Bone Microarchitectural Deterioration Research Articles

Osteoporosis in postmenopausal women is associated with disturbances in gut microbiota and migration of peripheral immune cells

BackgroundPostmenopausal osteoporosis (PMO) results from a reduction in bone mass and microarchitectural deterioration in bone tissue due to estrogen deficiency, which may increase the incidence of fragility fractures. In recent years, the “gut-immune response-bone” axis has been proposed as a novel potential approach in the prevention and treatment of PMO. Studies on ovariectomized murine model indicated the reciprocal role of Th17 cells and Treg cells in the aetiology of osteoporosis. However, the relationship among gut microbiota, immune cells and bone metabolic indexes remains unknown in PMO.MethodsA total of 77 postmenopausal women were recruited for the study and divided into control (n = 30), osteopenia (n = 19), and osteoporosis (n = 28) groups based on their T score. The frequency of Treg and Th17 cells in lymphocytes were analyzed by flow cytometry. The serum levels of interleukin (IL)-10, 17 A, 1β, 6, tumor necrosis factor (TNF)-α, and lipopolysaccharide (LPS) were determined via enzyme-linked immunosorbent assay. Additionally, 16S rRNA gene V3-V4 region sequencing analysis was performed to investigate the gut microbiota of the participants.ResultsThe results demonstrated decreased bacterial richness and diversed intestinal composition in PMO. In addition, significant differences of relative abundance of the gut microbial community in phylum and genus levels were found, mainly including increased Bacteroidota, Proteobacteria, and Campylobacterota, as well as reduced Firmicutes, Butyricicoccus, and Faecalibacterium. Intriugingly, in the osteoporosis group, the concentration of Treg cells and associated IL-10 in peripheral circulation was negatively regulated, while other chronic systemic proinflammatory cytokines and Th17 cells showed opposite trends. Moreover, significantly elevated plasma lipopolysaccharide (LPS) in patients with osteoporosis indicated that disrupted intestinal integrity and permeability. A correlation analysis showed close relationships between gut bacteria and inflammation.ConclusionsCollectively, these observations will lead to a better understanding of the relationship among bone homeostasis, the microbiota, and circulating immune cells in PMO. The elevated LPS levels of osteoporosis patients which not only indicate a breach in intestinal integrity but also suggest a novel biomarker for assessing osteoporosis risk linked to gut health.

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.

The role of short-chain fatty acids in the regulation of osteoporosis: new perspectives from gut microbiota to bone health: A review.

Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration, resulting in increased fracture risk. With an aging population, osteoporosis imposes a heavy burden worldwide. Current pharmacotherapies such as bisphosphonates can reduce fracture risk but have limitations. Emerging research suggests that gut microbiota regulates bone metabolism through multiple mechanisms. Short-chain fatty acids (SCFAs) produced from microbial fermentation of dietary fiber beneficially impact bone health. Preclinical studies indicate that SCFAs such as butyrate and propionate prevent bone loss in osteoporosis models by inhibiting osteoclastogenesis and immune modulation. Early clinical data also suggest that SCFA supplementation may improve bone turnover markers in postmenopausal women. SCFAs likely act via inhibition of osteoclast differentiation, stimulation of osteoblast activity, regulation of T cells, and other pathways. However, optimal dosing, delivery methods, and long-term safety require further investigation. Modulating the gut-bone axis via supplementation, prebiotics/probiotics, diet, and lifestyle interventions represents an innovative therapeutic approach for osteoporosis. Harnessing the interplay between microbiome, metabolism, immunity, and bone may provide new directions for managing osteoporosis in the future.

The Value of Mandibular Indices on Cone Beam Computed Tomography in Secondary Causes of Low Bone Mass.

