Bone Microarchitecture Research Articles

Influence of Osteoporosis on the Course of Apical Periodontitis.

Osteoporosis is a disease characterized by disruption of the bone microarchitecture. It is observed in both sexes, but to a greater extent in women. It affects the whole body, including the jaws. The main indicator of the presence of osteoporosis accepted by the World Health Organization is bone mineral density. The aim of this article is to find data on the influence of osteoporosis on apical periodontitis, to investigate how the intake of osteoporosis drugs affects apical periodontitis, and to establish various data that may be of benefit to the dental practitioner when treating patients with osteoporosis and apical periodontitis. Open-access publications are included. The presence of osteoporosis is important to the dentist. Apical periodontitis in these patients has a faster progression. They are characterized by inflammation and destruction of the tissues located around the tooth root. Osteoporosis has a destructive effect on bone tissue through different mechanisms: nuclear factor-κβ ligand and NLRP3/Caspase-1/IL-1β cascade. It is also associated with low estrogen levels. Various medications such as corticosteroids, bisphosphonates (alendronate, zoledronate (Zoledronic acid), calcitonin, raloxifene, and strontium used to treat osteoporosis can affect the course of apical periodontitis. When treating patients with periapical lesions, the dentist must take a proper medical history and general medical history. In cases of osteoporosis or taking bisphosphonates and other medications, consideration should be given to whether consultation with a specialist is necessary, what treatment approach would be most appropriate, and what the prognosis will be. Chronic diseases affect both the general state of the body and dental health. It has been found that in patients with osteoporosis, inflammation of the apical periodontium develops with faster bone resorption. Before starting dental treatment, it is important to specify the etiology of osteoporosis, the bone density of each patient, as well as the medications they are taking.

Role and mechanism of Actein on condylar bone metabolism in APOE deletion-induced osteoporotic mice

AimsTo investigate the effects of Actein from Cimicifugae Rhizoma on condylar bone and cartilage in APOE deletion-induced osteoporotic mice, and to preliminarily explore the underlying mechanism. MethodsSixty 8-week-old female mice were used, which underwent APOE−/− and ovariectomy procedures, followed by oral administration of Actein (15 mg/kg) and Atorvastatin Calcium (AC, 3 mg/kg) for eight weeks. Body weight, uterine weight, and systemic indexes related to bone metabolism and lipid metabolism were assessed in each group. Changes in condylar bone histomorphometric parameters were evaluated using Micro-CT. Morphological changes in the condyle were observed with Hematoxylin-Eosin (H&E), Safranin O/Fast Green, and Alcian Blue Hematoxylin/Orange G (ABH/OG) staining, with OARSI pathology scoring performed. Sirius red staining and immunofluorescence were used to determine the expression levels of Collagen I (Col I) and Collagen III (Col III) in bone matrix, and Col II in cartilage matrix. Immunohistochemistry assessed the relative expression levels of ALP and proteins associated with the Wnt/β-catenin/RUNX2 signaling pathway. ResultsAPOE−/− exacerbates ovariectomy -induced osteoporosis (OP) in condylar of mice. Actein and AC significantly reversed OP, improved bone mineral density (BMD), increased bone microarchitecture, and restored abnormal calcium and phosphorus metabolism in the blood and urine. Morphologically, APOE−/− and ovariectomy reduced condylar cartilage thickness, disrupted chondrocyte arrangement, chondrocyte cleavage, and clustered aggregation, resembling osteoarthritis (OA)-like changes. Actein and AC partially restored the disrupted chondrocyte arrangement, smoothed chondrocyte cleavage, and up-regulated the levels of chondrocyte matrix (Col II, aggrecan) and bone matrix (Col III, ALP). Actein reversed the OA process, potentially through the Wnt/β-catenin/RUNX2 signaling pathway. ConclusionAPOE−/− and ovariectomy induced OP, leading to OA-like lesions in condylar of mice. Actein promoted cartilage repair and trabecular bone recovery by increasing extracellular matrix synthesis (Col II, Col III, aggrecan), reversing the OA process, possibly through the Wnt/β-catenin/RUNX2 signaling pathway.

Bazi Bushen attenuates osteoporosis in SAMP6 mice by regulating PI3K-AKT and apoptosis pathways.

