Cortical Bone Geometry Research Articles

Ontogenetic biomechanics of tufted (Sapajus) and untufted (Cebus) capuchin mandibles.

Cortical bone geometry is commonly used to investigate biomechanical properties of primate mandibles. However, the ontogeny of these properties is less understood. Here we investigate changes in cortical bone cross-sectional properties throughout capuchin ontogeny and compare captive versus wild, semi-provisioned groups. Tufted capuchins (Sapajus spp.) are known to consume relatively hard/tough foods, while untufted capuchins (Cebus spp.) exploit less mechanically challenging foods. Previous research indicates dietary differences are present early in development and adult Sapajus mandibles can resist higher bending/shear/torsional loads. This study utilized microCT scans of 22 Cebus and 45 Sapajus from early infancy to adulthood from three sample populations: one captive Cebus, one captive Sapajus, and one semi-provisioned, free-ranging Sapajus. Mandibular cross-sectional properties were calculated at the symphysis, P3, and M1. If the tooth had not erupted, its position within the crypt was used. A series of one-way ANOVAs were performed to assess differences between and within the sample populations. Mandible robusticity increases across ontogeny for all three sample populations. Sapajus were better able to withstand bending and torsional loading even early in ontogeny, but no difference in shear resistance was found. Semi-provisioned, free-ranging Sapajus tend to show increased abilities to resist bending and torsional loading but not shear loading compared to captive Sapajus. This study helps advance our understanding of the primate masticatory system development and opens the door for further studies into adaptive plasticity in shaping the masticatory apparatus of capuchins and differences in captive versus free-ranging sample populations.

Site specific differences in vBMD and geometry in postmenopausal women with primary hyperparathyroidism.

Primary Hyperparathyroidism (PHPT) is associated with catabolic effects at both trabecular and cortical bone. Mechanical loading is one of the most important natural anabolic stimuli for bone at all ages. The present study was designed to assess the impact of PHPT on vBMD and bone geometry using peripheral quantitative computed tomography (pQCT) at the radius and tibia, sites with similar structural characteristics, but subject to different loading conditions. We evaluated the impact of PHPT on bone, by comparing the z-scores of volumetric Bone Mineral Density (vBMD) and indices of bone geometry simultaneously at the tibia and the radius by pQCT, skeletal sites with similar structure, but subject to different loading conditions. Forty-one postmenopausal women with PHPT and 79 controls, comprised the study group. At both trabecular and cortical sites, vBMD and bone geometry indices were significantly lower in patients compared with controls. In patients with PHPT, apart from a lower z-score for total vBMD (p = 0.01) at the radius, there was no other difference between the radius and the tibia at the trabecular sites. On the contrary, at cortical sites, the z-scores of cortical bone mineral content (p = 0.02), cortical vBMD (p = 0.01) and cortical cross-sectional area (p = 0.05) were significantly lower at the radius compared with the tibia, indicating that cortical bone at the weight bearing tibia might be less affected by the catabolic actions of continuous parathyroid hormone (PTH) exposure. PTH levels were positively associated with the difference in z-scores of cort BMD (r = 0.439, p < 0.01) indicating that in more severe cases, as expressed by higher PTH levels, the deleterious effects at the non-weight bearing radius might be accentuated. We found that in postmenopausal women with PHPT, both trabecular and cortical bone are adversely affected. However, at the weight bearing tibia as compared with the radius, the deleterious effects, especially on cortical bone, seem to be attenuated. NCT05426512, 21/06/2022, "retrospectively registered".

Automated, calibration-free quantification of cortical bone porosity and geometry in postmenopausal osteoporosis from ultrashort echo time MRI and deep learning.

