Vertebral size, bone density, and strength in men and women matched for age and areal spine BMD.

To explore the possible mechanisms underlying sex-specific differences in skeletal fragility that may be obscured by two-dimensional areal bone mineral density (aBMD) measures, we compared quantitative computed tomography (QCT)-based vertebral bone measures among pairs of men and women from the Framingham Heart Study Multidetector Computed Tomography Study who were matched for age and spine aBMD. Measurements included vertebral body cross-sectional area (CSA, cm(2) ), trabecular volumetric BMD (Tb.vBMD, g/cm(3) ), integral volumetric BMD (Int.

Bone loss after bariatric surgery: discordant results between DXA and QCT bone density.

Several studies, using dual-energy X-ray absorptiometry (DXA), have reported substantial bone loss after bariatric surgery. However, profound weight loss may cause artifactual changes in DXA areal bone mineral density (aBMD) results. Assessment of volumetric bone mineral density (vBMD) by quantitative computed tomography (QCT) may be less susceptible to such artifacts.

Microstructural failure mechanisms in the human proximal femur for sideways fall loading.

The etiology of hip fractures remains unclear but might be elucidated by an improved understanding of the microstructural failure mechanisms of the human proximal femur during a sideways fall impact. In this context, we biomechanically tested 12 cadaver proximal femurs (aged 76 ± 10 years; 8 female, 4 male) to directly measure strength for a sideways fall and also performed micro-computed tomography (CT)-based, nonlinear finite element analysis of the same bones (82-micron-sized elements, ∼120 million elements per model) to estimate the amount and location of internal tissue-level failure (by ductile yielding) at initial structural failure of the femur. We found that the correlation between the directly measured yield strength of the femur and the finite element prediction was high (R(2) = 0.

Insights into foraminiferal influences on microfabrics of microbialites at Highborne Cay, Bahamas.

Microbialites, which are organosedimentary structures formed by microbial communities through binding and trapping and/or in situ precipitation, have a wide array of distinctive morphologies and long geologic record. The origin of morphological variability is hotly debated; elucidating the cause or causes of microfabric differences could provide insights into ecosystem functioning and biogeochemistry during much of Earth's history. Although rare today, morphologically distinct, co-occurring extant microbialites provide the opportunity to examine and compare microbial communities that may be responsible for establishing and modifying microbialite microfabrics.

Differences in skeletal microarchitecture and strength in African-American and white women.

African-American women have a lower risk of fracture than white women, and this difference is only partially explained by differences in dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD). Little is known about racial differences in skeletal microarchitecture and the consequences for bone strength. To evaluate potential factors underlying this racial difference in fracture rates, we used high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess cortical and trabecular bone microarchitecture and estimate bone strength using micro-finite element analysis (µFEA) in African-American (n = 100) and white (n = 173) women participating in the Study of Women's Health Across the Nation (SWAN).

Premenopausal women with a distal radial fracture have deteriorated trabecular bone density and morphology compared with controls without a fracture.

Background: Measurement of bone mineral density by dual x-ray absorptiometry combined with clinical risk factors is currently the gold standard in diagnosing osteoporosis. Advanced imaging has shown that older patients with fragility fractures have poor bone microarchitecture, often independent of low bone mineral density. We hypothesized that premenopausal women with a fracture of the distal end of the radius have similar bone mineral density but altered bone microarchitecture compared with control subjects without a fracture.

Adolescent girls with anorexia nervosa have impaired cortical and trabecular microarchitecture and lower estimated bone strength at the distal radius.

Context: Adolescents with anorexia nervosa (AN) have low areal bone mineral density (aBMD) at both cortical and trabecular sites, and recent data show impaired trabecular microarchitecture independent of aBMD. However, data are lacking regarding both cortical microarchitecture and bone strength assessment by finite element analysis (FEA) in adolescents with AN. Because microarchitectural abnormalities and FEA may predict fracture risk independent of aBMD, these data are important to obtain.

Osteoblast-restricted Disruption of the Growth Hormone Receptor in Mice Results in Sexually Dimorphic Skeletal Phenotypes.

Growth hormone (GH) exerts profound anabolic actions during postnatal skeletal development, in part, through stimulating the production of insulin-like growth factor-1 (IGF-1) in liver and skeletal tissues. To examine the requirement for the GH receptor (GHR) in osteoblast function in bone, we used Cre-LoxP methods to disrupt the GHR from osteoblasts, both in vitro and in vivo. Disruption of GHR from primary calvarial osteoblasts in vitro abolished GH-induced signaling, as assessed by JAK2/STAT5 phosphorylation, and abrogated GH-induced proliferative and anti-apoptotic actions.

