Estradiol increases cortical and trabecular bone accrual and bone strength in an adolescent male-to-female mouse model of gender-affirming hormone therapy.

The effects of gender-affirming hormone therapy on the skeletal integrity and fracture risk in transitioning adolescent trans girls are unknown. To address this knowledge gap, we developed a mouse model to simulate male-to-female transition in human adolescents in whom puberty is first arrested by using gonadotrophin-releasing hormone analogs with subsequent estradiol treatment. Puberty was suppressed by orchidectomy in male mice at 5 weeks of age. At 3 weeks post-surgery, male-to-female mice were treated with a high dose of estradiol (~0.85 mg) by intraperitoneal silastic implantation for 12 weeks. Controls included intact and orchidectomized males at 3 weeks post-surgery, vehicle-treated intact males, intact females and orchidectomized males at 12 weeks post-treatment. Compared to male controls, orchidectomized males exhibited decreased peak bone mass accrual and a decreased maximal force the bone could withstand prior to fracture. Estradiol treatment in orchidectomized male-to-female mice compared to mice in all control groups was associated with an increased cortical thickness in the mid-diaphysis, while the periosteal circumference increased to a level that was intermediate between intact male and female controls, resulting in increased maximal force and stiffness. In trabecular bone, estradiol treatment increased newly formed trabeculae arising from the growth plate as well as mineralizing surface/bone surface and bone formation rate, consistent with the anabolic action of estradiol on osteoblast proliferation. These data support the concept that skeletal integrity can be preserved and that long-term fractures may be prevented in trans girls treated with GnRHa and a sufficiently high dose of GAHT. Further study is needed to identify an optimal dose of estradiol that protects the bone without adverse side effects.

Hyperprolactinemia Due to Prolactinoma has an Adverse Impact on Bone Health with Predominant Impact on Trabecular Bone: A Systematic Review and Meta-Analysis.

BACKGROUND: No meta-analysis has holistically analysed and summarized the effect of prolactin excess due to prolactinomas on bone mineral metabolism. We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for studies having patients with hyperprolactinemia due to prolactinoma and the other being a matched control group. The primary outcome was to evaluate the differences in BMD Z-scores at different sites. The secondary outcomes of this study were to evaluate the alterations in bone mineral density, bone mineral content and the occurrence of fragility fractures. RESULTS: Data from 4 studies involving 437 individuals was analysed to find out the impact of prolactinoma on bone mineral metabolism. Individuals with prolactinoma had significantly lower Z scores at the lumbar spine [MD -1.08 (95 % CI: -1.57 - -0.59); P < 0.0001; I2 = 54 % (moderate heterogeneity)] but not at the femur neck [MD -1.31 (95 % CI: -3.07 - 0.45); P = 0.15; I2 = 98 % (high heterogeneity)] as compared to controls. Trabecular thickness of the radius [MD -0.01 (95 % CI: -0.02 - -0.00); P = 0.0006], tibia [MD -0.01 (95 % CI: -0.02 - -0.00); P=0.03] and cortical thickness of the radius [MD -0.01 (95 % CI: -0.19 - -0.00); P = 0.04] was significantly lower in patients with prolactinoma as compared to controls. The occurrence of fractures was significantly higher in patients with prolactinoma as compared to controls [OR 3.21 (95 % CI: 1.64 - 6.26); P = 0.0006] Conclusion: Bone mass is adversely affected in patients with hyperprolactinemia due to prolactinoma with predominant effects on the trabecular bone.

Trabecular bone score in type 1 diabetes: a meta-analysis of cross-sectional studies.

