Bone Microarchitecture and Strength Adaptation to Physical Activity: A Within-Subject Controlled HRpQCT Study.

PURPOSE: Physical activity benefits bone mass and cortical bone size. The current study assessed the impact of chronic (≥10 yr) physical activity on trabecular microarchitectural properties and microfinite element analyses of estimated bone strength. METHODS: Female collegiate-level tennis players (n = 15; age = 20.3 ± 0.9 yr) were used as a within-subject controlled model of chronic unilateral upper-extremity physical activity. Racquet-to-nonracquet arm differences at the distal radius and radial diaphysis were assessed using high-resolution peripheral quantitative computed tomography. The distal tibia and the tibial diaphysis in both legs were also assessed, and cross-country runners (n = 15; age = 20.8 ± 1.2 yr) included as controls. RESULTS: The distal radius of the racquet arm had 11.8% (95% confidence interval [CI] = 7.9% to 15.7%) greater trabecular bone volume/tissue volume, with trabeculae that were greater in number, thickness, connectivity, and proximity to each other than that in the nonracquet arm (all P < 0.01). Combined with enhanced cortical bone properties, the microarchitectural advantages at the distal radius contributed a 18.7% (95% CI = 13.0% to 24.4%) racquet-to-nonracquet arm difference in predicted load before failure. At the radial diaphysis, predicted load to failure was 9.6% (95% CI = 6.7% to 12.6%) greater in the racquet versus nonracquet arm. There were fewer and smaller side-to-side differences at the distal tibia; however, the tibial diaphysis in the leg opposite the racquet arm was larger with a thicker cortex and had 4.4% (95% CI = 1.7% to 7.1%) greater strength than the contralateral leg. CONCLUSION: Chronically elevated physical activity enhances trabecular microarchitecture and microfinite element estimated strength, furthering observations from short-term longitudinal studies. The data also demonstrate that tennis players exhibit crossed symmetry wherein the leg opposite the racquet arm possesses enhanced tibial properties compared with in the contralateral leg.

Bilateral asymmetry and developmental plasticity of the humerus in modern humans.

OBJECTIVE: This study investigates bilateral asymmetry in the humerus of modern human populations with differing activity patterns to assess the relative plasticity of different bone regions in response to environmental influences, particularly the biomechanical demands of handedness. METHODS: External breadths, cross-sectional properties, and centroid sizes were used to quantify directional and absolute asymmetry of humeral diaphyseal, distal periarticular, and articular regions in six populations with differing subsistence strategies (total n = 244). Geometric section properties were measured using computed tomography at six locations along the distal humerus, while centroid sizes of the distal articular and periarticular regions, as well as eight segments of the diaphysis, were extracted from external landmark data. Bilateral asymmetries were compared between populations and sexes. Each property was also tested for correlation with bilateral asymmetry at 40% of bone length, which has been shown to correlate with handedness. RESULTS: Asymmetry is highest in the diaphysis, but significant through all distal bone regions. Asymmetry increases in the region of the deltoid tuberosity, and progressively declines distally through the shaft and distal periarticular region. Articular asymmetry is higher than periarticular asymmetry, approaching levels seen just proximal to the olecranon fossa, and is weakly but significantly correlated with diaphyseal asymmetry. Hunter-gatherers from Indian Knoll have significantly higher levels of asymmetry than other groups and are more sexually dimorphic, particularly in cross-sectional properties of the diaphysis. CONCLUSIONS: Humeral dimensions throughout the diaphysis, including regions currently used in taxonomic assignments of fossil hominins, likely respond to in vivo use, including population and sex-specific behaviors.

Age-related site-specific modifications in diaphyseal structural properties of the human fibula: Furrows and cross-sectional geometry.

