Evaluation of food and nutrient intake in a population of subjects affected by periodontal disease with different levels of bone mineral density.

Introduction: Both osteoporosis and periodontitis are pathologies characterized by an imbalance in the bone tissue. Vitamin C is an important factor involved in maintaining the health of the periodontium; its deficiency causes characteristic lesions to periodontal tissues such as bleeding and redness of the gums. Among the essential minerals for the health of the periodontium we find instead calcium.Objectives of the study: The objectives of the proposed study are to study the association between the presence of osteoporosis and periodontal disease. We tried to identify the possible connections between particular dietary patterns and therefore the etiopathogenesis of periodontal disease and secondarily of osteoporosis.Materials and methods: 110 subjects were recruited in a single-center observational cross-sectional study carried through the collaboration between the University of Florence and the private institute of dentistry Excellence Dental Network based in Florence, suffering of periodontitis, 71 osteoporotic/osteopenic and 39 non-osteoporotic/osteopenic. Anamnestic data and information on eating habits were collected. Results: The population showed eating habits that do not meet the intake levels recommended by the L.A.R.N. Regarding the relationship between nutrient intake and plaque index, it appears that in the population, the higher the intake of vitamin C through food, the lower the plaque index value is. This result could reinforce the scientific evidence that there is a protective factor in the onset of periodontal disease by the consumption of vitamin C which to date is still the subject of investigation. In addition, the same type of trend would also have been observed for calcium intake, but a larger sample size would be required to make this effect significant. Conclusions: The relationship between osteoporosis and periodontitis and the role of nutrition in influencing the evolution of these pathologies still seems to be deeply explored. However, the results obtained seem to consolidate the idea that there is a relationship between these two diseases and that eating habits play an important role in their prevention.

Osteoporosis and Celiac Disease: Updates and Hidden Pitfalls.

Celiac disease (CD) is an autoimmune disorder caused by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms (e.g., diarrhea, bloating, and chronic abdominal pain), CD may also present with a broad spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. The etiopathology of bone lesions in CD is multifactorial and other conditions, rather than mineral and vitamin D malabsorption, may affect skeletal health, especially those related to the endocrine system. Here, we describe CD-induced osteoporosis in an attempt to enlighten new and less-known aspects, such as the influence of the intestinal microbiome and sex-related differences on bone health. This review describes the role of CD in the development of skeletal alterations to provide physicians with an updated overview on this debated topic and to improve the management of osteoporosis in CD.

Risk Factors for Osteoporosis among Patients with Inflammatory Bowel Disease-Do We Already Know Everything?

INTRODUCTION: There are many known risk factors for osteoporosis (OST) among patients with inflammatory bowel disease (IBD), one of which is physical activity. MATERIAL AND METHODS: The aim of the study is to assess the frequency and risk factors of OST among 232 patients with IBD compared to a group of 199 patients without IBD. The participants underwent dual-energy X-ray absorptiometry, laboratory tests, and completed a questionnaire about their physical activity. RESULTS: It was found that 7.3% of IBD patients suffered from OST. Male gender, ulcerative colitis, extensive inflammation in the intestine, exacerbation of disease, rare physical activity, other forms of physical activity, past fractures, lower levels of osteocalcin, and higher levels of C-terminal telopeptide of type 1 collagen were risk factors for OST. As many as 70.6% of OST patients were rarely physically active. CONCLUSIONS: OST is a common problem in IBD patients. OST risk factors differ significantly between the general population and those with IBD. Modifiable factors can be influenced by patients and by physicians. The key to OST prophylaxis may be regular physical activity, which should be recommended in clinical remission. It may also prove valuable to use markers of bone turnover in diagnostics, which may enable decisions regarding therapy.

A single-center study of bone mineral density in adult patients with severe hemophilia A in correlation with markers of bone metabolism.

