Bone Microarchitectural Deterioration Research Articles

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.

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.

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.

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.

Association of serum phosphate, calcium and alkaline phosphatase with risk of incident fractures in healthy older adults.

Aging increases fracture risk through bone loss and microarchitecture deterioration due to an age-related imbalance in bone resorption and formation during bone remodelling. We examined the associations between levels of phosphate, calcium, and alkaline phosphatase, and fracture risk in initially-healthy older individuals. A post-hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial recruited 16,703 Australian participants aged ≥70 years and 2,411 US participants aged ≥65 years. Analyses were conducted on ASPREE-Fracture substudy participants from Australia with serum calcium, phosphate, and alkaline phosphatase measurement. Fracture data were collected post-randomization. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs). Phosphate, calcium, and alkaline phosphatase were analysed in deciles (D1-D10), with deciles 4-7 (31-70%) as the reference category. Restricted cubic spline curves were used to identify nonlinear associations. Of the 9915 participants, 907 (9·2%) persons had incident fractures recorded over 3·9 (SD 1·4) years. In the fully adjusted model, males in the top decile (D10) of phosphate had 78% higher risk of incident fracture (HR 1·78, 95% CI 1·25-2·54). No such association was observed for females (HR 1·09, 95% CI 0·83-1·44). The population attributable fraction in men within the D10 phosphate category is 6·9%. This result confirms that, high-normal serum phosphate levels are associated with increased fracture risk in older men.

The prevention effect of pulsed electromagnetic fields treatment on senile osteoporosis in vivo via improving the inflammatory bone microenvironment

ABSTRACT This study aimed to assess PEMF in a rat model of senile osteoporosis and its relationship with NLRP3-mediated low-grade inflammation in the bone marrow microenvironment. A total of 24 Sprague Dawley (SD) rats were included in this study. Sixteen of them were 24-month natural-aged male SD rats, which were randomly distributed into the Aged group and the PEMF group (n = 8 per group). The remaining 8 3-month -old rats were used as the Young positive control group (n = 8). Rats in the PEMF group received 12 weeks of PEMF with 40 min/day, five days per week, while the other rats received placebo PEMF intervention. Bone mineral density/microarchitecture, serum levels of CTX-1 and P1CP, and NLRP3-related signaling genes and proteins in rat bone marrow were then analyzed. The 12-week of PEMF showed significant mitigation of aging-induced bone loss and bone microarchitecture deterioration, i.e. PEMF increased the bone mineral density of the proximal femur and L5 vertebral body and improved parameters of the proximal tibia and L4 vertebral body. Further analysis showed that PEMF reversed aging-induced bone turnover, specifically, decreased serum CTX-1 and elevated serum P1CP. Furthermore, PEMF also dramatically inhibited NLRP3-mediated low-grade inflammation in the bone marrow, i.e. PEMF inhibited the levels of NLRP3, proCaspase1, cleaved Caspase1, IL-1β, and GSDMD-N. The study demonstrated that PEMF could mitigate the aging-induced bone loss and reverses the deterioration of bone microarchitecture probably through inhibiting NLRP3-mediated low-grade chronic inflammation to improve the inflammatory bone microenvironment in aged rats.

Exploring the Nexus of lower extremity proprioception and postural stability in older adults with osteoporosis: a cross-sectional investigation.

