An investigation of composition, morphology, mechanical properties, and microdamage accumulation of human type 2 diabetic bone.

This study investigates the biomechanics of type 2 diabetic bone fragility through a multiscale experimental strategy that considers structural, mechanical, and compositional components of ex vivo human trabecular and cortical bone. Human tissue samples were obtained from the femoral heads of patients undergoing total hip replacement. Mechanical testing was carried out on isolated trabecular cores using monotonic and cyclic compression loading and nanoindentation experiments, with bone microdamage analysed using micro-computed tomography (CT) imaging. Bone composition was evaluated using Raman spectroscopy, high-performance liquid chromatography, and fluorometric spectroscopy. It was found that human type 2 diabetic bone had altered mechanical, compositional, and morphological properties compared to non-type 2 diabetic bone. High-resolution micro-CT imaging showed that cores taken from the central trabecular region of the femoral head had higher bone mineral density (BMD), bone volume, trabecular thickness, and reduced trabecular separation. Type 2 diabetic bone also had enhanced macro-mechanical compressive properties under mechanical loading compared to non-diabetic controls, with significantly higher apparent modulus, yield stress, and pre-yield toughness evident, even when properties were normalised against the bone volume. Using nanoindentation, there were no significant differences in the tissue-level mechanical properties of cortical or trabecular bone in type 2 diabetic samples compared to controls. Through compositional analysis, higher levels of furosine were found in type 2 diabetic trabecular bone, and an increase in both furosine and carboxymethyl-lysine (an advanced glycation end-product) was found in cortical bone. Raman spectroscopy showed that type 2 diabetic bone had a higher mineral-to-matrix ratio, carbonate substitution, and reduced crystallinity compared to the controls. Together, this study shows that type 2 diabetes leads to distinct changes in both organic and mineral phases of the bone tissue matrix, but these changes did not coincide with any reduction in the micro- or macro-mechanical properties of the tissue under monotonic or cyclic loading.

Evaluation of bone density and microarchitecture in adult patients with X-linked hypophosphatemic rickets: A pilot longitudinal study.

X-linked Hypophosphatemia (XLH) is the most common type of inherited rickets. Although the clinical features are well characterized, bone structure, mineralization, and biomechanical properties are poorly known. Our aim was to analyze bone properties in the appendicular and axial skeleton of adults with XLH. In this observational case-control study, each affected patient (N = 14; 9 females; age 50 ± 15 years) was matched by sex, age and body mass index to a minimum of two healthy controls (N = 34). Dual-energy X-ray Absorptiometry (DXA) analyses revealed that areal bone mineral density (aBMD) was higher in XLH patients at the lumbar spine (Z score mean difference = +2.47 SD, P value = 1.4 × 10-3). Trabecular Bone Score was also higher at the lumbar spine (P value = 1.0 × 10-4). High Resolution peripheral Quantitative Computed Tomography (HRpQCT) demonstrated that bone cross-sectional area was larger at the distal radius (P value = 6 × 10-3). Total and trabecular volumetric BMD were lower at both sites. Trabecular bone volume fraction was also lower with fewer trabecular numbers at both sites. However, bone strength evaluated by micro-finite element analyzes revealed unaffected bone stiffness and maximum failure load. Evaluation of bone mineralization with aBMD by DXA at the distal radius correlated with vBMD by HRpQCT measurements at both sites. PTH levels were inversely correlated with trabecular vBMD and BV/TV at the tibia. We then followed a subset of nine patients (median follow-up of 4 years) and reassessed HRpQCT. At the tibia, we observed a greater decrease than expected from an age and sex standardized normal population in total and cortical vBMD as well as a trabecularization of the cortical compartment. In conclusion, in adult patients with XLH, bone mineral density is high at the axial skeleton but low at the appendicular skeleton. With time, microarchitectural alterations worsen. We propose that noninvasive evaluation methods of bone mineralization such as DXA including the radius should be part of the management of XLH patients. Larger studies are needed to evaluate the clinical significance of BMD changes in XLH patients under conventional or targeted therapies.

Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

Trabecular bone mineral density as measured by thoracic vertebrae predicts incident hip and vertebral fractures: the multi-ethnic study of atherosclerosis.