BACKGROUND: Bone fragility is a recognized complication of type 1 diabetes (T1D). Thus, lower trabecular bone score (TBS) measurements in T1D patients can be predicted. However, the results of current studies on TBS in patients with T1D are inconsistent. In this context, the present study aimed to test the hypothesis that T1D is associated with lower TBS through a meta-analysis. METHODS: An electronic search of the literature was conducted using PubMed, Embase and Web of science databases to identify studies related to TBS and T1D, supplemented by an additional manual check of the reference list of relevant original and review articles. All data was analyzed using a random effects model. Results were compared using standardized mean differences (SMD) and 95% confidence intervals (CI). P ≤ 0.05 was considered statistically significant. Review Manager 5.4 software and Stata 17.0 software were used for statistical analysis. RESULTS: Seven cross-sectional studies involving 848 participants were included. TBS was lower in T1D patients than in healthy controls on random effects analysis, with no heterogeneity (SMD = - 0.39, 95% CI [- 0.53, - 0.24], P < 0.001; I2 = 0%). In addition, by subgroup analysis, T1D patients were strongly associated with reduced TBS in different regions and age groups, and the results were independent of covariate adjustment. CONCLUSION: This study showed that TBS was lower in patients with T1D than in healthy individuals with normal blood glucose levels, suggesting that TBS may be a useful measure to assess fracture risk in T1D.

Neuropilin 2 in osteoblasts regulates trabecular bone mass in male mice.

Introduction: Neuropilin 2 (NRP2) mediates the effects of class 3 semaphorins and vascular endothelial growth factor and is implicated in axonal guidance and angiogenesis. Moreover, NRP2 expression is suggested to be involved in the regulation of bone homeostasis. Indeed, osteoblasts and osteoclasts express NRP2 and male and female global Nrp2 knockout mice have a reduced bone mass accompanied by reduced osteoblast and increased osteoclast counts. Methods: We first examined the in vitro effect of the calciotropic hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on Nrp2 transcription in osteoblasts. We next generated mice with a conditional deletion of Nrp2 in the osteoblast cell lineage under control of the paired related homeobox 1 promoter and mice with a conditional Nrp2 knockdown in osteoclasts under control of the Lysozyme promoter. Mice were examined under basal conditions or after treatment with either the bone anabolic vitamin D3 analog WY 1048 or with 1,25(OH)2D3. Results and discussion: We show that Nrp2 expression is induced by 1,25(OH)2D3 in osteoblasts and is associated with enrichment of the vitamin D receptor in an intronic region of the Nrp2 gene. In male mice, conditional deletion of Nrp2 in osteoblast precursors and mature osteoblasts recapitulated the bone phenotype of global Nrp2 knockout mice, with a reduced cortical cross-sectional tissue area and lower trabecular bone content. However, female mice with reduced osteoblastic Nrp2 expression display a reduced cross-sectional tissue area but have a normal trabecular bone mass. Treatment with the vitamin D3 analog WY 1048 (0.4 µg/kg/d, 14 days, ip) resulted in a similar increase in bone mass in both genotypes and genders. Deleting Nrp2 from the osteoclast lineage did not result in a bone phenotype, even though in vitro osteoclastogenesis of hematopoietic cells derived from mutant mice was significantly increased. Moreover, treatment with a high dose of 1,25(OH)2D3 (0.5 µg/kg/d, 6 days, ip), to induce osteoclast-mediated bone resorption, resulted in a similar reduction in trabecular and cortical bone mass. In conclusion, osteoblastic Nrp2 expression is suggested to regulate bone homeostasis in a sex-specific manner.

Trabecular Bone Score as a More Sensitive Tool to Evaluate Bone Involvement in MEN1-related Primary Hyperparathyroidism.

