Association of coffee intake with bone mineral density: a Mendelian randomization study.

Background: In observational studies, the relationship between coffee intake and bone mineral density (BMD) is contradictory. However, residual confounding tends to bias the results of these studies. Therefore, we used a two-sample Mendelian randomization (MR) approach to further investigate the potential causal relationship between the two. Methods: Genetic instrumental variables (IVs) associated with coffee intake were derived from genome-wide association studies (GWAS) of the Food Frequency Questionnaire (FFQ) in 428,860 British individuals and matched using phenotypes in PhenoScanner. Summarized data on BMD were obtained from 537,750 participants, including total body BMD (TB-BMD), TB-BMD in five age brackets ≥60, 45-60, 30-45, 15-30, and 0-15 years, and BMD in four body sites: the lumbar spine, the femoral neck, the heel, and the ultradistal forearm. We used inverse variance weighting (IVW) methods as the primary analytical method for causal inference. In addition, several sensitivity analyses (MR-Egger, Weighted median, MR-PRESSO, Cochran's Q test, and Leave-one-out test) were used to test the robustness of the results. Results: After Bonferroni correction, Coffee intake has a potential positive correlation with total body BMD (effect estimate [Beta]: 0.198, 95% confidence interval [Cl]: 0.05-0.35, P=0.008). In subgroup analyses, coffee intake was potentially positively associated with TB-BMD (45-60, 30-45 years) (Beta: 0.408, 95% Cl: 0.12-0.69, P=0.005; Beta: 0.486, 95% Cl: 0.12-0.85, P=0.010). In addition, a significant positive correlation with heel BMD was also observed (Beta: 0.173, 95% Cl: 0.08-0.27, P=0.002). The results of the sensitivity analysis were generally consistent. Conclusion: The results of the present study provide genetic evidence for the idea that coffee intake is beneficial for bone density. Further studies are needed to reveal the biological mechanisms and offer solid support for clinical guidelines on osteoporosis prevention.

Prolonged bone health benefits for breast cancer patients following adjuvant bisphosphonate therapy: the BoHFAB study.

Adjuvant bisphosphonates are often recommended in postmenopausal women with early breast cancer at intermediate-to-high risk of disease recurrence, but the magnitude and duration of their effects on bone mineral density (BMD) and bone turnover markers (BTMs) are not well described. We evaluated the impact of adjuvant zoledronate on areal BMD and BTMs in a sub-group of patients who had completed the large 5-yr randomized Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial. About 224 women (recurrence free) who had completed the AZURE trial within the previous 3 mo were recruited from 20 UK AZURE trial sites. One hundred twenty had previously been randomized to zoledronate (19 doses of 4 mg over 5 yr) and 104 to the control arm. BMD and BTMs were assessed at sub-study entry, 6 (BTMs only), 12, 24, and 60 mo following the completion of AZURE. As expected, mean BMD, T-scores, and Z-scores at sub-study entry were higher in the zoledronate vs the control arm. At the lumbar spine, the mean (SD) standardized BMD (sBMD) was 1123 (201) and 985 (182) mg/cm2 in the zoledronate and control arms, respectively (P < .0001). The baseline differences in sBMD persisted at all assessed skeletal sites and throughout the 5-yr follow-up period. In patients completing zoledronate treatment, BTMs were significantly lower than those in the control arm (α- and ß-urinary C-telopeptide of type-I collagen, both P < .00001; serum intact pro-collagen I N-propeptide, P < .00001 and serum tartrate-resistant acid phosphatase 5b, P = .0001). Some offset of bone turnover inhibition occurred in the 12 mo following the completion of zoledronate treatment. Thereafter, during the 60 mo of follow-up, all BTMs remained suppressed in the zoledronate arm relative to the control arm. In conclusion, in addition to the known anti-cancer benefits of adjuvant zoledronate, there are likely to be positive, lasting benefits in BMD and bone turnover.

Female rats consuming an iron and omega-3 fatty acid deficient diet preconception require combined iron and omega-3 fatty acid supplementation for the prevention of bone impairments in offspring.

