The complex relationship between trace elements and skeletal health has received increasing attention in the scientific community. Among these minerals, manganese (Mn) has emerged as a key element affecting bone metabolism and integrity. This review examines the multifaceted role of Mn in bone health, including its effects on bone regeneration, mineralization, and overall skeletal strength. This review article is based on a synthesis of experimental models, epidemiologic studies, and clinical trials of the mechanisms of the effect of Mn on bone metabolism. Current research data show that Mn is actively involved in the processes of bone remodeling by modulating the activity of osteoblasts and osteoclasts, as well as the main cells that regulate bone formation and resorption. Mn ions have a profound effect on bone mineralization and density by intricately regulating signaling pathways and enzymatic reactions in these cells. Additionally, Mn superoxide dismutase (MnSOD), located in bone mitochondria, plays a crucial role in osteoclast differentiation and function, protecting osteoclasts from oxidative damage. Understanding the nuances of Mn\'s interaction with bone is essential for optimizing bone strategies, potentially preventing and managing skeletal diseases. Key findings include the stimulation of osteoblast proliferation and differentiation, the inhibition of osteoclastogenesis, and the preservation of bone mass through the RANK/RANKL/OPG pathway. These results underscore the importance of Mn in maintaining bone health and highlight the need for further research into its therapeutic potential.

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.

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.

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.

Thanks to recent progress in cancer research, most children treated for cancer survive into adulthood. Nevertheless, the long-term consequences of anticancer agents are understudied, especially in the pediatric population. We and others have shown that routinely administered chemotherapeutics drive musculoskeletal alterations, which contribute to increased treatment-related toxicity and long-term morbidity. Yet, the nature and scope of these enduring musculoskeletal defects following anticancer treatments and whether they can potentially impact growth and quality of life in young individuals remain to be elucidated. Here, we aimed at investigating the persistent musculoskeletal consequences of chemotherapy in young (pediatric) mice. Four-week-old male mice were administered a combination of 5-FU, leucovorin, irinotecan (a.k.a., Folfiri) or the vehicle for up to 5 wk. At time of sacrifice, skeletal muscle, bones, and other tissues were collected, processed, and stored for further analyses. In another set of experiments, chemotherapy-treated mice were monitored for up to 4 wk after cessation of treatment. Overall, the growth rate was significantly slower in the chemotherapy-treated animals, resulting in diminished lean and fat mass, as well as significantly smaller skeletal muscles. Interestingly, 4 wk after cessation of the treatment, the animals exposed to chemotherapy showed persistent musculoskeletal defects, including muscle innervation deficits and abnormal mitochondrial homeostasis. Altogether, our data support that anticancer treatments may lead to long-lasting musculoskeletal complications in actively growing pediatric mice and support the need for further studies to determine the mechanisms responsible for these complications, so that new therapies to prevent or diminish chemotherapy-related toxicities can be identified.

The silent information regulator T1 (SIRT1) is linked to longevity and is a crucial mediator of osteoblast function. We investigated the direct role of Sirt1 during bone modeling and remodeling stages in vivo using Tamoxifen-inducible osteoblast-specific Sirt1 conditional knockout (cKO) mice. cKO mice exhibited lower trabecular and cortical bone mass in the distal femur. These phenotypes were coupled with lower bone formation and bone resorption. Metabolomics analysis revealed that the metabolites involved in glycolysis were significantly decreased in cKO mice. Further analysis of the quantitative acetylome revealed 11 proteins with upregulated acetylation levels in both the femur and calvaria of cKO mice. Cross-analysis identified four proteins with the same upregulated lysine acetylation site in both the femur and calvaria of cKO mice. A combined analysis of the metabolome and acetylome, as well as immunoprecipitation, gene knockout, and site-mutation experiments, revealed that Sirt1 deletion inhibited glycolysis by directly binding to and increasing the acetylation level of Glutamine oxaloacetic transaminase 1 (GOT1). In conclusion, our study suggested that Sirt1 played a crucial role in regulating osteoblast metabolism to maintain bone homeostasis through its deacetylase activity on GOT1. These findings provided a novel insight into the potential targeting of osteoblast metabolism for the treatment of bone-related diseases.