We evaluated the relationship of bone mineral density (BMD) by computed tomography (CT), to predict fractures in a multi-ethnic population. We demonstrated that vertebral and hip fractures were more likely in those patients with low BMD. This is one of the first studies to demonstrate that CT BMD derived from thoracic vertebrae can predict future hip and vertebral fractures. PURPOSE/INTRODUCTION: Osteoporosis affects an enormous number of patients, of all races and both sexes, and its prevalence increases as the population ages. Few studies have evaluated the association between the vertebral trabecular bone mineral density(vBMD) and osteoporosis-related hip fracture in a multiethnic population, and no studies have demonstrated the predictive value of vBMD for fractures. METHOD: We sought to determine the predictive value of QCT-based trabecular vBMD of thoracic vertebrae derived from coronary artery calcium scan for hip fractures in the Multi-Ethnic Study of Atherosclerosis(MESA), a nationwide multicenter cohort included 6814 people from six medical centers across the USA and assess if low bone density by QCT can predict future fractures. Measures were done using trabecular bone measures, adjusted for individual patients, from three consecutive thoracic vertebrae (BDI Inc, Manhattan Beach CA, USA) from non-contrast cardiac CT scans. RESULTS: Six thousand eight hundred fourteen MESA baseline participants were included with a mean age of 62.2 ± 10.2 years, and 52.8% were women. The mean thoracic BMD is 162.6 ± 46.8 mg/cm3 (95% CI 161.5, 163.7), and 27.6% of participants (n = 1883) had osteoporosis (T-score 2.5 or lower). Over a median follow-up of 17.4 years, Caucasians have a higher rate of vertebral fractures (6.9%), followed by Blacks (4.4%), Hispanics (3.7%), and Chinese (3.0%). Hip fracture patients had a lower baseline vBMD as measured by QCT than the non-hip fracture group by 13.6 mg/cm3 [P < 0.001]. The same pattern was seen in the vertebral fracture population, where the mean BMD was substantially lower 18.3 mg/cm3 [P < 0.001] than in the non-vertebral fracture population. Notably, the above substantial relationship was unaffected by age, gender, race, BMI, hypertension, current smoking, medication use, or activity. Patients with low trabecular BMD of thoracic vertebrae showed a 1.57-fold greater risk of first hip fracture (HR 1.57, 95% CI 1.38-1.95) and a nearly threefold increased risk of first vertebral fracture (HR 2.93, 95% CI 1.87-4.59) compared to normal BMD patients. CONCLUSION: There is significant correlation between thoracic trabecular BMD and the incidence of future hip and vertebral fracture. This study demonstrates that thoracic vertebrae BMD, as measured on cardiac CT (QCT), can predict both hip and vertebral fractures without additional radiation, scanning, or patient burden. Osteopenia and osteoporosis are markedly underdiagnosed. Finding occult disease affords the opportunity to treat the millions of people undergoing CT scans every year for other indications.

Accuracy of osseointegrated screw-bone construct stiffness and peri-implant loading predicted by homogenized FE models relative to micro-FE models.

Computational predictions of stiffness and peri-implant loading of screw-bone constructs are highly relevant to investigate and improve bone fracture fixations. Homogenized finite element (hFE) models have been used for this purpose in the past, but their accuracy has been questioned given the numerous simplifications, such as neglecting screw threads and modelling the trabecular bone structure as a continuum. This study aimed to investigate the accuracy of hFE models of an osseointegrated screw-bone construct when compared to micro-FE models considering the simplified screw geometry and different trabecular bone material models. Micro-FE and hFE models were created from 15 cylindrical bone samples with a virtually inserted, osseointegrated screw (fully bonded interface). Micro-FE models were created including the screw with threads (=reference models) and without threads to quantify the error due to screw geometry simplification. In the hFE models, the screws were modelled without threads and four different trabecular bone material models were used, including orthotropic and isotropic material derived from homogenization with kinematic uniform boundary conditions (KUBC), as well as from periodicity-compatible mixed uniform boundary conditions (PMUBC). Three load cases were simulated (pullout, shear in two directions) and errors in the construct stiffness and the volume average strain energy density (SED) in the peri-implant region were evaluated relative to the micro-FE model with a threaded screw. The pooled error caused by only omitting screw threads was low (max: 8.0%) compared to the pooled error additionally including homogenized trabecular bone material (max: 92.2%). Stiffness was predicted most accurately using PMUBC-derived orthotropic material (error: -0.7 ± 8.0%) and least accurately using KUBC-derived isotropic material (error: +23.1 ± 24.4%). Peri-implant SED averages were generally well correlated (R2 ≥ 0.76), but slightly over- or underestimated by the hFE models and SED distributions were qualitatively different between hFE and micro-FE models. This study suggests that osseointegrated screw-bone construct stiffness can be predicted accurately using hFE models when compared to micro-FE models and that volume average peri-implant SEDs are well correlated. However, the hFE models are highly sensitive to the choice of trabecular bone material properties. PMUBC-derived isotropic material properties represented the best trade-off between model accuracy and complexity in this study.