INTRODUCTION: Osteopenia and osteoporosis are well-known hemophilia A comorbidities. The pathogenesis of bone turnover alteration resulting in reduced bone mass includes impaired osteoblastic differentiation and disinhibition of RANKL-induced osteoclastogenesis as a result of a low FVIII level. AIM: To evaluate the bone mineral density (BMD) in adult patients with severe hemophilia A and assess a possible correlation with the bone remodeling biomarkers OPG/RANKL, CTX-1, osteocalcin, and Vit D. MATERIALS AND METHODS: 28 male subjects with severe hemophilia A and 33 age-matched controls were recruited. The biomarkers were tested with the ELISA assay and BMD with DEXA of the lumbar spine (LS) and total hip (TH). RESULTS: The patients had lower LS-BMD (-0.955±0.145 vs. 1.118±0.079, p=0.05) and TH-BMD (-0.840±0.147 vs. 0.951±0.075, p=0.05) than those of the controls. The TH T-scores were -1.41±0.91 vs. 0.4±0.49 (p=0.05) and the LS T-scores -1.16±1.046 vs. 0.14±0.72 (p=0.05). 66.6% of patients under 50 years had osteopenia and 8.3% had osteoporosis. Fifty percent of those over 50 years old had osteopenia and 20% had osteoporosis. We found significantly higher OPG levels (123.69±107.05 vs. 41.98±18.95, p=0.05) than that in controls and lower sRANKL levels (23.49±29.39 vs. 131.32±201.27, p=0.05) and sRANKL/OPG ratio (0.27±0.35 vs. 5.28±10.01, p=0.05) than those in controls. A positive correlation was found between sRANKL and the BMD T-score of lumbar spine (p=0.001) in the patient group. CONCLUSIONS: sRANKL level and ratio can be used as predictors of low BMD.

The impact of vitamin D deficiency on clinical, biochemical and metabolic parameters in primary hyperparathyroidism.

BACKGROUND: It has been suggested that vitamin D deficiency is associated with worse clinical outcomes in primary hyperparathyroidism (PHPT). We aimed to evaluate the relationship between vitamin D deficiency and clinical, biochemical and metabolic parameters in PHPT patients. METHODS: A total of 128 patients with biochemically confirmed PHPT were included. Patients were categorized as vitamin D deficient if 25-OH vitamin D was <50nmol/L, or normal if vitamin D was ≥50nmol/L. Biochemical parameters, bone mineral densitometry (BMD), and urinary tract and neck ultrasonography were assessed. RESULTS: In the study group, 66 (51.6%) patients had vitamin D deficiency and 60 (48.4%) had normal vitamin D levels. Nephrolithiasis and osteoporosis were found in 26.6% and 30.5% of subjects, respectively. The prevalence of metabolic syndrome (MetS), obesity (BMI≥30kg/m2) and hypertension (HTN) were higher in the vitamin D deficient group when compared to the normal group (p=0.04, p=0.01 and p=0.03, respectively). There was no difference regarding the presence of nephrolithiasis and osteoporosis between the groups. The mean adenoma size was similar in both groups. CONCLUSIONS: Vitamin D deficiency was not associated with osteoporosis, nephrolithiasis, adenoma size or biochemical parameters in PHPT. However, vitamin D deficiency may be a risk factor for developing HTN and MetS in PHPT.

Risk Factors and Preventive Strategies for Perioperative Distal Femoral Fracture in Patients Undergoing Total Knee Arthroplasty.

