Polar Moment Of Inertia Research Articles

COMPUTER TECHNOLOGIES IN THE CALCULATION OF GEOMETRIC CHARACTERISTICS OF COMPLEX SECTIONS

None of the calculations for machine parts, structure elements and constructions for strength, rigidity and stability can be performed without using the geometric cross-section characteristics. These include: cross-sectional area, axial, centrifugal and polar moments of inertia, radius of gyration, axial and polar resistance moments of cross-section, etc. The article discusses the problem of technical specialties students` training quality improvement with information technologies aids. There is a review and proposed methodology of usage the software for calculating the geometric cross-sections properties. There are two groups of software: 1) software developed by teachers of higher educational institutions to use in the educational process; 2) industrial software for design engineers, which can also be used during the educational process. Using as an example the calculation of the geometric cross-sections properties of a complex section formed from several rolled profiles, it is demonstrated that the usage of programs "Geom 2006", "Compass 3D", "Consul" and "Constructor of sections" has the following advantages: decrease the costs of effort and time for routine mathematical calculations, makes it easier to find and correct errors made by manual calculations during individual study, which has a positive effect on the learning process; the implementation of calculation and graphic tasks using computer software significantly increases the interest of students for the discipline that is being studied and contributes to the better consolidation of theoretical knowledge and practical skills; students acquire skills in creating design schemes, preparing initial data, analyzing the obtained results, which are necessary for their further work with software systems for structures calculations during the course and for diploma design; it is especially useful to use the proposed programs for distance learning as an effective tool to organize individ-ual study.

Optimal design and experiment study of the double spherical rotor of the MSCSG.

The magnetically suspended control and sense gyroscope (MSCSG) integrates spacecraft attitude measurement and control function; this paper proposes a double spherical rotor (DSR) for MSCSG. The DSR realizes the five degrees of freedom (DOFs) full active control and full channel magnetic path decoupling by the following design: the spherical axial/radial reluctance magnetic bearings are adopted to control the 3DOFs translation of rotor in the range of double spherical envelope, Lorentz force magnetic bearing (LFMB) is used to precisely drive the 2DOFs universal deflection of rotor. The optimization model is established based on the structural mechanical analysis, taking the deviation between rotor centroid and shape center as the optimization objective, choosing the first order resonance frequency, maximum equivalent stress, rigid body displacement, polar moment of inertia and inertia ratio as constraints. Then the DSR is optimized and simulated by the finite element, the MSCSG principle prototype based on DSR is successfully developed, the online dynamic balance experiment and modal test of the DSR are conducted, where the vibration amount of the DSR decreases from 20 μm before the experiment to 0.14 μm after the experiment, which decreases by 99.3%, the first test modal is 2881 Hz which is 5% different from the finite element simulation value of 3034 Hz. The results show that the DSR has the good mechanical properties and magnetic circuit decoupling characteristics.

Collagen X Biomarker (CXM), Linear Growth, and Bone Development in a Vitamin D Intervention Study in Infants.

ABSTRACTCollagen X biomarker (CXM) is suggested to be a biomarker of linear growth velocity. However, early childhood data are limited. This study examines the relationship of CXM to the linear growth rate and bone development, including the possible modifying effects of vitamin D supplementation. We analyzed a cohort of 276 term‐born children participating in the Vitamin D Intervention in Infants (VIDI) study. Infants received 10 μg/d (group‐10) or 30 μg/d (group‐30) vitamin D3 supplementation for the first 2 years of life. CXM and length were measured at 12 and 24 months of age. Tibial bone mineral content (BMC), volumetric bone mineral density (vBMD), cross‐sectional area (CSA), polar moment of inertia (PMI), and periosteal circumference (PsC) were measured using peripheral quantitative computed tomography (pQCT) at 12 and 24 months. We calculated linear growth as length velocity (cm/year) and the growth rate in length (SD unit). The mean (SD) CXM values were 40.2 (17.4) ng/mL at 12 months and 38.1 (12.0) ng/mL at 24 months of age (p = 0.12). CXM associated with linear growth during the 2‐year follow‐up (p = 0.041) but not with bone (p = 0.53). Infants in group‐30 in the highest tertile of CXM exhibited an accelerated mean growth rate in length compared with the intermediate tertile (mean difference [95% CI] −0.50 [−0.98, −0.01] SD unit, p = 0.044) but not in the group‐10 (p = 0.062) at 12 months. Linear association of CXM and growth rate until 12 months was weak, but at 24 months CXM associated with both length velocity (B for 1 increment of √CXM [95% CI] 0.32 [0.12, 0.52] cm/yr, p = 0.002) and growth rate in length (0.20 [0.08, 0.32] SD unit, p = 0.002). To conclude, CXM may not reliably reflect linear growth from birth to 12 months of age, but its correlation with growth velocity improves during the second year of life. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Exploring changes in bone mass in individuals with a chronic spinal cord injury.