Osteoporosis update from the 2012 Santa Fe Bone Symposium.

The core of the 2012 Santa Fe Bone Symposium consisted of plenary presentations on new developments in the fields of osteoporosis and metabolic bone disease, with a focus on current and future implications for patient care. These were complemented by oral abstracts, interactive discussions of challenging cases, a debate on benefits and risks of long-term bisphosphonate therapy, and a panel discussion of controversial issues in the management of osteoporosis. Other topics included a review of the most important scientific publications in the past year, new and emerging therapy for osteoporosis, the benefits and limitations of clinical practice guidelines in the care of individual patients, the effects of metallic elements on skeletal health, clinical applications of bone turnover markers, an engineering perspective of skeletal health and disease, and an update on the role of the International Society for Clinical Densitometry in education, certification, accreditation, and advocacy for high-quality bone density testing.

The effects of GATA-1 and NF-E2 deficiency on bone biomechanical, biochemical, and mineral properties.

Mice deficient in GATA-1 or NF-E2, transcription factors required for normal megakaryocyte (MK) development, have increased numbers of MKs, reduced numbers of platelets, and a striking high bone mass phenotype. Here, we show the bone geometry, microarchitecture, biomechanical, biochemical, and mineral properties from these mutant mice. We found that the outer geometry of the mutant bones was similar to controls, but that both mutants had a striking increase in total bone area (up to a 35% increase) and trabecular bone area (up to a 19% increase).

Lumbar vertebral body bone microstructural scaling in small to medium-sized strepsirhines.

Bone mass, architecture, and tissue mineral density contribute to bone strength. As body mass (BM) increases any one or combination of these properties could change to maintain structural integrity. To better understand the structural origins of vertebral fragility and gain insight into the mechanisms that govern bone adaptation, we conducted an integrative analysis of bone mass and microarchitecture in the last lumbar vertebral body from nine strepsirhine species, ranging in size from 42 g (Microcebus rufus) to 2,440 g (Eulemur macaco).

Nocturnal oxytocin secretion is lower in amenorrheic athletes than nonathletes and associated with bone microarchitecture and finite element analysis parameters.

Objective: Preclinical data indicate that oxytocin, a hormone produced in the hypothalamus and secreted into the peripheral circulation, is anabolic to bone. Oxytocin knockout mice have severe osteoporosis, and administration of oxytocin improves bone microarchitecture in these mice. Data suggest that exercise may modify oxytocin secretion, but this has not been studied in athletes in relation to bone.

Parental diabetes: the Akita mouse as a model of the effects of maternal and paternal hyperglycemia in wildtype offspring.

Aim/hypothesis: Maternal diabetes and high-fat feeding during pregnancy have been linked to later life outcomes in offspring. To investigate the effects of both maternal and paternal hyperglycemia on offspring phenotypes, we utilized an autosomal dominant mouse model of diabetes (hypoinsulinemic hyperglycemia in Akita mice). We determined metabolic and skeletal phenotypes in wildtype offspring of Akita mothers and fathers.

Partial reductions in mechanical loading yield proportional changes in bone density, bone architecture, and muscle mass.

Although the musculoskeletal system is known to be sensitive to changes in its mechanical environment, the relationship between functional adaptation and below-normal mechanical stimuli is not well defined. We investigated bone and muscle adaptation to a range of reduced loading using the partial weight suspension (PWS) system, in which a two-point harness is used to offload a tunable amount of body weight while maintaining quadrupedal locomotion. Skeletally mature female C57Bl/6 mice were exposed to partial weight bearing at 20%, 40%, 70%, or 100% of body weight for 21 days.

Sclerostin antibody inhibits skeletal deterioration due to reduced mechanical loading.

Sclerostin, a product of the SOST gene produced mainly by osteocytes, is a potent negative regulator of bone formation that appears to be responsive to mechanical loading, with SOST expression increasing following mechanical unloading. We tested the ability of a murine sclerostin antibody (SclAbII) to prevent bone loss in adult mice subjected to hindlimb unloading (HLU) via tail suspension for 21 days. Mice (n = 11-17/group) were assigned to control (CON, normal weight bearing) or HLU and injected with either SclAbII (subcutaneously, 25 mg/kg) or vehicle (VEH) twice weekly.

Multicenter precision of cortical and trabecular bone quality measures assessed by high-resolution peripheral quantitative computed tomography.

High-resolution peripheral quantitative computed tomography (HR-pQCT) has recently been introduced as a clinical research tool for in vivo assessment of bone quality. The utility of this technology to address important skeletal health questions requires translation to standardized multicenter data pools. Our goal was to evaluate the feasibility of pooling data in multicenter HR-pQCT imaging trials.