OBJECTIVES: Fibular structure is related to locomotor behavior, which allows an exploration of mobility in past human populations with diaphyseal cross-sectional geometry (CSG). However, bone structure depends on age-related changes. Nonmechanical alterations can affect biomechanical investigations. In this study, we examined how the cortical area and the variables used as functional markers in the fibular diaphysis (i.e., CSG and furrows) change with aging. We predict classic and specific modifications, and we discuss functional interpretations based on bone structure. MATERIALS AND METHODS: The sample consisted of 124 individuals of known age in whom the fibular furrow depths were measured with calipers. Microcomputed tomography (micro-CT) scanning of 38 individuals provided CSG (e.g., cortical area, shape index, and robusticity) and fibular furrow indices. CSG was studied at five cross sections taken along the diaphysis. Linear regression analyses and age group comparisons were conducted. RESULTS: The cross-sectional shape summary by fibular furrows and shape index and the total area did not change with aging; in contrast, the cortical area and the robusticity (Zp-std) decreased with age. DISCUSSION: The decrease in robusticity (Zp-std) with aging is due to the maintenance of total area, which is related to the specific mechanical environment of the fibula, and to the loss of cortical bone and not to the decrease in mechanical stress. This finding is consistent with the lower bone modeling capacity in aged individuals, which also explains the lack of significant changes in the diaphyseal shape. Thus, fibular structure in older individuals is due to a combination of early bone adaptations to stress and aging effects.

Femoral neck and shaft structure in Homo naledi from the Dinaledi Chamber (Rising Star System, South Africa).

The abundant femoral assemblage of Homo naledi found in the Dinaledi Chamber provides a unique opportunity to test hypotheses regarding the taxonomy, locomotion, and loading patterns of this species. Here we describe neck and shaft cross-sectional structure of all the femoral fossils recovered in the Dinaledi Chamber and compare them to a broad sample of fossil hominins, recent humans, and extant apes. Cross-sectional geometric (CSG) properties from the femoral neck (base of neck and midneck) and diaphysis (subtrochanteric region and midshaft) were obtained through CT scans for H. naledi and through CT scans or from the literature for the comparative sample. The comparison of CSG properties of H. naledi and the comparative samples shows that H. naledi femoral neck is quite derived with low superoinferior cortical thickness ratio and high relative cortical area. The neck appears superoinferiorly elongated because of two bony pilasters on its superior surface. Homo naledi femoral shaft shows a relatively thick cortex compared to the other hominins. The subtrochanteric region of the diaphysis is mediolaterally elongated resembling early hominins while the midshaft is anteroposteriorly elongated, indicating high mobility levels. In term of diaphyseal robusticity, the H. naledi femur is more gracile that other hominins and most apes. Homo naledi shows a unique combination of characteristics in its femur that undoubtedly indicate a species committed to terrestrial bipedalism but with a unique loading pattern of the femur possibly consequence of the unique postcranial anatomy of the species.

Do bone geometric properties of the proximal femoral diaphysis reflect loading history, muscle properties, or body dimensions?

OBJECTIVES: The aim of this study was to investigate activity-induced effects from bone geometric properties of the proximal femur in athletic vs nonathletic healthy females by statistically controlling for variation in body size, lower limb isometric, and dynamic muscle strength, and cross-sectional area of Musculus gluteus maximus. METHODS: The material consists of hip and proximal thigh magnetic resonance images of Finnish female athletes (N = 91) engaged in either high jump, triple jump, soccer, squash, powerlifting, endurance running or swimming, and a group of physically active nonathletic women (N = 20). Cross-sectional bone geometric properties were calculated for the lesser trochanter, sub-trochanter, and mid-shaft of the femur regions. Bone geometric properties were analyzed using a general linear model that included body size, muscle size, and muscle strength as covariates. RESULTS: Body size and isometric muscle strength were positively associated with bone geometric properties at all three cross-sectional levels of the femur, while muscle size was positively associated with bone properties only at the femur mid-shaft. When athletes were compared to nonathletic females, triple jump, soccer, and squash resulted in greater values in all studied cross-sections; high jump and endurance running resulted in greater values at the femoral mid-shaft cross-section; and swimming resulted in lower values at sub-trochanter and femur mid-shaft cross-sections. CONCLUSIONS: Activity effects from ground impact loading were associated with higher bone geometric values, especially at the femur mid-shaft, but also at lesser and sub-trochanter cross-sections. Bone geometric properties along the femur can be used to assess the mechanical stimuli experienced, where ground impact loading seems to be more important than muscle loading.