(1) To explore changes in bone [primary measure: trabecular volumetric bone mineral density (vBMD); secondary measures: cortical vBMD, cortical thickness, cortical cross-sectional area (CSA), and polar moment of inertia] over 2years in individuals with a chronic spinal cord injury (SCI). (2) To explore whether muscle density changes were potential correlates of the observed bone changes. This study is a secondary data analysis of a prospective, observational study involving 70 people with a chronic SCI (≥ 2years post injury). The study included 4 strata of participants with diverse impairments: (1) Paraplegia (T1-T12) motor complete American Spinal Injury Association Impairment Scale (AIS) A/B (n = 23), (2) Paraplegia motor incomplete AIS C/D (n = 11), (3) Tetraplegia (C2-C8) AIS A/B (n = 22), and (4) Tetraplegia AIS C/D (n = 14). Peripheral quantitative computed tomography scans were taken at the 4% (distal tibia), 38% (diaphyseal tibia), and 66% (muscle cross-sectional area) tibia sites by measuring from the distal to proximal tibia starting at the inferior border of the medial malleolus. The tibia sites were assessed annually over a span of 2years. Comparisons were made using a paired-samples t test and simple linear regression was used to adjust for sex, time post injury, and bisphosphonate use. We observed no changes in trabecular vBMD at the 4% tibia site, but there was a statistically significant decline in cortical vBMD, cortical thickness, and CSA at the 38% tibia site. Changes in muscle density were not associated with the decreases observed in cortical bone. Our findings suggest that individuals with chronic SCI (mean duration of injury: 15.5 ± 10years) may have reached a plateau in bone loss with respect to trabecular bone, but cortical bone loss can continue well into the chronic stages.

Peripheral quantitative computed tomography (pQCT) in 12- and 24-month-old children - Practical aspects and descriptive data.

Peripheral quantitative computed tomography (pQCT) is a useful tool to assess detailed bone characteristics. Its utility in infants is however limited due to lack of reference data and technical challenges. The purpose of this study was to provide data on length- and weight-adjusted pQCT values and to present a quality grading system for healthy children aged 12 and 24months. As a part of the Vitamin D intervention in Infants (VIDI) trial, we collected pQCT and anthropometric data from 855 children at 12months and from 784 children at 24months. Bone mineral content (BMC; mg/mm), volumetric bone mineral density (vBMD; mg/cm3), cross-sectional area (CSA; mm2), polar-moment of inertia (PMI; mm4), and periosteal circumference (PsC; mm) were assessed for total bone at 20% distal site of the left tibia using pQCT (Stratec XCT2000L). We evaluated the impact of scan quality on bone measures. Total bone parameters were assessed for boys and girls separately. The means of the bone parameters were also compared in relation to age. The associations between bone parameters and weight, length, sex and scan quality were analyzed. We included scans with sufficient quality (Grade 1-5) in the final analyses: 679/855 (79%) at 12months and 709/784 (90%) at 24months. Altogether 39% of the scans at 12months and 51% at 24months were of good or excellent quality (Grade 1-2). Scan quality had an impact on BMCs at 12 and 24months (p=0.001 and p=0.017, respectively) but not on other bone parameters. Boys presented greater total bone BMC, CSA, PMI and PsC values at 12 and 24months but vBMDs were similar. All bone parameters showed a significant increase between 12 and 24months for both sexes. When adjusting bone parameters for weight, length and scan quality, differences between sexes disappeared. Weight was the strongest modifier of BMC, CSA, PMI and PsS at 12 and 24months. This study increases our understanding on bone parameters in young children and demonstrates the suitability of pQCT in bone research in infants. The described pQCT data and scan quality grading system should prove useful in evaluating data reliability in research settings. NCT1723852.

