Changes In Bone Strength Research Articles

Hormonal and non-hormonal oral contraceptives given long-term to pubertal rats differently affect bone mass, quality and metabolism.

We investigated the effects of hormonal and non-hormonal oral contraceptives (OCs) on bone mass, mineralization, composition, mechanical properties, and metabolites in pubertal female SD rats. OCs were given for 3-, and 7 months at human equivalent doses. The combined hormonal contraceptive (CHC) was ethinyl estradiol and progestin, whereas the non-hormonal contraceptive (NHC) was ormeloxifene. MicroCT was used to assess bone microarchitecture and BMD. Bone formation and mineralization were assessed by static and dynamic histomorphometry. The 3-point bending test, nanoindentation, FTIR, and cyclic reference point indentation (cRPI) measured the changes in bone strength and material composition. Bone and serum metabolomes were studied to identify potential biomarkers of drug efficacy and safety and gain insight into the underlying mechanisms of action of the OCs. NHC increased bone mass in the femur metaphysis after 3 months, but the gain was lost after 7 months. After 7 months, both OCs decreased bone mass and deteriorated trabecular microarchitecture in the femur metaphysis and lumbar spine. Also, both OCs decreased the mineral: matrix ratio and increased the unmineralized matrix after 7 months. After 3 months, the OCs increased carbonate: phosphate and carbonate: amide I ratios, indicating a disordered hydroxyapatite crystal structure susceptible to resorption, but these changes mostly reversed after 7 months, indicating that the early changes contributed to demineralization at the later time. In the femur 3-point bending test, CHC reduced energy storage, resilience, and ultimate stress, indicating increased susceptibility to micro-damage and fracture, while NHC only decreased energy storage. In the cyclic loading test, both OCs decreased creep indentation distance, but CHC increased the average unloading slope, implying decreased microdamage risk and improved deformation resistance by the OCs. Thus, reduced bone mineralization by the OCs appears to affect bone mechanical properties under static loading, but not its cyclic loading ability. When compared to an age-matched control, after 7 months, CHC affected 24 metabolic pathways in bone and 9 in serum, whereas NHC altered 17 in bone and none in serum. 6 metabolites were common between the serum and bone of CHC rats, suggesting their potential as biomarkers of bone health in women taking CHC. Both OCs have adverse effects on various skeletal parameters, with CHC having a greater negative impact on bone strength.

The effects of BPA-BNCT on normal bone: determination of the CBE value in mice‡.

Boron neutron capture therapy (BNCT) with p-boronophenylalanine (BPA) is expected to have less effect on the decrease in normal bone strength than X-ray therapy. However, the compound biological effectiveness (CBE) value necessary to convert the boron neutron capture reaction (BNCR) dose into a bioequivalent X-ray dose has not been determined yet. The purpose of this study was to evaluate the influence of BNCT on normal bone in mice and to elucidate the CBE factor. We first searched the distribution of BPA in the normal bone of C3H/He mice and then measured the changes in bone strength after irradiation. The CBE value was determined when the decrease in bone strength was set as an index of the BNCT effect. The 10B concentrations in the tibia after subcutaneous injection of 125, 250 and 500mg/kg BPA were measured by prompt gamma-ray spectroscopy and inductively coupled plasma (ICP)-atomic emission spectrometry. The 10B mapping in the tibia was examined by alpha-track autoradiography and laser ablation-ICP-mass spectrometry. The 10B concentration increased dose-dependently; moreover, the concentrations were maintained until 120min after BPA administration. The administered 10B in the tibia was abundantly accumulated in the growth cartilage, trabecular bone and bone marrow. The bone strength was analyzed by a three-point bending test 12weeks after irradiation. The bending strength of the tibia decreased dose-dependently after the irradiation of X-ray, neutron and BNCR. The CBE factor was obtained as 2.27 by comparing these dose-effect curves; the value determined in this study will enable an accurate dosimetry of normal bone.

Fracture risk assessment in diabetes mellitus.

Growing evidence suggests that diabetes mellitus is associated with an increased risk of fracture. Bone intrinsic factors (such as accumulation of glycation end products, low bone turnover, and bone microstructural changes) and extrinsic factors (such as hypoglycemia caused by treatment, diabetes peripheral neuropathy, muscle weakness, visual impairment, and some hypoglycemic agents affecting bone metabolism) probably contribute to damage of bone strength and the increased risk of fragility fracture. Traditionally, bone mineral density (BMD) measured by dual x-ray absorptiometry (DXA) is considered to be the gold standard for assessing osteoporosis. However, it cannot fully capture the changes in bone strength and often underestimates the risk of fracture in diabetes. The fracture risk assessment tool is easy to operate, giving it a certain edge in assessing fracture risk in diabetes. However, some parameters need to be regulated or replaced to improve the sensitivity of the tool. Trabecular bone score, a noninvasive tool, indirectly evaluates bone microstructure by analyzing the texture sparsity of trabecular bone, which is based on the pixel gray level of DXA. Trabecular bone score combined with BMD can effectively improve the prediction ability of fracture risk. Quantitative computed tomography is another noninvasive examination of bone microstructure. High-resolution peripheral quantitative computed tomography can measure volume bone mineral density. Quantitative computed tomography combined with microstructure finite element analysis can evaluate the mechanical properties of bones. Considering the invasive nature, the use of microindentation and histomorphometry is limited in clinical settings. Some studies found that the changes in bone turnover markers in diabetes might be associated with fracture risk, but further studies are needed to confirm this. This review focused on summarizing the current development of these assessment tools in diabetes so as to provide references for clinical practice. Moreover, these tools can reduce the occurrence of fragility fractures in diabetes through early detection and intervention.