Assessment of cortical bone porosity and geometry by imaging in vivo can provide useful information about bone quality that is independent of bone mineral density (BMD). Ultrashort echo time (UTE) MRI techniques of measuring cortical bone porosity and geometry have been extensively validated in preclinical studies and have recently been shown to detect impaired bone quality in vivo in patients with osteoporosis. However, these techniques rely on laborious image segmentation, which is clinically impractical. Additionally, UTE MRI porosity techniques typically require long scan times or external calibration samples and elaborate physics processing, which limit their translatability. To this end, the UTE MRI-derived Suppression Ratio has been proposed as a simple-to-calculate, reference-free biomarker of porosity which can be acquired in clinically feasible acquisition times. To explore whether a deep learning method can automate cortical bone segmentation and the corresponding analysis of cortical bone imaging biomarkers, and to investigate the Suppression Ratio as a fast, simple, and reference-free biomarker of cortical bone porosity. In this retrospective study, a deep learning 2D U-Net was trained to segment the tibial cortex from 48 individual image sets comprised of 46 slices each, corresponding to 2208 training slices. Network performance was validated through an external test dataset comprised of 28 scans from 3 groups: (1) 10 healthy, young participants, (2) 9 postmenopausal, non-osteoporotic women, and (3) 9 postmenopausal, osteoporotic women. The accuracy of automated porosity and geometry quantifications were assessed with the coefficient of determination and the intraclass correlation coefficient (ICC). Furthermore, automated MRI biomarkers were compared between groups and to dual energy X-ray absorptiometry (DXA)- and peripheral quantitative CT (pQCT)-derived BMD. Additionally, the Suppression Ratio was compared to UTE porosity techniques based on calibration samples. The deep learning model provided accurate labeling (Dice score 0.93, intersection-over-union 0.88) and similar results to manual segmentation in quantifying cortical porosity (R2≥0.97, ICC≥0.98) and geometry (R2≥0.82, ICC≥0.75) parameters in vivo. Furthermore, the Suppression Ratio was validated compared to established porosity protocols (R2≥0.78). Automated parameters detected age- and osteoporosis-related impairments in cortical bone porosity (P≤.002) and geometry (P values ranging from <0.001 to 0.08). Finally, automated porosity markers showed strong, inverse Pearson's correlations with BMD measured by pQCT (|R|≥0.88) and DXA (|R|≥0.76) in postmenopausal women, confirming that lower mineral density corresponds to greater porosity. This study demonstrated feasibility of a simple, automated, and ionizing-radiation-free protocol for quantifying cortical bone porosity and geometry in vivo from UTE MRI and deep learning.

Rapid Transition from a High-Fat, High-Fructose to a Low-Fat, Low-Fructose Diet Reverses Gains in Bone Mass and Strength.

Obesity is thought to negatively impact bone quality and strength despite improving bone mineral density. We hypothesized that 1) continuous consumption of a high-fat, high-sugar (HFS) diet would impair bone quality and strength, and 2) a change from an HFS diet to a low-fat, low-sugar (LFS) would reverse HFS-induced impairments to bone quality and strength. Six-week-old male C57Bl/6 mice ( n = 10/group) with access to a running wheel were randomized to an LFS diet or an HFS diet with simulated sugar-sweetened beverages (20% fructose in place of regular drinking water) for 13 wk. HFS mice were subsequently randomized to continuing HFS feeding (HFS/HFS) or transition to the LFS diet (HFS/LFS) for four additional weeks. HFS/HFS mice exhibited superior femoral cancellous microarchitecture (i.e., greater BV/TV, Tb.N, Tb.Th, and decreased Tb.Sp) and cortical bone geometry (i.e., lower Ct.CSA and pMOI) compared with all other groups. At the femoral mid-diaphysis, structural, but not material, mechanical properties were greatest in HFS/HFS mice. However, HFS/HFS exhibited greater femoral neck strength only when compared with mice assigned to diet transition (HFS/LFS). Osteoclast surface and the percentage of osteocytes staining positive for interferon-gamma were greater in HFS/LFS mice, consistent with reduced cancellous microarchitecture postdiet transition. HFS feeding enhanced bone anabolism and structural, but not material, mechanical properties in exercising mice. A change from an HFS to LFS diet returned the bone structure to that of continuously LFS-fed mice while compromising strength. Our results indicate rapid weight loss from obese states should be performed with caution to prevent bone fragility. A deeper analysis into the altered bone phenotype in diet-induced obesity from a metabolic standpoint is needed.

SHP-1 Protein Tyrosine Phosphatase Affects Early Postnatal Bone Development in Mice.

The Src homology region 2 domain-containing phosphatase-1 (SHP-1) is an intracellular tyrosine phosphatase that plays a negative regulatory role in immune cell signaling. Absent or diminished SHP-1 catalytic activity results in reduced bone mass with enhanced bone resorption. Here, we sought to investigate if Shp1 overexpression leads to increased bone mass and improved mechanical properties. Male and female wildtype (WT) and SHP1-transgenic (Tg) mice at 28, 56, and 84days of age were compared. We applied microcomputed tomography to assess femoral cortical bone geometry and trabecular architecture and 3-point mechanical bending to assess mid-diaphyseal structural and estimated material properties. Serum OPG, RANKL, P1NP, and CTX-1 concentrations were measured by enzyme-linked immunoassay. The majority of transgene effects were restricted to the 28-day-old mice. Trabecular bone volume per total volume, trabecular number, and connectivity density were greater in 28-day-old female SHP1-Tg mice when compared to WTs. SHP1-Tg female mice showed increased total and medullary areas, with no difference in cortical area and thickness. Cortical tissue mineral density was strongly genotype-dependent. Failure load, yield load, ultimate stress, and yield stress were all lower in 28-day-old SHP1-Tg females. In 28-day-old SHP1-Tg females, circulating levels of OPG and P1NP were higher and RANKL levels were lower than WT controls. Our study demonstrates a role for SHP-1 in early postnatal bone development; SHP-1 overexpression negatively impacted whole bone strength and material properties in females.