We previously showed in rats that pre- and postnatal deficiencies in iron and omega-3 (n-3) fatty acids can impair bone development, with additive and potentially irreversible effects when combined. This study aimed to investigate, in female rats consuming a combined iron and n-3 fatty acid deficient (ID + n-3 FAD) diet preconception, whether supplementation with iron and docosahexaenoic/eicosapentaenoic acid (DHA/EPA), alone and in combination, can prevent bone impairments in offspring. Using a 2 × 2 factorial design, female Wistar rats consuming an ID + n-3 FAD diet preconception were randomised to receive an: 1) iron supplemented (Fe + n-3 FAD), 2) DHA/EPA supplemented (ID + DHA/EPA), 3) Fe + DHA/EPA, or 4) ID + n-3 FAD diet from gestational day 10 throughout pregnancy and lactation. Post-weaning, offspring (n = 24/group; male:female = 1:1) remained on the respective experimental diets for three weeks until postnatal day 42-45. Offspring born to female rats consuming a control diet preconception and an Fe+DHA/EPA diet throughout pregnancy and lactation served as non-deficient reference group (Control+Fe+DHA/EPA). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry and bone strength using three-point bending tests. Only offspring in the Fe+DHA/EPA group had significantly higher spine and femur BMD, and higher femur stiffness than offspring in the ID + n-3 FAD group, and had similar spine BMD and femur stiffness as the Control + Fe + DHA/EPA group. Offspring in the Fe + DHA/EPA group further had significantly higher femur strength (ultimate load) than the other experimental groups, and a similar femur strength as the Control + Fe + DHA/EPA group. This study shows that only combined iron and DHA/EPA supplementation can prevent bone impairments in offspring of female rats consuming an iron and n-3 FA deficient diet preconception.

Bone mineral density in adults with arthrogryposis multiplex congenita: a retrospective cohort analysis.

The primary objective of this study was to evaluate the prevalence of low femoral and lumbar spine bone mineral density (BMD) in adults with arthrogryposis multiplex congenita (AMC). We performed a retrospective cohort analysis of adults with AMC who were enrolled in the French Reference Center for AMC and in the Pediatric and Adult Registry for Arthrogryposis (PARART, NCT05673265). Patients who had undergone dual-energy X-ray absorptiometry (DXA) and/or vitamin D testing were included in the analysis. Fifty-one patients (mean age, 32.9 ± 12.6 years) were included; 46 had undergone DXA. Thirty-two (32/51, 62.7%) patients had Amyoplasia, and 19 (19/51, 37.3%) had other types of AMC (18 distal arthrogryposis, 1 Larsen). Six patients (6/42, 14.3%) had a lumbar BMD Z score less than - 2. The mean lumbar spine Z score (- 0.03 ± 1.6) was not significantly lower than the expected BMD Z score in the general population. Nine (9/40, 22.5%) and 10 (10/40, 25.0%) patients had femoral neck and total hip BMD Z scores less than - 2, respectively. The mean femoral neck (- 1.1 ± 1.1) and total hip (- 1.2 ± 1.2) BMD Z scores in patients with AMC were significantly lower than expected in the general population (p < 0.001). Femoral neck BMD correlated with height (rs = 0.39, p = 0.01), age (rs = - 0.315, p = 0.48); total hip BMD correlated with height (rs = 0.331, p = 0.04) and calcium levels (rs = 0.41, p = 0.04). Twenty-five patients (25/51, 49.0%) reported 39 fractures. Thirty-one (31/36, 86.1%) patients had 25-hydroxyvitamin D levels less than 75 nmol/l, and 6 (6/36, 16.7%) had 25-hydroxyvitamin D levels less than 75 nmol/l. Adults with AMC had lower hip BMD than expected for their age, and they more frequently showed vitamin D insufficiency. Screening for low BMD by DXA and adding vitamin D supplementation when vitamin D status is insufficient should be considered in adults with AMC, especially if there is a history of falls or fractures.

Influence of Various Strontium Formulations (Ranelate, Citrate, and Chloride) on Bone Mineral Density, Morphology, and Microarchitecture: A Comparative Study in an Ovariectomized Female Mouse Model of Osteoporosis.