Age Related Trends in Structural Indices of Proximal Femur in Women Aged 20-70 in Southern Sri Lanka

Age related trends of the indices of hip structure help understanding how bone strength changes with age and the increased bone fragility in old age. Community-dwelling women aged 20-70years (n = 419) were selected by stratified random method and divided into age categories; 20-29years (n-69), 30-39years (n = 60), 40-49years (n = 69), 50-59years (n = 107) and 60-70years (n = 114). All subjects underwent dual energy x-ray absorptiometry (DXA) and hip structure analysis using Hologic Discovery scanner (Hologic Inc, Bedford, USA). Measured indices included hip axis length (HAL) and neck shaft angle (NSA) of the proximal femur. Cross sectional area (CSA), cross sectional moment of inertia (CSMI), section modulus (SM), cortical thickness (CT), buckling ration (BR) of three regions of interest; narrow neck, intertrochanteric region and femoral shaft, were also measured. Age related trends of all indices were studied with Locally Weighted Scatterplot Smoothing lines (LOESS) and ANOVA. Mean HAL and NSA values were not different between age categories. CSA, CSMI, SM and CT in three different regions showed curvilinear relationships with age. These indices gradually increased with age between 20-50 years and the maximum values were seen in the 40-49years age category and they declined afterwards. The decline of these indices was more rapid in the narrow neck and intertrochanter regions when compared with femoral shaft and the lowest mean CSA, CSMI, SM and CT in these two regions were seen in the 60-70 age category. BR showed a gradual decrease with age between 20-50 years and the lowest mean value was seen in the 40-49 age category. BR increased afterwards and the maximum mean value was seen in the 60-70 age category. This study demonstrates the dynamics of structural properties of proximal femur in the three selected cross sections of community-dwelling women aged 20-70 years and the increased bone fragility in old age.

Age-Related Changes in Trabecular Bone Score and Bone Mineral Density in Chinese Men: A Cross-Sectional and Longitudinal Study.

PurposeThis study was designed to explore age-related changes in trabecular bone score (TBS) and bone mineral density (BMD) in Chinese men through cross-sectional and longitudinal studies.Patients and MethodsWe included adult men who had at least twice TBS and BMD examinations in our hospital between January 2013 and December 2020. All men were divided into an age subgroup per 10 years, comparing differences in baseline lumbar spine (LS) TBS and BMD at various parts between each age group and analyzing age-related changes in TBS and BMD during follow-up.ResultsBaseline data showed that in men aged 36 to 85 years, BMD in the hip region showed a decreasing trend with age (P for trend < 0.01). However, TBS reached a high value around the age of 50, after which it decreased with age (P for trend = 0.03). During a mean follow-up of 3 years, the average annual change rate at TBS was −0.17% in men aged 36 to 85 years, with the fastest decrease rate −1.08% at 66 to 75 years (P < 0.05). The mean annual rate of change in LS BMD in different age subgroups increased with age (P for trend = 0.001). There was no significant decrease in mean annual change in BMD in hip regions.ConclusionIn men aged 36~85 years, the trend of TBS was inconsistent with BMD. Men experience a high value of LS TBS around age 50, later than the commonly believed age of peak BMD, which may reflect developmental differences between bone microstructure and bone minerals. The TBS may be used as a better indicator of changes in bone strength than BMD in adult men at short-term follow-up. The rapid loss of TBS at age 66 to 75 may have implications for the prevention and medication of osteoporosis in men.