Background: As implant treatment cases increase, many cases of failure/side effects also occur. Generally, dental clinics determine the density of the jawbone using cone beam CT (CBCT). Considering the known potential role of this tool for bone assessment in primary osteoporosis, this study evaluated patients with secondary endocrine causes of low bone mass. Methods: The study included 83 patients with endocrine causes of osteoporosis who were evaluated by dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS), and mental foramen (MF) region CBCT. The following CBCT indices were measured: anterior (A)-thickness of inferior mandibular cortex 10 mm anterior from MF; molar (M)-thickness of inferior mandibular cortex 10 mm posterior from MF; posterior (P)-thickness of inferior mandibular cortex 25 mm posterior from MF; symphysis (S)-thickness of inferior mandibular cortex equidistant from the centers of right and left MF. Results: The highest correlation coefficient in the secondary causes group was between the A index and the lumbar BMD (r = 0.375, p = 0.001) and the P index and the femoral neck BMD (r = 0.38, p = 0.001). Hypercortisolism seems to be the most predictable cause of secondary osteoporosis using the A, M, and P indices. The A, M, and P indices showed predictive values of the bone micro-architecture that was evaluated using TBS score, and were statistically significant. The symphysis index does not significantly predict osteoporosis or impaired bone micro-architecture. Conclusions: These findings support the potential usefulness of A, M, and P CBCT-derived radiomorphometric mandibular indices in secondary osteoporosis, underlining the well-known effects of these pathologies on bone micro-architecture rather than bone quantity.

CROHN'S DISEASE AND OSTEOPOROSIS: RISK FACTORS, DIAGNOSIS AND CLINICAL TREATMENT

Crohn's disease (CD) is a chronic inflammatory bowel disease that affects any part of the gastrointestinal tract. Osteoporosis, in turn, is a skeletal disease characterized by decreased bone mass and deterioration of bone microarchitecture, increasing the risk of fractures. The association between these two diseases has been increasingly investigated, with evidence suggesting that patients with CD are at increased risk of developing osteoporosis. This comorbidity can be attributed to several factors, including corticosteroid use, nutrient malabsorption, chronic inflammation, and hormonal dysfunction. Objective: The objective of this systematic review was to identify and synthesize the available scientific evidence on the relationship between Crohn's disease and osteoporosis, focusing on risk factors, diagnosis, and clinical treatment. Methodology: A systematic review of the literature was performed, following the recommendations of the PRISMA statement. The PubMed, Scielo and Web of Science databases were searched using the following descriptors: “Crohn’s disease”, “Osteoporosis”, “Risk factors”, “Diagnosis” and “Treatment”. Original articles published in the last 10 years, in Portuguese or English, that investigated the association between CD and osteoporosis in adults were included. Case studies, narrative reviews and articles that did not address the relationship between the two diseases were excluded. Results: The results of the review demonstrated that osteoporosis is a frequent complication in patients with CD. Several risk factors were identified, including the use of corticosteroids, malabsorption of calcium and vitamin D, chronic inflammation and hormonal dysfunction. The diagnosis of osteoporosis in patients with CD can be challenging due to the presence of other factors that can affect bone mineral density, such as malnutrition and immobilization. Treatment of osteoporosis in patients with CD should be individualized and may include pharmacological and non-pharmacological measures, such as calcium and vitamin D supplementation, regular physical activity, and reduced tobacco and alcohol consumption. Conclusion: Crohn's disease represents a significant risk factor for the development of osteoporosis. The association between these two diseases is complex and multifactorial, involving several pathogenic mechanisms. Early diagnosis and appropriate treatment of osteoporosis in patients with CD are essential to prevent fractures and improve the quality of life of these patients. It is essential that health professionals are aware of this comorbidity and offer integrated clinical management for these patients.

Risk Factors for Bone Microarchitecture Impairments in Older Men with Type 2 Diabetes - The MrOS Study.