Osteoporosis stands out as a prevalent skeletal ailment, prompting exploration into potential treatments, including dietary strontium ion supplements. This study assessed the efficacy of supplementation of three strontium forms-strontium citrate (SrC), strontium ranelate (SrR), and strontium chloride (SrCl)-for enhancing bone structure in 50 female SWISS mice, aged seven weeks. In total, 40 mice underwent ovariectomy, while 10 underwent sham ovariectomy. Ovariectomized (OVX) mice were randomly assigned to the following groups: OVX (no supplementation), OVX + SrR, OVX + SrC, and OVX + SrCl, at concentrations equivalent to the molar amount of strontium. After 16 weeks, micro-CT examined trabeculae and cortical bones, and whole-bone strontium content was determined. Results confirm strontium administration increased bone tissue mineral density (TMD) and Sr content, with SrC exhibiting the weakest effect. Femur morphometry showed limited Sr impact, especially in the OVX + SrC group. This research highlights strontium's potential in bone health, emphasizing variations in efficacy among its forms.

Secondary hyperparathyroidism: Predictors and relationship with vitamin D status, bone turnover markers and bone mineral density.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) has adverse implications for bone health but is relatively understudied. In this study we examine the prevalence and determinants of SHPT and describe the relationship of SHPT with bone turnover markers and bone mineral density (BMD) in older Irish adults. METHOD: Eligible participants (n = 4139) were identified from the Trinity-Ulster-Department of Agriculture (TUDA) study, a cohort of Irish adults aged ≥60 years. Exclusion criteria included an estimated glomerular filtration rate (eGFR) <30 ml/min and serum calcium >2.5 mmol/l to remove hyperparathyroidism due to advanced chronic kidney disease (CKD) and primary hyperparathyroidism respectively. The relationship between SHPT and bone turnover markers and BMD (measured by densitometry) was examined in a subsample (n = 1488). Vitamin D deficiency was defined as 25-hydroxyvitamin D [25 (OH)D] <30 nmol/l. RESULTS: Participants had a mean age of 73.6 ± 7.9 years, 65.1 % were female and 19.4 % were found to be vitamin D deficient. The prevalence of SHPT decreased as vitamin D increased, from 30.6 % in those deficient to 9.8 % in those with 25(OH)D ≥ 50 nmol/l and increased with declining kidney function. In non­calcium supplement users, principal determinants of SHPT were vitamin D deficiency (OR 4.18, CI 3.05-5.73, p < 0.001), eGFR 30-44 ml/min (OR 3.69, CI 2.44-5.57, p < 0.001), loop diuretic use (OR 3.52, CI 2.59-4.79, p < 0.001) and to a lesser extent body mass index (p = 0.001), eGFR 45-59 ml/min (p < 0.001) and 25(OH)D level 30-49 nmol/l (p = 0.002). Similar findings were observed in calcium supplement users, though proton pump inhibitors were also associated with SHPT (OR 1.55, CI 1.08-2.22, p = 0.018) while vitamin D 30-49 nmol/l was not. In participants with SHPT versus those without, bone turnover markers were higher: bone alkaline phosphatase (p = 0.017) and tartrate-resistant acid phosphatase (p = 0.033), whilst there was lower BMD at the neck of femur (0.880 vs. 0.903 g/cm2, p = 0.033) and total hip (0.968 vs. 0.995 g/cm2, P = 0.017). DISCUSSION: The results show that up to one in six older Irish adults had SHPT and this was associated with lower BMD and higher concentrations of bone turnover markers. Both vitamin D deficiency and 25(OH)D level 30-49 nmol/l were important predictors of SHPT. Loop diuretics and PPIs may also increase the risk of SHPT, and their use may need to be carefully considered in this population. Further studies examining the potential impact of these factors on bone health in similar populations to our study sample are warranted.

Effect of nutritional supplementation on bone mineral density in children with sickle cell disease: protocol for an open-label, randomised controlled clinical trial.

INTRODUCTION: Children with sickle cell disease show a significant decrease in bone mineral density, an increase in resting energy expenditure of more than 15%, a decrease in fat and lean mass as well as a significant increase in protein turnover, particularly in bone tissue. This study aims to evaluate the effectiveness of an increase in food intake on bone mineral density and the clinical and biological complications of paediatric sickle cell disease. METHODS AND ANALYSIS: The study is designed as an open-label randomised controlled clinical trial conducted in the Paediatrics Unit of the Orléans University Hospital Centre. Participants aged 3-16 years will be randomly divided into two groups: the intervention group will receive oral nutritional supplements (pharmacological nutritional hypercaloric products) while the control group will receive age-appropriate and gender-appropriate nutritional intake during 12 months. Total body less head bone mineral density will be measured at the beginning and the end of the trial. A rigorous nutritional follow-up by weekly 24 hours recall dietary assessment and planned contacts every 6 weeks will be carried out throughout the study. A school absenteeism questionnaire, intended to reflect the patient's school productivity, will be completed by participants and parents every 3 months. Blood samples of each patient of both groups will be stocked at the beginning and at the end of the trial, for future biological trial. Clinical and biological complications will be regularly monitored. ETHICS AND DISSEMINATION: The protocol has been approved by the French ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre-Mer 2, Toulouse; approval no: 2-20-092 id9534). Children and their parents will give informed consent to participate in the study before taking part. Results will be disseminated through peer-reviewed journals or international academic conferences. TRIAL REGISTRATION NUMBER: NCT04754711.