Regeneration enhanced in critical-sized bone defects using bone-specific extracellular matrix protein.

Extracellular matrix (ECM) products have the potential to improve cellular attachment and promote tissue-specific development by mimicking the native cellular niche. In this study, the therapeutic efficacy of an ECM substratum produced by bone marrow stem cells (BM-MSCs) to promote bone regeneration in vitro and in vivo were evaluated. Fluorescence-activated cell sorting analysis and phenotypic expression were employed to characterize the in vitro BM-MSC response to bone marrow specific ECM (BM-ECM). BM-ECM encouraged cell proliferation and stemness maintenance. The efficacy of BM-ECM as an adjuvant in promoting bone regeneration was evaluated in an orthotopic, segmental critical-sized bone defect in the rat femur over 8 weeks. The groups evaluated were either untreated (negative control); packed with calcium phosphate granules or granules+BM-ECM free protein and stabilized by collagenous membrane. Bone regeneration in vivo was analyzed using microcomputed tomography and histology. in vivo results demonstrated improvements in mineralization, osteogenesis, and tissue infiltration (114 ± 15% increase) in the BM-ECM complex group from 4 to 8 weeks compared to mineral granules only (45 ± 21% increase). Histological observations suggested direct apposition of early bone after 4 weeks and mineral consolidation after 8 weeks implantation for the group supplemented with BM-ECM. Significant osteoid formation and greater functional bone formation (polar moment of inertia was 71 ± 0.2 mm4 with BM-ECM supplementation compared to 48 ± 0.2 mm4 in untreated defects) validated in vivo indicated support of osteoconductivity and increased defect site cellularity. In conclusion, these results suggest that BM-ECM free protein is potentially a therapeutic supplement for stemness maintenance and sustaining osteogenesis.

The future large obliquity of Jupiter

Aims. We aim to determine whether Jupiter’s obliquity is bound to remain exceptionally small in the Solar System, or if it could grow in the future and reach values comparable to those of the other giant planets. Methods. The spin-axis of Jupiter is subject to the gravitational torques from its regular satellites and from the Sun. These torques evolve over time due to the long-term variations of its orbit and to the migration of its satellites. With numerical simulations, we explore the future evolution of Jupiter’s spin axis for different values of its moment of inertia and for different migration rates of its satellites. Analytical formulas show the location and properties of all relevant resonances. Results. Because of the migration of the Galilean satellites, Jupiter’s obliquity is currently increasing, as it adiabatically follows the drift of a secular spin-orbit resonance with the nodal precession mode of Uranus. Using the current estimates of the migration rate of the satellites, the obliquity of Jupiter can reach values ranging from 6° to 37° after 5 Gyr from now, according to the precise value of its polar moment of inertia. A faster migration for the satellites would produce a larger increase in obliquity, as long as the drift remains adiabatic. Conclusions. Despite its peculiarly small current value, the obliquity of Jupiter is no different from other obliquities in the Solar System: It is equally sensitive to secular spin-orbit resonances and it will probably reach comparable values in the future.

The "Goldilocks Day" for Children's Skeletal Health: Compositional Data Analysis of 24-Hour Activity Behaviors.