Background and Objectives Perioperative distal femoral fracture is rare in patients undergoing total knee arthroplasty (TKA). In such rare cases, additional fixation might be required, and recovery can be delayed. Several studies have focused on perioperative distal femoral fractures in TKA, but there remains a lack of information on risk factors. The purpose of this study was to investigate risk factors for perioperative distal femoral fractures in patients undergoing TKA and suggest preventive strategies. Materials and Methods: This retrospective study included a total of 5364 TKA cases in a single institution from 2011 to 2022. Twenty-four distal femoral fractures occurred during TKA or within one month postoperatively (0.45%). Patient demographics, intraoperative findings, and postoperative progress were obtained from patient medical records and radiographs. Risk factors for fractures were analyzed using multivariate Firth logistic regression analysis. Results: Although all 24 distal femoral fractures occurred in female patients (24 of 4819 patients, 0.50%), the incidence rate of fracture between male and female patients was not significantly different (p = 0.165). The presence of osteoporosis and insertion of a polyethylene (PE) insert with knee dislocation were statistically significant risk factors (p = 0.009 and p = 0.046, respectively). However, multivariate logistic regression analysis showed that only osteoporosis with bone mineral density (BMD) < -2.8 (odds ratio (2.30), 95% CI (1.03-5.54), p = 0.043) was an independent risk factor for perioperative distal femoral fracture in TKA patients. Conclusions: Our results suggest that osteoporosis with BMD < -2.8 is a risk factor for distal femoral fractures in patients undergoing TKA. In these patients, careful bone cutting, adequate gap balancing, and especially the use of the sliding method for insertion of a PE insert are recommended as preventive strategies.

Probucol suppresses osteoclastogenesis via activating Nrf2 signaling and ameliorates ovariectomy-induced bone loss.

Osteoporosis is a systemic and endocrine bone disorder distinguished by declined bone mineral density, compromised bone strength, and destruction of trabecular structure. The abnormally excessive osteoclastogenesis and bone erosion play imperative roles in the progression of osteoporosis. However, treatment of osteoporosis is far from satisfactory due to poor adherence to existing medications and adverse reactions, there is an urgent to develop novel therapies for osteoporosis. Probucol, a synthetic compound with two characteristic phenolic rings, owns anti-inflammatory and antioxidant properties. Accumulating evidence have indicated that intracellular reactive oxygen species (ROS) is closely related to osteoclastogenesis. Hence, we investigated the potential effects of probucol on osteoclastogenesis in vivo and in vitro. In this study, TRAP staining and bone slice resorption assay showed that probucol suppressed RANKL-induced osteoclast formation and function. The mRNA and protein levels of osteoclastogenesis marker genes were reduced by probucol in a concentration-dependent manner. Besides, probucol suppressed osteoclast differentiation by inhibiting ROS production, MAPKs and NF-κB signaling pathways, while Nrf2 silencing reversed the inhibitory effect of probucol on osteoclast formation and function. Consistent with the above findings, in vivo experiments demonstrated that probucol visibly alleviated bone loss caused by estrogen deficiency. In brief, these results showed the potential of anti-oxidant compound probucol in the treatment of osteoporosis, highlighting Nrf2 as a promising target in osteoclast-related disease.

Effect of Menaquinone-4 on Receptor Activator of Nuclear Factor κB Ligand-Induced Osteoclast Differentiation and Ovariectomy-Induced Bone Loss.

Osteoporosis is a progressive metabolic disease characterized by decreased bone mineral density and increased fracture risk. Previous studies have shown that higher intake of vitamin K (VK) correlates with a reduced risk of osteoporosis. However, the effect of menaquinone-4 (MK-4), a specific form of VK, still remains obscure. Therefore, in this study, we investigated the effects of MK-4 on osteoclast differentiation by differentiating RAW 264.7 cells into osteoclasts with the help of receptor activator of nuclear factor-kappa B ligand (RANKL), assessed the mRNA expression of osteoclast-specific genes, and studied the effects of MK-4 in vivo in ovariectomized mice, a postmenopausal osteoporosis murine model. MK-4 inhibited osteoclast differentiation, decreased the mRNA expression of nuclear factor of activated T cells c1 (NFATc1), osteoclast-associated receptor (OSCAR), and cathepsin K (CTSK), and inhibited bone loss in ovariectomized mice. The findings strongly suggest that MK-4 is a therapeutic alternative for postmenopausal osteoporosis.