The effects on type 2 diabetes mellitus mouse femoral bone achieved by anti-osteoporosis exercise interventions.

Exercise therapy and key regulators of bone quality exert anti-hyperglycemic effects on type 2 diabetes mellitus (T2DM) mice. A number of programs have been reported to have an effect on bone disease in T2DM. Major unanswered questions concern the potential correlation of exercise with the improvement of bone quality in T2DM mice and how the nonlinear optical properties of bone are correlated with changes to its crystal structure. Subjects were randomly divided into six groups: 1) control (C) group, which was fed a normal diet (n=8); 2) T2DM quiet group, which was given a high-fat diet and quiet (n=8); 3) T2DM plus swimming (T2DM+S) group, which received T2DM and swim training (n=8); 4) T2DM plus resistance exercise (T2DM+RE) group, which was given T2DM and resistance exercise (n=8); 5) T2DM plus aerobic exercise (T2DM+AE) group, with T2DM and medium-intensity treadmill exercise (n=8); and 6) T2DM plus high-intensity interval training (T2DM+HIIT), with T2DM and high-intensity variable-speed intervention (n=8). The levels of runt-related transcription factor 2 (RUNX2), osterix (OSX), and alkaline phosphatase (ALP), as well as the bone microstructure and morphometry, were measured at the end of the 8-week exercise intervention. Compared with the C group, the bone microstructure indexes [bone mineral density (BMD), bone volume/tissue volume (BV/TV), cortical thickness (Ct.Th), and connectivity density (Conn.D)], the bone biomechanical properties (maximum load, fracture load, yield stress, and elastic modulus), and the osteogenic differentiation factors (RUNX2, OSX, and BMP2) of the T2DM group were significantly decreased (all p<0.05). Compared with the T2DM group, there were obvious improvements in the osteogenic differentiation factor (OSX) and Th.N, while the separation of trabecular bone (Tb.Sp) decreased in the T2DM+AE and T2DM+HIIT groups (all p<0.05). In addition, the bone microstructure indicators BV/TV, tissue mineral density (TMD), Conn.D, and degree of anisotropy (DA) also increased in the T2DM+HIIT group, but the yield stress and Ct.Th deteriorated compared with the T2DM group (all p<0.05). Compared with the T2DM+S and T2DM+RE groups, the BV/TV, trabecular number (Tb.N), Tb.Sp, and Conn.D in the T2DM+AE and T2DM+HIIT groups were significantly improved, but no significant changes in the above indicators were found between the T2DM+S and T2DM+RE groups (all p<0.05). In addition, the BMD and the expression of ALP in the T2DM+AE group were significantly higher than those in the T2DM+HIIT group (all p<0.05). There was a significant deterioration in femur bone mass, trabecular bone microarchitecture, cortical bone geometry, and bone mechanical strength in diabetic mice. However, such deterioration was obviously attenuated in diabetic mice given aerobic and high-intensity interval training, which would be induced mainly by suppressing the development of T2DM. Regular physical exercise may be an effective strategy for the prevention of not only the development of diabetes but also the deterioration of bone properties in patients with chronic T2DM.

Effects of whole body vibration on bone properties in growing rats

ABSTRACT This study aimed to examine the continuous effects of whole body vibration (WBV) on bone properties, in growing rats. Fifty 5-week-old male rats were divided into control and experimental groups. Each experimental group underwent WBV at 50 Hz (0.5 g, 15 min/day, 5 days/week) for 5 or 10 weeks. Bone size, muscle weight and bone mechanical strength of the right tibia were measured. Trabecular bone microstructure, cortical bone geometry and bone mass of the left tibia were analyzed by micro-CT. Serum levels of bone formation/resorption markers were also measured. In rats that underwent 5-week WBV, tibial cortical bone mineral content and cortical bone area significantly increased (p < 0.05), and tibial cortical bone volume, thickness, maximum load, break point and stiffness tended to be increased (p = 0.05–0.09), compared with control rats. In rats that underwent 10-week WBV, stiffness tended to be increased (p = 0.07), and the serum level of osteocalcin decreased, compared with control rats. These findings suggest that 5-week WBV had beneficial effects on bone properties, and that increased bone mineral content and cortical bone geometry may lead to higher bone mechanical strength. Further studies will be needed to determine the optimal conditions of WBV for improving bone properties in the growth stage.