Optimization of children's activity behaviors for skeletal health is a key public health priority, yet it is unknown how many hours of moderate to vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior, or sleep constitute the best day-the "Goldilocks Day"-for children's bone structure and function. To describe the best day for children's skeletal health, we used data from the cross-sectional Child Health CheckPoint. Included participants (n = 804, aged 10.7 to 12.9 years, 50% male) underwent tibial peripheral quantitative CT to assesses cross-sectional area, trabecular and cortical density, periosteal and endosteal circumference, polar moment of inertia, and polar stress-strain index. Average daily time-use composition (MVPA, LPA, sedentary time, and sleep) was assessed through 8-day, 24-hour accelerometry. Skeletal outcomes were regressed against time-use compositions expressed as isometric log-ratios (with quadratic terms where indicated), adjusted for sex, age, pubertal status, and socioeconomic position. The models were used to estimate optimal time-use compositions (associated with best 5% of each skeletal outcome), which were plotted in three-dimensional quaternary figures. The center of the overlapping area was considered the Goldilocks Day for skeletal health. Children's time-use composition was associated with all skeletal measures (all p ≤ 0.001) except cross-sectional area (p = 0.72). Days with more sleep and MVPA, less sedentary time, and moderate LPA were beneficially associated with skeletal measures, except cortical density, which was adversely associated. The Goldilocks daily time-use composition for overall skeletal health was center (range): 10.9 (10.5 to 11.5) hours sleep; 8.2 (7.8 to 8.8) hours sedentary time; 3.4 (2.8 to 4.2) hours LPA, and 1.5 (1.3 to 1.5) hours MVPA. Estimated optimal sleep duration is consistent with current international guidelines (9 to 11 hours), while estimated optimal MVPA exceeds recommendations of at least 60 min/d. This first study to describe optimal durations of daily activities for children's skeletal health provides evidence to underpin guidelines. © 2020 American Society for Bone and Mineral Research (ASBMR).

Oxytocin and bone quality in the femoral neck of rats in periestropause

The objective of this study is to identify whether oxytocin (OT) contributes to the reduction of osteopenia in the femoral neck of rats in periestropause. Animals in irregular estrous cycles received two NaCl injections (0.15 mol/L) or OT (134 μg/kg) over a 12-h interval, and after thirty-five days without treatments, the biological sample collection was performed. The oxytocin group (Ot) demonstrated the highest enzymatic activity of alkaline phosphatase (p = 0.0138), lowest enzymatic activity of tartrate-resistant acid phosphatase (p = 0.0045), higher percentage of compact bone (p = 0.0359), cortical expression of runt-related transcription factor 2 (p = 0.0101), osterix (p = 0.0101), bone morphogenetic protein-2/4 (p = 0.0101) and periostin (p = 0.0455). Furthermore, the mineral-to-matrix ratio (ν1PO4/Proline) was higher and type-B carbonate substitution (CO3/ν1PO4) was lower (p = 0.0008 and 0.0303) in Ot group. The Ot showed higher areal bone mineral density (p = 0.0050), cortical bone area (p = 0.0416), polar moment of inertia, maximum, minimum (p = 0.0480, 0.0480, 0.0035), bone volume fraction (p = 0.0166), connectivity density (p < 0.0001), maximal load (p = 0.0003) and bone stiffness (p = 0.0145). In Ot percentage of cortical pores (p = 0.0102) and trabecular number (p = 0.0088) was lower. The results evidence action of OT in the reduction of osteopenia, suggesting that it is a promising anabolic strategy for the prevention of primary osteoporosis during the periestropause period.

Rigid slab foundation subjected to strike–slip faulting: mechanisms and insights

In this paper, the interaction of rigid slab foundations with a strike–slip fault is studied. A three-dimensional finite-element model of the soil–foundation system is developed, employing a thoroughly validated constitutive model that incorporates strain softening. The widely used rigid box type boundaries are compared to periodic boundaries, demonstrating their superiority. Allowing the soil to deform freely, periodic boundaries allow realistic simulation of fault rupture propagation through soil and minimisation of parasitic boundary effects. An approximate dimensional formulation is presented and verified by comparing the response of two self-similar systems. A parametric study is conducted, revealing two distinct kinematic mechanisms: a rotational one, where the foundation mainly rotates; and a translational one, where the foundation either displaces parallel to the fault trace or remains almost stationary. It is shown that the response is controlled by the presence of the foundation, acting as a kinematic constraint, which can be quantified by its polar moment of inertia, Iz. The rotational mechanism leads to positive bending moments of larger magnitude, whereas the translational leads to negative moments of larger magnitude. The effect of key dimensionless parameters is parametrically investigated, including the fault rupture location, the surcharge load, the interface friction coefficient and the foundation aspect ratio. Shorter foundations (parallel to the fault trace) tend to rotate, whereas longer ones tend to displace. Fault rupture locations close to the foundation sides lead to translation, whereas locations close to its centreline lead to rotation. The development of the translation mechanism is facilitated by the increase of surcharge load and interface friction coefficient.