Preclinical Evaluation of a Novel 3D-Printed Movable Lumbar Vertebral Complex for Replacement: In Vivo and Biomechanical Evaluation of Goat Model.

PURPOSE: This was an in vivo study to develop a novel movable lumbar artificial vertebral complex (MLVC) in a goat model. The purpose of this study was to evaluate clinical and biomechanical characteristics of MLVC and to provide preclinical data for a clinical trial in the future. METHODS: According to the preoperative X-ray and CT scan data of the lumbar vertebrae, 3D printing of a MLVC was designed and implanted in goats. The animals were randomly divided into three groups: intact, fusion, and nonfusion. In the intact group, only the lumbar vertebrae and intervertebral discs were exposed during surgery. Both the fusion and nonfusion groups underwent resection of the lumbar vertebral body and the adjacent intervertebral disc. Titanium cages and lateral plates were implanted in the fusion group. MLVC was implanted in the nonfusion group. All groups were evaluated by CT scan and micro-CT to observe the spinal fusion and tested using the mechanical tester at 6 months after operation. RESULTS: The imaging results showed that with the centrum, the artificial endplates of the titanium cage and MLVC formed compact bone trabeculae. In the in vitro biomechanical test, the average ROM of L3-4 and L4-5 for the nonfusion group was found to be similar to that of the intact group and significantly higher in comparison to that of the fusion group (P < 0.05). The average ROM of flexion, extension, lateral bending, and rotation in the L2-3 intervertebral space significantly increased in the fusion group compared with the intact group and the nonfusion group (P < 0.001). There were no significant differences in flexion, extension, lateral bending, and rotation between the nonfusion and intact groups (P > 0.05). The average ROM of flexion, extension, lateral bending, and rotation in the L2-5 intervertebral space was not significantly different between the intact group, the fusion group, and the nonfusion group, and there was no statistical significance (P > 0.05). HE staining results did not find any metal and polyethylene debris caused by abrasion. CONCLUSION: In vivo MLVC can not only reconstruct the height and stability of the centrum of the operative segment but also retain the movement of the corresponding segment.

Fibroblast Growth Factor 23 and Klotho Are Associated With Trabecular Bone Score but Not Bone Mineral Density in the Early Stages of Chronic Kidney Disease: Results of the Cross-Sectional Study.

This study evaluates bone mineral density (BMD) and trabecular bone score (TBS) in relationship with new markers of chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23), and klotho. The patients in this cross-sectional study were divided as follows: group A -patients in stages G1-3; group B -patients in stages G4 - 5 according to KDIGO. Plasma levels of soluble klotho and FGF23 were determined by ELISA. Bone mineral density (BMD) and trabecular bone score (TBS) were measured. 74 patients with CKD (mean age 68.8 years) were included in the study. Higher levels of FGF23 were observed in group B (N=15) compared to group A (N=59; p=0.001) were observed. FGF23 was higher in group A compared to group B. Significant difference in TBS within the first 3 stages of CKD was observed (mean TBS in G1=1.375 vs. G2=1.340 vs. G3a=1.24; p<0.05) and negative correlation of FGF23 and TBS (R=-0.33; p=0.05) and positive correlation between klotho and TBS (R=0.419; p=0.04) was observed. This study confirmed that FGF23 and klotho are associated with TBS, but TBS reflects a decrease in kidney function only in the first 3 stages of CKD. Thus, FGF23 and klotho together with TBS are promising markers of early trabecular bone impairment in CKD.

Tributyltin protects against ovariectomy-induced trabecular bone loss in C57BL/6J mice with an attenuated effect in high fat fed mice.