Impaired bone microarchitecture, assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), may contribute to bone fragility in type 2 diabetes (T2DM) but data on men are lacking. To investigate the association between T2DM and HR-pQCT parameters in older men. HR-pQCT scans were acquired on 1794 participants in the Osteoporotic Fractures in Men (MrOS) study. T2DM was ascertained by self-report or medication use. Linear regression models, adjusted for age, race, BMI, limb length, clinic site, and oral corticosteroid use, were used to compare HR-pQCT parameters by diabetes status. Among 1777 men, 290 had T2DM (mean age 84.4 years). T2DM men had smaller total cross-sectional area (Tt.AR) at the distal tibia (p=0.028) and diaphyseal tibia (p=0.025), and smaller cortical area at the distal (p= 0.009) and diaphyseal tibia (p= 0.023). Trabecular indices and cortical porosity were similar between T2DM and non-T2DM. Among men with T2DM, in a model including HbA1c, diabetes duration, and insulin use, diabetes duration ≥ 10 years, compared with <10 years, was significantly associated with higher cortical porosity but with higher trabecular thickness at the distal radius. Insulin use was significantly associated with lower cortical area and thickness at the distal radius and diaphyseal tibia and lower failure load at all three scan sites. Lower cortical area, cortical thickness, total BMD, cortical BMD, and failure load of the distal sites were associated with increased risk of incident non-vertebral fracture in T2DM. Older men with T2DM have smaller bone size compared to non-T2DM, which may contribute to diabetic skeletal fragility. Longer diabetes duration was associated with higher cortical porosity and insulin use with cortical bone deficits and lower failure load.

Systematical Mutational Analysis of FRATtide against Osteoclast Differentiation by Alanine Scanning.

Osteoporosis, a global bone disease, results in decreased bone density, mass, and microarchitecture deterioration, increasing fracture risk. In previous research, FRATtide, a peptide derived from a glycogen synthase kinase-3 binding protein, effectively hindered osteoclast differentiation to yield therapeutically potent derivatives via single and double stapling. However, FRATtide's structure-activity relationship remains unclear. This study synthesized 25 FRATtide-derived peptides through systematic alanine scanning and evaluated their activities. Substitutions in Pro2, Leu5, Leu9, Val10, Leu11, Ser12, Asn14, Leu15, Ile16, Glu18, Arg22, Ser25, and Arg26 showed reduced activity, while FRT13 and FRT20 with Gly13 and Arg21 substitutions, respectively, displayed enhanced activities. F-actin binding and bone resorption assays on FRT13 and FRT20 showed better inhibition of osteoclast differentiation and bone resorption compared with FRATtide. This study elucidated FRATtide's structure-activity relationship, thereby facilitating future structural optimization for osteoporosis treatment.

Dynamic spinal orthoses self-reported effects in patients with back pain due to vertebral fragility fractures: A multi-center prospective cohort study.

Vertebral fragility fractures (VFFs) commonly result from low bone mass and microarchitecture deterioration of bone tissue. spinal orthoses are common non-pharmacological options for managing vertebral fracture pain. However, the effects of spinal orthoses on pain, physical functioning, and quality of life (QoL) are still debated. This survey aimed to investigate the patients-reported outcomes of a dynamic spinal orthosis prescribed in the routine clinical practice of VFFs management. This multi-center national-wide prospective cohort study assessed older patients (aged > 60years) diagnosed with acute VFFs and prescribed with a dynamic spinal orthosis (Spinfast®). A survey questionnaire was realized and included sections on patient characterization, osteoporosis characterization, spinal orthosis, clinical outcomes, pain medications, and osteoporosis medications. The questionnaire was administered at baseline and after three months. A total of 68 patients completed the questionnaire at three months. Most patients had one or two VFFs and were treated with pain medications and osteoporosis medications. Compliance and tolerability of the spinal orthosis were assessed, and clinical outcomes such as pain intensity, physical functioning, and QoL were measured. The results showed no significant differences in outcomes between age subgroups. Italian physical medicine and rehabilitation physicians were commonly involved in the management of VFFs patients. Sixty-six patients completed the questionnaire. The results showed that pain intensity, physical functioning and QoL improved after three months of spinal orthosis wearing (p< 0.0001). The correct management of VFFs is mandatory to improve pain and reduce disability, and our findings suggested a positive role of dynamic spinal orthosis to improve the comprehensive management of VFFs patients. However, high-quality research trials are warranted to provide clear recommendations for the correct clinical management of VFF.