CONTEXT: The skeletal involvement of multiple endocrine neoplasia type 1-related primary hyperparathyroidism (MHPT) is not exactly the same as that of sporadic primary hyperparathyroidism (SHPT). Trabecular bone score (TBS) as a texture parameter has been reported to reflect trabecular bone damage. OBJECTIVE: This study aimed to compare the clinical characteristics, especially the skeletal involvement, between patients with MHPT and SHPT. METHODS: The clinical characteristics were retrospectively collected in 120 patients with MHPT and compared with 360 patients with SHPT in the same period. Dual-energy X-ray absorptiometry were conducted in some patients with MHPT, in whom bone mineral density (BMD) and calculated TBS derived from lumbar spine dual-energy X-ray absorptiometry images were compared with those of patients with SHPT. RESULTS: Although the duration of disease in the MHPT group was longer, the age at hospital visit was significantly lower than that in the SHPT group (43.5 [interquartile range, 31.5-52.0] vs 52.0 [interquartile range, 40.5-61.0], P < .001). The proportion of skeletal involvement in the MHPT group was significantly lower. However, in the subgroup of MHPT cases (n = 86) with data of BMD, there was no significant difference in skeletal involvement from SHPT cases matched for gender and age. Although the BMD and TBS in the lumbar spines of patients with MHPT were lower than those of patients with SHPT (BMD: 0.91 ± 0.18 g/cm2 vs 1.01 ± 0.17 g/cm2; TBS: 1.22 ± 0.14 vs 1.29 ± 0.11, P < .001). According to TBS, among 34 patients with MHPT with normal BMD, 15 patients had bone microstructure damage. CONCLUSION: The cancellous bone microarchitecture was more severely damaged in patients with MHPT according to TBS, which suggested that TBS could be a sensitive supplemental index in addition to BMD to identify bone-involvement risk in patients with MHPT.

Trabecular bone score and bone mineral density as indices of skeletal fragility in endogenous Cushing's syndrome.

OBJECTIVE: Endogenous Cushing's syndrome (CS) is a known cause of secondary osteoporosis. Vertebral fractures (VFs) in endogenous CS may occur despite normal bone mineral density (BMD). Trabecular bone score (TBS) is a relatively new, non-invasive technique to assess bone microarchitecture. The objective of our study was to analyse the BMD and bone microarchitecture using TBS in endogenous CS and compare it with a group of age and sex-matched healthy controls, and also analyse the factors predicting BMD and TBS. DESIGN: Cross-sectional study of cases and controls. PATIENTS AND MEASUREMENTS: We included 40 female patients with overt endogenous CS, out of which 32 were adrenocorticotropic hormone (ACTH)-dependent CS and 8 were ACTH-independent. We also included 40 healthy, female controls. Both patients and controls were subjected to an assessment of biochemical parameters and BMD and TBS. RESULTS: Patients with endogenous CS had significantly lower BMD at the lumbar spine, femoral neck, and total hip and significantly lower TBS than healthy controls (all p < .001), while no significant difference was noted in the distal radius BMD (p = .055). In endogenous CS, a large proportion of patients, n = 13 (32.5%) had normal BMD for age (BMD Z-score ≥ -2.0) with low TBS (L1 -L4 TBS ≤ 1.34). TBS correlated negatively with HbA1c (p = .006), and positively with serum T4 (p = .027). CONCLUSION: TBS should be considered an important complementary tool in addition to BMD for the routine assessment of skeletal health in CS.

Fracture risk gradient assessed by categories of bone mineral density and trabecular bone score: the Manitoba BMD Registry.

Trabecular bonescore (TBS) helps to predict fracture risk in older adults. In this registry-based cohort study of patients aged 40 years and older, reduction in bone mineral density (BMD) and TBS are complementary for fracture risk prediction enhancement with lower BMD imparting greater risk than reduction in TBS. PURPOSE: Trabecular bone score (TBS) enhances fracture risk prediction independent of bone mineral density (BMD) in older adults. The purpose of this study was to further evaluate the gradient of fracture risk based on TBS tertile categories and WHO BMD categories, adjusted for other risk factors. METHODS: Using the Manitoba DXA registry, patients aged 40 years and older with spine/hip DXA and L1-L4 TBS were identified. Any incident fractures, major osteoporotic fractures (MOF), and hip fractures were identified. Cox regression models were used to estimate unadjusted and covariate-adjusted hazard ratios (HR, 95%CI) for incident fracture by BMD and TBS category and for each SD decrease in BMD and TBS. RESULTS: The study population included 73,108 individuals, 90% female with mean age 64 years. Mean (SD) minimum T-score was - 1.8 (1.1), and mean L1-L4 TBS was 1.257 (0.123). Lower BMD and TBS, both per SD, by WHO BMD category and by TBS tertile category, were significantly associated with MOF, hip, and any fracture (all HRs p < 0.001). However, the quantum of risk was consistently greater for BMD than TBS, with HRs showing non-overlapping CIs. CONCLUSION: TBS is complementary to BMD in prediction of incident major, hip, and any osteoporosis-related fracture, but reductions in BMD impart greater risk than reductions in TBS on both continuous and categorical scales.