Osteoporosis, characterized by reduced bone mass and micro-architectural deterioration, poses a significant public health concern due to increased fracture susceptibility. Beyond bone health, this cross-sectional study aimed to assess and compare lower extremity proprioception and postural stability in individuals with and without osteoporosis and to explore their correlation within the osteoporosis group. In this prospective cross-sectional study, 80 participants were divided into two groups: osteoporosis (n = 40) and control (n = 40). The demographic characteristics and clinical parameters of the participants were as follows: Age (years) - Osteoporosis group: 65.04 ± 4.33, Control group: 65.24 ± 4.63; Sex (%) - Osteoporosis group: Male 30%, Female 70%; Control group: Male 30%, Female 70%; Body mass index (kg/m2) - Osteoporosis group: 23.7 ± 3.2, Control group: 24.5 ± 4.6; T-score (Lumbar) - Osteoporosis group: -2.86 ± 1.23, Control group: 0.27 ± 0.58; T-score (hip) - Osteoporosis group: -2.28 ± 0.79, Control group: 0.68 ± 0.86. Joint Position Sense (JPS) at the hip, knee, and ankle was assessed using a digital inclinometer, and postural stability was measured using computerized force platforms. Osteoporosis participants exhibited higher errors in hip (5.63° vs. 2.36°), knee (4.86° vs. 1.98°), and ankle (4.46° vs. 2.02°) JPS compared to controls. Postural stability measures showed increased anterior-posterior sway (10.86 mm vs. 3.98 mm), medial-lateral sway (8.67 mm vs. 2.89 mm), and ellipse area (966.88 mm2 vs. 446.19 mm2) in osteoporosis participants. Furthermore, correlation analyses within the osteoporosis group unveiled significant positive associations between lower extremity proprioception and postural stability. Specifically, hip JPS exhibited a strong positive correlation with anterior-posterior sway (r = 0.493, p = 0.003), medial-lateral sway (r = 0.485, p = 0.003), and ellipse area (r = 0.496, p < 0.001). Knee JPS displayed a moderate positive correlation with anterior-posterior sway (r = 0.397, p = 0.012), medial-lateral sway (r = 0.337, p = 0.032), and ellipse area (r = 0.378, p < 0.001). Similarly, ankle JPS showed a moderate positive correlation with anterior-posterior sway (r = 0.373, p = 0.023), medial-lateral sway (r = 0.308, p = 0.045), and ellipse area (r = 0.368, p = 0.021). These findings underscore the interplay between proprioceptive deficits, compromised postural stability, and osteoporosis, emphasizing the need for targeted interventions to improve fall prevention strategies and enhance the quality of life for individuals with osteoporosis.

Narrative Review of Effects of Glucagon-Like Peptide-1 Receptor Agonists on Bone Health in People Living with Obesity.

Glucagon-like peptide-1 Receptor agonists (GLP-1Ras) such as liraglutide and semaglutide have been recently approved as medications for chronic weight management in people living with obesity (PwO); GLP-1 may enhance bone metabolism and improve bone quality. However, the effects of GLP-1Ras on skeletal health remain to be determined and that's the purpose of this narrative review. Nevertheless, bone consequences of intentional weight loss interventions in PwO are well known: (i) significant weight loss induced by caloric restriction and bariatric surgery results in accelerated bone turnover and bone loss, and (ii) unlike caloric restriction interventions, PwO experience a substantial deterioration in bone microarchitecture and strength associated with an increased risk of fracture after bariatric surgery especially malabsorptive procedures. Liraglutide seems to have a positive effect on bone material properties despite significant weight loss in several rodent models. However, most of positive effects on bone mineral density and microarchitecture were observed at concentration much higher than approved for obesity care in humans. No data have been reported in preclinical models with semaglutide. The current evidence of the effects of GLP-1Ra on bone health in PwO is limited. Indeed, studies on the use of GLP-1Ra mostly included patients with diabetes who were administered a dose used in this condition, did not have adequate bone parameters as primary endpoints, and had short follow-up periods. Further studies are needed to investigate the bone impact of GLP-1Ra, dual- and triple-receptor agonists for GLP-1, glucose-dependent insulin releasing polypeptide (GIP), and glucagon in PwO.

Isolation and characterization of a novel homopolysaccharide (SFP-1) from Sargassum fusiforme: Promising anti-osteoporosis activity by modulating adipo-osteogenic differentiation

Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue, thereby increasing the risk of fracture. An increasing number of studies have focused on the discovery of anti-osteoporosis drugs derived from natural polysaccharides isolated from traditional Chinese medicines. In this study, a novel homopolysaccharide (SFP-1) was isolated from Sargassum fusiforme, a traditional marine Chinese medicine. The monosaccharide composition, FT-IR, methylation, GC–MS and NMR analyses revealed that SFP-1 was composed of α-D-Glcp-1→, →4,6)-α-D-Glcp-(1→, and →4)-α-D-Glcp-(1→. Additionally, its osteogenic activities were evaluated using C3H10 cells in vitro and zebrafish skull models in vivo. The results demonstrated that SFP-1 significantly inhibited adipogenesis and substantially alleviated intracellular lipid accumulation by down-regulating the expression of adipogenic transcription factors, such as PPARγ, FABP4, and FASN. Moreover, SFP-1 enhanced the osteogenic activity of C3H10 cells by up-regulating the expression of osteogenic factors comprising RUNX2, COL1A2, OCN, OSX, and SPARC. Furthermore, it also significantly increased bone mass in zebrafish skull models. These results collectively suggest that SFP-1 is a promising anti-osteoporosis drug that functions by modulating the balance of adipo-osteogenic differentiation.

Quantitative osteoporosis diagnosis of porous cancellous bone using poroelastodynamic modal analysis.