Changes of Bone Strength Evaluated by CT-based Finite Element Methods in Radiotherapy for Bone Metastases of the Spine in Comparison With Bone Density

Radiotherapy (RT) is performed not only to reduce pain but also to prevent pathological fractures due to bone metastases of the spine. However, it is unclear to what extent radiotherapy increases bone strength. Bone density is sometimes used as a marker for assessment of local response to RT in spinal bone metastases. The purpose of this study was to evaluate the changes of bone strength using CT-based finite element (FE) methods in radiotherapy for metastases at the lumber vertebra in comparison with bone density.Five patients with metastases to the lumber vertebra who could be followed for more than 6 months were included. Primary lesions were lung cancer in all patients. All patients had osteolytic changes of the bone cortex in the vertebral body. Median radiation dose was 37.8 Gy in 14 fractions. CT images were taken before and at 1, 3, 6, 9 and 12 months after irradiation. Bone density was measured in Hounsfield units (HU) in each CT scan. The regions of interest were set to include the whole vertebral body of the metastatic spine and that of a non-irradiated unaffected neighboring spine used for reference. The 3-dimensional FE models of the same vertebrae were constructed from each CT image. The models consisted of 1- or 2-mm linear tetrahedral elements and the cortical shell with a thickness of 0.1 mm. A uniaxial compressive load with uniform distribution was applied on the upper surface of the vertebral body with the lower surface completely restrained. The predicted fracture load was defined to be present when at least one element or cortical shell failed. The ratios of the values on the follow-up CT to the values on the pre-irradiation CT were calculated, and single regression equations were determined for these ratios.At one month after irradiation, the bone density decreased in all except one case of the affected vertebral bodies, and the predicted fracture load decreased in all except one case of the unaffected vertebral bodies. In the affected vertebral bodies, the slopes of the single regression equations of bone density were positive in 4 out of 5 cases. The slopes of those of predicted fracture loads were negative in 3 out of that 4 cases. In the unaffected vertebral bodies, the slopes of the single regression equations of bone density were positive in 3 out of 5 cases. The slopes of predicted fracture loads were positive in those 3 cases.The bone strength might not improve in one month after irradiation. The predicted fracture load did not necessarily increase even if the bone density increased in the irradiated affected vertebral bodies. Bone density alone might not be sufficient as an indicator of bone strength. The FE method could evaluate the changes in bone strength in radiotherapy for bone metastases based on predicted fracture loads.

The Association Between Long-term Exposure to Ambient Air Pollution and Bone Strength in China

Evidence regarding the association of long-term exposure to air pollution on bone strength or osteoporosis is rare, especially in highly polluted low- and middle-income countries. Little is known about whether the association between air pollution and bone strength changes at different bone strength distributions. Using the baseline data from the China Multi-Ethnic Cohort, we investigated the association between long-term air pollution exposure and bone strength. We used multiple linear models to estimate the association between air pollution and bone strength, and we conducted quantile regression models to investigate the variation of this association in the distribution of bone strength. The 3-year concentrations of PM1, PM2.5, PM10, and NO2 for each participant were assessed using spatial statistical models. Bone strength was expressed by the calcaneus quantitative ultrasound index (QUI) measured by quantitative ultrasound, with higher QUI values indicating greater bone strength. A total of 66 598 participants were included. Our analysis shows that every 10 μg/m3 increase in 3-year average PM1, PM2.5, PM10, and NO2 was associated with -5.38 units (95% CI: -6.17, -4.60), -1.89 units (95% CI: -2.33, -1.44), -0.77 units (95% CI: -1.08, -0.47), and -2.02 units (95% CI: -2.32, -1.71) changes in the QUI, respectively. In addition, populations with higher bone strength may be more susceptible to air pollution. Long-term exposure to PM1, PM2.5, PM10, and NO2 was significantly associated with decreased bone strength in southwestern China adults. Air pollution exposure has a more substantial adverse effect on bones among populations with higher bone strength.

Bone Mechanoregulation Allows Subject-Specific Load Estimation Based on Time-Lapsed Micro-CT and HR-pQCT in Vivo.

Patients at high risk of fracture due to metabolic diseases frequently undergo long-term antiresorptive therapy. However, in some patients, treatment is unsuccessful in preventing fractures or causes severe adverse health outcomes. Understanding load-driven bone remodelling, i.e., mechanoregulation, is critical to understand which patients are at risk for progressive bone degeneration and may enable better patient selection or adaptive therapeutic intervention strategies. Bone microarchitecture assessment using high-resolution peripheral quantitative computed tomography (HR-pQCT) combined with computed mechanical loads has successfully been used to investigate bone mechanoregulation at the trabecular level. To obtain the required mechanical loads that induce local variances in mechanical strain and cause bone remodelling, estimation of physiological loading is essential. Current models homogenise strain patterns throughout the bone to estimate load distribution in vivo, assuming that the bone structure is in biomechanical homoeostasis. Yet, this assumption may be flawed for investigating alterations in bone mechanoregulation. By further utilising available spatiotemporal information of time-lapsed bone imaging studies, we developed a mechanoregulation-based load estimation (MR) algorithm. MR calculates organ-scale loads by scaling and superimposing a set of predefined independent unit loads to optimise measured bone formation in high-, quiescence in medium-, and resorption in low-strain regions. We benchmarked our algorithm against a previously published load history (LH) algorithm using synthetic data, micro-CT images of murine vertebrae under defined experimental in vivo loadings, and HR-pQCT images from seven patients. Our algorithm consistently outperformed LH in all three datasets. In silico-generated time evolutions of distal radius geometries (n = 5) indicated significantly higher sensitivity, specificity, and accuracy for MR than LH (p < 0.01). This increased performance led to substantially better discrimination between physiological and extra-physiological loading in mice (n = 8). Moreover, a significantly (p < 0.01) higher association between remodelling events and computed local mechanical signals was found using MR [correct classification rate (CCR) = 0.42] than LH (CCR = 0.38) to estimate human distal radius loading. Future applications of MR may enable clinicians to link subtle changes in bone strength to changes in day-to-day loading, identifying weak spots in the bone microstructure for local intervention and personalised treatment approaches.