Genistein Supplementation and Bone Health in Breast Cancer in Rats.

The aim of our study was to analyse the effect of supplementation with various forms of genistein (nano-, micro-, and macro-) on the mineral status of rat femurs in conditions of DMBA-induced mammary gland neoplasia. Thirty-two 30-day-old Sprague Dawley rats were used in the study. The rats were divided into four experimental groups: a control group (without supplementation) and groups supplemented with nanosized (92 ± 41 nm), microsized (587 ± 83 nm), and macrosized genistein. Micromorphometric and histological examination of the rat femurs were performed, as well as analysis of the weight and mineral composition (17 elements). Quadrupole ICP-MS was used for analysis of all trace elements. Supplementation with genistein (nano-, micro-, and macro-) was shown to cause changes in the mineral composition of the bones. In the rats receiving nanogenistein, disintegration of the bone tissue was observed. The femurs of these animals had higher content of calcium (by nearly 300%) and potassium (by 25%) than the other groups, while the level of magnesium was about 22% lower. In the case of microelements, there were increases in copper (by 67%), boron (48%), manganese (13%), and nickel (100%), and a 16% decrease in strontium compared to the bones of rats without genistein supplementation. Changes in micromorphometric parameters, resulting in increased bone fragility, were observed. Administration of genistein was found to have an effect on the amount of trace elements in the bone tissue of rats with breast cancer.

Prevalence and risk factors of osteoporotic fracture among the elderly population in China: a multicenter cross-sectional study.

PURPOSE: Prevalence of osteoporotic fracture (OPF) is increasing with ageing, resulting in a significant financial burden for healthcare. However, research on the nationwide epidemiological data of OPF in Chinese elderly is still scarce. The aim of this study was to investigate the prevalence and risk factors of OPF in Chinese population aged 60 years or order. METHODS: A cross-sectional survey was conducted in an elderly Chinese population in five centres. Questionnaire investigation and imaging examination were taken in all participants to identify OPF prevalence and risk factors. Diagnosis of OPF was determined based on imaging of vertebral fractures or history of fall-related fractures. We then used multivariate logistic regression model to analyze the associations between the potential risk factors and OPF. RESULTS: The overall prevalence of OPF in population aged 60 years or older was 24.7% (1,071/4,331), showing an increasing trend with age (P < 0.001). The prevalence of OPF was geographically distinct (P < 0.001), but similar between men and women (P > 0.05). Up to 96.8% of OPFs consisted of vertebral fractures, especially involving T11, T12, and L1 segments. Advanced age (≥ 80), vision loss, severe hearing loss, multiple exercise forms, chronic kidney disease, osteoarthritis, and trauma-related vertebral fractures were significantly associated with risk factors, while education level and vitamin D supplementation were associated with protective factors of OPF. CONCLUSION: High prevalence of OPF is a serious threat to bone health among elderly people in China. There is an urgent need for effective strategies to diagnose, prevent, and treat OPF in elderly adults.

Influence of vitamin D supplementation on bone mineral content, bone turnover markers, and fracture risk in South African schoolchildren: multicenter double-blind randomized placebo-controlled trial (ViDiKids).