Risk factors for poor bone quality include estrogen loss at menopause, a high fat diet and exposures to drugs/chemicals that activate peroxisome proliferator activated receptor gamma (PPARγ). We previously reported that the PPARγ and retinoid X receptor dual ligand, tributyltin (TBT), repressed periosteal bone formation but enhanced trabecular bone formation in vivo. Here, we examined the interaction of diet, ovariectomy (OVX) and TBT exposure on bone structure. C57BL/6J mice underwent either sham surgery or OVX at 10 weeks of age. At 12 weeks of age, they were placed on a low (10% kcal) or high (45% kcal) fat, sucrose-matched diet and treated with vehicle or TBT (1 or 5 mg/kg) for 14 weeks. OVX increased body weight gain in mice on either diet. TBT enhanced body weight gain in intact mice fed a high fat diet, but decreased weight gain in OVX mice. Elemental tin concentrations increased dose-dependently in bone. TBT had marginal effects on cortical and trabecular bone in intact mice fed either diet. OVX caused a reduction in cortical and trabecular bone, regardless of diet. In high fat fed OVX mice, TBT further reduced cortical thickness, bone area and total area. Interestingly, TBT protected against OVX-induced trabecular bone loss in low fat fed mice. The protective effect of TBT was nullified by the high fat. These results show that TBT protects against trabecular bone loss, even in the presence of a strongly resorptive environment, at an even lower level of exposure than we showed repressed homeostatic resorption.

Metabolic Profile and Bone Status in Post-Menopausal Women with Rheumatoid Arthritis: A Monocentric Retrospective Survey.

Background: Rheumatoid arthritis (RA) and metabolic syndrome (MetS) are chronic conditions that share common inflammatory mechanisms. Both diseases can lead to an impairment of the bone microarchitecture. The aims of our study were to evaluate clinical, metabolic, and bone parameters in RA patients with or without MetS (MetS+, MetS-) and potential correlations between the glico-lipidic profile, RA disease activity, and bone status. Methods: A total of thirty-nine RA female post-menopausal patients were recruited (median age 66.6 ± 10.4, disease duration 3 ± 2.7). Anthropometric data, medical history, and current treatment were recorded along with basal blood tests, bone, and lipid metabolism biomarkers. RA disease activity and insulin resistance were evaluated through standard scores. Quantitative assessment of the bone (bone mineral density-BMD) was performed by dual-energy-X ray absorption (DXA), whereas bone quality was quantified with the trabecular bone score (TBS). Results: No statistically significant differences concerning both BMD and TBS were detected between the MetS+ and MetS- RA patients. However, the MetS+ RA patients exhibited significantly higher disease activity and lower serum 25-hydroxyvitamin D [25(OH)D] concentrations (respectively, p = 0.04 and p = 0.01). In all RA patients, a significant negative correlation emerged between the BMD of the femoral trochanter with plasmatic triglycerides (TG) concentrations (r = -0.38, p = 0.01), whereas the lumbar BMD was positively correlated with the abdominal waist (AW) and fasting glucose (FG) concentrations. On the other hand, the TBS was negatively correlated with insulin concentrations, FG, and RA disease activity (respectively, r = -0.45, p = 0.01, r = -0.40, p = 0.03, r = -0.37, p = 0.04), the last one was further negatively correlated with 25-OHD serum concentrations (r = -0.6, p = 0.0006) and insulin-resistance (r = 0.3, p = 0.04). Conclusions: Bone quantity (BMD) and quality (TBS) do not seem significantly changed among MetS+ and MetS- RA patients; however, among MetS+ patients, both significantly higher disease activity and lower vitamin D serum concentrations were observed. In addition, the significant negative correlations between the alterations of metabolic parameters limited to the TBS in all RA patients might suggest that qualitative bone microarchitecture impairments (TBS) might manifest despite unchanged BMD values.

Recovery of the maternal skeleton after lactation is impaired by advanced maternal age but not by reduced IGF availability in the mouse.