Novel CT-Based Bone Strength Assessment By Finite Element Analysis for Monitoring Bone Involvement in Myeloma: a Proof of Concept Study

IntroductionMyeloma (MM) is characterized by osteolytic bone disease, detected in up to 80% of patients, increasing the risk for skeletal related events (SREs), causing morbidity, undermining quality of life and impairing survival. Current imaging modalities provide qualitative measures of bone involvement, often after irreversible damage has occurred.Bone strains are a biomechanical measure of bone strength which quantifies bone relative deformation in response to applied force. As a result of load on bone strains develop which may lead to fracture, once strain magnitude reaches the yield strain. Lytic bone lesions cause local weakening expressed by an increase in local strains.We developed CT-based finite element analysis (CTFEA), a novel measure designed to accurately estimate bone strains based on conventional CT scans. We hypothesize this tool may enable quantifying changes in bone strength over time, by monitoring strain. In this concept study we explore the sensitivity and responsiveness of CTFEA in myeloma patients to detect bone-disease progression and treatment response, and explore clinical correlates.MethodsPatients: A pilot retrospective study. After approval by the institutional ethics committee, 16 MM patients, with at least 2 consecutive CT scans including the spine and at least the proximal 1/3 of the femur since 2010 were identified. Demographic, clinical and radiographic data were abstracted from medical records.CTFEA: Femurs of interest were segmented from the CT scan, and a computational model was created with “stiffness” changing from point to point according to CT's gray values. The computational model was loaded virtually with a physiological stance position contact hip force (2.5 X body weight) applied on the femur's head. An elastic finite element analysis was performed that predicts the displacements and strains at any point within the bone (Figure 1). The locations of interest where the larger change in material properties may occur between consecutive CT scans were determined by computing the relative difference in Hounsfield unit (HU) radio-density along bone's axis. At these locations the principal strains were extracted and monitored. A monotonic increase in strains implies deterioration of bone strength, and vice versa. For patients with lytic lesions, bone strength is quantified by monitoring the principal strains in lesions vicinity. Healing is quantified by a decrease in strains. The CTFEA results were compared to conventional radiographic and laboratory measures.ResultsTable 1 summarizes individual patient clinical data at the time points of each of the CT-scans as well as the calculated CTFEA strain values at the location of maximum HU change of the initial 7 patients. Complete analysis of femur and vertebral strain for 16 patients will be presented at the meeting. Indeed no visible change in strain is demonstrated for smoldering MM (SMM) patients (Pts 15 and 16), whereas a monotonic increase is seen for patient 3, RRMM, with successive relapses without visible tumor identified in the femur in CT scans.Patient 17 (RRMM) with a lytic tumor at the distal femur, shows an initial deterioration of bone strength followed by a monotonic improvement until almost full regain of strength after 19 months.Patient 10 (NDMM) with a lytic tumor in the vicinity of the lesser trochanter, achieved a partial response of MM following anti-myeloma induction within 6 weeks, and as well as a significant increase in bone strength. Patient 13 had a rapid MM response but parallel worsening strain in the right femur, patient 18 had a MM partial response over 5 months with slight worsening of strain.ConclusionsPromising trends were found between CTFEA strain prediction and MM clinical course. SMM patients had minimal changes whereas a patient with progressive disease had a monotonic increase in strains. A decrease in strain was seen in some but not all who responded to therapy. The preliminary study is to be enhanced by considering vertebrae, analyzing further patients as well as prospective validation against SREs, to refine calibrate and tailor this measurement. By providing a quantitative metric of bone strain, this tool may allow monitoring bone strength throughout myeloma evolvement, prior to development of SREs. This may support physicians making personalized medical and surgical treatment decisions and provide a useful surrogate endpoint for clinical drug development. [Display omitted] DisclosuresYosibash:PerSimiO: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Trabelsi:PerSimiO: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Using 3D image registration to maximize the reproducibility of longitudinal bone strength assessment by HR-pQCT and finite element analysis