Denosumab Prevents Bone Loss and Microarchitectural Deterioration in Premenopausal Women With Breast Cancer Receiving Estradiol Suppression Therapy: A Randomized Controlled Trial.

Suppression of ovarian function and aromatase inhibition (AI) increases disease-free survival in premenopausal women with estrogen receptor (ER)-positive early-stage breast cancer but accelerates bone loss. We therefore hypothesized that suppressing bone remodeling using denosumab (DMAB) would prevent bone loss in these women. In a 12-month double-blind randomized trial, 68 women with ER-positive early-stage breast cancer commencing ovarian function suppression and AI were randomly assigned to 60 mg DMAB (n = 34) or placebo (PBO; n = 34) once every 6 months (at 0 and 6 months). Volumetric bone mineral density (BMD), microarchitecture, and estimated bone strength of the distal tibia and distal radius were measured using high-resolution peripheral quantitative computed tomography, and spine and hip BMD were measured using dual-energy X-ray absorptiometry at 0, 6, and 12 months. The primary end point and treatment effect was the mean adjusted between group difference (MAD; [95% CI]) in distal tibial total volumetric BMD over 12 months, with a single P value tested over all time points. The study is registered with the Australian New Zealand Clinical Trials Registry (anzctr.org.au; identifier: ACTRN12616001051437). Intention-to-treat analysis included all 68 randomly assigned women. Over 12 months, compared with PBO, DMAB prevented the decrease in distal tibial total BMD (MAD, 20.8 mg HA/cm3 [95% CI, 17.3 to 24.2]), cortical BMD (42.9 mg HA/cm3 [95% CI, 32.1 to 53.9]), trabecular BMD (3.32 mg HA/cm3 [95% CI, 1.45 to 5.20], P = .004), estimated stiffness (11.6 kN/m [95% CI, 7.6 to 15.6]), and failure load (563 N [95% CI, 388 to 736]). Findings were similar at the distal radius. Decreases in BMD at the lumbar spine (MAD, 0.13 g/cm2 [95% CI, 0.11 to 0.15]), total hip (0.08 g/cm2 [95% CI, 0.07 to 0.09], and femoral neck (0.06 g/cm2 [95% CI, 0.05 to 0.07]) were also prevented. All P < .001 unless otherwise noted. Treatment with DMAB at commencement of estradiol suppression therapy preserves BMD, bone microarchitecture, and estimated strength, and is likely to increase fracture-free survival.

Anabolic treatment for osteoporosis and fragility fracture risk: one year in review 2024.

Osteoporosis is a skeletal disease characterised by reduced bone mass and deterioration of bone microarchitecture, underlying a higher risk of fragility fractures. Several options are available for its treatment, including both anti-resorptive and anabolic agents. The present review discusses and summarises the most recent literature on anabolic treatment, with a focus on abaloparatide, and on the assessment of fragility fracture risk, with a focus on trabecular bone score. Finally, we provide a discussion on the effects of different antiosteoporotic medications in terms of fragility fracture risk reduction.

Bone mass, microarchitecture and turnover among young Indian women with non-alcoholic fatty liver disease.