MRL/MpJ Mice Resist to Age-Related and Long-Term Ovariectomy-Induced Bone Loss: Implications for Bone Regeneration and Repair.

Osteoporosis and age-related bone loss increase bone fracture risk and impair bone healing. The need for identifying new factors to prevent or treat bone loss is critical. Previously, we reported that young MRL/MpJ mice have superior bone microarchitecture and biomechanical properties as compared to wild-type (WT) mice. In this study, MRL/MpJ mice were tested for resistance to age-related and long-term ovariectomy-induced bone loss to uncover potential beneficial factors for bone regeneration and repair. Bone tissues collected from 14-month-old MRL/MpJ and C57BL/6J (WT) mice were analyzed using micro-CT, histology, and immunohistochemistry, and serum protein markers were characterized using ELISAs or multiplex assays. Furthermore, 4-month-old MRL/MpJ and WT mice were subjected to ovariectomy (OV) or sham surgery and bone loss was monitored continuously using micro-CT at 1, 2, 4, and 6 months (M) after surgery with histology and immunohistochemistry performed at 6 M post-surgery. Sera were collected for biomarker detection using ELISA and multiplex assays at 6 M after surgery. Our results indicated that MRL/MpJ mice maintained better bone microarchitecture and higher bone mass than WT mice during aging and long-term ovariectomy. This resistance of bone loss observed in MRL/MpJ mice correlated with the maintenance of higher OSX+ osteoprogenitor cell pools, higher activation of the pSMAD5 signaling pathway, more PCNA+ cells, and a lower number of osteoclasts. Systemically, lower serum RANKL and DKK1 with higher serum IGF1 and OPG in MRL/MpJ mice relative to WT mice may also contribute to the maintenance of higher bone microarchitecture during aging and less severe bone loss after long-term ovariectomy. These findings may be used to develop therapeutic approaches to maintain bone mass and improve bone regeneration and repair due to injury, disease, and aging.

Bone loss in chronic liver diseases: Could healthy liver be a requirement for good bone health?

Given that the liver is involved in many metabolic mechanisms, it is not surprising that chronic liver disease (CLD) could have numerous complications. Secondary osteoporosis and increased bone fragility are frequently overlooked complications in CLD patients. Previous studies implied that up to one-third of these individuals meet diagnostic criteria for osteopenia or osteoporosis. Recent publications indicated that CLD-induced bone fragility depends on the etiology, duration, and stage of liver disease. Therefore, the increased fracture risk in CLD patients puts a severe socioeconomic burden on the health system and urgently requires more effective prevention, diagnosis, and treatment measures. The pathogenesis of CLD-induced bone loss is multifactorial and still insufficiently understood, especially considering the relative impact of increased bone resorption and reduced bone formation in these individuals. It is essential to note that inconsistent findings regarding bone mineral density measurement were previously reported in these individuals. Bone mineral density is widely used as the "golden standard" in the clinical assessment of bone fragility although it is not adequate to predict individual fracture risk. Therefore, microscale bone alterations (bone microstructure, mechanical properties, and cellular indices) were analyzed in CLD individuals. These studies further support the thesis that bone strength could be compromised in CLD individuals, implying that an individualized approach to fracture risk assessment and subsequent therapy is necessary for CLD patients. However, more well-designed studies are required to solve the bone fragility puzzle in CLD patients.

Risk factors associated with low bone mineral density in children with idiopathic scoliosis: a scoping review.

