Calcium-based phosphate binders and bone mineral density in patients undergoing hemodialysis: a retrospective cohort study.

BACKGROUND: Calcium supplements are commonly prescribed to prevent fractures in patients with osteoporosis. Nonetheless, they are generally eschewed in hemodialysis patients because they increase vascular calcification and induce cardiovascular disease. This retrospective cohort study aimed to investigate the effect of calcium-based phosphate binders (CBPB) on bone mineral density (BMD) in hemodialysis patients. METHODS: Outpatients on dialysis who underwent BMD measurement from January to December 2017, whose data on BMD trends and CBPB administration were recorded over the next 4 years, were enrolled. Patients receiving anti-osteoporotic medications were excluded. The association between the presence and duration of CBPB administration and changes in BMD was evaluated. RESULTS: The femoral neck's BMD decreased from 0.836 g/cm2 (0.702-0.952) to 0.764 g/cm2 (0.636-0.896) (P < 0.001) in the non-CBPB group (patients who never received CBPB over 4 years, n = 32). The CBPB group (n = 56) exhibited only a minute decrease from 0.833 g/cm2 (0.736-0.965) to 0.824 g/cm2 (0.706-0.939) (P = 0.004). Multivariate linear regression analysis revealed better BMD maintenance in the CBPB group [ß-coefficient (95% CI): 0.033 (0.001-0.065); P = 0.046] than in the non-CBPB group. Additionally, the prolonged-CBPB administration group showed superior BMD preservation [ß-coefficient (95% CI): 0.038 (0.001-0.076); P = 0.042]. CONCLUSION: CBPB administration may be associated with BMD maintenance.

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.

Icariin promotes bone marrow mesenchymal stem cells osteogenic differentiation via the mTOR/autophagy pathway to improve ketogenic diet-associated osteoporosis.

BACKGROUND: Icariin, a traditional Chinese medicine, has demonstrated anti-osteoporotic properties in ovariectomized mice. However, its effectiveness in preventing bone loss induced by ketogenic diet (KD), which mimics osteoporosis in human, remains unexplored. This study aims to investigate icariin's impact on KD-induced bone loss in mice. METHODS: Thirty mice were divided into: sham, KD, and KD + icariin groups. Post a 12-week intervention, evaluation including bone microstructures, serum concentrations of tartrate-resistant acid phosphatase (TRAP) and bone-specific alkaline phosphatase (ALP), and femoral tissue expression levels of osteocalcin (OCN) and TRAP. The expression levels of mammalian target of rapamycin (mTOR), ALP, peroxisome proliferator-activated receptor gamma (PPAR-γ), phosphorylated mTOR (p-mTOR), and the autophagy adaptor protein (p62) were also analyzed. Alizarin granule deposition and cellular ALP levels were measured following the induction of bone marrow mesenchymal stem cells (BMSCs) into osteogenesis. RESULTS: The study found that KD significantly impaired BMSCs' osteogenic differentiation, leading to bone loss. Icariin notably increased bone mass, stimulated osteogenesis, and reduced cancellous bone loss. In the KD + icariin group, measures such as bone tissue density (TMD), bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were significantly higher than in the KD group. Additionally, bone trabecular separation (Tb.Sp) was markedly lower in the KD + icariin group. Moreover, icariin increased OCN and ALP levels while suppressing PPAR-γ, TRAP, p62, and p-mTOR. In cellular studies, icariin encouraged osteogenic development in BMSCs under KD conditions. CONCLUSIONS: Icariin effectively counteracts bone thinning and improves bone microstructure. Its mechanism likely involves stimulating BMSCs osteogenic differentiation and inhibiting bone resorption, potentially through mTOR downregulation. These findings suggest icariin's potential as an alternative treatment for KD-induced bone loss.

Osteoporosis and cement usage in total hip arthroplasty.

PURPOSE: Cement usage in total hip arthroplasty (THA) is increasingly common. However, osteoporosis-related fracture risk in cemented vs uncemented THA patients is poorly characterized. We aim to analyze the usage of metabolic bone care and osteoporosis fracture risk in cemented vs uncemented THA patients using FRAX and radiographic bone measurements. METHODS: Chart review on 250 THA patients was performed retrospectively. Demographics, FRAX scores, hip radiograph measurements, osteoporosis diagnosis, treatment and screening were compared between cemented and uncemented THA patients. Logistic regression model was used to analyze factors influencing cement usage. RESULTS: Cemented THA patients have significantly higher osteoporosis-related fracture risk as measured by FRAX major (20% vs 13%) and FRAX hip (8% vs 5%). There is no significant difference in osteoporosis treatment, vitamin D / calcium supplementation, or metabolic bone disease screening based on patients' cement status. Female sex and rheumatoid arthritis status significantly predict cement usage, but FRAX scores do not predict cement usage. Additionally, 50% (10/20) of patients with Dorr C classification were uncemented. CONCLUSION: Although some patients undergoing THA with high osteoporosis-related fracture risk were identified and cemented, some risk factors including poor proximal femur shape (by Dorr classification) and poor bone quality (as measured by FRAX score) were potentially overlooked. Cemented patients had an increased risk for fractures but did not receive appropriately increased osteoporosis screening or treatment. LEVEL OF EVIDENCE: III.