Bone accrual and structural changes over one year in youth with cystic fibrosis

BackgroundPediatric bone accrual governs peak bone mass and strength. Longitudinal studies of bone health in youth with cystic fibrosis (CF) may provide insight into CF-related bone disease (CFBD), a prevalent co-morbidity in adults with CF. MethodsThis one-year longitudinal study of youth with pancreatic insufficient CF, enrolled in a nutrition intervention study [n = 62 (36 M/26F)] 1) examined dual-energy x-ray absorptiometry (DXA)-defined lumbar spine (LS) and total body less head (TBLH) bone accrual and 2) compared their changes in peripheral quantitative computed tomography (pQCT) cortical and trabecular tibial bone density and geometry to those of a healthy reference group [n = 143 (68 M/75F)].Main outcome measures were 1) DXA: lumbar spine areal bone mineral density (LSaBMD) and total body less head bone mineral content (TBLH-BMC), sex- and pubertal status-specific, height velocity (HV)-adjusted or HV and lean body mass velocity (HV-LBMV)-adjusted annualized velocity-Z scores and 2) pQCT: age, sex, pubertal status and, when appropriate, tibial length adjusted Z-scores for bone architecture measures.DXA velocity-Z were compared to expected mean of 0 and correlations with clinical parameters (age, BMI-Z and FEV1%-predicted) tested. Within-subject comparisons of HV-adjusted and LBMV-HV-adjusted DXA velocity-Z were conducted in CF.pQCT Z-scores were compared between the two groups over one year using longitudinal models. Longitudinal relationships between measures of bone health and clinical parameters (age, BMI-Z and FEV1%-predicted) were examined in individuals with CF. ResultsDXA velocity-Z were higher than normal in females (p < 0.05) but not males with CF. HV-adjusted and LBMV-HV-adjusted velocity-Z did not differ for LSaBMD or TBLH-BMC.In males with CF, both HV-adjusted and LBMV-HV-adjusted LSaBMD velocity-Z scores correlated negatively with age (HV rho: −0.35; p = 0.045 and LBMV-HV rho: −0.47; p = 0.0046). In males with CF BMI-Z correlated positively with HV-adjusted LSaBMD velocity-Z (rho: 0.37; p = 0.034), but this relationship did not persist for LBMV-HV (rho: 0.14; p = 0.42). In females with CF, no correlations between LSaBMD velocity-Z scores and age or BMI-Z were found (all p > 0.05). No correlations between LSaBMD velocity-Z scores and FEV1%-predicted were seen in either sex (all p > 0.12). TBLH-BMC velocity Z-scores were not correlated with clinical parameters in either sex (all p > 0.1).At baseline, multiple pQCT parameters were lower in CF (p < 0.05). pQCT Z-scores did not differ between baseline and one-year in either CF or reference group. In a longitudinal model comparing pQCT-Z changes in CF and reference, multiple pQCT-Z outcomes remained lower in CF, but the changes in parameters did not differ in CF vs reference (all p > 0.26). Lower pQCT outcomes in CF were largely restricted to males (CF group*female sex interaction beta coefficients > 0). In this combined longitudinal model, of both CF and reference, BMI-Z was positively associated with pQCT-Z parameters(p < 0.001).Multiple pQCT-Z outcomes positively correlated with both BMI-Z and FEV1%-predicted in males with CF, and with FEV1%-predicted in females with CF (p < 0.05). Age was negatively associated with section modulus (p = 0.001) in males and with cortical density-Z in females (p < 0.001). ConclusionsWith improved longevity, bone health in CF is of increasing importance. On average, bone accrual was preserved in youth with CF, and while deficits in bone geometry and strength were found, these deficits did not worsen over the one-year study. Lower LS bone accrual with increasing age suggests emerging adulthood is a period of vulnerability in CF while the role of LBM in bone health is underscored by the lack of relationship between LBMV-adjusted accrual and BMI. These findings may be useful in targeting screening practices and interventions.

Muscle attachment sites and behavioral reconstruction: An experimental test of muscle-bone structural response to habitual activity.

Behavioral reconstruction from muscle attachment sites (entheses) is a common practice in anthropology. However, experimental evidence provides mixed support for the assumed association between enthesis size and shape with changes in habitual activity. In this study, a laboratory mouse model was used to experimentally test whether activity level and type alters muscle architecture and the underlying bone cross-sectional geometry of entheses in order to assess the underlying assumption that behavioral changes lead to quantifiable differences in both muscle and enthesis morphology. Female wild-type mice were separated into one control group and two experimentally increased activity groups (running, climbing) over an 11-week study period. At the start of the experiment, half of the mice were 4 weeks and half were 7 weeks of age. The postmortem deltoideus and biceps brachii muscles were measured for potential force production (physiological cross-sectional area) and potential muscle excursion (fiber length). Bone cross-sectional geometry variables were measured from microCT scans of the humerus and radius at the enthesis and non-enthesis regions of interest across activity groups. Activity level and type altered potential force production and potential muscle excursion of both muscles in the younger cohort. We observed differences in cortical bone geometry in both the humerus enthesis and radius non-enthesis region driven exclusively among the younger wheel-running mice. These results indicate that in addition to muscle architectural changes, bone structural properties at the enthesis do show an adaptive response to increased activity, such as running but only during earlier development. However, further research is required in order to apply these findings to the reconstruction of living behavior from anthropological specimens.

