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). Bone mass and architecture were assessed via µCT for the whole body and spherical volumes of interest (VOI). Allometric equations were estimated and compared with predictions for geometric scaling, assuming axial compression as the dominant loading regime. Bone mass, microarchitectural, and vertebral body geometric variables predominantly scaled isometrically. Among structural variables, the degree of anisotropy (Tb.DA) was the only parameter independent of BM and other trabecular architectural variables. Tb.DA was related to positional behavior. Orthograde primates had higher average Tb.DA (1.60) and more craniocaudally oriented trabeculae while lorisines had the lowest Tb.DA (1.25), as well as variably oriented trabeculae. Finally, lorisines had the highest ratio of trabecular bone volume to cortical shell volume (∼3x) and while there appears to be flexibility in this ratio, the total bone volume (trabecular + cortical) scales isometrically (BM(1.23) , r(2) = 0.93) and appears tightly constrained. The common pattern of isometry in our measurements leaves open the question of how vertebral bodies in strepsirhine species compensate for increased BM.

Regressions for estimating muscle parameters in the thoracic and lumbar trunk for use in musculoskeletal modeling.

Musculoskeletal modeling requires information on muscle parameters such as cross-sectional area (CSA) and moment arms. A variety of previous studies have reported muscle parameters in the trunk based on in vivo imaging, but there remain gaps in the available data as well as limitations in the generalizability of such data. Specifically, available trunk muscle CSA data is very limited for older adults, lacking entirely in the thoracic region. In addition, previous studies have made measurements in groups of healthy volunteers or hospital patients who may not be representative of the population in general. Finally, such studies have not reported data for the major muscles connecting the upper limb to the thoracic trunk. In this study, muscle morphology measurements were made for major muscles present in the trunk between vertebral levels T6 and L5 using quantitative computed tomography scans from a community-based sample of 100 men and women aged 36-87. We present regression equations to predict trunk muscle CSA and position relative to the vertebral body in the transverse plane from sex, age, height and weight at vertebral levels T6 to L5. Regressions were also developed for predicting anatomical CSA and muscle moment arms, which were estimated using literature data on muscle line of action. This work thus provides a resource for estimating muscle parameters in the general population for musculoskeletal modeling of the thoraco-lumbar trunk.

A biomechanical model for estimating loads on thoracic and lumbar vertebrae.

BACKGROUND: Biomechanical models are commonly used to estimate loads on the spine. Current models have focused on understanding the etiology of low back pain and have not included thoracic vertebral levels. Using experimental data on the stiffness of the thoracic spine, ribcage, and sternum, we developed a new quasi-static stiffness-based biomechanical model to calculate loads on the thoracic and lumbar spine during bending or lifting tasks. METHODS: To assess the sensitivity of the model to our key assumptions, we determined the effect of varying ribcage and sternal stiffness, maximum muscle stress, and objective function on predicted spinal loads. We compared estimates of spinal loading obtained with our model to previously reported in vivo intradiscal pressures and muscle activation patterns. FINDINGS: Inclusion of the ribs and sternum caused an average decrease in vertebral compressive force of 33% for forward flexion and 18% in a lateral moment task. The impact of maximum muscle stress on vertebral force was limited to a narrow range of values. Compressive forces predicted by our model were strongly correlated to in vivo intradiscal pressure measurements in the thoracic (r=0.95) and lumbar (r=1) spine. Predicted trunk muscle activity was also strongly correlated (r=0.95) with previously published EMG data from the lumbar spine. INTERPRETATION: The consistency and accuracy of the model predictions appear to be sufficient to justify the use of this model for investigating the relationships between applied loads and injury to the thoracic spine during quasi-static loading activities.

Treatment with a soluble receptor for activin improves bone mass and structure in the axial and appendicular skeleton of female cynomolgus macaques (Macaca fascicularis).

A recent study suggests that activin inhibits bone matrix mineralization, whereas treatment of mice with a soluble form of the activin type IIA receptor markedly increases bone mass and strength. To further extend these observations, we determined the skeletal effects of inhibiting activin signaling through the ActRIIA receptor in a large animal model with a hormonal profile and bone metabolism similar to humans. Ten female cynomolgus monkeys (Macaca fascicularis) were divided into two weight-matched groups and treated biweekly, for 3 months, with either a subcutaneous injection 10 mg/kg of a soluble form of the ActRIIA receptor fused with the Fc portion of human IgG(1) (ACE-011) or vehicle (VEH). Bone mineral density (BMD), micro-architecture, compressive mechanical properties, and ash fraction were assessed at the end of the treatment period. BMD was significantly higher in ACE-011 treated individuals compared to VEH: +13% (p=0.003) in the 5th lumbar vertebral body and +15% (p=0.05) in the distal femur. In addition, trabecular volumetric bone density at the distal femur was 72% (p=0.0004) higher than the VEH-treated group. Monkeys treated with ACE-011 also had a significantly higher L5 vertebral body trabecular bone volume (p=0.002) and compressive mechanical properties. Ash fraction of L4 trabecular bone cores did not differ between groups. These results demonstrate that treatment with a soluble form of ActRIIA (ACE-011) enhances bone mass and bone strength in cynomolgus monkeys, and provide strong rationale for exploring the use of ACE-011 to prevent and/or treat skeletal fragility.

Specimen size and porosity can introduce error into microCT-based tissue mineral density measurements.

The accurate measurement of tissue mineral density, rho(m), in specimens of unequal size or quantities of bone mineral using polychromatic microCT systems is important, since studies often compare samples with a range of sizes and bone densities. We assessed the influence of object size on microCT measurements of rho(m) using (1) hydroxyapatite rods (HA), (2) precision-manufactured aluminum foams (AL) simulating trabecular bone structure, and (3) bovine cortical bone cubes (BCt). Two beam-hardening correction (BHC) algorithms, determined using a 200 and 1200 mg/cm(3) HA wedge phantom, were used to calculate rho(m) of the HA and BCt. The 200 mg/cm(3) and an aluminum BHC algorithm were used to calculate the linear attenuation coefficients of the AL foams. Equivalent rho(m) measurements of 500, 1000, and 1500 mg HA/cm(3) rods decreased (r(2)>0.96, p<0.05 for all) as HA rod diameter increased in the 200 mg/cm(3) BHC data. Errors averaged 8.2% across these samples and reached as high as 29.5%. Regression analyses suggested no size effects in the 1200 mg/cm(3) BHC data but differences between successive sizes still reached as high as 13%. The linear attenuation coefficients of the AL foams increased up to approximately 6% with increasing volume fractions (r(2)>0.81, p<0.05 for all) but the strength of the size-related error was also BHC dependent. Equivalent rho(m) values were inversely correlated with BCt cube size (r(2)>0.92, p<0.05). Use of the 1200 mg/cm(3) BHC ameliorated the size-related artifact compared to the 200 mg/cm(3) BHC but errors with this BHC were still significant and ranged between 5% and 12%. These results demonstrate that object size, structure, and BHC algorithm can influence microCT measurements of rho(m). Measurements of rho(m) of specimens of unequal size or quantities of bone mineral must be interpreted with caution unless appropriate steps are taken to minimize these potential artifacts.