Osteoporosis (OP), a systemic skeletal disease, is characterized by low bone mass, bone tissue degradation and bone microarchitecture disturbance. Bazi Bushen, a Chinese patented medicine, has been demonstrated to be effective in attenuating OP, but the pharmacological mechanism remains predominantly unclear. In this study, the senescence-accelerated mouse prone 6 (SAMP6) model was used to explore bone homeostasis and treated intragastrically for 9 weeks with Bazi Bushen. Invivo experiments showed that Bazi Bushen treatment not only upregulated the levels of bone mineral density and bone mineral content but also increased the content of RUNX2 and OSX. Furthermore, the primary culture of bone mesenchymal stem cells (BMSCs) in SAMP6 mice was used to verify the effects of Bazi Bushen on the balance of differentiation between osteoblasts and adipocytes, as well as ROS and aging levels. Finally, the pharmacological mechanism of Bazi Bushen in attenuating OP was investigated through network pharmacology and experimental verification, and we found that Bazi Bushen could significantly orchestrate bone homeostasis and attenuate the progression of OP by stimulating PI3K-Akt and inhibiting apoptosis. In summary, our work sheds light on the first evidence that Bazi Bushen attenuates OP by regulating PI3K-AKT and apoptosis pathways to orchestrate bone homeostasis.

MORPHOLOGICAL CHANGES IN OSTEOPOROTIC BONES: A COMPARATIVE ANALYSIS USING BIOCHEMICAL AND IMAGING METHODS

Osteoporosis leads to significant bone mass loss and structural deterioration, increasing fracture risk. Objective: This study explores the morphological changes in osteoporotic bones through a comparative analysis using biochemical markers and imaging techniques. Methods: A cohort of 55 osteoporotic patients underwent evaluation. Biochemical markers were measured, including serum calcium, phosphorus, alkaline phosphatase, and vitamin D. Imaging assessments involved dual-energy X-ray absorptiometry (DEXA) for bone mineral density (BMD) and high-resolution computed tomography (HRCT) for bone microarchitecture analysis. Correlations between biochemical data and imaging results were examined. Results: Biochemical analysis showed elevated alkaline phosphatase levels (mean: 210 IU/L) and widespread vitamin D deficiency (mean: 16 ng/mL). DEXA revealed significant reductions in BMD (mean T-score: -3.2), while HRCT detected substantial trabecular thinning (mean trabecular thickness: 0.12 mm) and increased cortical porosity. A strong inverse correlation (r = -0.75, p < 0.01) between BMD and alkaline phosphatase was observed, indicating a link between high bone turnover and reduced density. Vitamin D deficiency correlated with greater cortical porosity (r = 0.60, p < 0.05). Conclusion: The study highlights that integrating biochemical markers and imaging methods provides a comprehensive understanding of osteoporotic bone morphology. These findings emphasize the need for multi-modal diagnostic approaches to enhance osteoporosis management and fracture risk assessment.

Early-Onset Osteoporosis: Molecular Analysis in Large Cohort and Focus on the PLS3 Gene.

Osteoporosis is a skeletal disorder characterized by abnormal bone microarchitecture and low bone mineral density (BMD), responsible for an increased risk of fractures and skeletal fragility. It is a common pathology of the aging population. However, when osteoporosis occurs in children or young adults, it strongly suggests an underlying genetic etiology. Over the past two decades, several genes have been identified as responsible for this particular kind of considered monogenic early-onset osteoporosis (EOOP) or juvenile osteoporosis, the main ones being COL1A1, COL1A2, LRP5, LRP6, WNT1, and more recently PLS3. In this study, the objective was to characterize a large cohort of patients diagnosed with primary osteoporosis and to establish its diagnosis yield. The study included 577 patients diagnosed with primary osteoporosis and its diagnosis yield was established. To this end, next-generation sequencing (NGS) of a panel of 21 genes known to play a role in bone fragility was carried out. A genetic etiology was explained in about 18% of cases, while the others remain unexplained. The most frequently identified gene associated with EOOP is LRP5, which was responsible for 8.2% of the positive results (47 patients). As unexpected, 17 patients (2.9%) had a variant in PLS3 which encodes plastin 3. Alterations of PLS3 are associated with dominant X-linked osteoporosis, an extremely rare disease. Given the rarity of this disease, we focused on it. It was observed that males were more affected than females, but it is noteworthy that three females with a particularly severe phenotype were identified. Of these three, two had a variant in an additional gene involved in EOP, illustrating the probable existence of digenism. We significantly increase the number of variants potentially associated with EOOP, especially in PLS3. The results of our study demonstrate that molecular analysis in EOOP is beneficial and useful.

Fractal Dimension and Lacunarity Analysis in the Dentulous and Edentulous Mandibular Posterior Region Using Cone-beam Computed Tomography: A Cross-sectional Retrospective Study.