Sciatic neurectomy-related cortical bone loss exhibits delayed onset yet stabilises more rapidly than trabecular bone

Disuse osteoporosis occurs after extended periods of bed rest or nerve damage leading to increased risk of fracture. It remains to be established, however, whether the trajectory of bone loss is equivalent in bone's cortical and trabecular compartments following long-term periods of reduced loading. Herein, we evaluate sciatic neurectomy-related cortical and trabecular bone loss in the tibia by microCT. The right hind limb of seventeen 12 week-old female mice was subjected to sciatic neurectomy (right, SN; left, contralateral internal control) and the animals were sacrificed in four groups (n = 3-5/group) at 5, 35, 65 and 95 days thereafter. Cortical bone mass, geometry and mineral density were evaluated along almost the entire tibial length and trabecular bone was examined at the proximal metaphysis. We found that trabecular bone volume (BV/TV) and number were decreased within 5 days, with a trajectory of loss that only plateaued after 65 days post-SN. In contrast, decreases in cortical thickness, cross-sectional area, second moment of inertia along minor and major axes and predicted resistance to torsion were unmodified during the early 5 day period, attaining significance only after 35 days post-SN and, thereafter showed no further deterioration. Only cortical ellipticity and periosteal enclosed area, continued to change in the SN limbs (vs. contralateral) between 35 and 95 days along the tibia length. On the other hand, cortical tissue mineral density was unmodified by SN at any time point. These data indicate that SN-related cortical bone loss extends along almost the entire tibia, exhibits delayed onset and yet stabilises its architecture more rapidly than trabecular bone. These data suggest that the cortical and trabecular compartments behave as distinct modules in response to SN even within an individual bone.

Biomechanical Basis of Predicting and Preventing Lower Limb Stress Fractures During Arduous Training.

Stress fractures at weight-bearing sites, particularly the tibia, are common in military recruits and athletes. This review presents recent findings from human imaging and biomechanics studies aimed at predicting and preventing stress fractures. Peripheral quantitative computed tomography (pQCT) provides evidence that cortical bone geometry (tibial width and area) is associated with tibial stress fracture risk during weight-bearing exercise. The contribution of bone trabecular microarchitecture, cortical porosity, and bone material properties in the pathophysiology of stress fractures is less clear, but high-resolution pQCT and new techniques such as impact microindentation may improve our understanding of the role of microarchitecture and material properties in stress fracture prediction. Military studies demonstrate osteogenic outcomes from high impact, repetitive tibial loading during training. Kinetic and kinematic characteristics may influence stress fracture risk, but there is no evidence that interventions to modify biomechanics can reduce the incidence of stress fracture. Strategies to promote adaptive bone formation, in combination with improved techniques to assess bone strength, present exciting opportunities for future research to prevent stress fractures.

Persistent Musculoskeletal Deficits in Pediatric, Adolescent and Young Adult Survivors of Allogeneic Hematopoietic Stem-Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a common therapy for pediatric hematologic malignancies. With improved supportive care, addressing treatment-related late effects is at the forefront of survivor long-term health and quality of life. We previously demonstrated that alloHSCT survivors had increased adiposity, decreased lean mass, and lower bone density and strength, 7 years (median) from alloHSCT compared to their healthy peers. Yet it is unknown whether these deficits persist. Our longitudinal study characterized changes in muscle and bone over a period of 3.4 (range, 2.0 to 4.9) years in 47 childhood alloHSCT survivors, age 5-26 years at baseline (34% female). Tibia cortical bone geometry and volumetric density and lower leg muscle cross-sectional area (MCSA) were assessed via peripheral quantitative computed tomography (pQCT). Anthropometric and pQCT measurements were converted to age, sex, and ancestry-specific standard deviation scores, adjusted for leg length. Muscle-specific force was assessed as strength relative to MCSA adjusted for leg length (strength Z-score). Measurements were compared to a healthy reference cohort (n=921), age 5-30 years (52% female). At baseline and follow-up, alloHSCT survivors demonstrated lower height Z-scores, weight Z-scores, and leg length Z-scores compared to the healthy reference cohort. Deficits in MCSA, trabecular volumetric bone density, and cortical bone size and estimated strength (section modulus) were evident in survivors (all p < 0.05). Between the two study time points, anthropometric, muscle, and bone Z-scores did not change significantly in alloHSCT survivors. Approximately 15% and 17% of alloHSCT survivors had MCSA and section modulus Z-score < -2.0, at baseline and follow-up, respectively. Furthermore, those with a history of total body irradiation compared to those without demonstrated lower MCSA at follow-up. The persistent muscle and bone deficits in pediatric alloHSCT survivors support the need for strategies to improve bone and muscle health in this at-risk population. © 2022 American Society for Bone and Mineral Research (ASBMR).