Osteoporosis and bone health in pediatric patients with epidermolysis bullosa: A scoping review.

Nutritional compromise, low levels of vitamin D, chronic inflammation, abnormal growth, and physical inactivity affect bone metabolism and compromise long-term bone health in individuals with epidermolysis bullosa (EB). The result is a high risk for osteopenia, osteoporosis, and pathologic fractures, but this important consequence of EB has been the focus of few investigations. Our scoping review found 21 publications that assessed the current understanding and clinical practices for monitoring of osteoporosis and its treatment in EB. Recommendations summarized from 13 of these publications include early nutritional and weight assessments before 2 years of age; bloodwork every 6-12 months starting at birth; Tanner stage assessments every 6 months to detect any pubertal delay; DEXA scans starting at age 6 years with repeated scans every 1-2 years, except in mild cases; and vitamin D supplementation of 80-320 IU daily for children 0-7 years and 720 IU for patients >8 years.

A Correlation Analysis Between Adult Hepatic Fibrosis and Bone Mineral Density of the Lumbar Spine and Hip.

Context: Osteoporosis (OP) is a common complication for patients who have liver cirrhosis or cholestatic liver disease or who have received a liver transplantation. Osteoporotic fractures are serious clinical consequences of OP, and they often occur in the spine, hip, and wrist; have a high disability and mortality rate; cause a serious, social, medical burden; and threaten people's health. Objective: The study intended to explore the correlation between different degrees of liver fibrosis and bone mineral density (BMD) of the lumbar spine and hip as well as the factors influencing those differences. Design: The research team performed a retrospective observational study. Setting: The study took place at the First Affiliated Hospital of the Medical College at Ningbo University (Bund Courtyard) in Ningbo, China. Participants: Participants were 164 patients who had received two-dimensional shear wave elastography (2D-SWE) to measure liver stiffness and dual-energy X-ray absorptiometry (DEXA) to measure bone density at the First Affiliated Hospital of Ningbo University (Bund Courtyard) in Ningbo from May 2020 to April 2022. Groups: According to the liver-stiffness value, the research team divided participants into three groups: (1) the F0-F1 group with no or mild liver fibrosis, (2) the F2 group with significant liver fibrosis, and (3) F3-F4 group with severe liver fibrosis. For the three groups, the research team also compared the differences between the groups-F0-F1 to F2, F0-F1 to F3-F4, and F2 to F3-F4-in the BMD of the lumbar spine-Total, L2, L3, L4-and of the hip-Total, Neck, and Troch. Outcome Measures: The research team: (1) determined participants' degrees of liver fibrosis to create the F0-F1, F2, and F3-F4 groups and compared the BMDs of the lumbar spine and hip among those groups; (2) compared the degrees of liver fibrosis for three age groups-<40, 40-60, and ≥60 years old; (3) compared the degrees of liver fibrosis for participants with two etiologies of the disease-hepatitis or other causes; and (4) analyzed the correlations between different degrees of liver fibrosis and BMD of the lumbar spine and hip and the factors influencing those relationships. Results: The study revealed significant differences among the F0-F1, F2, and F3-F4 groups in terms of age group, degree of liver fibrosis, and bone mineral density (BMD) at various sites. Specifically, there were significant age group differences between individuals aged 40-60 years and those aged ≥60 years (P < .05). There were also significant differences noted in the degree of liver fibrosis with mean values of 5.59 ± 0.81, 7.43 ± 0.26, and 15.48 ± 10.02 for the F0-F1, F2, and F3-F4 groups, respectively (P < .05). The BMDs of the lumbar spine (L2, L3, L4, and Total values) and hip (Total values, right femoral neck (Neck), and trochantor (Troch)) showed significant differences (all P < .05). However, no significant differences were found in the BMDs for the L1 vertebra and Ward's triangle among the groups (both P > .05). The analysis also revealed that the mean BMDs of the F2 group were significantly higher than those of the F0-F1 and F3-F4 groups. Furthermore, there was a positive correlation between the F2 and F0-F1 groups and a negative correlation between the F2 and F3-F4 groups (P < .05). The logistic regression analysis showed that age group (OR = 2.047, 95% CI: 0.135-1.298, P = .016) and Total BMD for the hip (OR = 176.368, 95% CI: 0.233-10.112, P = .040) were significantly, independently correlated with the degree of liver fibrosis. Conclusions: According to the findings of the present study, a positive correlation was observed between liver stiffness and bone mineral density (BMD) values in patients at the F0-F1 to F2 stage of liver fibrosis. In contrast, a significant negative correlation was identified between these parameters in patients at the F2 to F3-F4 stage, indicating that BMD tends to decrease as the degree of liver fibrosis increases. These results suggest a potential link between liver fibrosis and bone health. The comparisons between groups F0-F1 and F3-F4 with group F2. Specifically, the study found that the BMD values of the F2 group were significantly higher than those of the F0-F1 and F3-F4 groups.