This cross-sectional retrospective study was conducted to assess the differences in the microarchitecture of the trabecular bone of the posterior mandibular region at dentulous and edentulous sites with the help of fractal dimension (FD) and lacunarity using cone-beam computed tomography (CBCT). Ninety CBCT scans were analyzed for the purpose of the present study. Inclusion criteria included subjects with unilaterally missing mandibular molars or premolars and an with intact contralateral opposing tooth. The coronal view of the dentulous and edentulous sites was used, and the region of interest (ROI) was selected 2.6 mm below the apex of the tooth present. These images were then transferred to ImageJ Software, and fractal analysis was done using the box-counting method of the FracLac plug-in. A paired samples t-test was performed to compare the means of FD and lacunarity, and a Kendall correlation was performed to check correlations. A p-value less than 0.05 was considered to indicate statistical significance. Statistical analysis revealed that the mean FD of the edentulous side was significantly greater than that of the dentulous side (p-value = 0.011). Additionally, the mean lacunarity of the edentulous side was marginally significantly greater than that of the dentulous side (p-value = 0.089). A significant negative correlation was detected between the FD and lacunarity of the edentulous region (p-value = 0.017), and a marginally significant negative correlation was detected between edentulous lacunarity and dentulous lacunarity (p-value = 0.081). The differences in occlusal forces exerted in dentulous and edentulous regions can lead to a change in the trabecular pattern of the bone in these regions. This change in the microarchitecture of bones can be detected by FD and lacunarity, which can further help us assess changes pre- and post-implant. The advanced technology, the assessment of microarchitecture of the bone has been made easy, using FD and lacunarity, as done in the present study. This analysis can further aid us in both pre- and post-implant analysis to prevent failure of the implant. How to cite this article: Bhoraskar M, Denny C, Srikant N, et al. Fractal Dimension and Lacunarity Analysis in the Dentulous and Edentulous Mandibular Posterior Region Using Cone-beam Computed Tomography: A Cross-sectional Retrospective Study. J Contemp Dent Pract 2024;25(6):581-587.

Beyond T-Trials, T4DM and TRAVERSE: the next large testosterone randomized controlled trial.

Lower testosterone concentrations have been associated with poorer health outcomes in ageing men, but proving causality and demonstrating potential for therapeutic benefit requires randomized clinical trials (RCTs). This review discusses recent observational findings and results of major testosterone RCTs, to explore the need for another, larger trial. Evidence of Leydig cell impairment emerges in men above the age of 70 years. Lower testosterone is associated with diabetes risk, and also risk of incident dementia. An individual participant data meta-analysis found that below thresholds of testosterone of 7.4 nmol/L and 5.3 nmol/l respectively, risks of all-cause mortality and cardiovascular deaths in men increased. Testosterone for the Prevention of Type 2 Diabetes Mellitus (T4DM), a multicentre RCT, showed that testosterone treatment prevented or reverted type 2 diabetes in men at high risk. Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE), a cardiovascular safety trial, demonstrated cardiovascular and prostate safety of testosterone treatment in men with or at risk of cardiovascular disease. T4DM confirmed findings from the Testosterone Trials (T-Trials) that testosterone improved sexual function, and bone microarchitecture and density. However, in TRAVERSE, testosterone-treated men had a higher risk of clinical bone fractures, but not major osteoporotic fractures. Men with disorders of the hypothalamic-pituitary-testicular (HPT) axis causing androgen deficiency warrant consideration for testosterone therapy. In men with an intact HPT axis, testosterone treatment is a pharmacological intervention which requires justification from high quality RCT data. Currently, there is insufficient evidence to justify wider use of testosterone for prevention of cardiometabolic disease. However, there is scope for another large testosterone RCT to investigate whether testosterone treatment might, in older men, extend disability-free survival.