Implant surface alters compartmental-specific contributions to fixation strength in rats.

Mechanical fixation of the implant to host bone is an important contributor to orthopedic implant survivorship. The relative importance of bone-implant contact, trabecular bone architecture, and cortical bone geometry to implant fixation strength has never been directly tested, especially in the settings of differential implant surface properties. Thus, using a rat model where titanium rods were placed into the intramedullary canal of the distal femur, we determined the relative contribution of bone-implant contact and peri-implant bone architecture to the fixation strength in implants with different surface roughness: highly polished and smooth (as-received) and dual acid-etched (DAE) implants. Using a training set that maximized variance in implant fixation strength, we initially examined correlation between implant fixation strength and outcome parameters from microcomputed tomography and found that osseointegration volume per total volume (OV/TV), trabecular bone volume per total volume (BV/TV), and cortical thickness (Ct.Th) were the single best compartment-specific predictors of fixation strength. We defined separate regression models to predict implant fixation strength for as-received and DAE implants. When the training set models were applied to independent validation sets, we found strong correlations between predicted and experimentally measured implant fixation strength, with r2 = .843 in as received and r2 = .825 in DAE implants. Interestingly, for as-received implants, OV/TV explained more of the total variance in implant fixation strength than the other variables, whereas in DAE implants, Ct.Th had the most explanatory power, suggesting that surface topography of implants affects which bone compartment is most important in providing implant fixation strength.

Higher fracture prevalence and smaller bone size in patients with hEDS/HSD-a prospective cohort study.

The Ehlers-Danlos syndromes (EDS) comprise a group of heritable connective tissue disorders caused by defects in the biosynthesis, secretion, and/or organization of fibrillar collagens which might impair bone strength. Our aim was to compare fracture prevalence, volumetric and areal bone mineral density (BMD), bone geometry, muscle size and the muscle-bone interaction, body composition and longitudinal changes therein between patients with hypermobile EDS (hEDS) or hypermobility spectrum disorder (HSD), and healthy control subjects. Cross-sectional data comprised 39 female hEDS/HSD patients (age 41 ± 11years) and 43 age-matched controls. After 8years, 27 hEDS/HSD and 17 control subjects were re-evaluated. Tibial trabecular and cortical volumetric BMD, bone mineral content (BMC), cortical bone geometry, and lower leg muscle cross-sectional area (CSA) were measured using pQCT. Body composition, areal BMD, and BMC were determined by DXA. At baseline, patients with hEDS/HSD presented with a smaller cortical bone area, smaller cortical thickness and muscle CSA, and a higher fracture prevalence than control subjects (all p < 0.05). No differences in areal or volumetric BMD were found. Longitudinally, muscle CSA decreased in both groups and muscle density decreased in the hEDS/HSD group (p < 0.001) whereas all bone parameters remained unchanged. hEDS/HSD patients have a cortical bone size deficit compared with controls, possibly contributing to their increased fracture risk. They presented with decreased muscle CSA but normal bone/muscle area ratio, suggesting that this bone size deficit is likely secondary to decreased mechanical loading. Further, there were no arguments for accelerated bone loss in hEDS/HSD subjects.

Impaired geometry, volumetric density, and microstructure of cortical and trabecular bone assessed by HR-pQCT in both sporadic and MEN1-related primary hyperparathyroidism

High-resolution peripheral quantitative CT is a novel imaging technique used to separately assess trabecular and cortical bone status of the radius and tibia in vivo. Using HR-pQCT, we aimed to evaluate bone features of primary hyperparathyroidism patients in a Chinese population and reveal similarities and differences in bone features in multiple endocrine neoplasia type 1-related PHPT and sporadic PHPT patients in the Chinese population. A case-control study was designed. In 58 PHPT patients and 58 sex- and age-matched healthy controls, the distal radius and tibia were scanned using HR-pQCT. Areal bone mineral density (aBMD) was also determined in PHPT patients using dual-energy X-ray absorptiometry (DXA). In comparison with controls, PHPT patients were observed to exhibit reduced volumetric BMD at the cortical and trabecular compartments, thinner cortices, and more widely spaced trabeculae. Significant differences were still observed when comparing data of female and male patients with age-matched controls separately. MHPT patients (n= 11) were found to have lower aBMD Z-scores in the lumbar spine, trochanteric region, and total hip compared with sporadic PHPT patients (n= 47), while no differences were observed in HR-pQCT indices between the two groups. In multiple linear regression models, no significant correlations were identified between PTH and HR-pQCT indices. However, height was found to positively correlate with HR-pQCT-derived trabecular indices at both the radius and tibia. PHPT affects geometry, volumetric density, and microstructure in both the cortical and trabecular bones in both male and female Chinese patients. MHPT patients were observed to have reduced aBMD as determined by DXA in the lumbar spine and hip in comparison with sporadic PHPT patients. However, HR-pQCT indices were not observed to differ.