We developed and validated a finite element (FE) approach for longitudinal high-resolution peripheral quantitative computed tomography (HR-pQCT) studies using 3D rigid-body registration (3DR) to maximize reproducibility by accounting for misalignment between images. In our proposed approach, we used the full common bone volume defined by 3DR to estimate standard FE parameters. Using standard HR-pQCT imaging protocols, we validated the 3DR approach with ex vivo samples of the distal radius (n = 10, four repeat scans) by assessing whether 3DR can reduce measurement variability from repositioning error. We used in vivo data (n = 40, five longitudinal scans) to assess the sensitivity of 3DR to detect changes in bone strength at the distal radius by the standard deviation of the rate of change (σ), where the ideal value of σ is minimized to define true change. FE estimates by 3DR were compared to estimates by no registration (NR) and slice-matching (SM). Group-wise comparisons of ex vivo variation (CVRMS, %) found that FE measurement precision was improved by SM (CVRMS < 0.80%) and 3DR (CVRMS < 0.62%) compared to NR (CVRMS~2%), and 3DR was advantageous as repositioning error increased. Longitudinal in vivo reproducibility was minimized by 3DR for failure load estimates (σ = 0.008 kN/month). Although 3D registration cannot negate motion artifacts, it plays an important role in detecting and reducing variability in FE estimates for longitudinal HR-pQCT data and is well suited for estimating effects of interventions in in vivo longitudinal studies of bone strength.

Prediction Method of Elastic Modulus of Trabecular Bone Based on SE-DenseVoxNet

Osteoporosis is one of the common metabolic diseases, which can easily lead to osteoporotic fractures. Accurate prediction of bone biomechanical properties is of great significance for the early prevention and diagnosis of osteoporosis. Bone mineral density measurement is currently used clinically as the gold standard for assessing bone strength and diagnosing osteoporosis, but studies have shown that bone mineral density can only explain 60% to 70% of bone strength changes, and trabecular bone microstructure is an important factor affecting bone strength. In order to establish the connection between trabecular bone microstructure and bone strength, this paper proposes a prediction method of trabecular bone modulus based on SE-DenseVoxNet. This method takes three-dimensional binary images of trabecular bone as input and predicts its elastic modulus in the z-axis direction. Experiments show that the error and bias between the predicted value of the method and the true value of the sample are small and have good consistency.

Testosterone therapy and bone quality in men with diabetes and hypogonadism: Study design and protocol

ContextType 2 diabetes mellitus (T2D) is often accompanied by male hypogonadism and both conditions are associated with increased risk for fractures. Testosterone (T) has been shown to improve the bone health of hypogonadal men but has not been tested in patients who also have T2D in addition to low T. To date, there is no treatment that is specifically recommended for bone disease among patients with T2D. This study will evaluate the effect of T therapy on the bone health of male veterans with low T who also have T2D. MethodsThis is a randomized double-blind placebo-controlled trial of 166 male veterans 35–65 years old, with T2D and hypogonadism, randomized to either T gel 1.62% or placebo for 12 months. We will evaluate the effect of T therapy on the following primary outcomes:1) changes in bone strength as measured by microfinite elements analysis (μFEA) using high-resolution peripheral quantitative computer tomography, 2) changes in bone turnover markers, and 3) changes in circulating osteoblast progenitors (COP) and osteoclast precursors cells. DiscussionWe anticipate that T therapy will result in improvement in bone strength owing to improvement in bone remodeling through an increase in osteoblastic differentiation and proliferation in patients with hypogonadism and T2D.

Influence of Changes in Soft Tissue Composition on Changes in Bone Strength in Peripubertal Girls: The STAR Longitudinal Study.

Obesity and osteoporosis remain two major public health concerns. Soft tissue composition and bone are interrelated; however, it is still not well understood how changes in adiposity during adolescence affect bone development. The aim of this study was to assess how changes in DXA-derived total body lean mass (TBLM) and total body fat mass (TBFM) associate with 2-year changes in bone outcomes at the 20% femur, 66% tibia, 66% radius, and 4% tibia, as measured by pQCT, during the years surrounding the onset of menarche in a cohort of 9- to 12-year-old (baseline) adolescent girls (70% Hispanic). From baseline to 2-year follow-up, girls showed statistically significant increases in all bone outcomes, except radial endosteal circumference. In separate linear regression models, change in TBLM and change in TBFM were both positively associated with 2-year changes in bone outcomes at all measured bone sites, after controlling for relevant covariates. However, when change in TBLM and change in TBFM were included in the same model, change in TBLM was the predominant predictor of bone outcomes, explaining 4% to 14% of the variance in bone strength outcomes. Change in TBFM remained a positive predictor of tibia polar strength strain index (SSIp) (2% variance explained). A significant interaction between change in TBFM and menarcheal status was identified at the radius for SSIp and indicated that greater gains in TBFM were beneficial for SSIp in girls that were premenarcheal at baseline but detrimental for girls who were postmenarcheal at baseline. The overall findings suggest that changes in TBLM during the peripubertal years have a greater influence on bone outcomes than changes in TBFM. While gains in TBFM might benefit the weight bearing 66% tibia, greater gains in TBFM may be detrimental to bone development at the non-weight bearing 66% radius after the onset of menarche. © 2020 American Society for Bone and Mineral Research (ASBMR).