Microstructural Analysis of Cancellous Bone in Fluorosis Rats.

Skeletal fluorosis likely alters bone structural properties on the cortical and cancellous tissue levels in view that fluorine ion replaces bone mineral composition. Our previous study showed high bone turnover occurred in cortical bone of skeletal fluorosis. Therefore, this study further analyzed the microstructure of cancellous bone in fluorosis rats. Rats were randomly assigned into three groups: the control, low-dose fluoride group (10 mgF-/kg·day), and high-dose fluoride group (20 mgF-/kg·day). Rats were orally administered with fluoride for 1, 2, and 3 months of periods. The trabecular bone parameters of tibia were detected with micro CT and analyzed with software. The activities of glutathione peroxidase (GPX), superoxide dismutase (SOD), and the content of malondialdehyde (MDA) in serum were measured. Results showed that severity of dental fluorosis rose with the increase of dose and prolongation of fluoride exposure. Meantime, the poorer connectivity and less trabecular bone network were observed in cancellous bone of rats treated with fluoride. Data analysis indicated that fluoride treatment significantly decreased bone volume and connectivity degree, but amplified trabecular space in 1 and 2 months of periods. Intriguingly, trabecular thickness significantly decreased in 1-month high-dose fluoride group, but returned to the control in 3 months of period. Fluoride treatment mainly inhibited the GPX activity and increased the MDA level to activate oxidative stress. This study confirmed that excessive fluoride impaired cancellous bone and caused redox imbalance.

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

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

Evaluation of mandibular bone density in bruxers: the value of panoramic radiographs.

OBJECTIVES: This study aimed to establish a difference in mandibular bone density between bruxer and non-bruxer patients, based on panoramic radiographs. METHODS: Panoramic radiographs of bruxer and non-bruxer patients were analyzed with ImageJ®. Several radiological determinants were studied on the patients' panoramic radiographs: gray values of cancellous bone and cortical bone, and bony exostoses at the mandibular angle. RESULTS: Thirty-seven bruxers and forty-seven non-bruxers were included in the study. A statistically significant difference (p < 0.05) was noted in the cancellous to cortical bone ratios of bruxers and non-bruxers: the density of cancellous bone was greater in bruxers than in non-bruxers. The number of bony exostoses at the mandibular angle was significantly higher in bruxers (p < 0.05). CONCLUSIONS: This study obtained radiological determinants of bruxism from panoramic radiographs. Further studies are needed to supplement this preliminary approach, especially via the analysis of three-dimensional imaging to overcome the limitations of panoramic radiography.

The association of opioid consumption and osteoporosis in old men: Bushehr Elderly Health (BEH) program.

In a population of 1156 men aged ≥ 60 years, opioid drug use was reported by 4.1% (n = 47) of participants. Among opioids, opium was the most prevalent consuming drug (83%). Adjusting for potential confounders, opioid consumption showed a positive association with osteoporosis. PURPOSE: Limited evidence suggest a relationship between opioid consumption and osteoporosis. This study aims to investigate the possible association of osteoporosis and drug use among older adult men of Bushehr, Iran. METHODS: In this study, 1156 men aged ≥ 60 years of Bushehr Elderly Health (BEH) were included. Bone density and trabecular bone score (TBS) were measured using dual-energy X-ray absorptiometry. Total osteoporosis was noted based on osteoporosis at either site of the lumbar spine, femoral neck, and total hip densitometry. Drug use was defined as a self-reported current use of opioid drugs, either regular (daily) use or irregular consumption. Multivariable modified Poisson regression analysis was used for investigating the association of opioids and osteoporosis, reporting the adjusted prevalence ratio (APR) with 95% confidence interval (CI). The association between drug use and TBS was evaluated using a linear regression model. RESULTS: Opioid drug use was reported by 4.1% (n = 47) of participants. Among drug users, opium was the most prevalent consuming drug (83%). In all, 38.3% of drug users and 22.4% of non-users had osteoporosis (p-value = 0.011). Multivariable analysis showed that adjusting by age, education, smoking, alcohol consumption, body mass index, diabetes, and physical activity, a positive and significant association was detected between opioid drug use and the likelihood of osteoporosis (APR: 1.46, 95%CI: 1.02-2.10). Considering the potential confounders, the results also showed a negative association between drug consumption and TBS (ß: - 0.027, 95%CI: - 0.053, - 0.001). CONCLUSION: Opioid drug use has a positive association with osteoporosis in elderly men, independent of other conventional risk factors. Elderly drug users might be at a higher risk for osteoporotic fractures, given the effect of substance use on cognition. So, osteoporosis among drug users would be of importance, especially in countries where opium consumption is prevalent.