Osteoporosis is a skeletal disease characterized by reduced bone mass and microarchitectural deterioration, leading to increased fragility. This study presents a novel three-dimensional poroelastodynamic model for analyzing cancellous bone free vibration responses. The model incorporates the Navier-Stokes equations of linear elasticity and the Biot theory of porous media, allowing the investigation of osteoporosis-related changes. The analysis considers parameters like porosity, density, elasticity, Poisson ratio, and viscosity of bone marrow within the porous medium. Our findings indicate that natural frequencies of cancellous bone play a crucial role in osteoporosis prediction. By incorporating experimental data from 12 mouse femurs, we unveil insights into osteoporosis prediction. Increased porosity reduces bone stiffness, lowering natural frequencies. However, it also increases bone mass loss relative to stiffness, leading to higher frequencies. Therefore, the natural frequencies of osteoporotic bone are always higher than the natural frequencies of normal bone. Additionally, an increase in bone marrow within the pores, while increasing damping effects, also increases natural frequencies, which is another indication of osteoporosis growth in bone. The presence of bone marrow within the pores further influences natural frequencies, providing additional insights into osteoporosis growth. Thinner and smaller bones are found to be more susceptible to osteoporosis compared to larger and bigger bones due to their higher natural frequencies at equivalent porosity levels.

Nodakenin alleviates ovariectomy-induced osteoporosis by modulating osteoblastogenesis and osteoclastogenesis

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

A pilot study: effect of irisin on trabecular bone in a streptozotocin-induced animal model of type 1 diabetic osteopathy utilizing a micro-CT.

Osteoporosis is a significant co-morbidity of type 1 diabetes mellitus (DM1) leading to increased fracture risk. Exercise-induced hormone 'irisin' in low dosage has been shown to have a beneficial effect on bone metabolism by increasing osteoblast differentiation and reducing osteoclast maturation, and inhibiting apoptosis and inflammation. We investigated the role of irisin in treating diabetic osteopathy by observing its effect on trabecular bone. DM1 was induced by intraperitoneal injection of streptozotocin 60 mg/kg body weight. Irisin in low dosage (5 µg twice a week for 6 weeks I/P) was injected into half of the control and 4-week diabetic male Wistar rats. Animals were sacrificed six months after induction of diabetes. The trabecular bone in the femoral head and neck was analyzed using a micro-CT technique. Bone turnover markers were measured using ELISA, Western blot, and RT-PCR techniques. It was found that DM1 deteriorates the trabecular bone microstructure by increasing trabecular separation (Tb-Sp) and decreasing trabecular thickness (Tb-Th), bone volume fraction (BV/TV), and bone mineral density (BMD). Irisin treatment positively affects bone quality by increasing trabecular number p < 0.05 and improves the BMD, Tb-Sp, and BV/TV by 21-28%. The deterioration in bone microarchitecture is mainly attributed to decreased bone formation observed as low osteocalcin and high sclerostin levels in diabetic bone samples p < 0.001. The irisin treatment significantly suppressed the serum and bone sclerostin levels p < 0.001, increased the serum CTX1 levels p < 0.05, and also showed non-significant improvement in osteocalcin levels. This is the first pilot study to our knowledge that shows that a low dose of irisin marginally improves the trabecular bone in DM1 and is an effective peptide in reducing sclerostin levels.

THU419 Comprehensive Evaluation Of Osteoporosis And Impaired Bone Micro Architecture In Patients With Transfusion Dependent Beta Thalassemia