The impact of terrain on lower limb bone structure.

OBJECTIVES: Lower limb diaphyseal geometry is often used to evaluate mobility in past populations. Diaphyseal dimensions such as high shape (IX /IY ) indices generally thought to reflect high mobility may also result from walking over rough terrain. This study investigates the possible effects of terrain on lower limb diaphyseal cross-sectional geometric dimensions. MATERIALS: The sample (N = 3,195) comprises adult skeletons from Europe, Africa, North America, and Asia, spanning from around 30,000 BP to mid-twentieth century. METHODS: Femoral and tibial shape and bending/torsional strength dimensions were gathered either as part of a previous project or were generously provided by researchers. Local terrain for each site was quantified with ArcGIS mapping software using geographic coordinates and USGS elevation data, and characterized as flat, hilly, or mountainous. RESULTS: Analysis of variance shows significant differences (p < .05) in midshaft femoral and tibial shape ratio and relative bending/torsional strength among the three terrain categories, with more AP oriented diaphyseal shapes and greater relative strength in hilly and mountainous groups, even after correcting for the effect of subsistence. As expected, the impact of terrain is much more marked for hunter-gatherers and agriculturalists than for more mechanized recent populations. Interestingly, the effect of terrain is confounded in higher latitude individuals that exhibit increased ML bending strength, probably reflecting larger body breadth. DISCUSSION: This study underscores the mechanical significance of traveling over rough terrain and highlights the complex interactions of mobility, terrain, and body shape that contribute to shaping lower limb bone diaphyseal structure.

Study of human radius construction systematics: evaluation by DXA in dry bone.

This study has been undertaken in order to describe the bone mass distribution of the dry human radius via dual x-ray absorptiometry (DXA) with a Norland XR-800 densitometer machine. A sample of 39 dry radius bones was used. Two projections were made: antero-posterior and lateral, and five regions of interest were selected. The bone densities and the bone mineral contents of the various regions of the radius in the two projections were compared using Student's t tests for paired samples, with statistically significant differences being found in all of the values, except in the proximal extremity (P Ext). The area of greatest bone mineral content (BMC) was the medial diaphysis (M Diaph), followed by the distal extremity (D Ext), with the lowest value being found in the proximal extremity (P Ext). As for bone mineral density (BMD), a great symmetry is observed if we take the mean point of the longitudinal axis as a reference, with it being distributed from highest to lowest from the central part to the extremities. A correlation study of the BMD and BMC values between the segments themselves and with the total, in both positions, provides us with a high correlation (p ≤ 0.01), with the highest correlation value being found for the proximal diaphysis (P Diaph) region, indicating the heterogeneous nature of the distribution of the radius bone mass. Bone densitometry via DXA is useful in order to establish an overview of the structural construction of the human radius.

Cross-sectional properties of the humeral diaphysis of Paranthropus boisei: Implications for upper limb function.

A ∼1.52 Ma adult upper limb skeleton of Paranthropus boisei (KNM-ER 47000) recovered from the Koobi Fora Formation, Kenya (FwJj14E, Area 1A) includes most of the distal half of a right humerus (designated KNM-ER 47000B). Natural transverse fractures through the diaphysis of KNM-ER 470000B provide unobstructed views of cortical bone at two sections typically used for analyzing cross-sectional properties of hominids (i.e., 35% and 50% of humerus length from the distal end). Here we assess cross-sectional properties of KNM-ER 47000B and two other P. boisei humeri (OH 80-10, KNM-ER 739). Cross-sectional properties for P. boisei associated with bending/torsional strength (section moduli) and relative cortical thickness (%CA; percent cortical area) are compared to those reported for nonhuman hominids, AL 288-1 (Australopithecus afarensis), and multiple species of fossil and modern Homo. Polar section moduli (Zp) are assessed relative to a mechanically relevant measure of body size (i.e., the product of mass [M] and humerus length [HL]). At both diaphyseal sections, P. boisei exhibits %CA that is high among extant hominids (both human and nonhuman) and similar to that observed among specimens of Pleistocene Homo. High values for Zp relative to size (M × HL) indicate that P. boisei had humeral bending strength greater than that of modern humans and Neanderthals and similar to that of great apes, A. afarensis, and Homo habilis. Such high humeral strength is consistent with other skeletal features of P. boisei (reviewed here) that suggest routine use of powerful upper limbs for arboreal climbing.