Psoas muscle cross sectional area relates to bone density and microarchitecture in candidates for spine fusion surgery

Prior studies demonstrate that muscle and bone health are integrally related, and both independently impact orthopedic surgery outcomes. However, relationships between bone density, in vivo microarchitecture, and muscle area have not been previously investigated in orthopedic surgery patients. This study assessed associations between psoas cross sectional area (CSA), bone mineral density (BMD), and microstructure in a cohort undergoing spine fusion. Pre-operatively, bilateral psoas CSA was measured on axial lumbar spine CT in the L3-L4 disc space. To adjust for body size, Psoas Muscle Index (PMI) was calculated (CSA divided by the square of patient height). High resolution peripheral quantitative CT (HR-pQCT, XtremeCT2) assessed volumetric BMD (vBMD), cortical (Ct) and trabecular (Tb) microarchitecture at the distal radius and tibia. Areal BMD (aBMD) was measured by DXA at the lumbar spine (LS), total hip (TH), femoral neck (FN), and the 1/3 radius (1/3R). Pearson correlations related psoas CSA and bone imaging parameters before and after correcting for height and weight. Among 88 patients included, mean age was 63 ± 12 years, BMI was 28 ± 7 kg/m2, 47 (53 %) were female. Larger psoas CSA was associated with higher vBMD, greater Ct thickness and better Tb microarchitecture (higher Tb number and lower Tb separation) at the tibia and radius. Larger psoas CSA was also associated with greater aBMD at TH and FN bilaterally and 1/3R (r 0.33 to 0.61; p < 0.002 for all comparisons). Psoas CSA was not associated with aBMD at the LS. Similar results were observed when relating PMI, and adjusting for age, height and weight to HR-pQCT and DXA measurements. Investigation of subgroups by sex demonstrated that relationships were similar magnitude among women but not the men. Patients who underwent primary compared to revision spine surgery had similar associations. Our results demonstrate a link between psoas muscle size and peripheral bone microarchitecture among patients undergoing posterior lumbar spinal fusion. Given the importance of both muscle and skeletal integrity to the success of spine surgery, further study regarding the associations between measurements of psoas muscle, bone microarchitecture, and surgical outcomes is warranted.

Increased cancellous bone mass accompanies decreased cortical bone mineral density and higher axial deformation in femurs of leptin-deficient obese mice

IntroductionLeptin is a pleiotropic hormone that regulates food intake and energy homeostasis with enigmatic effects on bone development. It is unclear if leptin promotes or inhibits bone growth. The aim of this study was to characterize the micro-architecture and mechanical competence of femur bones of leptin-deficient mice. Materials and methodsRight femur bones of 15-week old C57BL/6 (n = 9) and leptin-deficient (ob/ob, n = 9) mice were analyzed. Whole bones were scanned using micro-CT and morphometric parameters of the cortex and trabeculae were assessed. Elastic moduli were determined from microindentations in midshaft cross-sections. Mineral densities were determined using quantitative backscatter scanning electron microscopy. 3D models of the distal femur metaphysis, cleared from trabecular bone, were meshed and used for finite element simulations of axial loading to identify straining differences between ob/ob and C57BL/6 controls. ResultsCompared with C57BL/6 controls, ob/ob mice had significantly shorter bones. ob/ob mice showed significantly increased cancellous bone volume and trabecular thickness. qBEI quantified a ∼7% lower mineral density in ob/ob mice in the distal femur metaphysis. Indentation demonstrated a significantly reduced Young's modulus of 12.14 [9.67, 16.56 IQR] GPa for ob/ob mice compared to 23.12 [20.70, 26.57 IQR] GPa in C57BL/6 mice. FEA revealed greater deformation of cortical bone in ob/ob as compared to C57BL/6 mice. ConclusionLeptin deficient ob/ob mice have a softer cortical bone in the distal femur metaphysis but an excessive amount of cancellous bone, possibly as a response to increased deformation of the bones during axial loading. Both FEA and direct X-ray and electron microscopy imaging suggest that the morphology and micro-architecture of ob/ob mice have inferior biomechanical properties suggestive of a reduced mechanical competence.

Intermittent fasting for systemic triglyceride metabolic reprogramming (IFAST): Design and methods of a prospective, randomized, controlled trial

BackgroundCaloric restriction prolongs lifespan in model organisms and improves metrics of aging-related diseases in humans, but daily compliance is challenging. Intermittent fasting improves metrics of lipid and glucose metabolism in the setting of weight loss but whether these metrics are improved independent of weight loss is not known. MethodsWe seek to address this gap with IFAST, a single-center, three-arm, prospective, randomized, controlled clinical trial. Eligible study participants are adults with no chronic medical conditions beyond prediabetes or overweight but who are at high risk for type 2 diabetes mellitus (T2D), defined as having a history of gestational diabetes or a first-degree relative with T2D. Participants will be randomized in a 1:2:2 schema to either a control group, a fasting group, or a fasting/weight maintenance group. The fasting groups will complete a 24-h fast one day per week for 12 weeks. The key mechanistic endpoint is change in triglyceride composition (defined by carbon content and degree of saturation) as measured by longitudinal metabolomics. The key safety endpoint is percent change from baseline in bone volume fraction (BV/TV; high-resolution peripheral quantitative CT) at the radius in the fasting group. Secondary endpoints include measures of insulin sensitivity (hyperinsulinemic-euglycemic clamp), clinical lipid profiling, systemic inflammation markers, hunger assessment, bone density, and bone microarchitecture with high-resolution peripheral quantitative CT. ConclusionIFAST will investigate intrinsic metabolic benefits of intermittent fasting beyond weight loss. Trial registrationClinicalTrials.gov ID NCT05722873.