Zuogui Wan alleviates ovariectomy-induced osteoporosis by maintaining FoxO3 and increasing NK1R.

Sixty Sprague-Dawley female rats were randomly divided into sham-operated groups and five ovariectomy (OVX) subgroups. Rats subjected to sham and OVX were treated with the vehicle, alendronate, and Zuogui Wan (ZGW) at the doses of low, medium and high lyophilized powder daily for 3 months, respectively. The gene or protein expression of NK1R, PPAR γ, and OSX were assayed by either quantitative polymerase chain reaction or Western blot analysis. The results showed that compared with the OVX group, ZGW could reduce the level of PPARγ and increase the levels of OSX and. Meanwhile, ZGW could prevent bone loss. In addition, we found ZGW upregulated for the NK1R mRNA or protein expression by promoting the expression level of transcription factor FoxO3 and increasing its binding to the NK1R promoter region -700/-200 sequence. These results suggest that the regulation of FoxO3 and NK1R played a role and contributed to the mechanism of ZGW underlying the increase in bone mass in the OVX rat model.

Mini review: A reevaluation of nutritional vitamin D in the treatment of chronic kidney disease.

Chronic kidney disease-mineral and bone disorder is a syndrome of mineral and bone metabolism abnormalities caused by chronic kidney disease. Osteoporosis is a systemic metabolic bone disease characterized by low bone mass, disruption of bone microstructure, increased brittleness, and a higher propensity for fractures. Both of these conditions significantly affect bone metabolism and substantially increase the risk of fractures. Nutritional vitamin D is an essential trace element in the human body and an important fat-soluble vitamin. One crucial physiological role of nutritional vitamin D is to achieve mineral-bone metabolism balance by regulating calcium homeostasis. This review summarized the metabolism of vitamin in normal population and its specificity in chronic kidney disease. Over the years, the understanding and application of vitamin D in patients with chronic renal failure is changing. As people pay more attention to hypercalcemia, vascular calcification, osteoporosis, nutritional vitamin D has come into people's attention again. More and more studies are discussing how to prescribe vitamin D supplementation in hemodialysis patients.

Association of selenium intake with bone mineral density and osteoporosis: the national health and nutrition examination survey.

Background: Osteoporosis (OP) is a systemic metabolic skeletal disorder characterized by a decrease in bone mineral density (BMD) and an increase in the risk of fracture. The level of selenium (Se) in serum is associated with BMD. However, the relationship between dietary and total selenium intake and parameters such as osteoporosis and BMD is unclear. By conducting National Health and Nutritional Examination Surveys (NHANES), in this study, we assessed the association of Se intake with BMD and the risk of OP among general middle-aged and elderly people. Methods: The data were collected from three cycles of NHANES [2009-2010, 2013-2014, and 2017-2020]. Information on the dietary and supplementary Se intake was obtained from 24-h dietary recall interviews. Additionally, dual-energy X-ray absorptiometry (DXA) was performed to measure BMD, which was later transformed into T-scores; OP was diagnosed when the T-score was ≤ -2.5. We constructed a logistic regression model for the association between selenium intake and the risk of OP based on the estimated odds ratios (ORs) and the 95% confidence intervals (CIs). We also constructed a multivariable linear regression model to analyze the relationship between selenium intake and BMD. Results: In this study, 3,250 individuals (average age: 60.01 ± 10.09 years; 51.88% females) participated. The incidence of OP was 9.35% (3.30% for males and 17.75% for females). In the logistic regression model adjusted for every interested covariate, a higher quartile of dietary Se intake (OR for quartile 4 vs. quartile 1: 0.63; 95% CI: 0.41-0.96; P for trend = 0.027) was related to a lower risk of OP relative to the lowest quartile. The total selenium intake also exhibited a consistent trend (OR for quartile 4 vs. quartile 1: 0.67; 95% CI: 0.44-1.01; P for trend = 0.049). The results of the adjusted multivariate linear regression model showed that the participants with the highest quartile of dietary Se intake (Q4) had higher BMD in the total femur (ß = 0.069, P = 0.001; P for trend = 0.001), femoral neck (ß = 0.064, P = 0.001; P for trend = 0.001), and total spine (ß = 0.030, P = 0.136; P for trend = 0.064) compared to those in quintile 1 (Q1). A similar trend of associations was observed for the total selenium intake with BMD, which was more prominent among females, as determined by the subgroup analysis. Conclusion: In this study, the dietary intake and total intake of selenium were positively associated with BMD, whereas they were negatively associated with the risk of OP among adults in the US. Further studies are required to verify our results and elucidate the associated biological mechanism.