BACKGROUND: Lactation results in substantial maternal bone loss that is recovered following weaning. However, the mechanisms underlying this recovery, and in particular the role of insulin-like growth factor 1 (IGF-I), is not clear. Furthermore, there is little data regarding whether recovery is affected by advanced maternal age. METHODS: Using micro-computed tomography, we studied bone recovery following lactation in mice at 2, 5 and 7 months of age. We also investigated the effects of reduced IGF-I availability using mice lacking PAPP-A2, a protease of insulin-like growth factor binding protein 5 (IGFBP-5). RESULTS: In 2 month old mice, lactation affected femoral trabecular and cortical bone, but only cortical bone showed recovery 3 weeks after weaning. This recovery was not affected by deletion of the Pappa2 gene. The amount of trabecular bone was reduced in 5 and 7 month old mice, and was not further reduced by lactation. However, the recovery of cortical bone was impaired at 5 and 7 months compared with at 2 months. CONCLUSIONS: Recovery of the maternal skeleton after lactation is impaired in moderately-aged mice compared with younger mice. Our results may be relevant to the long-term effects of breastfeeding on the maternal skeleton in humans, particularly given the increasing median maternal age at childbearing.

Loss of longitudinal superiority marks the microarchitecture deterioration of osteoporotic cancellous bones.

Osteoporosis (OP), a skeletal disease making bone mechanically deteriorate and easily fracture, is a global public health issue due to its high prevalence. It has been well recognized that besides bone loss, microarchitecture degradation plays a crucial role in the mechanical deterioration of OP bones, but the specific role of microarchitecture in OP has not been well clarified and quantified from mechanics perspective. Here, we successfully decoupled and identified the specific roles of microarchitecture, bone mass and tissue property in the failure properties of cancellous bones, through µCT-based digital modeling and finite element method simulations on bone samples from healthy and ovariectomy-induced osteoporotic mice. The results show that the microarchitecture of healthy bones exhibits longitudinal superiority in mechanical properties such as the effective stiffness, strength and toughness, which fits them well to bearing loads along their longitudinal direction. OP does not only reduce bone mass but also impair the microarchitecture topology. The former is mainly responsible for the mechanical degradation of bones in magnitude, wherever the latter accounts for the breakdown of their function-favorable anisotropy, the longitudinal superiority. Hence, we identified the microarchitecture-deterioration-induced directional mismatch between material and loading as a hazardous feature of OP and defined a longitudinal superiority index as measurement of the health status of bone microarchitecture. These findings provide useful insights and guidelines for OP diagnosis and treat assessment.

Discriminative ability of trabecular bone score over bone mineral density for vertebral and fragility fracture in patients treated with long-term and low-dose glucocorticoid.

AIM: To evaluate the ability of the trabecular bone score (TBS) to discriminate vertebral fracture (VF) and fragility fracture (FF) in patients with chronic inflammatory rheumatic diseases on long-term and low-dose glucocorticoid (GC) treatment and those without exposure to GC. METHODS: This study assessed TBS and bone mineral density (BMD) in chronic GC users, defined as ≥2.5 mg/d of prednisone for >3 months (n = 89, mean age: 62.5 ± 11 years), and in controls (n = 59, mean age: 60.3 ± 9.6 years). Osteoporosis risk factors, radiographs of the thoracolumbar spine, non-VF history, osteoporosis drugs, and current/cumulative GC doses were collected. Patients were classified as high (TBS <1.23), intermediate (1.23-1.31), or low risk (>1.31), according to the fracture risk based on a recent meta-analysis. RESULTS: The mean current dose and duration of GC treatment were 3.9 ± 1.9 mg/d and 3.9 ± 4.2 years, respectively. The prevalence of VF was significantly higher in chronic GC users than in controls (20.2% vs 5.1%, P = .010), although the prevalence of non-VF was similar (11.2% vs 5.1%). The GC group had significantly lower L1-L4 TBS and femur total BMD than did the controls (all with P < .01) without significantly different lumbar BMD. TBS (<1.31) showed a higher sensitivity for patients with VF and FF (83.3% and 81.8%, respectively) than with densitometric osteoporosis in the GC group (61.1% and 59.1%, respectively). Using the receiver operating characteristic curve, TBS <1.31 showed better diagnostic accuracy than TBS <1.23 and BMD in chronic GC users. CONCLUSION: TBS is more sensitive than BMD in detecting VF and FF in chronic GC users, even at a lower dose.

Is There an Association Between Bone Microarchitecture and Fracture in Patients who were Treated for High-grade Osteosarcoma? A Controlled Study at Long-term Follow-up Using High-resolution Peripheral Quantitative CT.