Trabecular bone score in the hip: a new method to examine hip bone microarchitecture-a feasibility study.

Our study found, in older adults who are residents of long-term care facilities, assessing hip microarchitecture with DXA-derived bone texture score may serve as a supplement to bone mineral density to improve fracture prediction and to facilitate decision-making for pharmacological management. PURPOSE: Many patients with high fragility fracture risk do not have a sufficiently low bone mineral density (BMD) to become eligible for osteoporosis treatment. They often have deteriorated bone microarchitecture despite a normal or only mildly abnormal BMD. We sought to examine the beta version of the trabecular bone score (TBS) algorithm for the hip: TBS Hip, an indirect index of bone microarchitecture, and assess if TBS Hip brings complementary information to other bone quality indices such as BMD and bone turnover markers (BTMs) to further improve identifying individuals who are at high risk for fractures. METHODS: In this analysis, we considered baseline TBS Hip at total hip, femoral neck, and greater trochanter, TBS at lumbar spine, BMD at all of these skeletal sites, and BTMs in 132 postmenopausal women who were residents of long-term care (LTC) facilities enrolled in a randomized placebo-controlled osteoporosis clinical trial. RESULTS: On average, participants were 85.2 years old and had a BMI of 26.9 kg/m2. The correlation coefficient between BMD and TBS Hip at total hip, femoral neck, and greater trochanter was 0.50, 0.32, and 0.39 respectively (all p < 0.0001). The correlation coefficient between BMD and lumbar spine TBS was 0.52 (p < 0.0001). There was no statistically significant correlation between BTMs with TBS at lumbar spine or TBS Hip at total hip, femoral neck, and greater trochanter. CONCLUSION: Among older women residing in LTC facilities, there was a moderate correlation between measures of BMD and TBS Hip at total hip, femoral neck, and greater trochanter, suggesting TBS Hip may provide complementary information to BMD .

Therapy With Intravenous Methylprednisolone Pulses Is Associated With Loss of Bone Microarchitecture in Trabecular Bone Score -Assessment Among Patients With Moderate-to-Severe Graves' Orbitopathy: A Pilot Study.

Background: Therapy with intravenous glucocorticoids (GCs) is associated with various side effects, however, the impact on bone remains elusive. Trabecular bone score (TBS) is a diagnostic tool providing information on bone microarchitecture based on images obtained from dual-energy X-ray absorptiometry. We investigated the influence of the intravenous methylprednisolone (IVMP) pulse administration on TBS in patients with moderate-to-severe Graves' orbitopathy (GO). Methods: Fifteen patients with GO were treated with 12 IVMP pulses (6x0.5g, 6x0.25 g on a weekly schedule). They received supplementation with 2000 IU of vitamin D and 1.0 g of calcium throughout the study period. TBS was assessed at baseline and after last IVMP pulse. To determine the difference between values at baseline and after treatment the least significant change (LSC) methodology was used. We compared pre- and posttreatment mean TBS values. Results: We found a significant decrease of TBS in 5 out of 15 (33%) patients. Mean TBS value decreased becoming 2.4% lower than at baseline (p<0.05). Conclusions: IVMP pulse therapy exerts negative effect on bone microarchitecture in TBS assessment. The analysis of the clinical risk factors for osteoporosis and the evaluation of bone mineral density and TBS should be considered before initiating IVMP therapy.