Nodakenin alleviates ovariectomy-induced osteoporosis by modulating osteoblastogenesis and osteoclastogenesis.

Osteoporosis, a systemic bone disease defined by decreased bone mass and deterioration of bone microarchitecture, is becoming a global concern. Nodakenin (NK) is a furanocoumarin-like compound isolated from the traditional Chinese medicine Radix Angelicae biseratae (RAB). NK has been reported to have various pharmacological activities, but osteoporosis has not been reported to be affected by NK. In this study, we used network pharmacology, molecular docking and molecular dynamics simulation techniques to identify potential targets and pathways of NK in osteoporosis. We found that NK treatment significantly promoted osteogenic differentiation of BMSCs while activating the PI3K/AKT/mTOR signalling pathway by measuring alkaline phosphatase activity and the expression of various osteogenic markers. In contrast, LY294002, an inhibitor of PI3K, reversed these changes and inhibited the osteogenic differentiation-enabling effect of NK. Meanwhile, prevent the Akt and NFκB signalling pathways by down-regulating c-Src and TRAF6 thereby effectively inhibiting RANKL-induced osteoclastogenesis. In addition, oral administration of NK to mice significantly elevated bone mass and ameliorated ovariectomized (OVX)-mediated bone microarchitectural disorders. In conclusion, these data suggest that NK attenuates OVX-induced bone loss by enhancing osteogenesis and inhibiting osteoclastogenesis.

Drynaria Naringin alleviated mechanical stress deficiency-caused bone loss deterioration via Rspo1/Lgr4-mediated Wnt/ß-catenin signalling pathway.

Osteoporosis is a metabolic condition distinguished by the degradation of bone microstructure and mechanical characteristics. Traditional Chinese medicine (TCM) has been employed in China for the treatment of various illnesses. Naringin, an ingredient found in Drynariae TCM, is known to have a significant impact on bone metabolism. For this research, we studied the precise potential effect of Drynaria Naringin on protecting against bone loss caused by stress deficiency. In this study, a tail-suspension (TS) test was performed to establish a mouse model with hind leg bone loss. Some mice received subcutaneous injections of Drynaria Naringin for 30 d. Trabecular bone microarchitecture was evaluated using micro-computed tomography analysis and bone histological analysis. Bone formation and resorption markers were quantified in blood samples from mice or in the supernatant of MC3T3-E1 cells by ELISA analysis, Western blotting, and PCR. Immunofluorescence was utilized to visualize the location of ß-catenin. Additionally, siRNA was employed to knockdown-specific genes in the cells. Our findings highlight the efficacy of Drynaria Naringin in protecting against the deterioration of bone loss and promoting bone formation and Rspo1 expression in a mouse model following the TS test. Specifically, in vitro experiments also indicated that Drynaria Naringin may promote osteogenesis through the Wnt/ß-catenin signalling pathway. Moreover, our results suggest that Drynaria Naringin upregulates the expression of Rspo1/Lgr4, leading to the promotion of osteogenesis via the Wnt/ß-catenin signalling pathway. Therefore, Drynaria Naringin holds potential as a therapeutic medication for osteoporosis. Drynaria Naringin alleviates bone loss deterioration caused by mechanical stress deficiency through the Rspo1/Lgr4-mediated Wnt/ß-catenin signalling pathway.

Hyperbaric oxygen therapy exerts anti-osteoporotic effects in obese and lean D-galactose-induced aged rats.