BACKGROUND: Neoadjuvant chemotherapy in patients with primary osteosarcoma improves survival rates, but it also causes side effects in various organs including bone. Low bone mineral density (BMD) can occur owing partly to chemotherapy or limited mobility. This can cause a higher risk of fractures compared with those who do not receive such treatment. Changes in BMD alone cannot explain the propensity of fractures. Studying microarchitectural changes of bone might help to understand the effect. QUESTIONS/PURPOSES: (1) Do patients who were treated for osteosarcoma (more than 20 years previously) have low BMD? (2) Do these patients experience more fractures than controls who do not have osteosarcoma? (3) What differences in bone microarchitecture are present between patients treated for high-grade osteosarcoma and individuals who have never had osteosarcoma? METHODS: We contacted 48 patients who were treated for osteosarcoma and who participated in an earlier study. These patients underwent multimodal treatment including chemotherapy more than 20 years ago. Of the original patient group, 60% (29 of 48) were missing, leaving 40% (19 of 48) available for inclusion in this study; all 19 agreed to participate. There were nine men and 10 women with a mean age of 46 ± 4 years and a mean time from surgery to examination of 28 ± 3 years. BMD was measured by dual-energy x-ray absorptiometry, and any fracture history was assessed using a questionnaire. Additionally, high-resolution peripheral quantitative CT was performed to compare the groups in terms of microarchitectural changes, such as cortical and trabecular area, cortical and trabecular thickness, cortical porosity, and endocortical perimeter. Participants in the control group were selected from a cohort consisting of a population-based random sample of 499 healthy adult women and men. Osteoporosis or low BMD was not an exclusion criterion for entering this study; however, the patients in the control group were selected based on a normal BMD (that is, T score > -1.0 at both the spine and hip). Also, the participants were matched based on age and sex. Differences between patients and controls were assessed using the Wilcoxon rank sum test for continuous variables and a chi-square test for categorical variables. A multiple regression analysis was performed. Model assumptions were checked using histograms and quantile-quantile plots of residuals. RESULTS: Twelve of 19 patients who were treated for osteosarcoma had either osteopenia (eight patients) or osteoporosis (four patients). More patients with osteosarcoma reported sustaining fractures (11 of 19 patients) than did control patients (2 of 19 controls; p < 0.001). Among all microarchitectural parameters, only the endocortical perimeter was increased in patients compared with the control group (75 ± 15 mm versus 62 ± 18 mm; p = 0.04); we found no differences between the groups in terms of cortical and trabecular area, cortical and trabecular thickness, or cortical porosity. CONCLUSION: Although patients who were treated for osteosarcoma had osteopenic or osteoporotic BMD and a higher proportion of patients experienced fractures than did patients in the control group, we could not confirm differences in microarchitectural parameters using high-resolution peripheral quantitative CT. Therefore, it seems that bone geometry and microstructural parameters are not likely the cause of the increased proportion of fractures observed in our patients who were treated for osteosarcoma. Until we learn more about the bone changes associated with chemotherapy in patients with osteosarcoma, we recommend that patients undergo regular BMD testing, and we recommend that physicians consider osteoporosis treatment in patients with low BMD. These data might provide the impetus for future multicenter prospective studies examining the association between chemotherapy and bone microarchitecture. LEVEL OF EVIDENCE: Level III, therapeutic study.

Evaluating the Value-Added of the Trabecular Bone Score in Patients with Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) presents with inflammation in the joints and bony tissues around them. The trabecular bone score (TBS) is a relatively new indicator that predicts fracture risk better than bone mineral density (BMD). The aim of the current study was to measure TBSs and BMD of patients with RA referring to Resalat Hospital, Tehran. METHODS: In this descriptive cross-sectional study, 129 men and women with RA entered the study through convenient sampling during 2016. TBS and BMD were measured in L1-L4. The relationships between age, sex, body mass index (BMI), duration of disease, and daily corticosteroids dose with TBS and BMD were determined by chi-square test, independent samples t test, Pearson correlation, and linear and logistic regression. RESULTS: The TBS of 34.9%, 31.8%, and 33.3% of study subjects were higher than 1.35, 1.25-1.35, and lower than 1.25, respectively. The prevalence of TBS lower than 1.25 was 48.7% in women aged age more than 50 years. Age was the only predictor of low TBS in patients with RA. TBS and BMD were positively correlated in vertebral and hip bones. In women older than 50 years, BMI (-1.292) and age (-1.330) were predictors of low TBS. CONCLUSION: One-third of patients with RA were at risk of fracture. Gender and BMI were two factors which affected the TBS. This index can show the effect of disease on bones, which is related to age.