Effects of Korean red ginseng on three-dimensional trabecular bone microarchitecture and strength in growing rats: Comparison with changes due to jump exercise.

OBJECTIVES: The preventive effects of Korean red ginseng (KRG) on bone loss and microarchitectural deterioration have been extensively studied in animal models. However, few results have been reported for the effects of KRG on the trabecular microarchitecture as compared to changes resulting from physiological stimuli such as exercise load. We compared the effects of KRG and jump exercise on improvements in trabecular microarchitecture and strength of the distal femoral metaphysis in rats. METHODS AND MATERIALS: Eleven-week-old male Wistar rats were divided into sedentary (CON), KRG-administered (KRG), and jump-exercised (JUM) groups. Rats were orally administered KRG extract (200 mg/kg body weight/day) once a day for 6 weeks. The jump exercise protocol comprised 10 jumps/day, 5 days/week at a jump height of 40 cm. We used microcomputed tomography to assess the microarchitecture, volumetric bone mineral density (vBMD), and fracture load as predicted by finite element analysis at the right distal femoral metaphysis. The left femur was used for the quantitative bone histomorphometry measurements. RESULTS: Although KRG produced significantly higher trabecular bone volume (BV/TV) than CON, BV/TV was even higher in JUM than in KRG, and differences in vBMD and fracture load were only significant between JUM and CON. In terms of trabecular microarchitecture, KRG increased trabecular number and connectivity, whereas the JUM group showed increased trabecular thickness. Bone resorption showed significant decrease by JUM and KRG group. In contrast, bone formation showed significant increase by JUM group. CONCLUSIONS: These data show that KRG has weak but significant positive effects on bone mass and suggest that the effects on trabecular microarchitecture differ from those of jump exercise. The effects of combined KRG and jump exercise on trabecular bone mass and strength should be investigated.

Vertebral fractures, trabecular bone score and their determinants in chronic hypoparathyroidism.

PURPOSE: Patients with hypoparathyroidism are at risk of vertebral fractures (VFs) despite high bone mineral density (BMD). We investigated this paradox by assessing trabecular bone score (TBS) and hip structural analysis (HSA) in non-surgical chronic hypoparathyroidism (cHypoPT) with and without VFs. METHODS: 152 cHypoPT patients (age 40.2 ± 13.4 years, M: F = 81:71) with a median follow-up of 8 (2-13) years were assessed for BMD, VFs, TBS, and HSA and compared with 152 healthy controls. VFs at T7-L4 were assessed by Genant's method. Average serum total calcium and phosphorus during follow-up were assessed. RESULTS: The lumbar spine and hip BMD were higher by 25.4 and 13.4% in cHypoPT than controls (P < 0.001). Paradoxically, VFs (30.9 vs.7.9%), including multiple (12.5 vs. 2.6%) were higher in cHypoPT (P < 0.001). Though overall average TBS (1.411 ± 0.091) was normal in cHypoPT, 25.4% of the females had subnormal TBS, more in post than pre-menopausal women (52.3 vs. 14%, P = 0.002) and as compared to males (6.1%, P = 0.001). TBS correlated with menopausal status and follow-up serum calcium-phosphorus product. For every gm/cm2 rise in BMD, TBS increase was only 0.227 in cHypoPT compared to 0.513 in controls. Frequency of VFs increased with declining TBS (P = 0.004). HSA was comparable between cHypoPT with and without VFs. 23.4% of cHypoPT with VFs had subnormal TBS. CONCLUSION: 31% of cHypoPT patients had VFs. TBS indicated degraded bone microarchitecture in 50% of the post-menopausal cHypoPT women. However, TBS has limitations to detect abnormal bone microarchitecture in cHypoPT as only one-fourth of patients with VFs showed low TBS.