To evaluate comprehensive bone health among young Indian women, including bone mass, microarchitecture, and turnover, in relation to their non-alcoholic fatty liver disease (NAFLD) status. This cross-sectional study (May 2018-November 2019) recruited women with a history of gestational diabetes mellitus (GDM) and normoglycemia in their index pregnancy, who were at least 6 months postpartum. All participants underwent abdominal ultrasonography for determination of NAFLD status (grades 2 and 3: severe NAFLD) and transient elastography (FibroScan) for hepatic fibrosis (LSM >6 kPa). Bone mass was assessed by DXA, bone microarchitecture with trabecular bone score {TBS} (low TBS ≤ 1.310) and bone turnover with markers of bone formation (osteocalcin and P1NP), and resorption (CTX). Bone mineral density (BMD) at femoral neck (p = 0.026) and total hip (p = 0.007) was significantly higher among women with NAFLD (n = 170) compared to those without (n = 124). There was no significant difference in bone turnover markers between the two groups. The presence of NAFLD [adjusted OR: 1.82 (1.07, 3.11)] was associated with low TBS, with a greater strength of association among women with severe NAFLD [adjusted OR: 2.97 (1.12, 7.88)]. However, these associations were attenuated and no longer significant after additionally adjusting for BMI. Women with NAFLD and hepatic fibrosis manifested significantly higher BMD at lumbar spine, femoral neck, and total hip (p < 0.001 for all) and significantly lower bone turnover markers (osteocalcin, p = 0.009 and CTX, p = 0.029), however, the association with low TBS was not observed. Among young Indian women, NAFLD is associated with increased bone mass and impaired bone microarchitecture, and hepatic fibrosis with increased bone mass and reduced bone turnover.

The impact of androgen deprivation therapy on bone microarchitecture in men with prostate cancer: A longitudinal observational study (The ANTELOPE Study)

IntroductionAndrogen Deprivation Therapy (ADT) for prostate cancer (PC) has substantial negative impacts on the musculoskeletal system and body composition. Many studies have focused on the effects of ADT on areal bone mineral density (aBMD), but aBMD does not capture key determinants of bone strength and fracture risk, for example volumetric bone density (vBMD), geometry, cortical thickness and porosity, trabecular parameters and rate of remodelling. More specialist imaging techniques such as high-resolution peripheral quantitative computed tomography (HR-pQCT) have become available to evaluate these parameters. Although it has previously been demonstrated that bone microarchitectural deterioration occurs in men undergoing ADT, the aim of the ANTELOPE study was to examine longitudinal changes in bone microstructure alongside a range of musculoskeletal parameters and frailty, comparing men with PC receiving ADT alone or ADT plus chemotherapy for metastatic disease, with a healthy age-matched population. MethodsWe used HR-pQCT to investigate effects of 12 months of ADT on vBMD and microstructural parameters, complemented by assessment of changes in aBMD, serum bone turnover markers, sex hormones, body composition, grip strength, physical and muscle function, frailty and fracture risk. We studied three groups: Group A − men with localised/locally advanced PC due to commence ADT; Group B − men with newly diagnosed hormone-sensitive, metastatic PC, starting ADT alongside docetaxel chemotherapy and steroids; Group C − healthy, age-matched men. The primary endpoint was change in vBMD (Group A vs Group C) at the distal radius. ResultsNinety-nine participants underwent baseline study assessments (Group A: n = 38, Group B: n = 30 and Group C: n = 31). Seventy-five participants completed all study assessments (Group A (29), Group B (18), Group C (28). At baseline, there were no significant differences between Groups A and C in any of the BMD or bone microstructure outcomes of interest. After 12 months of ADT treatment, there was a significantly greater decrease in vBMD (p < 0.001) in Group A (mean 12-month change = -13.7 mg HA/cm3, −4.1 %) compared to Group C (mean 12-month change = -1.3 mg HA/cm3, −0.4 %), demonstrating achievement of primary outcome. Similar effects were observed when comparing the change in vBMD between Group B (mean 12-month change = -13.5 mg HA/cm3, −4.3 %) and Group C. These changes were mirrored in aBMD. ADT resulted in microstructural deterioration, a reduction in estimated bone strength and an increase in bone turnover. There was evidence of increase in total fat mass and trunkal fat mass in ADT-treated patients, with marked loss in upper limb mass, along with BMI gain. Frailty increased and physical performance and strength deteriorated in both ADT groups, relative to the healthy control group. ConclusionThe study showed that ADT has profound effects on vBMD, aBMD, bone microstructure and strength and body composition, and important impacts on frailty and physical performance. Whilst DXA remains a valuable tool (changes in aBMD are of the same magnitude as those observed for vBMD), HR-pQCT should be considered for assessing the effects of anti-androgens and other newer PC therapies on bone, as well as potential mitigation by bone-targeted agents.