High correlation between mechanical properties and bone mineral parameters in embalmed femurs after long-term storage.

BACKGROUND: Fresh frozen human femurs are considered "the gold standard" in biomechanical studies of hip fractures, resembling the in vivo situation mostly. A more readily available alternative is formalin embalmed femurs. However, to which extent formalin affects key features of bone; its mechanical properties, bone mineral content and their mutual relationship over time, remains unknown. Accordingly, we measured the mineral parameters and related them to the mechanical properties of formalin fixed femurs after long-term storage. METHODS: 36 paired femurs from human donors, fixed in formalin and stored for a mean period of 4.6 (3.5-6) years. Quantitative CT was performed to measure the bone mineral density and mass at the mainly cortical mid shaft and the center of the mainly cancellous condyles. Each pair was subjected to local tests by three-point bending and screw pullout of the shaft and lateral punch and metaphyseal cube compression of the condyles. FINDINGS: Neither mechanical nor bone mineral data were significantly correlated to storage time. Well-known associations for bone parameters with age and gender were retrieved. Maximum force of the cortical bone tests was highly correlated to the diaphyseal bone mass; (r = 0.80-0.87, p = 0.01), while maximum force of the cancellous bone tests correlated well to the density of the condylar bone; (r = 0.70, p = 0.01). INTERPRETATION: Our results indicate that mechanical and bone mineral data and their mutual relationship are conserved in formalin fixed femurs even after long-term storage. Formalin fixed femurs may serve as an alternative to fresh frozen femurs in biomechanical testing.

The daily grind: Sex- and age-related activity patterns inferred from cross-sectional geometry of long bones in a pre-Columbian muisca population from Tibanica, Colombia.

OBJECTIVES: Daily activities involve biomechanical strains acting on skeletal structures. This study identifies differences in activity patterns between males and females, and between young, middle, and older aged individuals within an excavated Muisca skeletal sample from the Eastern Andes region of Northern South America. MATERIALS AND METHODS: The Tibanica archaeological site (AD 1000-1400) is located at 2600 masl on the Sabana de Bogotá, Colombia. Cross-sectional geometric analysis of femurs from 63 individuals and paired-humerii from 33 individuals was used to examine bone size (TA), strength (J) and diaphyseal shape (Imax /Imin , Ix /Iy ). RESULTS: The findings indicate both age- and sex-related differences in activity patterns. An emphasis on upper body strength and robusticity was observed in the females, while males performed more strenuous work using their lower bodies, suggesting gender-based differences in labor. Men showed significant asymmetry in their humerii, with most showing right-hand dominance for upper body activities, while females showed high levels of humeral symmetry indicating similar levels of biomechanical stress for both arms. Female femoral diaphyseal shape changes with age, suggesting more mobility in youth and decreased mobility in middle and older ages. DISCUSSION: These results suggest that daily life may have been structured through patterns of routine labor that united and divided particular age and sex groups. Cross-sectional geometry data indicate women likely spent significant time and energy preparing food, especially grinding maize or other foods, while men may have done more long-distance walking potentially to work in agricultural fields or procure other resources.

Finite element analysis of the femoral diaphysis of fresh-frozen cadavers with computed tomography and mechanical testing.