BACKGROUND: Children with idiopathic scoliosis (IS) have a high risk of osteoporosis and IS with low bone mineral density (BMD) are susceptible to curve progression. This review aims to explore the risk factors of low BMD in children with IS. METHODS: Studies were retrieved from 5 databases that were published up to January 2022. Search terms are keywords in titles or abstracts, including subject headings related to "Scoliosis", "Bone Mineral Density", and "Risk Factors". Observational studies on risk factors of low BMD in children with IS were enrolled in this review. The number of studies, sample size, outcome measures, research type, endocrine, and lifestyle-related factors, gene/signal pathway, and other contents were extracted for qualitative analysis. RESULTS: A total of 56 studies were included in this scoping review. Thirty studies involved genetic factors that may affect BMD, including the Vitamin-D receptor gene, RANK/RANKL signal pathway, the function of mesenchymal stem cells, Runx2, Interleukin-6 (IL-6), and miR-145/ß-catenin pathway. Eight studies mentioned the influence of endocrine factors on BMD, and the results showed that serum levels of IL-6, leptin and its metabolites, and ghrelin in children with IS were different from the age-matched controls. In addition, there were 18 articles on lifestyle-related factors related to low BMD in children with IS, consisting of physical activity, calcium intake, Vitamin D level, and body composition. CONCLUSIONS: Genetic, endocrine, and lifestyle-related factors might relate to low BMD and even osteoporosis in IS. To prevent osteoporosis, the effectiveness of regular screening for low BMD risk factors in children with IS needs to be investigated. Additionally, clear risk factors suggest strategies for bone intervention. Future studies should consider the effectiveness of calcium and vitamin D supplements and physical activity in BMD improvement.

Association of hepatic/pancreatic iron overload evaluated by quantitative T2* MRI with bone mineral density and trabecular bone score.

BACKGROUND: Iron-overloaded patients are recognized as presenting an increased risk of osteoporosis. However, studies on the correlation between osteoporosis and organ iron overload are controversial or scarce. The aim of this study is to assess bone mineral density (BMD) and trabecular bone score (TBS) in correlation with hepatic and pancreatic iron overload. METHODS: Forty-one patients diagnosed with hemoglobinopathies, were studied. BMDs of the lumbar spine (LS), femoral neck (FN), and total hip (TH) were analyzed by Dual-energy X-ray absorptiometry (DXA) scan. LS bone quality was derived from each spine DXA examination using the TBS analysis. Hepatic and pancreatic iron overload were obtained with a multi-echo gradient echo T2* technique. RESULTS: Abnormal microarchitecture and abnormal bone mass were observed in 19/41 (46.3%) and 9/41 (22.0%) patients, respectively. For 26 males, BMD, T-score and Z-score of LS were significantly lower among subjects with moderate-severe hepatic iron-overload than their counterparts, as it is between no- and pancreatic iron-overload groups. For 15 females, patients with moderate-severe hepatic iron-overload had significantly lower BMD and T-score of FN and TH, and patients with pancreatic iron-overload had significantly lower BMD, T-score of FN, and lower BMD, T-score and Z-score of TH than their counterparts. Moreover, pancreatic T2*-value was positively correlated with BMD and T-score at all analyzed sites and Z-score at TH. CONCLUSION: These data showed lower bone mass in patients with organ iron overload, particularly for LS in males, FN and TH in females. TBS may well represent a complementary tool for the evaluation of bone quality and the risk of fracture in iron-overloaded patients.

Prevalence of osteoporosis in patients with diabetes mellitus: a systematic review and meta-analysis of observational studies.

BACKGROUND: Osteoporosis (OP) and diabetes mellitus (DM) are two major healthcare issues in the world. Numerous population based-studies have reported an increased prevalence of OP among individuals with DM, though, estimates vary significantly. PURPOSE: The objective of this study is to estimate the prevalence of OP in patients with DM. METHODS: To identify relevant literature, PubMed, Embase, Medline, CBM and Cochrane Library were searched for studies published from inception till July 2022, The search was conducted, and studies were included without countries and language restrictions. For full-text articles included in the study, the references were also independently searched. Random inverse variance-weighted models were used by Stata version 17.0 to estimate the prevalence of OP in patients with diabetes across studies. The heterogeneity was examined with I2 via the χ2 test on Cochrane's Q statistic. Subgroup analysis and meta-regression were used to explore potential sources of heterogeneity. Egger's test was used to assess publication bias. RESULTS: A high OP prevalence of 27.67% (95% confidence interval (CI) 21.37-33.98%) was found in a pooled analysis of 21 studies involving 11,603 T2DM patients. Methodological value of the included articles was high, with only three medium-quality studies and no low-quality studies. A significantly high heterogeneity (I2 = 98.5%) was observed. CONCLUSIONS: Worldwide, a high prevalence of OP was found in patients with T2DM. Therefore, strong measures to prevent and treat osteoporosis in diabetic patients are required. TRIAL REGISTRATION: This study has been registered on PROSPERO, number CRD42021286580 .