Genetic Insights and Genetic Predisposition of Osteoporosis – A Systematic Review

Abstract Osteoporosis (OP) is a condition characterized by fragile and easily broken bones, impacting around 200 million individuals worldwide. OP is defined by reduced bone mineral density (BMD) and deterioration of bone microarchitecture, both of which greatly heighten the likelihood of fractures. It is now widely recognized that OP is a complex condition resulting from the interplay between genetic factors and environmental influences. Identification of markers with a genetic predisposition to OP is crucial in the development of disease prevention. In the recent past, the scientific community has concentrated on understanding the genetic basis of OP. This review focuses on genetic insights of OP and different gene polymorphisms associated with BMD and OP. Molecular screening of individuals could be useful to identify susceptibility genes of OP for better individualized clinical management of the disease.

Ångstrom-scale gold particles loaded with alendronate via alpha-lipoic acid alleviate bone loss in osteoporotic mice

Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles.

Preparation of Puerarin Long Circulating Liposomes and its Effect on Osteoporosis in Castrated Rats

Osteoporosis is a disease that causes low bone mass and deterioration of bone microarchitecture. Puerarin is a natural isoflavone compound that has been shown to possess anti-inflammatory, antioxidant and ameliorative effects on osteoporosis with less adverse reactions. However, its fast metabolism and low oral bioavailability limit its application. This study aimed to prepare d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)- modified Puerarin Long Circulating Liposomes (TPGS-Puerarin-liposomes), in order to improve the oral bioavailability of puerarin, before evaluation of its pharmacological activity in vitro and in vivo. We employed film dispersion method to develop TPGS-Puerarin-liposomes before appropriate characterizations. Afterwards, we utilized in vivo imaging, pharmacokinetic analysis and in vitro drug release testing to further evaluate the in vivo and in vitro delivery efficiency. In addition, we established a castrated osteoporosis rat model to observe the changes in femur tissue structure and bone micromorphology via hematoxylin-eosin (HE) staining and Micro Computed Tomography (Micro CT). Besides, levels of oxidative stress and inflammatory indicators, as well as expression of wnt/β-catenin pathway-related proteins were detected. In terms of physiochemical properties, the respective mean particle size (PS) and zeta potential (ZP) of TPGS-Puerarin-liposomes were 76.63±0.59 nm and -25.54±0.11 mV. The liposomal formulation exhibited encapsulation efficiency (EE) of 95.08±0.25% and drug loading (DL) of 7.84±0.07%, along with excellent storage stability. Compared with free drugs, the TPGS-Puerarin-liposomes demonstrated a sustained release effect and could increase blood concentration of puerarin in rats, thereby significantly improving its bioavailability. Also, in vivo studies have confirmed potential of the liposomes to promote bone tissue targeting and accumulation of puerarin, coupled with significant improvement of the osteoporotic status. Besides, the liposomes could also reduce levels of oxidative stress and inflammatory factors in serum and bone tissue. Additionally, we discovered that TPGS-Puerarin-liposomes increased Wnt, β-catenin and T-cell factor (TCF) expressions at protein level in the wnt/β-catenin signaling pathway. This study has demonstrated the potential of TPGS-Puerarin-liposomes for treatment of osteoporosis.