BACKGROUND: The purpose of this study was to validate a diaphyseal femoral fracture model using a finite element analysis (FEA) with mechanical testing in fresh-frozen cadavers. METHODS: We used 18 intact femora (9 right and 9 left) from 9 fresh-frozen cadavers. Specimens were obtained from 5 males and 4 females with a mean age of 85.6 years. We compared a computed tomography (CT)-based FEA model to diaphyseal femoral fracture loads and stiffness obtained by three-point bending. Four material characteristic conversion equations (the Keyak, Carter, and Keller equations plus Keller's equation for the vertebra) with different shell thicknesses (0.3, 0.4, and 0.5 mm) were compared with the mechanical testing. RESULTS: The average fracture load was 4582.8 N and the mean stiffness was 942.0 N/mm from actual mechanical testing. FEA prediction using Keller's equation for the vertebra with a 0.4-mm shell thickness showed the best correlations with the fracture load (R2 = 0.76) and stiffness (R2 = 0.54). Shell thicknesses of 0.3 and 0.5 mm in Keller's equation for the vertebra also showed a strong correlation with fracture load (R2 = 0.66 for both) and stiffness (R2 = 0.50 and 0.52, respectively). There were no significant correlations with the other equations. CONCLUSION: We validated femoral diaphyseal fracture loads and stiffness using an FEA in a cadaveric study.

Using modern human cortical bone distribution to test the systemic robusticity hypothesis.

The systemic robusticity hypothesis links the thickness of cortical bone in both the cranium and limb bones. This hypothesis posits that thick cortical bone is in part a systemic response to circulating hormones, such as growth hormone and thyroid hormone, possibly related to physical activity or cold climates. Although this hypothesis has gained popular traction, only rarely has robusticity of the cranium and postcranial skeleton been considered jointly. We acquired computed tomographic scans from associated crania, femora and humeri from single individuals representing 11 populations in Africa and North America (n = 228). Cortical thickness in the parietal, frontal and occipital bones and cortical bone area in limb bone diaphyses were analyzed using correlation, multiple regression and general linear models to test the hypothesis. Absolute thickness values from the crania were not correlated with cortical bone area of the femur or humerus, which is at odds with the systemic robusticity hypothesis. However, measures of cortical bone scaled by total vault thickness and limb cross-sectional area were positively correlated between the cranium and postcranium. When accounting for a range of potential confounding variables, including sex, age and body mass, variation in relative postcranial cortical bone area explained ∼20% of variation in the proportion of cortical cranial bone thickness. While these findings provide limited support for the systemic robusticity hypothesis, cranial cortical thickness did not track climate or physical activity across populations. Thus, some of the variation in cranial cortical bone thickness in modern humans is attributable to systemic effects, but the driving force behind this effect remains obscure. Moreover, neither absolute nor proportional measures of cranial cortical bone thickness are positively correlated with total cranial bone thickness, complicating the extrapolation of these findings to extinct species where only cranial vault thickness has been measured.

Femur loading in feet-first fall experiments using an anthropomorphic test device.

BACKGROUND: Femur fractures are a common orthopedic injury in young children. Falls account for a large portion of accidental femur fractures in young children, but there is also a high prevalence of femur fractures in child abuse, with falls often provided as false histories. Objective information regarding fracture potential in short distance fall scenarios may aid in assessing whether a child's injuries are the result of abuse or an accidental fall. Knowledge of femur loading is the first step towards understanding likelihood of fracture in a fall. OBJECTIVE: Characterize femur loading during feet-first free falls using a surrogate representing a 12-month-old child. METHODS: The femur and hip joint of a surrogate representing a 12-month-old were modified to improve biofidelity and measure femur loading; 6-axis load cells were integrated into the proximal and distal femur. Femur modification was based upon CT imaging of cadaveric femurs in children 10-14 months of age. Using the modified 12-month-old surrogate, feet-first free falls from 69 cm and 119 cm heights onto padded carpet and linoleum were conducted to assess fall dynamics and determine femur loading. Femur compression, bending moment, shear and torsional moment were measured for each fall. RESULTS: Fall dynamics differed across fall heights, but did not substantially differ by impact surface type. Significant differences were found in all loading conditions across fall heights, while only compression and bending loads differed between carpet and linoleum surfaces. Maximum compression, bending, torsion and shear occurred in 119 cm falls and were 572 N, 23 N-m, 11 N-m and 281 N, respectively. CONCLUSIONS: Fall dynamics play an important role in the biomechanical assessment of falls. Fall height was found to influence both fall dynamics and femur loading, while impact surface affected only compression and bending in feet-first falls; fall dynamics did not differ across carpet and linoleum. Improved pediatric thresholds are necessary to predict likelihood of fracture, but morphologically accurate representation of the lower extremity, along with accurate characterization of loading in falls are a crucial first step.