The effects of spaceflight and fracture healing on distant skeletal sites

Spaceflight results in reduced mechanical loading of the skeleton, which leads to dramatic bone loss. Low bone mass is associated with increased fracture risk, and this combination may compromise future, long-term, spaceflight missions. Here, we examined the systemic effects of spaceflight and fracture surgery/healing on several non-injured bones within the axial and appendicular skeleton. Forty C57BL/6, male mice were randomized into the following groups: (1) Sham surgery mice housed on the earth (Ground + Sham); (2) Femoral segmental bone defect surgery mice housed on the earth (Ground + Surgery); (3) Sham surgery mice housed in spaceflight (Flight + Sham); and (4) Femoral segmental bone defect surgery mice housed in spaceflight (Flight + Surgery). Mice were 9 weeks old at the time of launch and were euthanized approximately 4 weeks after launch. Micro-computed tomography (μCT) was used to evaluate standard bone parameters in the tibia, humerus, sternebra, vertebrae, ribs, calvarium, mandible, and incisor. One intriguing finding was that both spaceflight and surgery resulted in virtually identical losses in tibial trabecular bone volume fraction, BV/TV (24–28% reduction). Another important finding was that surgery markedly changed tibial cortical bone geometry. Understanding how spaceflight, surgery, and their combination impact non-injured bones will improve treatment strategies for astronauts and terrestrial humans alike.

86 Skeletal response to whole body vibration and dietary calcium and phosphorus in growing pigs

Abstract Whole body vibration (WBV) is reported to elicit increased bone mass and strength. This experiment was designed to determine the effects of whole body vibration (WBV) and dietary calcium (Ca) and phosphorus (P) on bone microarchitecture and turnover. A total of 26 growing pigs were utilized in a 60-d experiment. Pigs were randomly assigned within group to a 2 × 2 factorial with Ca and P concentration (low and adequate) and WBV. Low Ca, P diets were 0.9 g/kg less than recommended levels of Ca and available P. Pigs receiving WBV were vibrated 30 min/d, 3 d/wk at a magnitude of 1-2mm and frequency of 50 Hz. On d 0, 30, and 60, digital radiographs were taken to determine bone mineral content by radiographic bone aluminum equivalency (RBAE) and blood was collected for bone formation biomarker (osteocalcin, OC) and bone resorption biomarker (carboxy-terminal collagen crosslinks, CTX-I). At d 60, pigs were harvested and the left third metacarpal bone was excised for analysis by micro computed tomography (microCT) to measure trabecular microarchitecture and cortical bone geometry. Maximum RBAE values for the medial or lateral cortices were not affected (P &gt; 0.05) by WBV. Pigs fed adequate Ca and P tended (P = 0.10) to have increased RBAE max values for the medial and lateral cortices. Vibrated pigs had decreased CTX-1 concentrations (P = 0.044). Pigs fed decreased Ca and P had increased (P &lt; 0.05) concentrations of OC. Vibrated pigs had lower trabecular number (P = 0.002) and increased trabecular separation (P = 0.003), whereas cortical bone parameters were not changed by WBV or diet (P &gt; 0.05). Whole body vibration in this study did not elicit an osteogenic response; however, early indications of bone turnover were observed.

Skeletal response to whole body vibration and dietary calcium and phosphorus in growing pigs.

The quality and strength of the skeleton is regulated by mechanical loading and adequate mineral intake of calcium (Ca) and phosphorus (P). Whole body vibration (WBV) has been shown to elicit adaptive responses in the skeleton, such as increased bone mass and strength. This experiment was designed to determine the effects of WBV and dietary Ca and P on bone microarchitecture and turnover. A total of 26 growing pigs were utilized in a 60-d experiment. Pigs were randomly assigned within group to a 2 × 2 factorial design with dietary Ca and P concentration (low and adequate) as well as WBV. The adequate diet was formulated to meet all nutritional needs according to the NRC recommendations for growing pigs. Low Ca, P diets had 0.16% lower Ca and 0.13% lower P than the adequate diet. Pigs receiving WBV were vibrated 30 min/d, 3 d/wk at a magnitude of 1 to 2 mm and a frequency of 50 Hz. On days 0, 30, and 60, digital radiographs were taken to determine bone mineral content by radiographic bone aluminum equivalency (RBAE) and serum was collected to measure biochemical markers of bone formation (osteocalcin, OC) and bone resorption (carboxy-terminal collagen crosslinks, CTX-I). At day 60, pigs were euthanized and the left third metacarpal bone was excised for detailed analysis by microcomputed tomography (microCT) to measure trabecular microarchitecture and cortical bone geometry. Maximum RBAE values for the medial or lateral cortices were not affected (P > 0.05) by WBV. Pigs fed adequate Ca and P tended (P = 0.10) to have increased RBAE max values for the medial and lateral cortices. WBV pigs had significantly decreased serum CTX-1 concentrations (P = 0.044), whereas animals fed a low Ca and P diet had increased (P < 0.05) OC concentrations. In bone, WBV pigs showed a significantly lower trabecular number (P = 0.002) and increased trabecular separation (P = 0.003), whereas cortical bone parameters were not significantly altered by WBV or diet (P > 0.05). In summary, this study confirmed the normal physiological responses of the skeleton to a low Ca, P diet. Interestingly, although the WBV protocol utilized in this study did not elicit any significant osteogenic response, decreases in CTX-1 in response to WBV may have been an early local adaptive bone response. We interpret these data to suggest that the frequency and amplitude of WBV was likely sufficient to elicit a bone remodeling response, but the duration of the study may not have captured the full extent of an entire bone remodeling cycle.