Randomized controlled trials (RCTs) to determine the influence of vitamin D on BMC and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n = 450) nested within a phase 3 RCT of weekly oral supplementation with 10 000 IU vitamin D3 vs placebo for 3 yr in HIV-uninfected Cape Town schoolchildren aged 6-11 yr. Outcomes were BMC at the whole body less head (WBLH) and LS and serum 25-hydroxyvitamin D3 (25(OH)D3), PTH, alkaline phosphatase, C-terminal telopeptide, and PINP. Incidence of fractures was a secondary outcome of the main trial (n = 1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (SD 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI, 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI, -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI, -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI, -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomized to vitamin D vs placebo (7/755 vs 10/758 attending at least 1 follow-up; adjusted odds ratio 0.70, 95% CI, 0.27 to 1.85). In conclusion, a 3-yr course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome.

Vitamin D­the "sunshine vitamin"­is essential for helping the body to absorb calcium from the diet, which is laid down in bone to improve its strength. There is a lack of clinical trials testing whether vitamin D supplements can improve bone content of calcium and other minerals, or reduce risk of bone fractures (broken bones) in children of Black African ancestry. We therefore conducted such a study, recruiting 1682 schoolchildren aged 6­11 yr living in Cape Town, South Africa. We found that a weekly dose of 10 000 international units (250 micrograms) of vitamin D3, given by mouth for 3 yr, was effective in boosting vitamin D levels in trial participants who received it. However, this did not have any effect on bone content of calcium and other minerals. Relatively few children experienced a broken bone during the study, so we were unable to say with confidence whether or not vitamin D supplements might affect this outcome.

Non-pharmacological and pharmacological treatments for bone health after stroke: Systematic review with meta-analysis.

BACKGROUND: Hemi-osteoporosis is a common secondary complication of stroke. No systematic reviews of pharmacological and non-pharmacological agents for post-stroke bone health have estimated the magnitude and precision of effect sizes to guide better clinical practice. OBJECTIVES: To examine the benefits and harms of pharmacological and non-pharmacological agents on bone health in post-stroke individuals. METHODS: Eight databases were searched (PubMed, Cochrane library, Scopus, CINAHL Complete, Embase, PEDro, Clinicaltrils.gov and ICTRP) up to June 2023. Any controlled studies that applied physical exercise, supplements, or medications and measured bone-related outcomes in people with stroke were included. PEDro and the GRADE approach were used to examine the methodological quality of included articles and quality of evidence for outcomes. Effect sizes were calculated as standardized mean differences (SMD) and risk ratio (RR). Review Manager 5.4 was used for data synthetization. RESULTS: Twenty-four articles from 21 trials involving 22,500 participants (3,827 in 11 non-pharmacological and 18,673 in 10 pharmacological trials) were included. Eight trials were included in the meta-analysis. The methodological quality of half of the included non-pharmacological studies was either poor or fair, whereas it was good to excellent in 8 of 10 pharmacological studies. Meta-analysis revealed a beneficial effect of exercise on the bone mineral density (BMD) of the paretic hip (SMD: 0.50, 95 % CI: 0.16; 0.85; low-quality evidence). The effects of anti-resorptive medications on the BMD of the paretic hip were mixed and thus inconclusive (low-quality evidence). High-quality evidence showed that the administration of antidepressants increased the risk of fracture (RR: 2.36, 95 % CI 1.64-3.39). CONCLUSION: Exercise under supervision may be beneficial for hip bone health in post-stroke individuals. The effect of anti-resorptive medications on hip BMD is uncertain. The adverse effects of antidepressants on fracture risk among post-stroke individuals warrant further attention. Further high-quality studies are required to better understand this issue. REGISTRATION: PROSPERO CRD42022359186.

Effect of sheep bone protein hydrolysate on promoting calcium absorption and enhancing bone quality in low-calcium diet fed rats.

Calcium deficiency is prone to fractures, osteoporosis and other symptoms. In this study, sheep bone protein hydrolysates (SBPHs) were obtained by protease hydrolysis. A low-calcium-diet-induced calcium-deficiency rat model was established to investigate the effects of SBPHs on calcium absorption and intestinal flora composition. The results showed that an SBPHs + CaCl2 treatment significantly increased the bone calcium content, bone mineral density, trabecular bone volume, and trabecular thickness, and reduced trabecular separation, and changed the level of bone turnover markers (P < 0.05). Supplementation of SBPHs + CaCl2 can remarkably enhance the bone mechanical strength, and the microstructure of bone was improved, and the trabecular network was more continuous, complete, and thicker. Additionally, SBPHs + CaCl2 dietary increased the abundance of Firmicutes and reduced the abundance of Proteobacteria and Verrucomicrobiota, and promoted the production of short chain fatty acids. This study indicated that SBPHs promoted calcium absorption and could be applied to alleviate osteoporosis.