Effects of chemotherapy agents used to treat pediatric acute lymphoblastic leukemia patients on bone parameters and longitudinal growth of juvenile mice

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Therapies for pediatric ALL have improved such that more than 80% of patients survive to 5 years post-therapy, and most survive to adulthood. These ALL patients experience long-term side effects that permanently affect their quality of life, with bone loss and reduced longitudinal growth being the most common skeletal complications. To determine the effects of the chemotherapeutic agents used in ALL induction therapy on bone density and longitudinal growth in mice, we treated juvenile mice with doxorubicin, dexamethasone, vincristine, l-asparaginase, or combination therapy. At adulthood, mice were culled and bones collected and scanned by micro-computed tomography (micro-CT). Mice that received doxorubicin and combination therapy exhibited reduced longitudinal growth and significant reductions in trabecular bone volume, trabecular thickness, and trabecular number, with increased trabecular separation. Mean cortical thickness, cortical area, marrow area, endocortical perimeter, and polar moment of inertia were significantly reduced by doxorubicin and combination therapy. Vincristine treatment significantly decreased trabecular bone volume, trabecular number, and increased trabecular separation but had no effects on cortical bone. Dexamethasone treatment increased trabecular bone separation, cortical marrow area, and cortical bone periosteal perimeter. Mice treated with l-asparaginase did not have any bone phenotypes. In conclusion, these data indicate that the majority of the chemotherapy agents used in induction therapy for pediatric ALL have long-term effects on bone in mice. A single dose of doxorubicin in juvenile mice was sufficient to cause the majority of the bone phenotypes, with combination therapy intensifying these effects.

Weighted geometric inequalities for hypersurfaces in sub‐static manifolds

We prove two weighted geometric inequalities that hold for strictly mean convex and star-shaped hypersurfaces in Euclidean space. The first one involves the weighted area and the area of the hypersurface and also the volume of the region enclosed by the hypersurface. The second one involves the total weighted mean curvature and the area of the hypersurface. Versions of the first inequality for the sphere and for the adS-Reissner-Nordstr\"om manifold are proven. We end with an example of a convex surface for which the ratio between the polar moment of inertia and the square of the area is less than that of the round sphere.

Engraftment of skeletal progenitor cells by bone-directed transplantation improves osteogenesis imperfecta murine bone phenotype.

Osteogenesis imperfecta (OI) is a genetic disorder most commonly caused by mutations associated with type I collagen, resulting in a defective collagen bone matrix. Current treatments for OI focus on pharmaceutical strategies to increase the amount of defective bone matrix, but do not address the underlying collagen defect. Introducing healthy donor stem cells that differentiate into osteoblasts producing normal collagen in OI patients has the potential to increase bone mass and correct the mutant collagen matrix. In this study, donor bone marrow stromal cells (BMSCs, also known as bone marrow mesenchymal stem cells) expressing both αSMACreERT2/Ai9 progenitor reporter and osteoblast reporter Col2.3GFP were locally transplanted into the femur of OI murine (OIM) mice. One month post-transplantation, 18% of the endosteal surface was lined by donor Col2.3GFP expressing osteoblasts indicating robust engraftment. Long-term engraftment in the marrow was observed 3 and 6 months post-transplantation. The presence of Col1a2-expressing donor cell-derived cortical bone matrix was detected in transplanted OIM femurs. Local transplantation of BMSCs increased cortical thickness (+12%), the polar moment of inertia (+14%), bone strength (+30%), and stiffness (+30%) 3 months post-transplantation. Engrafted cells expressed progenitor markers CD51 and Sca-1 up to 3 months post-transplantation. Most importantly, 3 months post-transplantation donor cells maintained the ability to differentiate into Col2.3GFP+ osteoblasts in vitro, and in vivo following secondary transplantation into OIM animals. Locally transplanted BMSCs can improve cortical structure and strength, and persist as continued source of osteoblast progenitors in the OIM mouse for at least 6 months.