[Osteoporosis: what's new in 2022]. / Ostéoporose : ce qui a changé en 2022.

The year 2022 has seen numerous studies: questioning the usefulness of vitamin D, the effect of osteoporosis treatments on mortality, and the benefit of parathyroidectomy on fractures in primary hyperparathyroidism. The efficacy of romosozumab is diminished by the treatments prescribed before its introduction. Finally, and fortunately, promising new molecules are available in various countries for the treatment of rare bone diseases.

L'année 2022 a vu de nombreuses études questionner l'utilité de la vitamine D et s'intéresser à l'effet des traitements de l'ostéoporose sur la mortalité ou encore au bénéfice de la parathyroïdectomie sur les fractures lors d'hyperparathyroïdie primaire. L'efficacité du romosozumab est diminuée selon les traitements prescrits avant son introduction. Finalement, et heureusement, de nouvelles molécules prometteuses sont disponibles dans différents pays pour le traitement des maladies osseuses rares.

The Possible Role of Electrical Stimulation in Osteoporosis: A Narrative Review.

Osteoporosis is mainly a geriatric disease with a high incidence, and the resulting spinal fractures and hip fractures cause great harm to patients. Anti-osteoporosis drugs are the main treatment for osteoporosis currently, but these drugs have potential clinical limitations and side effects, so the development of new therapies is of great significance to patients with osteoporosis. Electrical stimulation therapy mainly includes pulsed electromagnetic fields (PEMF), direct current (DC), and capacitive coupling (CC). Meanwhile, electrical stimulation therapy is clinically convenient without side effects. In recent years, many researchers have explored the use of electrical stimulation therapy for osteoporosis. Based on this, the role of electrical stimulation therapy in osteoporosis was summarized. In the future, electrical stimulation might become a new treatment for osteoporosis.

Does resveratrol favor peri-implant bone repair in rats with ovariectomy-induced osteoporosis? Gene expression, counter-torque and micro-CT analysis.

This study investigated the influence of resveratrol on peri-implant repair and its effects on bone-related markers in ovariectomy-induced osteoporosis in rats. Animals were divided into: OVX+PLAC (n = 10): ovariectomized animals treated with placebo; OVX+RESV (n = 10): OVX treated with resveratrol; OVX+PLAC+ZOL (n = 10): OVX treated with PLAC and zoledronate; OVX+RESV+ZOL (n = 10): OVX treated with RESV and ZOL; and SHOVX+PLAC (n = 10): sham ovariectomy treated with PLAC. RESV and PLAC were administrated after ovariectomy and ZOL after six weeks after OVX, until the end of experiment. One implant was inserted in each tibiae of animals 18 weeks after ovariectomy. After 4 weeks, one implant was removed for counter-torque, and peri-implant tissue was collected for mRNA quantification of several osteogenic markers by PCR. The other tibia was submitted to micro-computed tomography analysis. Reduced counter-torque values, bone-implant contact (BIC) and bone volume fraction (BV/TV), and higher bone porosity (BP) were detected in OVX+PLAC group when compared to SHOVX+PLAC (p < 0.05). OVX+RESV rats presented lower BIC, BV/TV, and trabecular number (Tb.N), and augmented BP and trabecular spacing (Tb.Sp) when compared to SHOVX+PLAC (p < 0.05). Higher Tb.N and connectivity density (Conn.Dn) and reduced Tb.Sp were observed in OVX rats treated with ZOL, independently of RESV, when compared to OVX+PLAC and OVX+RESV groups (p < 0.05), whereas the combination ZOL+RESV promoted lower BP when compared to OVT+PLAC and OVX+RESV (p < 0.05). Gene expression was not influenced by RESV (p > 0.05), whereas ZOL promoted up-regulation of BMP-2 (p<0.05). RESV did not improve peri-implant bone repair in rats with ovariectomy-induced osteoporosis.