Resveratrol enhances the protective effects of calcium supplements on spinal cord injury-induced osteoporosis by targeting the SIRT1/FOXO3a pathway.

Spinal cord injury (SCI) often leads to osteoporosis due to factors like immobilization and hormonal imbalances. Calcium supplements are prescribed to help maintain bone health, but their efficacy may be limited. This study investigated whether resveratrol (RSV), a polyphenolic compound, could enhance the protective effects of calcium supplements on SCI-induced osteoporosis via the SIRT1/FOXO3a pathway, which regulates bone metabolism. Surgical cord transection induced SCI at the T9 vertebral level. An SCI mouse model was used with four groups: sham, SCI, SCI + 2% calcium, and SCI + calcium + RSV (20mg/kg body weight). ‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌Biomechanical testing, gene expression, and Western blots were performed. Resveratrol and calcium supplementation synergistically preserved bone mass, microarchitecture, strength, and fracture resistance compared to calcium alone after SCI. This was accompanied by upregulated osteoblast markers, downregulated osteoclast markers, and increased SIRT1/FOXO3a expression and activation. The results suggest resveratrol enhances calcium's bone-protective effects in SCI-induced osteoporosis by modulating the SIRT1/FOXO3a pathway and osteoblast/osteoclast activities. Combining resveratrol with calcium supplementation may be a promising therapeutic approach for managing SCI-induced osteoporosis.

Role of Wnt5a in modulation of osteoporotic adipose-derived stem cells and osteogenesis.

Osteoporosis, a condition marked by the deterioration of bone microarchitecture and increased facture risk, arises from a disruption in bone metabolism, with osteoclasts surpassing osteoblasts in bone resorption versus formation. The Wnt signalling pathway, a key regulator of bone maintenance, remains partially understood in osteoporosis. Our research delves into the role of Wnt-related molecules in this disease. In osteoporotic adipose-derived stem cells (OP-ASCs), we detected a significant decrease in Ctnnb1 and Frizzled-6 (Fzd6), contrasted by an increase in Gsk-3β and Wnt5a. Activation of the Wnt pathway by LiCl resulted in elevated Ctnnb1 and Fzd6, but decreased Gsk-3β and Wnt5a levels, promoting OP-ASCs' bone-formation capacity. In contrast, inhibition of this pathway by DKK-1 led to diminished Ctnnb1 and Fzd6, and increased Gsk-3β and Wnt5a, adversely affecting osteogenesis. Furthermore, our findings show that overexpressing Wnt5a impedes, while silencing it enhances the bone-forming capability of OP-ASCs. In a cranial bone defect model, the implantation of Wnt5a-silenced OP-ASCs with biphasic calcium phosphate scaffolds significantly promoted new bone formation. These observations indicated a repression of the canonical Wnt pathway and a stimulation of the non-canonical pathway in OP-ASCs. Silencing Wnt5a increased the osteogenic and regenerative abilities of OP-ASCs. Our study suggests targeting Wnt5a could be a promising strategy for enhancing bone regeneration in post-menopausal osteoporosis.

Prediction of micro-scale bone adaptation of human trabecular bone under different implanted conditions

Background and objectiveDifferent bone remodeling algorithms are used to predict bone adaptation and to understand how bones respond to the mechanical stimuli altered by implants. This paper introduces a novel micro-scale bone remodeling algorithm, which deviates from conventional methods by focusing on structure-based bone adaptation instead of density-based approaches. MethodsThe proposed model simulated cellular activities such as bone resorption, new bone formation, and maturation of newly formed bone. These activities were assumed to be triggered by mechanical stimuli. Model parameters were evaluated for the 3D geometries of trabecular bone from intact femur developed from micro computed tomography (CT) scan data. Two different hip implants, solid and porous were used, and two different bone remodeling methods were performed using the proposed and conventional methods. ResultsResults showed that micro CT scan-based finite element (FE) models accurately captured the microarchitecture and anisotropy of trabecular bone. The predicted bone resorption rate at the peri-prosthetic regions for the solid and porous implants was in the range of 17–27% and 4.5–7.3%, respectively, for a simulated period of four years. ConclusionsThe results obtained from FE analysis strongly align with clinical findings, confirming the effectiveness of the proposed algorithm. By emphasizing the structural aspect of bone adaptation, the proposed algorithm brings a fresh perspective on bone adaptation at the peri-prosthetic bone. This method can help researchers and clinicians to improve implant designs for better clinical outcomes.