Sleep disorders among women with post-menopausal osteoporosis

IntroductionOsteoporosis (OP) is characterized by low bone mass and microarchitectural deterioration of bone tissue. Recent studies have suggested that sleep may significantly influence the pathophysiology of OP.Objectives In the present study, we aimed to determine sleep disorders among women with post-menopausal OP.MethodsA cross-sectional study was conducted between January and June 2023. Patients with post-menopausal OP who visited the rheumatology department in a university hospital in Tunisia were interviewed. The Pittsburgh Sleep Quality Index (PSQI). It is a seven-component scale, including: sleep quality (C1), sleep latency (C2), sleep duration (C3), sleep efficiency (C4), sleep disturbances (C5), sleep medication use (C6), and daytime dysfunction (C7).PSQI ≤ 7 indicated normal sleep quality, and PSQI &gt; 7 indicated poor sleep quality.Results Ninety-three women diagnosed with post-menopausal OP were interviewed. the number of complete questionnaires was 72. The valid rate was 77.4%. All were women. The mean age was 72.5 (±1.08). The median duration of menopause was 23 years (IIQ= [10.5-28.5]). Forty-five women were diagnosed with bone fractures (62%). Thirty-three patients (45.8%) were obese (IMC&gt;30). The median PSQI score was 16 (IIQ = [6-18]). Forty-seven participants (65.3%) had poor sleep quality (PSQI &gt; 7). According to the items of PSQI: the median score of sleep duration, sleep Efficiency and sleep disturbances was 1 (IIQ= [1 -2]) for each item. The median score of sleep latency was 3 (IIQ=[2-3]). For daytime dysfunction, the median score was 2 (IIQ=[0-3]). Study analytics revealed a significant association between daytime dysfunction and the presence of bone fractures (p=10-3), the same was with sleep disturbances and bone fractures (p=10-3). Body mass index (BMI) was significantly and inversely associated with sleep quality (r= -0.313; p= 0.007). Sleep latency was significantly associated with physical activity (p&lt;10-3).ConclusionsIn conclusion, our results suggest that sleep quality is associated with physical activity and BMI. This is consistent with the most recent evidence in the literature. These findings support expanding the scope of wellness programs to promote healthy sleep among osteoporotic women.Disclosure of InterestNone Declared

Long-term bisphosphonates use and atypical femoral fracture

Osteoporosis is a systemic skeletal disorder characterized by low bone mass and microarchitectural deterioration, increasing the risk of fractures. As the global incidence of osteoporosis rises, it has become a pressing concern for healthcare professionals. Long-term use of bisphosphonates (BPs), commonly prescribed for osteoporosis, has been associated with atypical femur fractures (AFFs). While AFFs are relatively rare, they are a serious concern due to their potential complications.

Instrumental parameters of bone mineral density in postmenopausal women: combined use of ultrasound densitometry and the FRAX model

Osteoporosis is a systemic widespread disease of the musculoskeletal system that leads to impaired bone microarchitecture with a risk of fractures. The menopause period is one of the leading factors that leads to dysfunction of the RANK/RANKL/OTG signaling pathway, activating systemic inflammation. The purpose of the study was to determine the mineral status of bone tissue in menopausal women with simultaneous assessment of the risk of low-trauma fractures using ultrasound densitometry and the FRAX computerized model. The study included 153 people aged 20 to 89 years (mean age 55.3±15.4 years). Depending on the presence of menopause and gender, the corresponding groups were formed: I - main (menopausal women), II - control (women of reproductive age), III - comparison (men). The results of the study revealed a decrease in bone mineral density in the main group (I), where the T-criterion was -1.45± -1.95, compared with the control group (II) and comparison group (III), where the index was -0.51±0.7 and 0.27±0.72, respectively. The 10-year risk of any osteoporotic fractures according to the FRAX model demonstrates significantly higher risks in group I ([7.4 [4.0-15.0] %) compared to groups II and III, where the risks were 2.7 [2.4 - 3.3] % and 3.2 [2.3 - 3.8] %, respectively, p&lt; 0.0001. As a result of the combined use of ultrasound densitometry and the FRAX model, lower bone mineral density of the radial bones in the main group was found compared to the control and comparison groups. The above results indicate that hypoestrogenism caused by the onset of menopause is a key factor in the development of osteodysmetabolic syndrome.