A computational framework for canonical holistic morphometric analysis of trabecular bone.

Bone is a remarkable, living tissue that functionally adapts to external loading. Therefore, bone shape and internal structure carry information relevant to many disciplines, including medicine, forensic science, and anthropology. However, morphometric comparisons of homologous regions across different individuals or groups are still challenging. In this study, two methods were combined to quantify such differences: (1) Holistic morphometric analysis (HMA) was used to quantify morphometric values in each bone, (2) which could then be mapped to a volumetric mesh of a canonical bone created by a statistical free-form deformation model (SDM). Required parameters for this canonical holistic morphometric analysis (cHMA) method were identified and the robustness of the method was evaluated. The robustness studies showed that the SDM converged after one to two iterations, had only a marginal bias towards the chosen starting image, and could handle large shape differences seen in bones of different species. Case studies were performed on metacarpal bones and proximal femora of different primate species to confirm prior study results. The differences between species could be visualised and statistically analysed in both case studies. cHMA provides a framework for performing quantitative comparisons of different morphometric quantities across individuals or groups. These comparisons facilitate investigation of the relationship between spatial morphometric variations and function or pathology, or both.

Micro-CT analysis of the mandibular bone microarchitecture of rats after radiotherapy and low-power laser therapy.

To investigate whether low-level laser therapy (LLLT), at different times of application (immediate and late) in the region of the parotid glands, has a distance effect on the microarchitecture of the trabecular bone in mandible of rats irradiated by volumetric modular arc therapy (VMAT). Thirty adult Wistar rats were randomly divided into placebo control groups (CG, n = 2), only radiotherapy (RG, n = 2), only LPLT (LG, n = 2), and two other groups using LLLT in the immediate time (24 h) (ILG, n = 12) and late (120 h) (LLG, n = 12) to radiotherapy by VMAT in a single dose of 12 Gy. LLLT with AsGaAl laser (660 nm, 100 mW), a spot size of 0.0028 cm2, was applied in three points in the region of the right parotid gland, with energy of 2 J/cm2, 20 s per point, for 10 consecutive days. After euthanasia, the right hemimandibles of each animal were dissected, prepared, and analyzed by computerized microtomography (micro-CT) and histomorphometry. The different groups were analyzed by the Tukey and Bonferroni multiple comparison tests. The micro-CT analysis found statistically significant differences between the groups, especially in the LLG, which had the highest average bone volume compared to the CG (p = 0.001) and ILG (p = 0.002) and a greater number of trabeculae than the CG (p = 0.000) and ILG (p = 0.031). The ILG also had a higher number of trabeculae than the CG (p = 0.005). Trabecula separation (Tb.Sp) was lower in the LLG (p = 0.000) and ILG (p = 0.002) when compared to the CG. In the histomorphometry, there was no statistical difference between the groups in relation to all the analyzed variables. Micro-CT analysis showed that the LLLT, even applied at a distance, both in the immediate and late VMAT times, has an effect on the mandibular bone microarchitecture by increasing the volume and number of trabeculae and decreasing the spaces between them.

Prediabetes and insulin resistance are associated with lower trabecular bone score (TBS): cross-sectional results from the Study of Women's Health Across the Nation TBS Study.