Strategic targeting of miR-183 and β-catenin to enhance BMSC stemness in age-related osteoporosis therapy

Age-related osteoporosis is a prevalent bone metabolic disorder distinguished by an aberration in the equilibrium between bone formation and resorption. The reduction in the stemness of Bone Marrow Mesenchymal Stem Cells (BMSCs) plays a pivotal role in the onset of this ailment. Comprehending the molecular pathways that govern BMSCs stemness is imperative for delineating the etiology of age-related osteoporosis and devising efficacious treatment modalities. The study utilized single-cell RNA sequencing and miRNA sequencing to investigate the cellular heterogeneity and stemness of BMSCs. Through dual-luciferase reporter assays and functional experiments, the regulatory effect of miR-183 on CTNNB1 (β-catenin) was confirmed. Overexpression and knockdown studies were conducted to explore the impact of miR-183 and β-catenin on stemness-related transcription factors Oct4, Nanog, and Sox2. Cell proliferation assays and osteogenic differentiation experiments were carried out to validate the influence of miR-183 and β-catenin on the stemness properties of BMSCs. Single-cell analysis revealed that β-catenin is highly expressed in both high stemness clusters and terminal differentiation clusters of BMSCs. Overexpression of β-catenin upregulated stemness transcription factors, while its suppression had the opposite effect, indicating a dual regulatory role of β-catenin in maintaining BMSCs stemness and promoting bone differentiation. Furthermore, the confluence of miRNA sequencing analyses and predictions from online databases revealed miR-183 as a potential modulator of BMSCs stemness and a novel upstream regulator of β-catenin. The overexpression of miR-183 effectively diminished the stemness characteristics of BMSCs by suppressing β-catenin, whereas the inhibition of miR-183 augmented stemness. These outcomes align with the observed alterations in the expression levels and functional assessments of transcription factors associated with stemness. This study provides evidence for the essential involvement of β-catenin in preserving the stemness of BMSCs, as well as elucidating the molecular mechanism through which miR-183 selectively targets β-catenin to modulate stemness. These results underscore the potential of miR-183 and β-catenin as molecular targets for augmenting the stemness of BMSCs. This strategy is anticipated to facilitate the restoration of bone microarchitecture and facilitate bone tissue regeneration by addressing potential cellular dysfunctions, thereby presenting novel targets and perspectives for the management of age-related osteoporosis.

Changes in bone density and microarchitecture following treatment of Graves' disease and the effects of vitamin D supplementation. A randomized clinical trial.

Vitamin D is important to skeletal health and ensuring a replete vitamin D status is recommended. In thyrotoxicosis, bone turnover is increased and bone mass density (BMD) reduced. We examined whether vitamin D supplementation improves bone recovery in thyrotoxicosis caused by Graves' disease (GD). Using a double-blinded design, hyperthyroid patients with GD were randomized to vitamin D3 70µg/day (2800IU) or similar placebo as add-on to antithyroid drugs (ATD). At baseline and 9months, we measured BMD and bone architecture using DXA and high resolution peripheral quantitative computerized tomography. Bone turnover markers (BTM) were measured at 3months also. Effect of vitamin D versus placebo and the response to ATD treatment were analyzed using linear mixed modelling. Eighty-six GD patients were included (age 41 ± 14years, 86% females). Compared to placebo, vitamin D3 did not improve BMD or microarchitecture. In response to ATD, BMD increased in the hip by 2% (95%CI: 1-4%). Cortical porosity decreased in tibia (- 7% [95%CI: - 12 to - 2%]) and radius [- 14% [95%CI: - 24 to - 3%]), and trabecular thickness increased (tibia (5% [95%CI: 2 - 9%]) and radius (4% [95%CI: 1-7%]). Changes in BTM, but not thyroid hormones, were associated with changes in BMD by DXA and with changes in the cortical compartment. In newly diagnosed GD, 9months of high dose vitamin D3 supplementation does not offer benefit by improving skeletal health. Treatment of thyrotoxicosis is associated with the recovery of BMD and microarchitecture. NCT02384668.