Obesity accelerates the aging processes, resulting in an aggravation of aging-induced osteoporosis. We investigated the anti-osteoporotic effect of hyperbaric oxygen therapy (HBOT) in obese- and lean-aged rats through measurement of cellular senescence, hypoxia, inflammation, antioxidants, and bone microarchitecture. Obese and lean male Wistar rats were injected with 150 mg/kg/day of D-galactose for 8 weeks to induce aging. Then, all rats were randomly given either sham or HBOT for 14 days. Metabolic parameters were determined. Expression by bone mRNA for cellular senescence, hypoxia, inflammation, antioxidative capacity, and bone remodeling were examined. Micro-computed tomography and atomic absorption spectroscopy were performed to evaluate bone microarchitecture and bone mineral profiles, respectively. We found that HBOT restored the alterations in the mRNA expression level of p16, p21, HIF-1α, TNF-α, IL-6, RANKL, RANK, NFATc1, DC-STAMP, Osx, ALP, and Col1a1 in the bone in obese-and lean- aging rats. In obese-aging rats, HBOT increased the level of expression of Sirt1 and CuZnSOD mRNA and diminished the expression level of HIF-2α and ctsk mRNA to the same levels as the control group. However, HBOT failed to alter catalase and OCN mRNA expression in obese-aged rats. HBOT partially improved the bone microarchitecture in obese-aged rats, but completely restored it in lean-aged rats. Interestingly, HBOT protected against obesity-induced demineralization in obese-aged rats. In summary, HBOT exerts an anti-osteoporotic effect in lean-aged rats and prevents some, but not all the negative effects of obese-aged conditions on bone health. Therefore, HBOT is considered as a potential therapy for aging-induced osteoporosis, regardless of obese status.

Osteoporosis and dermatoporosis: a review on the role of vitamin D.

Osteoporosis (OP) and Dermatoporosis (DP) are expressions of the aging process at the skin and bone levels, respectively. Both conditions are associated with increased morbidity for elderly people, and this requires necessary interventions. They share many common risk factors; among these, vitamin D (VD) deficiency appears to have a role. VD is involved in either disease with many mechanisms, among which immunomodulation. VD deficiency has been linked to OP because it inhibits the body's capacity to absorb calcium and maintain optimal bone health. Available evidence suggests that proper vitaminosis D also appears to be vital in preventing skin age-related issues. DP is often seen in elderly individuals, particularly those with long-term sun exposure and a history of chronic sun damage. VD deficiency can be linked to DP, since its involvement in collagen production, epidermal barrier function, inflammation regulation, wound healing, and sun protection. Aim of this review is to summarize the most updated existing evidence on the role of VD in the development of fragility syndromes such as DP and OP and the possible benefits of VD supplementation as a simple and harmful weapon against aging.

AR/PCC herb pair inhibits osteoblast pyroptosis to alleviate diabetes-related osteoporosis by activating Nrf2/Keap1 pathway.

Osteoporosis is a prevalent complication of diabetes, characterized by systemic metabolic impairment of bone mass and microarchitecture, particularly in the spine. Anemarrhenae Rhizoma/Phellodendri Chinensis Cortex (AR/PCC) herb pair has been extensively employed in Traditional Chinese Medicine to manage diabetes; however, its potential to ameliorate diabetic osteoporosis (DOP) has remained obscure. Herein, we explored the protective efficacy of AR/PCC herb pair against DOP using a streptozotocin (STZ)-induced rat diabetic model. Our data showed that AR/PCC could effectively reduce the elevated fasting blood glucose and reverse the osteoporotic phenotype of diabetic rats, resulting in significant improvements in vertebral trabecular area percentage, trabecular thickness and trabecular number, while reducing trabecular separation. Specifically, AR/PCC herb pair improved impaired osteogenesis, nerve ingrowth and angiogenesis. More importantly, it could mitigate the aberrant activation of osteoblast pyroptosis in the vertebral bodies of diabetic rats by reducing increased expressions of Nlrp3, Asc, Caspase1, Gsdmd and IL-1ß. Mechanistically, AR/PCC activated antioxidant pathway through the upregulation of the antioxidant response protein Nrf2, while concurrently decreasing its negative feedback regulator Keap1. Collectively, our in vivo findings demonstrate that AR/PCC can inhibit osteoblast pyroptosis and alleviate STZ-induced rat DOP, suggesting its potential as a therapeutic agent for mitigating DOP.

Eicosapentaenoic acid supplementation modulates the osteoblast/osteoclast balance in inflammatory environments and protects against estrogen deficiency-induced bone loss in mice.