Bone functional adaptation does not erase neutral evolutionary information.

OBJECTIVES: To investigate whether diaphyseal and craniofacial variation similarly reflect neutral genetic variation among modern European and South Africans. MATERIALS AND METHODS: Diaphyseal and craniofacial data were collected on English, South European, and South African samples. The Relethford-Blangero model was used to compare predicted among-population relationships generated by limb bones relative to those generated by the crania and, further, to test whether adaptive plasticity affected these predicted relationships. Evidence of adaptive plasticity was confirmed by comparing J, an indicator of limb bone robusticity, among individuals who worked different occupations in industrializing Lisbon (Portugal) and Bologna (Italy). RESULTS: Diaphyses were more variable than were crania and more robust in individuals with physically demanding occupations-both consistent with expectations of adaptive plasticity. However, diaphyseal variation still generated among-population relationships consistent with neutral genetic predictions and Mantel tests confirmed a high, significant correlation between diaphyseal and craniofacial distance matrices. This pattern was not strongly affected by adaptive plasticity. DISCUSSION: Among-population patterns of diaphyseal variation are consistent with neutral expectations and are consistent with historical data on population composition, genetics, and migration. Furthermore, plasticity induced by Industrial-era levels of physical activity does not erase these neutral signatures. Diaphyseal variation may therefore be useful to infer neutral (presumably genetic) information across populations, and controlling for existing relationships may strengthen inferences of physical activity made when comparing limb bone structure across populations.

Sex-specific functional adaptation of the femoral diaphysis to body composition.

OBJECTIVES: The human femoral diaphysis is often used to reconstruct loading histories (mobility, activity, body mass). The proximal femur is known to be differentially affected by changes in total fat-mass (FM), fat-free mass (FFM), and body fat percentage (BF%), but the adaptation of the entire diaphysis to body composition has not been thoroughly characterized to date. Understanding how the femoral diaphysis adapts to body components would benefit biomechanical interpretations of the femoral variation and nutrition-related studies. METHODS: Combining various methods from clinical nutrition, biological anthropology, and geometric morphometrics, we evaluated the correlation of measures taken on the entire femoral diaphysis with estimated FM, FFM, and BF% from 61 CT scans (17 females, 44 males). The sample was predominantly composed of people with obesity. RESULTS: Cortical area of the cross-sections and local cortical thickness showed high correlation with BF% in particular, in females only. The curvature significantly decreased with FM and BF% in both sexes. The lowest correlations are found with FFM. CONCLUSIONS: The observed sexual dimorphism is consistent with differing aging processes; cortical bone decreases in females through endosteal resorption while it remains almost constant in males who compensate for endosteal resorption by periosteal apposition on the diaphyseal surface. The functional adaptation to compressive forces indicates a systemic endosteal apposition of bone material with increased BF% and FM in females only. FM and BF% are linked to a straighter femur in both sexes, suggesting an optimization of the resistance to compressive loads by distributing them more linearly along the entire diaphysis.

Phylogenetic and environmental effects on limb bone structure in gorillas.