Different methionine to cysteine supplementation ratios altered bone quality of broilers with or without Eimeria challenge assessed by dual energy X-ray absorptiometry and microtomography.

Despite the acknowledged significance of nutrition in bone development, effects of methionine (Met) and cysteine (Cys) on bone quality remain under-researched, particularly during Eimeria challenge. We investigated the effects of different supplemental Met to Cys ratios (MCR) on bone quality of broilers under Eimeria challenge. A total of 720 fourteen-day old Cobb500 broilers were allocated into a 5 × 2 factorial arrangement. Five diets with Met and Cys supplemented at MCR of 100:0, 75:25, 50:50, 25:75, and 0:100 were fed to the birds with or without Eimeria challenge. Body composition was measured by dual energy x-ray absorptiometry, and the femur bone characteristics were assessed by microtomography. Data were analyzed by two-way ANOVA and orthogonal polynomial contrast. The results reaffirmed the detrimental effects of Eimeria challenge on bone quality. On 9 d post inoculation (DPI), significant interaction effects were found for whole body bone mineral content (BMC), lean tissue weight, and body weight (P < 0.05); in the nonchallenged group (NCG), these parameters linearly decreased as MCR decreased (P < 0.05). In the challenged group (CG), body weight and lean tissue weight were unaffected by MCR, and BMC linearly increased as MCR decreased (P < 0.05). For the cortical bone of femoral metaphysis on 6 DPI, bone mineral density (BMD) linearly increased as MCR decreased (P < 0.05). Bone volume to tissue volume ratio (BV/TV) in the CG linearly increased as MCR decreased (P < 0.05). On 9 DPI, BMC and TV linearly increased as MCR decreased (P < 0.05) in the NCG. BMD and BV/TV changed quadratically as MCR decreased (P < 0.05). For the trabecular bone of femoral metaphysis on 9 DPI, BV/TV, and trabecular number linearly increased as MCR decreased (P < 0.05) in the NCG. For the femoral diaphysis, BV, TV, BMC on 6 DPI, and BMD on 9 DPI linearly increased as MCR decreased (P < 0.05). In conclusion, this study showed that both Eimeria challenge and varying supplemental MCR could influence bone quality of broilers.

Systemic Inflammatory Regulators Associated with Osteoporosis: A Bidirectional Mendelian Randomization Study.

To elucidate the precise upstream and downstream regulatory mechanisms of inflammatory factors in osteoporosis (OP) progression and to establish a causal relationship between inflammatory factors and OP. We conducted bidirectional Mendelian randomization (MR) analyses using data for 41 cytokines obtained from three independent cohorts comprising 8293 Finnish individuals. Estimated bone mineral density (eBMD) data were derived from 426,824 UK Biobank White British individuals (55% female) and fracture data from 416,795 UK Biobank participants of European ancestry. The inverse variance-weighted method was the primary MR analysis approach. We employed other methods as complementary approaches for mutual corroboration. To test for pleiotropy and heterogeneity, we used the MR-Egger regression, MR-pleiotropy residual sum and outlier global test, and the Cochrane Q test. Macrophage inflammatory protein (MIP)-1α and interleukin (IL)-12p70 expression associated negatively and causally with eBMD (ß = -0.017 [MIP-1α], ß = -0.011 [IL-12p70]). Conversely, tumor necrosis factor-related apoptosis-inducing ligand was associated with a decreased risk of fractures (Odds Ratio: 0.980). Additionally, OP influenced the expression of multiple inflammatory factors, including growth-regulated oncogene-α, interferon-gamma, IL-6, beta nerve growth factor, and IL-2. Finally, we discovered complex bidirectional causal relationships between IL-8, IL-10, and OP. Specific inflammatory factors may contribute to OP development or may be causally affected by OP. We identified a bidirectional causal relationship between certain inflammatory factors and OP. These findings provide new perspectives for early prediction and targeted treatment of OP. Larger cohort studies are necessary in the future to further validate these findings.

Folic acid supplementation prevents high body fat-induced bone loss through TGR5 signaling pathways.