BACKGROUND: An imbalance of osteoblasts (OBs) and osteoclasts (OCs) in a chronic inflammatory microenvironment is an important pathological factor leading to osteoporosis. Eicosapentaenoic acid (EPA) has been shown to suppress inflammation in macrophages and adipocytes. However, the effect of EPA on OBs and OCs has yet to be fully elucidated. AIMS: We explored the roles of EPA in the differentiation of OBs and OCs, as well as the coupling between OBs and OCs in an inflammatory microenvironment. The effects of EPA on estrogen deficiency-induced osteoporosis were also evaluated. METHODS: Mouse bone marrow mesenchymal stem cells (mBMSCs) and mouse bone marrow-derived macrophages (mBMMs) were used for in vitro OBs and OCs differentiation. TNF-α was used to create an inflammatory microenvironment. We examined the effects of EPA on osteoblastogenesis in the absence or presence of TNF-α and collect OBs' culture medium as the conditioned medium (CM). Then we examined the effects of EPA and CM on RANKL-induced osteoclastogenesis. The in vivo effects of EPA were determined using an ovariectomized (OVX) mouse model treated with EPA or vehicle. RESULTS: High-dose EPA was shown to promote osteoblastogenesis in an inflammatory environment in vitro, as well as upregulate expression of OBs-specific proteins and genes. ARS and ALP staining also showed that high-dose EPA-treated groups restored mBMSCs' impaired osteogenic capacity caused by TNFa. Mechanistically, EPA suppressed the NF-κB pathway activated by TNF-α in mBMSCs and rescued TNF-α-mediated inhibition of osteoblastogenesis. EPA was also shown to inhibit expression of RANKL and decrease the RANKL/OPG ratio in OBs in an inflammatory environment. CM from TNF-α-stimulated OBs promoted osteoclastogenesis of mBMMs; EPA-treated CM prevented this. In the OVX mouse model, EPA supplementation prevented bone loss in an estrogen deficiency-induced inflammatory environment. CONCLUSIONS: EPA was demonstrated for the first time to restore mBMSCs' impaired osteogenic capacity caused by TNFa-induced inflammation and rescue the OBs/OCs balance via regulation of RANKL and OPG expression in OBs. EPA showed a remarkable ability to prevent bone loss in OVX mice, suggesting a potential application of EPA in postmenopausal osteoporosis.

Gleditsiae fructus regulates osteoclastogenesis by inhibiting the c­Fos/NFATc1 pathway and alleviating bone loss in an ovariectomy model.

Medical and economic developments have allowed the human lifespan to extend and, as a result, the elderly population has increased worldwide. Osteoporosis is a common geriatric disease that has no symptoms and even a small impact can cause fractures in patients, leading to a serious deterioration in the quality of life. Osteoporosis treatment typically involves bisphosphonates and selective estrogen receptor modulators. However, these treatments are known to cause severe side effects, such as mandibular osteonecrosis and breast cancer, if used for an extended period of time. Therefore, it is essential to develop therapeutic agents from natural products that have fewer side effects. Gleditsiae fructus (GF) is a dried or immature fruit of Gleditsia sinensis Lam. and is composed of various triterpenoid saponins. The anti­inflammatory effect of GF has been confirmed in various diseases, and since the anti­inflammatory effect plays a major role in inhibiting osteoclast differentiation, GF was expected to be effective in osteoclast differentiation and menopausal osteoporosis; however, to the best of our knowledge, it has not yet been studied. Therefore, the present study was designed to examine the effect of GF on osteoclastogenesis and to investigate the mechanism underlying inhibition of osteoclast differentiation. The effects of GF on osteoclastogenesis were determined in vitro by tartrate­resistant acid phosphatase (TRAP) staining, pit formation assays, filamentous actin (F­actin) ring formation assays, western blotting and reverse transcription­quantitative PCR analyses. Furthermore, the administration of GF to an animal model exhibiting menopausal osteoporosis allowed for the analysis of alterations in the bone microstructure of the femur using micro­CT. Additionally, assessments of femoral tissue and serum were conducted. The present study revealed that the administration of GF resulted in a reduction in osteoclast levels, F­actin rings, TRAP activity and pit area. Furthermore, GF showed a dose­dependent suppression of nuclear factor of activated T­cells cytoplasmic, c­Fos and other osteoclastogenesis­related markers.

Dietary Calcium Intake and Osteoporosis Risk in Arab Adults.

Osteoporosis is a major public health concern in Saudi Arabia's aging population. There is particularly limited information on how diet affects bone loss in this ethnic group. The purpose of this study was to examine the association between dietary calcium (Ca) intake and osteoporosis risk in Saudi adults. A total of 1950 patients (416 males and 1534 females) with known risk factors for osteoporosis participated in this cross-sectional study. A short questionnaire (CaQ) was used to assess dietary Ca intakes in patients attending tertiary hospitals in Riyadh City. The prevalence of osteoporosis was 21.3% and was more common in females (93.5%). Patients with osteoporosis were older (p < 0.001) and had lower BMI (p < 0.001). Results showed that the overall mean Ca intake was only 445.1 mg/day (recommended dietary intake of 1300 mg/day). Tea intake (OR = 0.8 95%CI: 0.7-1.0; p = 0.02) and consumption of fish and eggs (OR = 0.9 95%CI: 0.8-1.0; p = 0.01) were significantly associated with a lower risk of osteoporosis. Furthermore, consumption of biscuits, cake and bread slices were significantly associated with higher incidence of osteoporosis (OR = 1.3 95%CI: 1.0-1.5; p = 0.02). In conclusion, extremely low dietary Ca intake was observed among Saudi adults already at risk of osteoporosis. A balanced diet including high amount of Ca, vitamin D and omega-3 fatty acids accompanied by limiting consumption of foods high in saturated fats and glycemic index may be helpful in reducing osteoporosis risk in the Saudi adult population.

