROI, there was often a trend toward significant familial resemblance and heritability (h2 and h2L).
CONCLUSIONS: This scoping review highlights the trends in bone health linked to familial resemblance, as well as the importance of menopause and late adolescence. This review compiles the commonalities and challenges within these studies to inform future research.

Radium 223 (Ra-223) is an α-emitting bone-homing radiopharmaceutical that targets tumor-induced osteoblasts and is used to reduce bone pain and prolong overall survival in men with bone-metastatic, castrate-resistant prostate cancer. However, increased fracture risk in skeletal sites with no bone metastasis has been observed in patients treated with Ra-223. Both luciferase- or green fluorescence protein (GFP)-labeled osteoblast reporter mice were used to monitor the effect of Ra-223 on resident osteoblasts and normal bone structure. Upon Ra-223 treatment, 70% of resident osteoblasts were reduced within 2 days, and the osteoblast reduction lasted for at least 18 weeks without detectable recovery, as measured by in vivo bioluminescent imaging. In GFP-labeled osteoblast reporter mice, Ra-223 mainly reduced osteoblasts localized in the trabecular bone areas; the osteoblasts in the growth plates were less affected. Micro-computed tomography analyses showed that Ra-223 significantly reduced bone mineral density and bone microstructure in the trabecular area of femurs but not in the cortical bone. Tumor-induced bone was generated by inoculating osteogenic TRAMP-BMP4 prostate cancer cells into the mouse femurs; Ra-223 treatment significantly reduced tumor-induced osteoblasts. Our study shows that Ra-223 affects bone structures that are not involved in bone metastasis. Strategies that improve bone health may reduce fracture risk in patients receiving Ra-223.

UNASSIGNED: Physical inactivity is considered an important risk factor for osteoporosis, however, some athletes performing extremely high training volumes can also develop bone mass loss. Moreover, the effect of total body mass or body surface area on bone mineral density remains controversial. Therefore, the aim of this study was to compare the absolute bone mineral density and bone mineral density adjusted to body surface area between amateur triathletes and nonactive women.
UNASSIGNED: Forty-two healthy women (23 amateur triathletes and 19 nonactive individuals) were evaluated for body composition using a dual-energy X-ray absorptiometry system.
UNASSIGNED: Compared to nonactive women, amateur triathletes exhibited lower body mass index (p < 0.001), lower bone mineral density (p < 0.001), and body surface area (p < 0.001). However, bone mineral density adjusted by body surface area in the triathletes was higher than in the nonactive women (p = 0.03).
UNASSIGNED: These findings showed that amateur triathles presented lower absolute bone mineral density, but higher bone mineral density adjusted to body surface area. Future studies are recommended to identify if the higher bone mineral density adjusted to body surface area are associated with a lower bone fragility.

Obesity and type 2 diabetes (T2D) are risk factors for fragility fractures. It is unknown whether this elevated risk is due to a diet favoring obesity or the diabetes that often occurs with obesity. Therefore, we hypothesized that the fracture resistance of bone is lower in mice fed with a high fat diet (45% kcal; HFD) than in mice that fed on a similar, control diet (10% kcal; LFD), regardless of whether the mice developed overt T2D. Sixteen-week-old, male NON/ShiLtJ mice (resistant to T2D) and age-matched, male NONcNZO10/LtJ (prone to T2D) received a control LFD or HFD for 21 weeks. HFD increased the bodyweight to a greater extent in the ShiLtJ mice compared to the NZO10 mice, while blood glucose levels were significantly higher in NZO10 than in ShiLtJ mice. As such, the glycated hemoglobin A1c (HbA1c) levels exceeded 10% in NZO10 mice, but it remained below 6% in ShiLtJ mice. Diet did not affect HbA1c. HFD lowered trabecular number and bone volume fraction of the distal femur metaphysis (micro-computed tomography or μCT) in both strains. For the femur mid-diaphysis, HFD significantly reduced the yield moment (mechanical testing by three-point bending) in both strains but did not affect cross-sectional bone area, cortical thickness, nor cortical tissue mineral density (μCT). Furthermore, the effect of diet on yield moment was independent of the structural resistance of the femur mid-diaphysis suggesting a negative effect of HFD on characteristics of the bone matrix. However, neither Raman spectroscopy nor assays of advanced glycation end-products identified how HFD affected the matrix. HFD also lowered the resistance of cortical bone to crack growth in only the diabetic NZO10 mice (fracture toughness testing of other femur), while HFD reduced the ultimate force of the L6 vertebra in both strains (compression testing). In conclusion, the HFD-related decrease in bone strength can occur in mice resistant and prone to diabetes indicating that a diet high in fat deleteriously affects bone without necessarily causing hyperglycemia.

Determining the optimal body weight for individuals with severe motor and intellectual disabilities (SMID) lacks a standardized approach. In this study, we aimed to develop a formula to estimate the ideal body weight for each SMID patient, considering factors such as reduced muscle and bone mass. We analyzed data from 111 SMID patients (56 male, 55 female; age range 20 to 73 y) who underwent blood tests measuring creatinine (Cr) and cystatin C (cysC) for clinical reasons between Feb. 2018 and Feb. 2023. To create the optimal body weight formula, we utilized three variables: height, estimated glomerular filtration (eGFR)-Cr, and eGFR-cysC. The validity of the formula was assessed by comparing the measured triceps subcutaneous fat thickness (TSF) to the reference TSF (%TSF), evaluating how accurately it reflects the appropriate physique. The derived optimal body weight formula is as follows: Optimal body weight=(height)2×(18.5-25.0)×{1-0.41×(1-eGFR-cysC/eGFR-Cr)}×0.93. Our formula demonstrated validity when using %TSF as an indicator. Establishing a method to determine optimal body weight in SMID patients, considering their low muscle and bone mass, is crucial for accurate nutritional assessment and subsequent nutritional management.

Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.