In pre- and early perimenopausal women, prediabetes (with blood glucose ≥ 110 mg/dL) and greater insulin resistance are associated with worse trabecular bone quality (as assessed by trabecular bone score). PURPOSE: Diabetes mellitus (DM) is associated with lower trabecular bone score (TBS) and fracture; less certain is whether the precursor states of prediabetes and increased insulin resistance are also related to adverse bone outcomes. We examined, in women who do not have DM, the associations of glycemic status (prediabetes vs. normal) and insulin resistance with TBS. METHODS: This was a cross-sectional analysis of baseline data collected from 42- to 52-year-old, pre- and perimenopausal participants in the Study of Women's Health Across the Nation (SWAN) TBS Study. Women with prediabetes were categorized as having either high prediabetes if their fasting glucose was between 110 and 125 mg/dL or low prediabetes if their fasting glucose was between 100 and 109 mg/dL. Normoglycemia was defined as a fasting glucose below 100 mg/dL. RESULTS: In multivariable linear regression, adjusted for age, race/ethnicity, menopause transition stage, cigarette use, calcium and vitamin D supplementation, lumbar spine bone mineral density, and study site, women with high prediabetes had 0.21 (p < 0.0001) standard deviations (SD) lower TBS than those with normoglycemia. Low prediabetes was not associated with lower TBS. When HOMA-IR levels were ≥ 1.62, each doubling of HOMA-IR was associated with a 0.11 SD decrement in TBS (p = 0.0001). CONCLUSION: Similar to diabetics, high prediabetics have lower TBS than normoglycemic individuals. Women with greater insulin resistance have lower TBS even in the absence of DM. Future studies should examine the associations of high prediabetes and insulin resistance with incident fracture.

Diosmin, a citrus fruit-derived phlebotonic bioflavonoid protects rats from chronic kidney disease-induced loss of bone mass and strength without deteriorating the renal function.

Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline has recommended treatment decisions for patients with chronic kidney disease (CKD) with osteoporosis and/or high risk of fracture. Bisphosphonates, the first-line anti-osteoporosis drugs have the concern of worsening kidney functions. Moreover, despite impaired bone formation in CKD patients, teriparatide, the formation-stimulating drug is not recommended. Thus, there is an urgent need for safe and effective treatment of osteoporosis in CKD patients. Here, in CKD rats, we tested the osteoprotective effect of diosmin, a citrus-derived bioflavonoid used as a phlebotonic in chronic venous insufficiency and has a renoprotective effect. CKD was developed by 5/6th nephrectomy and diosmin at the human equivalent dose (100 mg kg-1) did not advance renal failure but reduced blood pressure to the level of sham control. Fibroblast growth factor-23 and parathyroid hormone were increased in CKD and diosmin suppressed both. CKD reduced bone mass and deteriorated the microarchitecture of trabecular bones, and diosmin maintained both to control levels. Bone formation and strength were impaired in the CKD and diosmin maintained these levels to control levels. Nanoindentation of bone showed that diosmin significantly increased tissue hardness over the control. Diosmetin, the metabolic surrogate of diosmin had comparable pharmacokinetic profiles between the control and CKD groups. Furthermore, diosmetin (50 mg kg-1) protected against CKD-induced bone loss. These data suggest that diosmin and its metabolic surrogate, diosmetin protect against CKD-induced osteopenia. Since diosmin has no renal adverse effect and protected bone mass and strength in CKD rats, we propose assessing its anti-osteoporosis effect in CKD patients.

Ethanolic extract of Pyrrosia lingua (Thunb.) Farw. ameliorates OVX-induced bone loss and RANKL-induced osteoclastogenesis.

Pyrrosia lingua (Thunb.) Farw is a common plant that has been widely used as a traditional herbal medicine in China and Korea to treat patients suffering from pain, vaginal bleeding and urolithiasis. However, the pharmacological effects of P. lingua on bone remain unknown. We investigated the anti-osteoporotic effects of an ethanolic extract of P. lingua (EEPL). We found that EEPL suppressed osteoclast differentiation by directly acting on osteoclast precursor cells. EEPL suppressed the expression of receptor activator of nuclear factor-κB ligand (RANKL)-induced nuclear factor of activated T cells 1, a major transcription factor for osteoclastogenesis, by inhibiting RANKL-induced expression of aryl hydrocarbon receptor/c-Fos, and activation of nuclear factor-κB and mitogen-activated protein kinases. Moreover, administration of EEPL inhibited trabecular bone loss and weight gain in ovariectomized mice. Furthermore, we identified phytochemicals in EEPL that are known to exert anti-osteoclastogenic or anti-osteoporotic effects using ultra-high-performance liquid chromatography-tandem mass-spectrometry analysis. Overall, the results of this study suggest that EEPL is effective therapeutic candidate that can be used to prevent or treat postmenopausal osteoporosis.