Determinants of bone microarchitecture and mechanical properties in obese men.

Context: Recent studies have suggested that obesity in men is associated with increased fracture risk. Obesity in men is also associated with dysregulation of the GH/IGF-I and gonadal steroid axes, important regulators of bone homeostasis.

Objective: The aim of the study was to investigate body composition and endocrine determinants of bone microarchitecture and mechanical properties in obese men.

Variations of CT-based trunk muscle attenuation by age, sex, and specific muscle.

Background: Fat accumulation in muscle may contribute to age-related declines in muscle function and is indicated by reduced attenuation of x-rays by muscle tissue in computed tomography scans. Reduced trunk muscle attenuation is associated with poor physical function, low back pain, and increased hyperkyphosis in older adults. However, variations in trunk muscle attenuation with age, sex and between specific muscles have not been investigated.

Cortical microstructure and estimated bone strength in young amenorrheic athletes, eumenorrheic athletes and non-athletes.

Context: Lower bone density in young amenorrheic athletes (AA) compared to eumenorrheic athletes (EA) and non-athletes may increase fracture risk during a critical time of bone accrual. Finite element analysis (FEA) is a unique tool to estimate bone strength in vivo, and the contribution of cortical microstructure to bone strength in young athletes is not well understood.

Objective: We hypothesized that FEA-estimated stiffness and failure load are impaired in AA at the distal radius and tibia compared to EA and non-athletes despite weight-bearing exercise.

Regulation of lean mass, bone mass, and exercise tolerance by the central melanocortin system.

Signaling via the type 4-melanocortin receptor (MC4R) is an important determinant of body weight in mice and humans, where loss of function mutations lead to significant obesity. Humans with mutations in the MC4R experience an increase in lean mass. However, the simultaneous accrual of fat mass in such individuals may contribute to this effect via mechanical loading.

A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength.

Diseases such as osteoporosis are associated with reduced bone mass. Therapies to prevent bone loss exist, but there are few that stimulate bone formation and restore bone mass. Bone morphogenetic proteins (BMPs) are members of the TGFβ superfamily, which act as pleiotropic regulators of skeletal organogenesis and bone homeostasis.

The effect of thoracic kyphosis and sagittal plane alignment on vertebral compressive loading.

To better understand the biomechanical mechanisms underlying the association between hyperkyphosis of the thoracic spine and risk of vertebral fracture and other degenerative spinal pathology, we used a previously validated musculoskeletal model of the spine to determine how thoracic kyphosis angle and spinal posture affect vertebral compressive loading. We simulated an age-related increase in thoracic kyphosis (T(1) -T(12) Cobb angle 50-75 degrees) during two different activities (relaxed standing and standing with 5-kg weights in the hands) and three different posture conditions: (1) an increase in thoracic kyphosis with no postural adjustment (uncompensated posture); (2) an increase in thoracic kyphosis with a concomitant increase in pelvic tilt that maintains a stable center of mass and horizontal eye gaze (compensated posture); and (3) an increase in thoracic kyphosis with a concomitant increase in lumbar lordosis that also maintains a stable center of mass and horizontal eye gaze (congruent posture). For all posture conditions, compressive loading increased with increasing thoracic kyphosis, with loading increasing more in the thoracolumbar and lumbar regions than in the mid-thoracic region.

Deletion of β-adrenergic receptor 1, 2, or both leads to different bone phenotypes and response to mechanical stimulation.

As they age, mice deficient for the β2-adrenergic receptor (Adrb2(-/-) ) maintain greater trabecular bone microarchitecture, as a result of lower bone resorption and increased bone formation. The role of β1-adrenergic receptor signaling and its interaction with β2-adrenergic receptor on bone mass regulation, however, remains poorly understood. We first investigated the skeletal response to mechanical stimulation in mice deficient for β1-adrenergic receptors and/or β2-adrenergic receptors.

Heritability of prevalent vertebral fracture and volumetric bone mineral density and geometry at the lumbar spine in three generations of the Framingham study.

Genetic factors likely contribute to the risk for vertebral fractures; however, there are few studies on the genetic contributions to vertebral fracture (VFrx), vertebral volumetric bone mineral density (vBMD), and geometry. Also, the heritability (h(2)) for VFrx and its genetic correlation with phenotypes contributing to VFrx risk have not been established. This study aims to estimate the h(2) of vertebral fracture, vBMD, and cross-sectional area (CSA) derived from quantitative computed tomography (QCT) scans and to estimate the extent to which they share common genetic association in adults of European ancestry from three generations of Framingham Heart Study (FHS) families.