Postmenopausal women with normal BMD who have fractures have deteriorated bone microarchitecture: A prospective analysis from The OFELY study

Most postmenopausal women who sustain fragility fracture (Fx) have their areal bone mineral density (BMD) above the osteoporosis threshold. A sizeable proportion of them have normal aBMD. This study aimed to prospectively investigate the association of fragility Fx with bone microarchitecture (MA) assessed by high-resolution peripheral computed tomography (HR-pQCT) in postmenopausal women without low BMD.At the 14th annual follow-up of the OFELY study, we measured bone MA at the distal radius and tibia with HR-pQCT in addition to areal BMD with DXA, in 586 postmenopausal women. Among them, 166 (29 %) women, mean (SD) age 65 (8) yr, had normal BMD defined as a T score ≥ −1 at the lumbar spine, femoral neck, and total hip. During a median [IQR] 15 [14–15] yr of follow-up, 46 of those women sustained incident fragility Fx, including 19 women with a major osteoporotic Fx (clinical spine, forearm, proximal humerus, hip). Women who sustained Fx did not differ for age, BMI, tobacco and alcohol use, diabetes, falls, FRAX®, aBMD, and TBS compared with women without incident Fx. In contrast, they had significant impairment of volumetric densities, cortical area (Ct. Ar) and thickness (Ct. Th), stiffness (K), and estimated failure load (FL) at the radius compared with women without incident Fx. At the radius, each SD decrease of volumetric densities, Ct.Ar, Ct.Th, K, and estimated FL were significantly associated with an increased risk of all fragility fractures with hazard ratios (HR) from 1.44 to 1.56 and of major osteoporotic fractures (HR from 1.66 to 2.57). Lesser impairment of bone MA was seen at the tibia.We conclude that even in women with normal areal BMD fragility fractures are associated with deterioration of bone microarchitecture.

Knowledge, Attitude, and Practices Towards Osteoporosis Among Adults in the United Arab Emirates (UAE) in 2023.

Osteoporosis, the silent epidemic, is defined as a systemic skeletal disease characterized by low mineral bone mass and micro-architectural deterioration of bone tissue. Osteoporosis is considered a burden to global economic, social, and health development. Osteoporosis exerts a substantial global influence, markedly influencing rates of illness and death on a broad scale. Clinical features of osteoporosis can include chronic back pain, loss of height, and a stooped posture, as well as an increased risk of fractures in the spine, hip, and wrist. Accurate identification and monitoring of these clinical features are essential for effective management and treatment of osteoporosis. This study aims to identify the knowledge, attitudes, and practices (KAP) of adults (over 18 years) about osteoporosis and identify relations between knowledge, attitudes, and practices with demographic data. Furthermore, to assess the risk factors and preventive measures for osteoporosis. Data from 446 responders were collected using a Google Forms questionnaire, including questions to assess knowledge, attitudes, and practice levels among adults 18 years and above in the United Arab Emirates (UAE). The collected data and statistical analysis were done through the IBM® SPSS® Statistics. Chi-Square was used in SPSS Statistics; the chi-square test was used for the relation between categorical variables, and P less than 0.05 was the cut-off level of significance. The research revealed that 41.9% of the participants had good knowledge, 38.8% had a positive attitude, and 45.3% had poor practices. The results also showed that there is a statistically significant correlation between gender and knowledge, attitudes, and practices. Our research demonstrates that there's a statistically significant correlation between gender variables with knowledge, attitudes, and practices. These findings have important implications in assessing the correlation between variables in our research that could be used to prevent osteoporosis further, target the specific demographic group, and provide the required education. Overall, our research contributes to a better understanding of the knowledge, attitude, and practices towards Osteoporosis among adults in the UAE and underscores the importance of further awareness in this area.