The crucial role of beta-catenin in the osteoprotective effect of semaglutide in an ovariectomized rat model of osteoporosis.

Postmenopausal osteoporosis is a common chronic medical illness resulting from an imbalance between bone resorption and bone formation along with microarchitecture degeneration attributed to estrogen deficiency and often accompanied by other medical conditions such as weight gain, depression, and insomnia. Semaglutide (SEM) is a recently introduced GLP-1 receptor agonist (GLP-1RA) for the treatment of obesity and type 2 diabetes mellitus by mitigating insulin resistance. It has been discovered that the beneficial effects of GLP-1 are associated with alterations in lipolysis, adipogenesis, and anti-inflammatory processes. GLP-1 analogs transmit signals directly to adipose tissue. Mesenchymal stem cells (MSCs) are multidisciplinary cells that originate from bone marrow, migrate to injury sites, and promote bone regeneration. MSCs can differentiate into osteoblasts, adipose cells, and cartilage cells. Our aim is to investigate the role of semaglutide on bone formation and the Wnt signaling pathway. Osteoporosis was induced in female rats by ovariectomy, and the ovariectomized rats were treated with alendronate as standard treatment with a dose of 3mg/kg orally and semaglutide with two doses (150 mcg/kg and 300 mcg/kg) S.C. for 10 successive weeks. Semaglutide ameliorates bone detrimental changes induced by ovariectomy. It improves bone microarchitecture and preserves bone mineral content. Semaglutide ameliorates ovariectomy-induced osteoporosis and increases the expression of β-catenin, leading to increased bone formation and halted receptor activator of nuclear factor kappa-Β ligand (RANKL's) activation. Semaglutide can be used as a potential prophylactic and therapeutic drug against osteoporosis, possibly by activating Wnt signaling and decreasing bone resorption.

Effects of Cannabidiol on Bone Quality in Ovariectomized Rats.

The incidence of osteoporosis and related fractures increases significantly with age, impacting public health and associated costs. Postmenopausal osteoporosis results from increased bone resorption due to decreased estrogen levels. The endocannabinoid system, especially cannabidiol (CBD), has shown therapeutic potential in modulating bone formation. This study investigated the effects of administration of CBD in rats after the onset of with ovariectomy-induced osteopenia (OVX). Forty-eight female Sprague‒Dawley rats were divided into four groups (n = 12): OVX + CBD, SHAM + CBD, OVX + vehicle, and SHAM + vehicle. CBD was administered intraperitoneally for 3weeks. After euthanasia, the bone quality, mechanical properties, and bone microarchitecture of the femurs and lumbar vertebrae were assessed by microcomputed tomography (micro-CT), bone densitometry, mechanical tests, and histological and immunohistochemical analyses. CBD treatment improved the bone mineral density (BMD) of the lumbar vertebrae and increased the BV/TV% and Tb.N in the femoral neck. There were also improvements in the mechanical properties, such as the maximum force and stiffness of the femurs and vertebrae. CBD significantly increased the bone matrix in osteopenic femurs and vertebrae, Although did not significantly influence the expression of RANKL and OPG, in ovariectomized animals, there was an increase in osteoblasts and a decrease in osteoclasts. Determining the optimal timing for CBD use in relation to postovariectomy bone loss remains a crucial issue. Understanding when and how CBD can be most effective in preventing or treating bone loss is essential to emphasize the importance of early diagnosis and treatment of osteoporosis. However, further studies are needed to explore in more detail the efficacy and safety of CBD in the treatment of postmenopausal osteoporosis.

Short-term risk of fracture is increased by deficits in cortical and trabecular bone microarchitecture independent of DXA BMD and FRAX: Bone Microarchitecture International Consortium (BoMIC) prospective cohorts.