Bone Material Strength Index as Measured by Impact Microindentation is Low in Patients with Primary Hyperparathyroidism.

CONTEXT: In primary hyperparathyroidism (PHPT) bone mineral density (BMD) is typically decreased in cortical bone and relatively preserved in trabecular bone. An increased fracture rate is observed however not only at peripheral sites but also at the spine, and fractures occur at higher BMD values than expected. We hypothesized that components of bone quality other than BMD are affected in PHPT as well. OBJECTIVE: To evaluate bone material properties using impact microindentation (IMI) in PHPT patients. METHODS: In this cross-sectional study, the Bone Material Strength index (BMSi) was measured by IMI at the midshaft of the tibia in 37 patients with PHPT (28 women), 11 of whom had prevalent fragility fractures, and 37 euparathyroid controls (28 women) matched for age, gender, and fragility fracture status. RESULTS: Mean age of PHPT patients and controls was 61.8 ±â€…13.3 and 61.0 ±â€…11.8 years, respectively, P = .77. Calcium and PTH levels were significantly higher in PHPT patients but BMD at the lumbar spine (0.92 ±â€…0.15 vs 0.89 ±â€…0.11, P = .37) and the femoral neck (0.70 ±â€…0.11 vs 0.67 ±â€…0.07, P = .15) were comparable between groups. BMSi however was significantly lower in PHPT patients than in controls (78.2 ±â€…5.7 vs 82.8 ±â€…4.5, P < .001). In addition, BMSi was significantly lower in 11 PHPT patients with fragility fractures than in the 26 PHPT patients without fragility fractures (74.7 ±â€…6.0 vs 79.6 ±â€…5.0, P = .015). CONCLUSION: Our data indicate that bone material properties are altered in PHPT patients and most affected in those with prevalent fractures. IMI might be a valuable additional tool in the evaluation of bone fragility in patients with PHPT.

Octanoic acid a major component of widely consumed medium-chain triglyceride ketogenic diet is detrimental to bone.

Octanoic acid is a medium-chained saturated fatty acid found abundantly in the ketogenic dietary supplements containing medium chained triglycerides (MCT) along with decanoic acid. The MCT ketogenic diet is commonly consumed for weight loss but has also showcased neuroprotective potential against neurodegenerative disorders. However, recent clinical findings have reported a critical disadvantage with the long-term consumption of ketogenic diet i.e. bone loss. The following study was employed to investigate whether the two major components of MCT diet also possess bone loss potential as observed with classical ketogenic diet. Swiss albino mice aged between 10 and 12 weeks, were divided into 3 treatment groups that were administered with oral suspensions of octanoic acid, decanoic acid and a combination of both for 4 weeks. Bone specific markers, microarchitectural parameters, using micro computed tomography, and biomechanical strength were analyzed. Remarkably deleterious alterations in the trabecular bone microarchitecture, and on bone markers were observed in the octanoic acid treated groups. Our results suggest significant negative effects on bone health by octanoic acid. These findings require further investigation and validation in order to provide significant clinically relevant data to possibly modify dietary composition of the MCT ketogenic diet.

Hand grip strength in predicting the risk of osteoporosis in Asian adults.

INTRODUCTION: There is a need for a cost-effective method to identify individuals with a high risk of osteoporosis. This study aimed to investigate the suitability of hand grip strength in predicting the risk of osteoporosis in Asian adults. MATERIALS AND METHODS: In this cross-sectional, hospital-based study of 1007 participants, the bone mineral density of the spine and hips was evaluated using dual-energy X-ray absorptiometry according to the 2019 International Society for Clinical Densitometry official positions. Bone microarchitecture was evaluated using the trabecular bone score, and hand grip strength was measured in the dominant hand using a hand digital dynamometer. RESULTS: Hand grip strength was significantly related to bone density and bone microarchitecture. Moreover, hand grip strength was a significant predictor of osteoporosis in both women and men. For osteoporosis prediction in women, a threshold of 21.9 kg of hand grip strength had a sensitivity of 59%, specificity of 59%, and area under the curve (AUC) of 0.61. In men, a threshold of 28.7 kg had a sensitivity of 66%, specificity of 78%, and AUC of 0.75. The optimal cutoff strengths for osteoporosis depended on age and sex. CONCLUSION: The measurement of hand grip strength is a simple, cost-effective and an easy assessment method for identifying individuals at a high risk of osteoporosis. The cutoff strength for evaluating osteoporosis in adults is age and sex specific.