Combined Hind Limb Suspension and sRANK-L on Bone Strength in Mice by Finite Element Analysis: Effects of Anatomic Model Height.

With commercial space travel on the horizon, it is important to understand how the microgravity environment of space effects bone strength. The reduction in skeletal loading is known to cause a rapid loss in bone density. How this corresponds to losses of bone strength is not well known, especially when combined with the osteoporotic effects of aging. In this study, a mouse model of hind limb suspension (HLS) was used to simulate the effects of gravitational unloading. This was combined with soluble receptor activator of nuclear factor kappa beta ligand (sRANK-L), which simulates age related osteoporosis. The proximal region of the tibia in mouse legs was scanned in-vivo pre-treatment as well as at the conclusion of the study with high resolution micro computed tomography (µCT). Subject specific finite element (FE) models were constructed from these 3D images to assess bone strength by simulating mechanical loading on these bone microstructures. Parameters indicative of bone strength obtained from the FE models were bone volume, stiffness, structural efficiency, and the 10th and 90th percentile nodal Von-Mises Stresses. Additionally, a model sensitivity analysis was performed to assess how these parameters varied with changes in anatomic model height. In regards to FE stiffness, HLS resulted in a 31% decline, sRANK-L resulted in a 16.8% decline, and HLS combined with sRANK-L (HLS+sRANK-L) resulted in a 38.6% decline. One interesting finding is that HLS caused a reduction in both bone stiffness and bone structural efficiency, while sRANK-L did not cause changes in bone structural efficiency, suggesting the importance of skeletal loading for maintaining bone health. In addition, sRANK-L combined with HLS caused an additional decline in bone stiffness, but did not further alter bone structural efficiency. In conclusion, this study shows that depending on the cause of osteoporosis, bone strength changes are not necessarily proportional to bone density changes. Thus, it is important to develop new clinical bone assessments beyond the current bone density measurement.Clinical Relevance- These parameters are associated with the microstructural mechanics of bone, and understanding how strength is decreased on a structural level may lead to the development of in-vivo bone strength testing clinically.

Greater maintenance of bone mineral content in male than female athletes and in sprinting and jumping than endurance athletes: a longitudinal study of bone strength in elite masters athletes

SummaryWe investigated longitudinal changes in tibia bone strength in master power (jumping and sprinting) and endurance (distance) athletes of both sexes. Bone mass but not cross-sectional moment of inertia was better maintained in power than endurance athletes over time, particularly in men and independent of changes in performance.ObjectiveAssessment of effects of sex and athletic discipline (lower limb power events, e.g. sprint running and jumping versus endurance running events) on longitudinal changes in bone strength in masters athletes.MethodsWe examined tibia and fibula bone properties at distal (4% distal-proximal tibia length) and proximal (66% length) sites using peripheral quantitative computed tomography (pQCT) in seventy-one track and field masters athletes (30 male, 41 female, age at baseline 57.0 ± 12.2 years) in a longitudinal cohort study that included at least two testing sessions over a mean period of 4.2 ± 3.1 years. Effects of time, as well as time × sex and time × discipline interactions on bone parameters and calf muscle cross-sectional area (CSA), were examined.ResultsEffects of time were sex and discipline-dependent, even following adjustment for enrolment age, sex and changes in muscle CSA and athletic performance. Male sex and participation in power events was associated with better maintenance of tibia bone mineral content (BMC, an indicator of bone compressive strength) at 4% and 66% sites. In contrast, there was no strong evidence of sex or discipline effects on cross-sectional moment of inertia (CSMI, an indicator of bone bending and torsional strength—P > 0.3 for interactions). Similar sex and discipline-specific changes were also observed in the fibula.ConclusionsResults suggest that male athletes and those participating in lower limb power-based rather than endurance-based disciplines have better maintenance of bone compressive but not bending and torsional strength.

Effect of stress-shielding-induced bone resorption on glenoid loosening in reverse total shoulder arthroplasty.

Aseptic loosening of the glenoid component is one of the main reasons for the high revision rates of reverse total shoulder arthroplasty (RTSA). It has been reported that the bulky implant designs may lead to stress shielding. However, it is uncertain whether the shielding effect is severe enough to lead to bone resorption and glenoid loosening. The purpose of this study was to evaluate the level of stress-shielding and assess whether bone resorption plays a role in aseptic glenoid loosening following RTSA. A cadaveric in vitro test model was used to validate a finite element model (FEM) of the scapula. The FEM of the scapula, incorporating adaptive bone remodeling algorithms, was used to predict changes in postoperative bone density after RTSA. Changes in bone strength after implantation were also analyzed. The strain values predicted from the FEM of the scapula were in agreement with the in vitro measurements. Analysis of postoperative bone adaptation revealed that strain-induced bone resorption began at the peg of the implant and around the resected bone surface and then gradually expended to the peripheral regions. The bone strength also reduced postoperatively and appeared particularly around the implant peg. Strain-induced bone resorption is a likely source of the bone loss commonly observed in RTSA. The finite element glenoid bone remodeling simulation may be used as a tool to evaluate glenoid implant design.