Identifying individuals at risk for short-term fracture is essential to offer prompt beneficial treatment, especially since many fractures occur in those without osteoporosis by DXA-aBMD. We evaluated whether deficits in bone microarchitecture and density predict short-term fracture risk independent of the clinical predictors, DXA-BMD and FRAX. We combined data from eight cohorts to conduct a prospective study of bone microarchitecture at the distal radius and tibia (by HR-pQCT) and 2-year incidence of fracture (non-traumatic and traumatic) in 7327 individuals (4824 women, 2503 men, mean 69 ± 9years). We estimated sex-specific hazard ratios (HR) for associations between bone measures and 2-year fracture incidence, adjusted for age, cohort, height, and weight, and then additionally adjusted for FN aBMD or FRAX for major osteoporotic fracture. Only 7% of study participants had FN T-score ≤ -2.5, whereas 53% had T-scores between -1.0 and -2.5 and 37% had T-scores ≥-1.0. Two-year cumulative fracture incidence was 4% (296/7327). Each SD decrease in radius cortical bone measures increased fracture risk by 38%-76% for women and men. After additional adjustment for FN-aBMD, risks remained increased by 28%-61%. Radius trabecular measures were also associated with 2-year fracture risk independently of FN-aBMD in women (HRs range: 1.21 per SD for trabecular separation to 1.55 for total vBMD). Decreased failure load (FL) was associated with increased fracture risk in both women and men (FN-aBMD ranges of adjusted HR = 1.47-2.42). Tibia measurement results were similar to radius results. Findings were also similar when models were adjusted for FRAX. In older adults, FL and HR-pQCT measures of cortical and trabecular bone microarchitecture and density with strong associations to short-term fractures improved fracture prediction beyond aBMD and FRAX. Thus, HR-pQCT may be a useful adjunct to traditional assessment of short-term fracture risk in older adults, including those with T-scores above the osteoporosis range.

Microarchitectural analysis of the metacarpophalangeal joint using HR-pQCT in patients with rheumatoid arthritis: A comparison with healthy controls

ObjectiveTo investigate which joint microarchitectural parameters measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) serve as imaging markers for rheumatoid arthritis (RA). MethodsThe second and third metacarpophalangeal (MCP) joints of 50 patients with RA and 50 healthy controls (HCs) (aged 50–79 years, all females) were scanned using a HR-pQCT. Joint space, trabecular bone microarchitecture, and erosion were measured and compared between RA patients and HCs. ResultsThere were no differences in joint space parameters between RA patients and HCs.For bone microarchitecture, RA patients had lower trabecular bone mineral density (127 vs. 167 mg/cm3), thinner trabecular thickness (0.20 vs. 0.21 mm), fewer trabecular number (1.49 vs. 1.55 /mm), more rod-like structure (1.68 vs. 1.23), and poorer trabecular connectivity (4.51 vs. 5.72 /mm3) than HCs.Regarding erosion, RA patients had a higher number of erosions per joint (36/100 vs. 18/100), larger volume (4.62 vs. 1.89 mm3), and longer width (2.40 vs. 1.82 mm) and longer length (2.34 vs. 1.64 mm) than HCs.Most of the erosions in HCs were <5 mm3 in volume (95 %) and located on the radial side (85 %). When erosions <5 mm3 were compared between RA patients and HCs, there were no differences in their location or morphology. ConclusionsDeterioration of bone microarchitecture and existences of erosions >5 mm3 in the MCP joints are sensitive imaging markers of RA. Erosions <5 mm3 in RA patients may include not only early pathological erosion but also physiological erosion because even HCs can have erosions <5 mm3.

SDSSD peptide modified polyvinylamine − A novel bone-targeting RNA delivery system

Bone-related disorders have become a prevailing concern in older men and postmenopausal women. Traditional methods of treatment, though have benefits, their inability to target specific cells or tissues increases their ineffectiveness and side effects. RNA therapy has emerged as an alternative to conventional therapy owing to its specific targeting ability. However, the lack of appropriate RNA vectors remains a major problem for successful RNA therapy. Here, we designed a delivery system, (SDSSD-PVAm (PS)) based on a cationic polymer, polyvinylamine (PVAm), and a bone-targeting peptide, SDSSD (Serine-Aspartate-Serine-Serine-Aspartate), to deliver a therapeutic RNA, anti-miR-138-5p, to the bone tissue. The results showed that the SDSSD modification not only had no negative effect on the RNA-carrying or protection abilities of PVAm but also improved targeting and RNA delivery to osteoblasts and improve osteogenic potential of the cells by improving the expression of osteogenic genes both at RNA and protein level. Recombinant anti-miR-138-5p delivered through PS was highly enriched in the bone tissue, and the resultant nanoparticles could circulate for a longer time in the blood with negligible toxicity. The results showed that improved RNA delivery through PS significantly increased the rate of bone formation and improved trabecular and cortical bone microarchitecture, resulting in enhanced bone mass in ovariectomy (OVX) and hind limb unloading (HLU) model mice. These results demonstrate that SDSSD-PVAm is a novel RNA delivery system for bone-related disorders, such as osteoporosis.