Study of the optimal reinforcing structure of the compressor wheel from composition material of the transport turbocharged engine

The purpose of the study was to find the optimal configuration of the main parameters of the reinforcing layer of a compressor wheel made of composite material. The optimization problem for an anisotropic system was solved using the Gauss-Seidel method. According to the results of calculations, it was established that under the condition of preserving the strength of the wheel, there is the possibility of transition to reinforcing layers in which the fibers are oriented only in the circumferential direction, which makes it possible to significantly simplify the technology of its manufacture. The use of reinforcement for compressor wheels made of composite material can significantly reduce its mass and polar moment of inertia, which contributes to the improvement of strength and performance of the turbocharger and the engine as a whole.

Long-term orbital and rotational motions of Ceres and Vesta

Context.The dwarf planet Ceres and the asteroid Vesta have been studied by the Dawn space mission. They are the two heaviest bodies of the main asteroid belt and have different characteristics. Notably, Vesta appears to be dry and inactive with two large basins at its south pole. Ceres is an ice-rich body with signs of cryovolcanic activity.Aims.The aim of this paper is to determine the obliquity variations of Ceres and Vesta and to study their rotational stability.Methods.The orbital and rotational motions have been integrated by symplectic integration. The rotational stability has been studied by integrating secular equations and by computing the diffusion of the precession frequency.Results.The obliquity variations of Ceres over [−20 : 0] Myr are between 2° and 20° and the obliquity variations of Vesta are between 21° and 45°. The two giant impacts suffered by Vesta modified the precession constant and could have put Vesta closer to the resonance with the orbital frequency 2s6−sV. Given the uncertainty on the polar moment of inertia, the present Vesta could be in this resonance where the obliquity variations can vary between 17° and 48°.Conclusions.Although Ceres and Vesta have precession frequencies close to the secular orbital frequencies of the inner planets, their long-term rotations are relatively stable. The perturbations of Jupiter and Saturn dominate the secular orbital dynamics of Ceres and Vesta and the perturbations of the inner planets are much weaker. The secular resonances with the inner planets also have smaller widths and do not overlap, contrary to the case of the inner planets.

Image Analysis Software as a Strategy to Improve the Radiographic Determination of Fracture Healing.

To develop and validate an unbiased, accurate, convenient, and inexpensive means of determining when an osseous defect has healed and recovered sufficient strength to allow weight bearing. A novel image processing software algorithm was created to analyze the radiographic images and produce a metric designed to reflect the bone strength. We used a rat femoral segmental defect model that provides a range of healing responses from complete union to nonunion. Femora were examined by x-ray, micro-computed tomography and mechanical testing. Accurate simulated radiographic images at different incident x-ray beam angles were produced from the micro-computed tomography data files. The software-generated metric (SC) showed high levels of correlation with both the mechanical strength (τMech) and the polar moment of inertia (pMOI), with the mechanical testing data having the highest association. The optimization analysis yielded optimal oblique angles θB of 125 degrees for τMech and 50 degrees for pMOI. The Pearson R values for the optimized model were 0.71 and 0.64 for τMech and pMOI, respectively. Further validation using true radiographs also demonstrated that the metric was accurate and that the simulations were realistic. The preliminary findings suggest a very promising methodology to assess bone fracture healing using conventional radiography. With radiographs acquired at appropriate incident angles, it proved possible to accurately calculate the degree of healing and the mechanical strength of the bone. Further research is necessary to refine this approach and determine whether it translates to the human clinical setting.