OBJECTIVES: The effects of phylogeny and locomotor behavior on long bone structural proportions are assessed through comparisons between adult and ontogenetic samples of extant gorillas. MATERIALS AND METHODS: A total of 281 wild-collected individuals were included in the study, divided into four groups that vary taxonomically and ecologically: western lowland gorillas (G. g. gorilla), lowland and highland grauer gorillas (G. b. graueri), and Virunga mountain gorillas (G. b. beringei). Lengths and articular breadths of the major long bones (except the fibula) were measured, and diaphyseal cross-sectional geometric properties determined using computed tomography. Ages of immature specimens (n = 145) were known or estimated from dental development. Differences between groups in hind limb to forelimb proportions were assessed in both adults and during development. RESULTS: Diaphyseal strength proportions among adults vary in parallel with behavioral/ecological differences, and not phylogeny. The more arboreal western lowland and lowland grauer gorillas have relatively stronger forelimbs than the more terrestrial Virunga mountain gorillas, while the behaviorally intermediate highland grauer gorillas have intermediate proportions. Diaphyseal strength proportions are similar in young infants but diverge after 2 years of age in western lowland and mountain gorillas, at the same time that changes in locomotor behavior occur. There are no differences between groups in length or articular proportions among either adults or immature individuals. CONCLUSION: Long bone diaphyseal strength proportions in gorillas are developmentally plastic, reflecting behavior, while length and articular proportions are much more genetically canalized. These findings have implications for interpreting morphological variation among fossil taxa.

Longitudinal Effects of Single Hindlimb Radiation Therapy on Bone Strength and Morphology at Local and Contralateral Sites.

Radiation therapy (RTx) is associated with increased risk for late-onset fragility fractures in bone tissue underlying the radiation field. Bone tissue outside the RTx field is often selected as a "normal" comparator tissue in clinical assessment of fragility fracture risk, but the robustness of this comparison is limited by an incomplete understanding of the systemic effects of local radiotherapy. In this study, a mouse model of limited field irradiation was used to quantify longitudinal changes in local (irradiated) and systemic (non-irradiated) femurs with respect to bone density, morphology, and strength. BALB/cJ mice aged 12 weeks underwent unilateral hindlimb irradiation (4 × 5 Gy) or a sham procedure. Femurs were collected at endpoints of 4 days before treatment and at 0, 1, 2, 4, 8, 12, and 26 weeks post-treatment. Irradiated (RTx), Contralateral (non-RTx), and Sham (non-RTx) femurs were imaged by micro-computed tomography and mechanically tested in three-point bending. In both the RTx and Contralateral non-RTx groups, the longer-term (12- to 26-week) outcomes included trabecular resorption, loss of diaphyseal cortical bone, and decreased bending strength. Contralateral femurs generally followed an intermediate response compared with RTx femurs. Change also varied by anatomic compartment; post-RTx loss of trabecular bone was more profound in the metaphyseal than the epiphyseal compartment, and cortical bone thickness decreased at the mid-diaphysis but increased at the metaphysis. These data demonstrate that changes in bone quantity, density, and architecture occur both locally and systemically after limited field irradiation and vary by anatomic compartment. Furthermore, the severity and persistence of systemic bone damage after limited field irradiation suggest selection of control tissues for assessment of fracture risk or changes in bone density after radiotherapy may be challenging. © 2017 American Society for Bone and Mineral Research.

Predicting the bending properties of long bones: Insights from an experimental mouse model.