Osteoporosis caused by bone loss is one of the serious global public health problems. Folic acid is a B vitamin with multiple physiological functions such as lipid regulation and antioxidant capacity, and its potential to improve bone loss has attracted our attention. Through NHANES database analysis, we found that folic acid intake was significantly correlated with whole-body bone mineral density (BMD) in people aged 20-60 years, and the association may be mediated by the body fat rate. Male C57Bl/6 mice were fed either a normal diet or a high-fat diet, and folic acid was added to drinking water for supplementation. Our results indicated that mice with high body fat showed bone microstructure damage and bone loss, while folic acid supplementation improved bone quality. At the same time, we found that mice with high body fat exhibited abnormal blood lipids, dysregulation of intestinal flora, and metabolic disorders. Folic acid supplementation improved these phenomena. Through the network analysis of intestinal flora and metabolites, we found that LCA and TGR5 may play important roles. The results showed that folic acid promoted the expression of LCA and TGR5 in mice, increased the phosphorylation of AMPK, and decreased the phosphorylation of NF-κB and ERK, thereby reducing bone loss. In summary, folic acid intake is closely related to BMD, and folic acid supplementation can prevent high body fat-induced bone loss. Our study provides new ideas and an experimental basis for preventing bone loss and osteoporosis.

Antidiabetic drug administration prevents bone mineral density loss: Evidence from a two-sample Mendelian randomization study.

The aim of this study was to investigate the effect of common antidiabetic drugs on BMD by two-sample Mendelian randomization (MR). The single nucleotide polymorphisms that were strongly associated with insulin, metformin, rosiglitazone and gliclazide were extracted as instrumental variables (IVs) for MR analysis. The inverse variance weighted (IVW) method was used as the primary MR method to assess the causal effect of antidiabetic drugs on BMD, and other MR methods, including Weighted median, MR Egger and Weighted mode, were used for complementary analysis. Reliability and stability were assessed by the leave-one-out test. In the present work, IVW estimation of the causal effect of insulin on heel BMD demonstrated that there was a null effect of insulin on heel BMD (ß = 0.765; se = 0.971; P = 0.430), while metformin treatment had a positive effect on heel BMD (ß = 1.414; se = 0.460; P = 2.118*10-3). The causal relationship between rosiglitazone and heel BMD analysed by IVW suggested that there was a null effect of rosiglitazone on heel BMD (ß = -0.526; se = 1.744; P = 0.763), but the causal effect of gliclazide on heel BMD evaluated by IVW demonstrated that there was a positive effect of gliclazide on heel BMD (ß = 2.671; se = 1.340; P = 0.046). In summary, the present work showed that metformin and gliclazide have a role in reducing BMD loss in patients with diabetes and are recommended for BMD loss prevention in diabetes.

Effects of Dietary Colostrum Basic Protein on Bone Growth and Calcium Absorption in Mice.

Colostrum basic protein (CBP) is a trace protein extracted from bovine colostrum. Previous studies have shown that CBP can promote bone cell differentiation and increase bone density. However, the mechanism by which CBP promotes bone activity remains unclear. This study investigated the mechanism of the effect of CBP on bone growth in mice following dietary supplementation of CBP at doses that included 0.015%, 0.15%, 1.5%, and 5%. Compared with mice fed a normal diet, feeding 5% CBP significantly enhanced bone rigidity and improved the microstructure of bone trabeculae. Five-percent CBP intake triggered significant positive regulation of calcium metabolism in the direction of bone calcium accumulation. The expression levels of paracellular calcium transport proteins CLDN2 and CLDN12 were upregulated nearly 1.5-fold by 5% CBP. We conclude that CBP promotes calcium absorption in mice by upregulating the expression of the calcium-transporting paracellular proteins CLND2 and CLND12, thereby increasing bone density and promoting bone growth. Overall, CBP contributes to bone growth by affecting calcium metabolism.

Adherence to the evidence-based recommendations in managing bone health, pain, and mobility of patients with multiple myeloma: a mixed method in the Palestinian healthcare system.