Enzymatic preparation of chondroitin sulfate oligosaccharides and its alleviating effect on ovariectomy-induced osteoporosis in rats.

Postmenopausal osteoporosis is the most common type of osteoporosis. Chondroitin sulfate (CS) has been successfully employed as food supplement against osteoarthritis, while the therapeutic potential on postmenopausal osteoporosis is little explored. In this study, CS oligosaccharides (CSOs) were enzymatically prepared through the lysis of CS by a chondroitinase from Microbacterium sp. Strain. The alleviating effects of CS, CSOs and Caltrate D (a clinically used supplement) on ovariectomy (OVX) - induced rat's osteoporosis were comparatively investigated. Our data showed that the prepared CSOs was basically unsaturated CS disaccharide mixture of ∆Di4S (53.1%), ∆Di6S (27.7%) and ∆Di0S (17.7%). 12 weeks' intragastric administration of Caltrate D (250 mg/kg/d), CS or CSOs (500 mg/kg/d, 250 mg/kg/d, 125 mg/kg/d) could obviously regulate the disorder of serum indices, recover the mechanical strength and mineral content of bone, improve the cortical bones' density and the number and length of trabecular bones in OVX rats. Both CS and CSOs in 500 mg/kg/d and 250 mg/kg/d could restore more efficiently the serum indices, bone fracture deflection and femur Ca than Caltrate D. As compared with CS at the same dosage, CSOs exhibited a more significant alleviating effect. These findings suggested that there was great potential of CSOs as daily interventions for delaying the progression of postmenopausal osteoporosis.

Treatment for osteoporosis in people with beta-thalassaemia.

BACKGROUND: Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with beta-thalassaemia, osteoporosis represents an important cause of morbidity and is due to a number of factors. First, ineffective erythropoiesis causes bone marrow expansion, leading to reduced trabecular bone tissue with cortical thinning. Second, excessive iron loading causes endocrine dysfunction, leading to increased bone turnover. Lastly, disease complications can result in physical inactivity, with a subsequent reduction in optimal bone mineralization. Treatments for osteoporosis in people with beta-thalassaemia include bisphosphonates (e.g. clodronate, pamidronate, alendronate; with or without hormone replacement therapy (HRT)), calcitonin, calcium, zinc supplementation, hydroxyurea, and HRT alone (for preventing hypogonadism). Denosumab, a fully human monoclonal antibody, inhibits bone resorption and increases bone mineral density (BMD). Finally, strontium ranelate simultaneously promotes bone formation and inhibits bone resorption, thus contributing to a net gain in BMD, increased bone strength, and reduced fracture risk. This is an update of a previously published Cochrane Review. OBJECTIVES: To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which includes references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of most recent search: 4 August 2022. SELECTION CRITERIA: Randomized controlled trials (RCTs) in people with beta-thalassaemia with: a BMD Z score below -2 standard deviations (SDs) for children aged under 15 years, adult males (aged 15 to 50 years) and premenopausal females aged over 15 years; or a BMD T score below -2.5 SDs for postmenopausal females and males aged over 50 years. DATA COLLECTION AND ANALYSIS: Two review authors assessed the eligibility and risk of bias of the included RCTs, and extracted and analysed data. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We included six RCTs (298 participants). Active interventions included bisphosphonates (3 trials, 169 participants), zinc supplementation (1 trial, 42 participants), denosumab (1 trial, 63 participants), and strontium ranelate (1 trial, 24 participants). The certainty of the evidence ranged from moderate to very low and was downgraded mainly due to concerns surrounding imprecision (low participant numbers), but also risk of bias issues related to randomization, allocation concealment, and blinding. Bisphosphonates versus placebo or no treatment Two RCTs compared bisphosphonates to placebo or no treatment. After two years, one trial (25 participants) found that alendronate and clodronate may increase BMD Z score compared to placebo at the femoral neck (mean difference (MD) 0.40, 95% confidence interval (CI) 0.22 to 0.58) and the lumbar spine (MD 0.14, 95% CI 0.05 to 0.23). One trial (118 participants) reported that neridronate compared to no treatment may increase BMD at the lumbar spine and total hip at six and 12 months; for the femoral neck, the study found increased BMD in the neridronate group at 12 months only. All results were of very low-certainty. There were no major adverse effects of treatment. Participants in the neridronate group reported less back pain; we considered this representative of improved quality of life (QoL), though the certainty of the evidence was very low. One participant in the neridronate trial (116 participants) sustained multiple fractures as a result of a traffic accident. No trials reported BMD at the wrist or mobility. Different doses of bisphosphonate compared One 12-month trial (26 participants) assessed different doses of pamidronate (60 mg versus 30 mg) and found a difference in BMD Z score favouring the 60 mg dose at the lumbar spine (MD 0.43, 95% CI 0.10 to 0.76) and forearm (MD 0.87, 95% CI 0.23 to 1.51), but no difference at the femoral neck (very low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment. Zinc versus placebo One trial (42 participants) showed zinc supplementation probably increased BMD Z score compared to placebo at the lumbar spine after 12 months (MD 0.15, 95% CI 0.10 to 0.20; 37 participants) and 18 months (MD 0.34, 95% CI 0.28 to 0.40; 32 participants); the same was true for BMD at the hip after 12 months (MD 0.15, 95% CI 0.11 to 0.19; 37 participants) and 18 months (MD 0.26, 95% CI 0.21 to 0.31; 32 participants). The evidence for these results was of moderate certainty. The trial did not report BMD at the wrist, fracture incidence, mobility, QoL, or adverse effects of treatment. Denosumab versus placebo Based on one trial (63 participants), we are unsure about the effect of denosumab on BMD Z score at the lumbar spine, femoral neck, and wrist joint after 12 months compared to placebo (low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment, but the investigators reported a reduction in bone pain measured on a visual analogue scale in the denosumab group after 12 months of treatment compared to placebo (MD -2.40 cm, 95% CI -3.80 to -1.00). Strontium ranelate One trial (24 participants) only narratively reported an increase in BMD Z score at the lumbar spine in the intervention group and no corresponding change in the control group (very low-certainty evidence). This trial also found a reduction in back pain measured on a visual analogue scale after 24 months in the strontium ranelate group compared to the placebo group (MD -0.70 cm (95% CI -1.30 to -0.10); we considered this measure representative of improved quality of life. AUTHORS' CONCLUSIONS: Bisphosphonates may increase BMD at the femoral neck, lumbar spine, and forearm compared to placebo after two years' therapy. Zinc supplementation probably increases BMD at the lumbar spine and hip after 12 months. Denosumab may make little or no difference to BMD, and we are uncertain about the effect of strontium on BMD. We recommend further long-term RCTs on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia-associated osteoporosis.