Abstract 1808: The anti-estrogen endoxifen altered bone morphology and reduced muscle function in mice

Abstract Endoxifen, the predominant CYP2D6 metabolite of the selective estrogen receptor modulator (SERM) tamoxifen, is currently being developed as a novel anti-estrogen therapy for the treatment of estrogen receptor (ER)+ breast cancer. Genetic polymorphism of CYP2D6 is a predictor of response to tamoxifen in patients, implicating endoxifen as one of the most active and relevant tamoxifen metabolites. Breast cancer patients treated with adjuvant endocrine therapies including aromatase inhibitors (AIs) and SERMs often report unmanageable musculoskeletal toxicities that can result in treatment discontinuation. While ER binding affinity and anti-tumor effects have been established in preclinical models, the effects of endoxifen on the musculoskeletal system are not fully known. Twenty-week female C57BL/6 mice underwent sham surgery or ovariectomy (OVX) and were treated daily with vehicle, the AI letrozole, or the SERM endoxifen. Body composition was assessed prospectively by DXA. Bone indices and marrow adipose tissue volume were measured by μCT and muscle contractility of the extensor digitorum longus (EDL) was measured ex vivo. After eight weeks, trabecular bone volume fraction (BV/TV) decreased by 50% in OVX-vehicle and OVX-letrozole mice, whereas BV/TV increased threefold in endoxifen mice relative to sham-vehicle. Despite the presence of significantly more trabecular bone following endoxifen treatment, cortical bone analyses revealed impaired periosteal and endosteal expansion of bone, resulting in reduced polar moment of inertia, which is a measure of resistance to fracture. Uterine weight increased significantly in endoxifen-treated mice relative to all OVX groups, similar to what is observed with tamoxifen treatment. Peripheral body fat, bone marrow adipose tissue, and circulating leptin were reduced by endoxifen, suggesting that the drug may elicit positive systemic metabolic effects. At the termination of the study, muscle-specific force was reduced in OVX-endoxifen mice relative to sham-vehicle, OVX-vehicle, and OVX-AI mice, despite no change in muscle mass. While endoxifen shows promise as a potent anti-estrogen therapy for the treatment of ER+ breast cancer, it may be important to monitor patients for endometrial proliferation, morphological changes in bone that increase fracture risk, and for musculoskeletal side effects that could reduce drug compliance. Citation Format: Laura Wright, Khalid Mohammad, Theresa Guise. The anti-estrogen endoxifen altered bone morphology and reduced muscle function in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1808.

Effect of Higher vs Standard Dosage of Vitamin D3 Supplementation on Bone Strength and Infection in Healthy Infants

Although guidelines for vitamin D supplementation in infants have been widely implemented, they are mostly based on studies focusing on prevention of rickets. The optimal dose for bone strength and infection prevention in healthy infants remains unclear. To determine whether daily supplementation with 1200 IU of vitamin D3 increases bone strength or decreases incidence of infections in the first 2 years of life compared with a dosage of 400 IU/d. A randomized clinical trial involving a random sample of 975 healthy term infants at a maternity hospital in Helsinki, Finland. Study recruitment occurred between January 14, 2013, and June 9, 2014, and the last follow-up was May 30, 2016. Data analysis was by the intention-to-treat principle. Randomization of 489 infants to daily oral vitamin D3 supplementation of 400 IU and 486 infants to 1200 IU from age 2 weeks to 24 months. Primary outcomes were bone strength and incidence of parent-reported infections at 24 months. Of the 975 infants who were randomized, 485 (49.7%) were girls and all were of Northern European ethnicity. Eight hundred twenty-three (84.4%) completed the 24-month follow-up. We found no differences between groups in bone strength measures, including bone mineral content (mean difference, 0.4 mg/mm; 95% CI, -0.8 to 1.6), mineral density (mean difference, 2.9 mg/cm3; 95% CI, -8.3 to 14.2), cross-sectional area (mean difference, -0.9 mm2; 95% CI, -5.0 to 3.2), or polar moment of inertia (mean difference, -66.0 mm4, 95% CI, -274.3 to 142.3). Incidence rates of parent-reported infections did not differ between groups (incidence rate ratio, 1.00; 95% CI, 0.93-1.06). At birth, 914 of 955 infants (95.7%) were vitamin D sufficient (ie, 25-hydroxyvitamin D [25(OH)D] concentration ≥20.03 ng/mL). At 24 months, mean 25(OH)D concentration was higher in the 1200-IU group than in the 400-IU group (mean difference, 12.50 ng/mL; 95% CI, 11.22-13.78). A vitamin D3 supplemental dose of up to 1200 IU in infants did not lead to increased bone strength or to decreased infection incidence. Daily supplementation with 400 IU vitamin D3 seems adequate in maintaining vitamin D sufficiency in children younger than 2 years. ClinicalTrials.gov Identifier: NCT01723852.