Changes in Bone Strength and Distal Femur Trabecular Thickness following Sleep‐Deprivation in Ovariectomized Rats Treated with Zoledronate

Osteoporosis is a disease that causes the density and quality of bone to be decreased, which can increase the risk of fracture. As bone is not a homogeneous tissue and bone mineral density (BMD) is a crude evaluation of the architectural changes seen in osteoporosis, the trabecular thickness may serve as a better single evaluation of bone health. 1 in 3 women over the age of 50 will be affected by osteoporosis. This study aimed to show how bone strength and distal femur trabecular thickness might be affected by sleep‐deprivation in estrogen‐deficient rats. Secondarily, we wanted to evaluate if Zoledronate would attenuate the deleterious consequences of sleep‐deprivation on bone. Wistar female rats were ovariectomized to contrive post‐menopausal estrogen‐deficiency. The rats were separated into 4 groups. The control group (C, n=4) was given an intraperitoneal (IP) injection of 0.45 mL of 0.9% saline, were housed in standard conditions permitting 12 hours light and 12 hours dark. The Zoledronate group (Z, n=8) were given an IP injection of 50 ug/kg of 10% Zoledronate and housed in standard conditions with a 12 hour light/dark cycle. The sleep‐deprived group (SD, n=8) were given the same IP injection as the rats in C, but were housed in chambers that did not permit sleep for 18 hours, then moved to sleep chambers for 6 hours. The sleep‐deprived Zoledronate group experienced the same sleep deprivation as the SD group, but received an IP injection of 50ug/kg body weight of 10% Zoledronate. After 5 weeks, tibiae and femora were harvested, wrapped in saline‐soaked gauze, and stored at −80F until a 3‐point bending test, high‐resolution micro‐CT and peripheral computed tomography was done. The SDZ group showed improved bone strength compared to the SD group (165.97 N and 162.21 N, respectively; N.S.). Also, the SDZ group showed improved distal femur trabecular thickness compared to the SD group (75.5 microns and 68.375 microns, respectively; p&lt;0.05). The value of bisphosphonates in bone preservation is well documented. We attempted to illuminate the value of a bisphosphonate in sleep‐deprived environments in the hopes of evaluating the efficacy and potential therapy for executive women who consistently work in sleep‐deprived states. Our findings are equivocal but encouraging to pursue studies of a longer duration.Support or Funding InformationSpecial thanks to the Novartis Pharmaceuticals Corporation for trabecular thickness analyses.

High-resolution Peripheral Quantitative Computed Tomography for the Assessment of Bone Strength and Structure in Obstructive Sleep Apnea Patients

Objective To evaluate the bone strength and structure of patients with obstructive sleep apnea(OSA)by the high-resolution peripheral quantitative computed tomography(HR-pQCT)and to explore the relationship between OSA and osteoporosis. Methods Male patients who visited the Sleep Respiratory Center of our hospital from August 2017 to January 2019 were consecutively recruited.Clinical data including the results of Epworth sleep scale(ESS)scoring and overnight polysomnography were collected.HR-pQCT was used to compare the differences in bone geometry,density,and microstructure between OSA patients and non-OSA people;also,the radius and tibia on the non-dominant side were measured to explore the relationship between OSA and osteoporosis. Results A total of 83 subjects were enrolled in the study.The number of patients in the mild,moderate,and severe OSA groups and non-OSA group were 21,18,34,and 10,respectively.There was no significant difference in age,blood pressure,ESS score,sleep stage,and sleep efficiency among these four groups(P>0.05).Body mass index(BMI)and neck circumference were significantly different among these groups(F=4.234,P=0.008;F=3.100,P=0.031).There was no significant difference in the radius indicators(P>0.05).For tibia,there were significant differences among the four groups in the cortical area(Ct.Ar)(F=3.937,P=0.011).There were also significant differences in the bone microstructural indicators including trabecular thickness(Tb.Th)and cortical thickness(Ct.Th)(F=6.247,P=0.001;F=3.746,P=0.014),which were significantly lower in the three OSA groups than in the control group.Pairwise comparisons showed that the Ct.Ar in the severe OSA group was significantly higher than that in the mild OSA group(P=0.019)and Tb.Th in the control group was significantly higher than those in the mild and moderate OSA groups(P=0.006,P=0.001).Correlation analysis showed that,within a certain range,total volumetric bone mineral density(Tt.vBMD)and Tb.Th of radius and tibia were negatively correlated with age(r=-0.312,P=0.004;r=-0.328,P=0.002;r=-0.265,P=0.015;r=-0.280,P=0.010)and positively correlated with BMI(r=0.240,P=0.029;r=0.369,P=0.004;r=0.299,P=0.006;r=0.416,P=0.010).Stepwise multiple regression analysis showed that Tb.Th of radius and tibia were mostly correlated with BMI(β=0.262,P=0.008,R 2=0.243,F=6.270,P=0.000;β=0.494,P=0.000,R 2=0.186,F=7.243,P=0.000)and age(β=-0.216,P=0.030,R 2=0.243,F=6.270,P=0.000;β=-0.306,P=0.003,R 2=0.186,F=7.243,P=0.000).Tt.vBMD of radius had a certain correlation with sleep efficiency and with the decreasing nocturnal mean oxygen saturation caused by OSA(β=0.312,P=0.002, β=-0.249,P=0.012,R 2=0.327,F=7.482,P=0.000). Conclusions In non-elderly male populations,OSA mainly causes a decrease in Tb.Th and Ct.Th of the tibia.The changes in bone strength and structure are mainly related with age and body size and also have certain correlations with sleep efficiency and with the decreasing nocturnal mean oxygen saturation caused by OSA.