Aging and Bone Metabolism.

Changes in bone architecture and metabolism with aging increase the likelihood of osteoporosis and fracture. Age-onset osteoporosis is multifactorial, with contributory extrinsic and intrinsic factors including certain medical problems, specific prescription drugs, estrogen loss, secondary hyperparathyroidism, microenvironmental and cellular alterations in bone tissue, and mechanical unloading or immobilization. At the histological level, there are changes in trabecular and cortical bone as well as marrow cellularity, lineage switching of mesenchymal stem cells to an adipogenic fate, inadequate transduction of signals during skeletal loading, and predisposition toward senescent cell accumulation with production of a senescence-associated secretory phenotype. Cumulatively, these changes result in bone remodeling abnormalities that over time cause net bone loss typically seen in older adults. Age-related osteoporosis is a geriatric syndrome due to the multiple etiologies that converge upon the skeleton to produce the ultimate phenotypic changes that manifest as bone fragility. Bone tissue is dynamic but with tendencies toward poor osteoblastic bone formation and relative osteoclastic bone resorption with aging. Interactions with other aging physiologic systems, such as muscle, may also confer detrimental effects on the aging skeleton. Conversely, individuals who maintain their BMD experience a lower risk of fractures, disability, and mortality, suggesting that this phenotype may be a marker of successful aging. © 2023 American Physiological Society. Compr Physiol 13:4355-4386, 2023.

25-Hydroxycholesterol-induced Osteoblast Oxiapoptophagy Is Involved in the Pathophysiological Process of Osteoporosis.

BACKGROUND/AIM: 25-hydroxycholesterol (25-HC) plays important roles in lipid metabolism, inflammatory responses, and apoptosis, but its pathophysiological association with osteoporosis (OP) has not been verified in osteoblasts. Hence, we studied the pathophysiological linkage and underlying cellular mechanisms of 25-HC in human osteoblast-like MG-63 cells and an ovariectomy-induced osteoporotic mouse model. MATERIALS AND METHODS: To investigate the pathophysiological linkage between 25-HC-induced osteoblast oxiapoptophagy and OP, 25-HC ELISA assay, MTT assay, cell live/dead staining, hematoxylin and eosin staining, DAPI staining, flow cytometry analysis, western blot, caspase-3 staining, reactive oxygen species (ROS) assay, autophagy staining, immunocytochemistry, Micro-CT image analysis and immunocytochemistry were performed in MG-63 cells and ovariectomy-induced OP animals. RESULTS: The expression of cholesterol-25-hydroxylase (CH25H), an enzyme catalyzing the conversion of cholesterol to 25-HC, and the production of 25-HC were increased by lipopolysaccharide in MG-63 cells. Cytotoxicity was increased by 25-HC in MG-63 cells. Apoptosis with condensed chromatin and altered morphology was induced by 25-HC through cleavage of caspases-8, -9, and -3 in MG-63 cells. 25-HC induced oxidative stress in MG-63 cells via elevation of ROS production, cyclooxygenase-2, and inducible nitric oxide synthase. Furthermore, the expression of autophagy biomarkers, including beclin-1 and microtubule-associated protein 1A/1B-light chain 3, was elevated by 25-HC in MG-63 cells. In addition, p53 expression was increased, whereas Akt phosphorylation was suppressed in 25-HC-incubated MG-63 cells. The expression of CH25H, cleaved caspase-3, and beclin-1 were up-regulated in the femoral bone of ovariectomy-induced mouse osteoporotic animals. CONCLUSION: 25-HC plays a role in OP via the induction of oxiapoptophagic osteoblast death.