Lnk Deficiency Leads to TPO-Mediated Osteoclastogenesis and Increased Bone Mass Phenotype.

The Lnk adapter protein negatively regulates the signaling of thrombopoietin (TPO), the main megakaryocyte (MK) growth factor. Lnk-deficient (-/-) mice have increased TPO signaling and increased MK number. Interestingly, several mouse models exist in which increased MK number leads to a high bone mass phenotype. Here we report the bone phenotype of these mice. MicroCT and static histomorphometric analyses at 20 weeks showed the distal femur of Lnk-/- mice to have significantly higher bone volume fraction and trabecular number compared to wild-type (WT) mice. Notably, despite a significant increase in the number of osteoclasts (OC), and decreased bone formation rate in Lnk-/- mice compared to WT mice, Lnk-/- mice demonstrated a 2.5-fold greater BV/TV suggesting impaired OC function in vivo. Additionally, Lnk-/- mouse femurs exhibited non-significant increases in mid-shaft cross-sectional area, yet increased periosteal BFR compared to WT femurs was observed. Lnk-/- femurs also had non-significant increases in polar moment of inertia and decreased cortical bone area and thickness, resulting in reduced bone stiffness, modulus, and strength compared to WT femurs. Of note, Lnk is expressed by OC lineage cells and when Lnk-/- OC progenitors are cultured in the presence of TPO, significantly more OC are observed than in WT cultures. Lnk is also expressed in osteoblast (OB) cells and in vitro reduced alkaline phosphatase activity was observed in Lnk-/- cultures. These data suggest that both direct effects on OB and OC as well as indirect effects of MK in regulating OB contributes to the observed high bone mass. J. Cell. Biochem. 118: 2231-2240, 2017. © 2017 Wiley Periodicals, Inc.

Adaptations in the Microarchitecture and Load Distribution of Maternal Cortical and Trabecular Bone in Response to Multiple Reproductive Cycles in Rats.

Pregnancy, lactation, and weaning result in dramatic changes in maternal calcium metabolism. In particular, the increased calcium demand during lactation causes a substantial degree of maternal bone loss. This reproductive bone loss has been suggested to be largely reversible, as multiple clinical studies have found that parity and lactation history have no adverse effect on postmenopausal fracture risk. However, the precise effects of pregnancy, lactation, and post-weaning recovery on maternal bone structure are not well understood. Our study aimed to address this question by longitudinally tracking changes in trabecular and cortical bone microarchitecture at the proximal tibia in rats throughout three cycles of pregnancy, lactation, and post-weaning using in vivo μCT. We found that the trabecular thickness underwent a reversible deterioration during pregnancy and lactation, which was fully recovered after weaning, whereas other parameters of trabecular microarchitecture (including trabecular number, spacing, connectivity density, and structure model index) underwent a more permanent deterioration, which recovered minimally. Thus, pregnancy and lactation resulted in both transient and long-lasting alterations in trabecular microstructure. In the meantime, multiple reproductive cycles appeared to improve the robustness of cortical bone (resulting in an elevated cortical area and polar moment of inertia), as well as increase the proportion of the total load carried by the cortical bone at the proximal tibia. Taken together, changes in the cortical and trabecular compartments suggest that whereas rat tibial trabecular bone appears to be highly involved in maintaining calcium homeostasis during female reproduction, cortical bone adapts to increase its load-bearing capacity, allowing the overall mechanical function of the tibia to be maintained. © 2017 American Society for Bone and Mineral Research.