ON THE ROLE OF HISTOMORPHOMETRIC (STEREOLOGICAL) MICROSTRUCTURE PARAMETERS IN THE PREDICTION OF VERTEBRAE COMPRESSION STRENGTH

The well-documented relation between bone mineral density (BMD) and bone compression strength constitutes the basis for osteoporosis diagnostics and the assessment of fracture risk. Simultaneously, this relation demonstrates a considerable scatter of results as bones of identical mineral density may have significantly different properties. The experimentally confirmed theorem that two materials or tissues of identical microstructure have identical properties leads to the evaluation of various quantitative stereological parameters (also referred to in biomedicine as histomorphology). These parameters, obtained from analysis of 2D or 3D images, have been used in numerous attempts to explain changes in bone strength. Although numerous correlation dependencies, often with high correlation coefficients, were evaluated, we do not know which parameters are worth evaluating, and there is no physical interpretation of these relations. An extended statistical analysis was accomplished on the basis of analysis of 3D images from 23 lumbar (L3) vertebrae scanned with micro-CT and the results of subsequent compression tests. A new parameter called SDF (structure destruction factor) was proposed in order to characterise the quality of 3D trabecular structures, and its significance was demonstrated. The final correlation function, which uses only three stereological parameters, made it possible to predict compression strength with considerable precision. The estimated values correlated very well with the apparent values (correlation coefficient r=0.96). Finally, the stereological parameters most suitable for characterisation of bone compression strength were chosen and a mechanism responsible for the changes in mechanical properties was proposed. The results obtained defined the necessary improvements in diagnostic techniques that would allow for more efficient quantitative microstructure evaluation and guidelines on how to improve treatment of patients with weakened bones.

Differential changes in bone strength of two inbred mouse strains following administration of a sclerostin-neutralizing antibody during growth.

Administration of sclerostin-neutralizing antibody (Scl-Ab) treatment has been shown to elicit an anabolic bone response in growing and adult mice. Prior work characterized the response of individual mouse strains but did not establish whether the impact of Scl-Ab on whole bone strength would vary across different inbred mouse strains. Herein, we tested the hypothesis that two inbred mouse strains (A/J and C57BL/6J (B6)) will show different whole bone strength outcomes following sclerostin-neutralizing antibody (Scl-Ab) treatment during growth (4.5–8.5 weeks of age). Treated B6 femurs showed a significantly greater stiffness (S) (68.8% vs. 46.0%) and maximum load (ML) (84.7% vs. 44.8%) compared to A/J. Although treated A/J and B6 femurs showed greater cortical area (Ct.Ar) similarly relative to their controls (37.7% in A/J and 41.1% in B6), the location of new bone deposition responsible for the greater mass differed between strains and may explain the greater whole bone strength observed in treated B6 mice. A/J femurs showed periosteal expansion and endocortical infilling, while B6 femurs showed periosteal expansion. Post-yield displacement (PYD) was smaller in treated A/J femurs (-61.2%, p < 0.001) resulting in greater brittleness compared to controls; an effect not present in B6 mice. Inter-strain differences in S, ML, and PYD led to divergent changes in work-to-fracture (Work). Work was 27.2% (p = 0.366) lower in treated A/J mice and 66.2% (p < 0.001) greater in treated B6 mice relative to controls. Our data confirmed the anabolic response to Scl-Ab shown by others, and provided evidence suggesting the mechanical benefits of Scl-Ab administration may be modulated by genetic background, with intrinsic growth patterns of these mice guiding the location of new bone deposition. Whether these differential outcomes will persist in adult and elderly mice remains to be determined.