Pregnancy- and lactation-induced osteoporosis: a social-media-based survey.

BACKGROUND: Pregnancy- and lactation-induced osteoporosis (PLO) presenting as spinal fractures is rare, and the spectrum of clinical presentation, risk factors and pathophysiology are incompletely understood. The aim of this study was to delineate clinical parameters, risk factors and osteoporosis-related quality of life (QOL) of women with PLO. METHODS: Participants of a social-media (WhatsApp) PLO group and mothers of a parents' WhatsApp group (control group) were offered to fill a questionnaire, including an osteoporosis-related QOL section. The groups were compared using the independent Students t test for numerical variables, and the Chi-square test or Fisher's exact test for categorical variables. RESULTS: Twenty-seven women with PLO and 43 in the control group (aged 36.2 ± 4.7 and 38.8 ± 4.3 years, respectively, p = 0.04) participated. Among women with PLO, more than 5 vertebrae were involved in 13 (48%), 4 vertebrae in 6 (22%), and 3 or fewer vertebrae in 8 (30%). Among the 24 women with relevant data, 21 (88%) had nontraumatic fractures; 3 (13%) women had fractures during pregnancy, and the remaining during the early postpartum period. Diagnosis was delayed for over 16 weeks for 11 (41%) women; 16 (67%) received teriparatide. Significantly lower proportions of women in the PLO group engaged in physical activity over 2 hours/week, before and during pregnancy (37 vs. 67%, p < 0.015 and 11 vs. 44%, p < 0.003, respectively). A lower proportion of the PLO than the control group reported calcium supplementation during pregnancy (7% vs. 30%, p = 0.03) and a higher proportion reported treatment with low-molecular-weight-heparin during pregnancy (p = 0.03). Eighteen (67%) of the PLO group expressed fear of fractures and 15 (56%) fear of falls, compared to none and 2%, respectively, of the control group (p < 0.00001 for both). CONCLUSIONS: Most of the women with PLO who responded to our survey reported spinal fractures involving multiple vertebrae, delayed diagnosis, and treatment with teriparatide. Compared to a control group, they reported less physical activity and impaired QOL. For this uncommon yet severe condition, a multidisciplinary effort should be exerted for early identification and treatment, to alleviate back pain, prevent subsequent fractures and improve QOL.