Bone geometry and trabecular bone score in transgender people before and after short- and long-term hormonal treatment.

Gender-affirming hormonal treatment (HT) in adult transgender people influences bone mineral density (BMD). Besides BMD, bone geometry and trabecular bone score are associated with fracture risk. However, it is not known whether bone geometry and TBS changes during HT. To investigate the bone geometry and TBS in adult transgender people at different time points, up to 25 years, of HT. A total of 535 trans women and 473 trans men were included, who were divided into three groups at time of their DXA: 20-29 years, 30-39 years, and 40-59 years. Subsequently, each group was divided into different HT durations: baseline, or after 5, 15, or 25 years of HT. Hip structure analysis was performed to measure subperiosteal width, endocortical diameter, average cortical thickness, and section modulus. TBS was calculated based on lumbar spine DXA images. In trans women in all age groups and in young trans men, no differences were observed in periosteal width, endocortical diameter, average cortical thickness, and section modulus for different durations of HT. In trans men aged 40-59 years, subperiosteal width, endocortical diameter, and section modulus were slightly higher in the groups who were using HT compared to the (peri- or postmenopausal) baseline group. In younger trans women, TBS tended to be higher in those using HT compared to the baseline groups, and in older trans women TBS was higher in those using HT for 25 years versus baseline (+0.04, 95%CI +0.00; +0.08). In younger trans men, TBS tended to be lower in those who used HT compared to the baseline groups, and in older trans men TBS was lower in those using 5 years HT versus baseline (-0.05, 95%CI -0.08; -0.01). No differences in cortical bone geometry parameters were found during different HT-durations. TBS increased in trans women and decreased in trans men, indicating that estrogens have positive effects on TBS. These data may be helpful in determining what sex reference values for calculating T-scores and Z-scores in adult transgender people should be used.

Exploring conditions that make cortical bone geometry optimal for physiological loading.

While physiological loading on lower long bones changes during bone development, the bone cross section either remains circular or slowly changes from nearly circular to other shapes such as oval and roughly triangular. Bone is said to be an optimal structure, where strength is maximized using the optimal distribution of bone mass (also called Wolff's law). One of the most appropriate mathematical validations of this law would be a structural optimization-based formulation where total strain energy is minimized against a mass and a space constraint. Assuming that the change in cross section during bone development and homeostasis after adulthood is direct result of the change in physiological loading, this work investigates what optimization problem formulation (collectively, design variables, objective function, constraints, loading conditions, etc.) results in mathematically optimal solutions that resemble bones under actual physiological loading. For this purpose, an advanced structural optimization-based computational model for cortical bone development and defect repair is presented. In the optimization problem, overall bone stiffness is maximized first against a mass constraint, and then also against a polar first moment of area constraint that simultaneously constrains both mass and space. The investigation is completed in two stages. The first stage is developmental stage when physiological loading on lower long bones (tibia) is a random combination of axial, bending and torsion. The topology optimization applied to this case with the area moment constraint results into circular and elliptical cross sections similar to that found in growing mouse or human. The second investigation stage is bone homeostasis reached in adulthood when the physiological loading has a fixed pattern. A drill hole defect is applied to the adult mouse bone, which would disrupt the homeostasis. The optimization applied after the defect interestingly brings the damaged section back to the original intact geometry. The results, however, show that cortical bone geometry is optimal for the physiological loading only when there is also a constraint on polar moment of area. Further numerical experiments show that application of torsion along with the gait-analysis-based physiological loading improves the results, which seems to indicate that the cortical bone geometry is optimal for some amount of torsion in addition to the gait-based physiological loading. This work has a potential to be extended to bone growth/development models and fracture healing models, where topology optimization and polar moment of area constraint have not been introduced earlier.