Abstract Disclosure: P. Dutta: None. comprehensive evaluation of osteoporosis and impaired bone micro architecture in patients with transfusion dependent beta thalassemia Authors: Pinaki Dutta, Liza Das, Alka Khadwal, Pankaj Malhotra, Sanjay Kumar Bhadada, Vandana Dhiman, Vivek Sharma, Raman Introduction: Thalassemia-related bone disease is an entity that includes low bone mass, fractures and impaired bone microarchitecture. The current study was designed to evaluate the prevalence and determinants of low bone mass, osteoporosis and microarchitectural parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with transfusion-dependent thalassemia (TDT). Patients and Methods TDT patients (n=42) and age- and BMI-matched controls (n=40) were recruited. Demographic, biochemical and hormonal parameters were assessed. Bone mineral density (BMD), T- and Z- scores were measured by DEXA using the HOLOGIC Discovery A Viewer 6 machine. Bone microarchitecture was estimated by HR-pQCT (XtremeCT II, Scanco Medical AG, Switzerland). Results: The mean age of thalassemia patients at recruitment was 26.9 ± 6.5 years and that of controls was 28.9 ± 7.9 years. The mean age of transfusion initiation was 7 months (IQR 3-18) and the median number of transfusions required was 24 (15-25) annually. Serum calcium in cases (8.87 ± 0.67mg/dl) was significantly lower than the controls (9.40 ± 0.45mg/dl), with 9 patients having hypocalcemia and 7 of these having hypoparathyroidism. Hypogonadism was present in 40.4% patients. Bone turnover markers (P1NP, β-CTX) were not significantly different between cases and controls, except alkaline phosphatase (ALP) which was higher in the cases (102.6 ± 60.7 U/l) as opposed to controls (78.2 ± 32.1 U/l). There was a significant correlation between ALP and liver dysfunction (alanine transaminase exceeding the upper normal limit) (r = 0.36, p=0.01) and 63.6% of those with elevated ALP had liver dysfunction. Low bone mass (Z ≤−2) was present in significantly greater proportion of patients versus controls at femoral neck (29.3% vs 2.4%) and at lumbar spine (52.4% vs 14.7%). Total, cortical and trabecular volumetric bone mineral density were significantly lower in cases as compared to controls(p&amp;lt;0.05). The trabecular number was significantly lower (p&amp;lt;0.0001) and trabecular separation significantly higher at radius and tibia (p&amp;lt;0.001). Cortical thickness at radius and tibia were also significantly lower in cases than controls (p&amp;lt;0.0001). Conclusion: Patients with transfusion-dependent thalassemia have significantly lower areal and volumetric BMD (both cortical and trabecular). The bone microarchitecture is also significantly impaired in terms of lower number and wider spacing of trabeculae as well as lower cortical thickness at both radius and tibia. Presentation: Thursday, June 15, 2023

THU415 Trabecular Bone Score In Hospitalized Patients With Heart Failure

Abstract Disclosure: F. Bandeira: None. L.B. Oliveira: None. M.A. Siqueira: None. M.A. Litvin: None. J.M. Garcia: None. L. Bandeira: None. Introduction: Heart failure (HF) is a clinical syndrome directly associated with functional impairment, which may be interrelated with skeletal consequences and an increased risk of fractures. The trabecular bone score (TBS) allows an indirect assessment of the bone microarchitecture, a helpful tool in fracture risk stratification. Objective: To evaluate the TBS and its relationship with bone mineral density (BMD) and cardiometabolic parameters in patients admitted with HF. Methods: Cross-sectional study was conducted in a Cardiology center, with patients aged 40 to 85 years hospitalized with HF. Clinical, echocardiographic, laboratory and BMD were evaluated. TBS &amp;lt;1.230 was characterized as bone degradation. Results: A total of 103 patients were evaluated, of which 53.4% were female. The mean age was 64.1 ± 9.4 years. The median left ventricular ejection fraction (LVEF) was 50.0% (interquartile range [IQR] 34.0-61.0%), with 50.5% having preserved LVEF (≥50%), 5.8% having mildly reduced LVEF (41-49%), and 43.7% having reduced LVEF (≤40%). 50.4% of patients had New York Heart Association Functional Classification (NYHA-FC) I-II and 49.6% NYHA-FC III-IV. The majority (67%) of patients had HF of ischemic etiology; 43.7% had diabetes mellitus and 30.0% had prediabetes. Bone degradation indicated by TBS was present in 33.0% of the sample, while BMD in the osteoporosis range was observed in 22.3%. There was no statistically significant difference between genders in the presence of bone degradation (22.9% of men vs. 36.4% of women, p = 0.138). Low TBS was associated with higher mean age (67.5 ± 9.1 vs. 62.7 ± 9.2 years, p = 0.016) and lower T-scores in the lumbar spine (−1.9 ± 1.3 vs. −0.7 ± 1,8, p = 0.001), femoral neck (−1.6 ± 1.2 vs. −1.1 ± 1.2, p = 0.030), and total femur (−1.3 ± 1.1 vs. −0.5 ± 1.3, p = 0.005). There was no association between low TBS and body mass index (28.0 ± 4.4 vs. 27.8 ± 5.3 kg/m², p = 0.828), LVEF (50.0% [30.0-59.0] vs. 55.0% [34.3-61.8], p = 0.183) and hemoglobin A1c (6.4% [5.7-7.9] vs. 6.2% [5.7-8.2], p = 0.920). Patients with NYHA-FC III-IV had lower mean TBS when compared to those with NYHA-FC I-II (1.273 ± 0.138 vs. 1.335 ± 0.149, p = 0.031). Conclusion: We found that bone microarchitecture deterioration was more frequent than osteoporosis in patients hospitalized with HF, with greater symptomatology being associated with lower TBS. Presentation: Thursday, June 15, 2023