BACKGROUND: Consensus/evidence-based recommendations for assessing, managing, and monitoring bone health, pain, and mobility in patients with multiple myeloma were developed. This study was conducted to assess the adherence of the hematologists-oncologists to the consensus/evidence-based recommendations for assessing, managing, and monitoring bone health, pain, and mobility in patients with multiple myeloma who received care in the Palestinian healthcare system. METHODS: A mixed method was used in this study. The consensus/evidence-based recommendations were identified through a systematic search in Scopus, PubMed, SpringerLink, ScienceDirect, and Google Scholar. A panel of 5 researchers (3 hematologists-oncologists, 3 medical students, and 1 pharmacologist) sorted the consensus/evidence-based recommendations and developed the survey tool during 3 iterative meetings. The extent to which the hematologists-oncologists in the 5 centers caring for patients with multiple myeloma adhered to the consensus/evidence-based recommendations was assessed using a questionnaire. RESULTS: Responses were collected from 10 hematologists-oncologists in all 5 healthcare centers where patients with multiple myeloma receive healthcare in the West Bank of Palestine. The median number of years in the practice of the hematologists-oncologists was 7.5 [2.75, 14.0] years and the median number of patients with multiple myeloma care per month was 12.5 [7.5, 21.25]. The vast majority (90%) of the hematologists-oncologists reported inadequate adherence to screening for medication problems related to bone health, pain, cardiopulmonary fitness, healthy behaviors, nutritional deficits, and mental health. Of the hematologists-oncologists, 70% reported inadequate adherence to ordering and evaluating calcium, vitamin D, alkaline phosphatase, electrolytes, and phosphorus levels to monitor bone health and 60% reported inadequate adherence to prescribing calcium and vitamin D supplements whenever there was a need. CONCLUSION: The findings of this study suggested inadequate adherence to the consensus/evidence-based recommendations and highlighted areas for improvement to ensure that patients receive optimal care. The findings suggested a need for further education and training on the latest guidelines and recommendations. Decision-makers and policymakers might need to design measures and implement policies to improve adherence to the consensus/evidence-based recommendations. Addressing these gaps in adherence to the consensus/evidence-based recommendations may improve the care and outcomes of patients with multiple myeloma.

Application of a Magnetic Resonance Imaging-Based Lumbar Vertebral Bone Quality Scoring System in Patients with Degenerative Lumbar Scoliosis.

BACKGROUND: Although dual-energy X-ray absorptiometry is still the gold standard for diagnosing osteoporosis, it can lead to inaccurate bone mineral density measurements due to lumbar degeneration and scoliosis. Many researchers have investigated diagnostic methods for osteoporosis in patients with degenerative lumbar scoliosis (DLS). This study aimed to investigate the differences between conventional vertebral bone quality (VBQ) scores and modified VBQ scores in patients with DLS and the influence of lumbar scoliosis on VBQ scores. METHODS: We retrospectively collected the clinical and radiological data of 68 patients with DLS admitted to Sun Yat-sen Memorial Hospital from July 2018 to April 2023. The patients were classified into one of 2 groups based on the T score of the left femoral neck. VBQ scores relative to cerebrospinal fluid at different levels, VBQ scores on different planes and single-level VBQ scores were compared. Receiver operating characteristic analysis was also performed. Different modified VBQ scores were compared between the moderate scoliosis group (10°

Sustained hypophosphatemia after denosumab in a patient on hemodialysis.

An 81-year-old Caucasian man who had commenced thrice weekly hemodialysis (HD) three months earlier, presented with a hip fracture, two vertebral fractures and a bone mineral density T-score of -3.6. He had received weekly iron sucrose infusions for 6 weeks and alphacalcidol on dialysis days. Although he suffered from coeliac disease and cirrhosis, he was fully ambulatory and well-nourished. He was normocalcaemic with a marginally low plasma phosphate and the PTH was 11.8 pmol/L (<2-times the upper range of the assay). In view of his severe osteoporosis, it was decided to treat him with denosumab (dmab). Laboratory assessment 2 weeks post dmab showed severe hypophosphatemia and hypocalcemia; phosphate 0.11 mmol/L and ionized calcium 0.83 mmol/L, and he was admitted for intravenous phosphate infusion. Three months later he remained on a phosphate supplement. The case illustrates that, in addition to the risks of hypocalcemia in patients with kidney failure and high bone turnover, kidney failure patients without evidence of high bone turnover, can also be at risk of hypocalcemia and severe hypophosphatemia requiring acute hospitalization and phosphate infusion. The potential role of compromised phosphate absorption versus increased deposition will be discussed. We recommend a cautious approach to dmab therapy in patients on dialysis, with evaluation of bone turnover and serum phosphate levels prior to initiation of treatment.