Degradation of subchondral bone collagen in the weight-bearing area of femoral head is associated with osteoarthritis and osteonecrosis.

BACKGROUND: The aim of the study was to evaluate the change of subchondral bone collagen and trabecular bone in the weight-bearing area of femoral head from patients with osteoarthritis (OA) or osteonecrosis of femoral head (ONFH), and discuss the effect of collagen degradation on OA and ONFH. METHODS: Femoral heads from patients with femoral neck fracture (FNF) were collected as control group. All collected samples were divided into OA group (N = 10), ONFH group (N = 10), and FNF group (N = 10). Differences of subchondral bone collagen were compared through scanning electron microscope (SEM) observation, immunohistochemistry staining, and Masson's trichrome staining. Alteration of subchondral bone was displayed through hematoxylin and eosin (H&E) staining and gross morphology. RESULTS: SEM results showed that collagen fibers in OA and ONFH group appeared to be thinner, rougher, sparser, and more wizened. Immunohistochemistry and Masson's trichrome staining results demonstrated that the content of collagen fibers in the OA and ONFH group was obviously less than the FNF group. H&E staining results showed that trabecular bone in OA and ONFH group appeared to be thinner and ruptured. Gross morphology results showed that the degeneration and destruction of cartilage and subchondral bone in OA and ONFH group were severer than FNF group. The characteristics mentioned above in ONFH group were more apparent than OA group. CONCLUSIONS: This study revealed that degradation of collagen fibers from subchondral bone in the weight-bearing area of femoral head was associated with OA and ONFH, which may help to find new therapeutic strategies of the diseases.

Examining trabecular morphology and chemical composition of peri-scaffold osseointegrated bone.

BACKGROUND: Porous titanium alloy scaffold fabricated by 3D printing technology could induce osseointegration well to repair bone defect during early postoperative period. However, trabecular histomorphological features and chemical compositions of ingrowth bone in the long term after surgery still lacked in-depth research. METHODS: Fourteen New Zealand rabbits were divided into two groups (7 rabbits in surgery group and 7 rabbits in control group). A 3D-printed porous titanium alloy scaffold was implanted into right femoral condyle of each rabbit in the surgery group. Preload was produced at the surface between bone tissue and scaffold through interference assembly during implantation process. Rabbits in the control group were feed free. All rabbits were sacrificed to extract femoral condyles at week 12 after surgery. All right femoral condyles were performed micro-CT scanning to test bone mineral density (BMD) and trabecular histomorphological parameters, including bone volume fraction (BV/TV), bone surface/volume ratio (BS/BV), bone surface density (BS/TV), structure model index (SMI), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), porosity (PO), connectivity density (Conn.Dn), and degree of anisotropy (DA). Scanning electron microscope was used to observe osteogenesis peri-scaffold. Fourier transform infrared spectroscopy (FTIR) scanning was performed to analyze chemical compositions of peri-scaffold trabeculae. All trabecular morphological parameters and BMDs were statistically analyzed between surgery group and control group. RESULTS: The pores of scaffold were filled with ingrowth bone tissues after 12 weeks osseointegration. However, the mean BMD peri-scaffold in surgery group was 800 ± 20 mg/cm3, which was 18.37% lower than that in the control group. There was a significant decrease in BV/TV, Tb.N, and BS/TV, and there was a significant increase in Tb.Sp and PO between the surgery group and control group (p < 0.05). There were no significant differences in Tb.Th, SMI, Conn.Dn, BS/BV, and DA. Although ingrowth of bone tissue was very effective, some fragmented connective tissues were still found instead of bone tissues on the partial beams of scaffolds through SEM images. It was found from FTIR that there was no significant hydroxyapatite peak signal in surgery group. Collagen in the control group mainly existed as cross-link structure, while non-cross-link structure in the surgery group. CONCLUSIONS: Preload could promote the same good osseointegration ability as chemical surface modification method in the early term after surgery, and better osseointegration effect than chemical surface modification method in the mid-long term after surgery. However, histomorphological features of peri-scaffold trabeculae were still in deterioration and low collagen maturity caused by stress shielding. It was suggested from this study that extra physical training should be taken to stimulate the bone remodeling process for recovering to a healthy level.