The Effect of Ceratonia siliqua Supplement on Bone Mineral Density in Ovariectomy-induced Osteoporosis in Rats.

AIM: This study aimed to investigate the effect of Ceratonia siliqua on bone mineral density (BMD) as a non-pharmaceutical alternative treatment for postmenopausal osteoporosis. MATERIALS AND METHODS: Thirty mature female Wistar rats were randomly separated into three groups of 10: Control, ovariectomized (OVX), and ovariectomized-plus-C. siliqua (OVX+CS). Total and proximal BMD were measured by dual-energy X-ray absorptiometry (DEXA) in all groups before ovariectomy, and at 3 and 6 months postoperatively. At the end of the study, the femurs were subjected to a three-point bending test. RESULTS: DEXA revealed no statistically significant difference in absolute values or percentage changes for total tibial BMD between OVX+CS and OVX groups throughout the study. In the proximal tibia, both absolute values and BMD percentage changes from baseline were higher in the OVX+CS group compared to the OVX group after 3 and 6 months of C. siliqua administration. Three-point bending test revealed a significantly higher thickness index in the OVX+CS group compared to the OVX group and a higher cross-sectional area index compared to the control group. CONCLUSION: Long-term administration of C. siliqua may be considered a non-pharmaceutical alternative treatment for postmenopausal osteoporosis. Further research is required to properly investigate the effects, and suitable treatment dose and schedule.

The Association of Beta-Blocker Use and Bone Mineral Density Level in Hemodialysis Patients: A Cross-Sectional Study.

Background and Objectives: Osteoporosis results in increasing morbidity and mortality in hemodialysis patients. The medication for treatment has been limited. There is evidence that beta-blockers could increase bone mineral density (BMD) and reduce the risk of fracture in non-dialysis patients, however, a study in hemodialysis patients has not been conducted. This study aims to determine the association between beta-blocker use and bone mineral density level in hemodialysis patients. Materials and Methods: We conducted a cross-sectional study in hemodialysis patients at Thammasat University Hospital from January 2018 to December 2020. A patient receiving a beta-blocker ≥ 20 weeks was defined as a beta-blocker user. The association between beta-blocker use and BMD levels was determined by univariate and multivariate linear regression analysis. Results: Of the 128 patients receiving hemodialysis, 71 were beta-blocker users and 57 were non-beta-blocker users (control group). The incidence of osteoporosis in hemodialysis patients was 50%. There was no significant difference in the median BMD between the control and the beta-blocker groups of the lumbar spine (0.93 vs. 0.91, p = 0.88), femoral neck (0.59 vs. 0.57, p = 0.21), total hip (0.73 vs. 0.70, p = 0.38), and 1/3 radius (0.68 vs. 0.64, p = 0.40). The univariate and multivariate linear regression analyses showed that the beta-blocker used was not associated with BMD. In the subgroup analysis, the beta-1 selective blocker used was associated with lower BMD of the femoral neck but not within the total spine, total hip, and 1/3 radius. The multivariate logistic regression showed that the factors of age ≥ 65 years (aOR 3.31 (1.25−8.80), p = 0.02), female sex (aOR 4.13 (1.68−10.14), p = 0.002), lower BMI (aOR 0.89 (0.81−0.98), p = 0.02), and ALP > 120 U/L (aOR 3.88 (1.33−11.32), p = 0.01) were independently associated with osteoporosis in hemodialysis patients. Conclusions: In hemodialysis patients, beta-blocker use was not associated with BMD levels, however a beta-1 selective blocker used was associated with lower BMD in the femoral neck.