OBJECTIVES: Analyses of bone cross-sectional geometry are frequently used by anthropologists and paleontologists to infer the loading histories of past populations. To address some underlying assumptions, we investigated the relative roles of genetics and exercise on bone cross-sectional geometry and bending mechanics in three mouse strains: high bone density (C3H/He), low bone density (C57BL/6), and a high-runner strain homozygous for the Myh4Minimsc allele (MM). METHODS AND MATERIALS: Weanlings of each strain were divided into exercise (wheel) or control (sedentary) treatment groups for a 7-week experimental period. Morphometrics of the femoral mid-diaphysis and mechanical testing were used to assess both theoretical and ex vivo bending mechanics. RESULTS: Across all measured morphological and bending traits, we found relatively small effects of exercise treatment compared to larger and more frequent interstrain differences. In the exercised group, total distance run over the experimental period was not a predictor of any morphological or bending traits. Cross-sectional geometry did not accurately predict bone response to loading. DISCUSSION: Results from this experimental model do not support hypothesized associations among extreme exercise, cross-sectional geometry, and bending mechanics. Our results suggest that analysis of cross-sectional geometry alone is insufficient to predict loading response, and questions the common assumption that cross-sectional geometry differences are indicative of differential loading history.

Effects of combination treatment with alendronate and raloxifene on skeletal properties in a beagle dog model.

A growing number of studies have investigated combination treatment as an approach to treat bone disease. The goal of this study was to investigate the combination of alendronate and raloxifene with a particular focus on mechanical properties. To achieve this goal we utilized a large animal model, the beagle dog, used previously by our laboratory to study both alendronate and raloxifene monotherapies. Forty-eight skeletally mature female beagles (1-2 years old) received daily oral treatment: saline vehicle (VEH), alendronate (ALN), raloxifene (RAL) or both ALN and RAL. After 6 and 12 months of treatment, all animals underwent assessment of bone material properties using in vivo reference point indentation (RPI) and skeletal hydration using ultra-short echo magnetic resonance imaging (UTE-MRI). End point measures include imaging, histomorphometry, and mechanical properties. Bone formation rate was significantly lower in iliac crest trabecular bone of animals treated with ALN (-71%) and ALN+RAL (-81%) compared to VEH. In vivo assessment of properties by RPI yielded minimal differences between groups while UTE-MRI showed a RAL and RAL+ALN treatment regimens resulted in significantly higher bound water compared to VEH (+23 and +18%, respectively). There was no significant difference among groups for DXA- or CT-based measures lumbar vertebra, or femoral diaphysis. Ribs of RAL-treated animals were smaller and less dense compared to VEH and although mechanical properties were lower the material-level properties were equivalent to normal. In conclusion, we present a suite of data in a beagle dog model treated for one year with clinically-relevant doses of alendronate and raloxifene monotherapies or combination treatment with both agents. Despite the expected effects on bone remodeling, our study did not find the expected benefit of ALN to BMD or structural mechanical properties, and thus the viability of the combination therapy remains unclear.

Intracortical stiffness of mid-diaphysis femur bovine bone: lacunar-canalicular based homogenization numerical solutions and microhardness measurements.

Microscale lacunar-canalicular (L-C) porosity is a major contributor to intracortical bone stiffness variability. In this work, such variability is investigated experimentally using micro hardness indentation tests and numerically using a homogenization scheme. Cross sectional rings of cortical bones are cut from the middle tubular part of bovine femur long bone at mid-diaphysis. A series of light microscopy images are taken along a line emanating from the cross-section center starting from the ring's interior (endosteum) ring surface toward the ring's exterior (periosteum) ring surface. For each image in the line, computer vision analysis of porosity is conducted employing an image segmentation methodology based on pulse coupled neural networks (PCNN) recently developed by the authors. Determined are size and shape of each of the lacunar-canalicular (L-C) cortical micro constituents: lacunae, canaliculi, and Haversian canals. Consequently, it was possible to segment and quantify the geometrical attributes of all individual segmented pores leading to accurate determination of derived geometrical measures such as L-C cortical pores' total porosity (pore volume fraction), (elliptical) aspect ratio, orientation, location, and number of pores in secondary and primary osteons. Porosity was found to be unevenly (but linearly) distributed along the interior and exterior regions of the intracortical bone. The segmented L-C porosity data is passed to a numerical microscale-based homogenization scheme, also recently developed by the authors, that analyses a composite made up of lamella matrix punctuated by multi-inclusions and returns corresponding values for longitudinal and transverse Young's modulus (matrix stiffness) for these micro-sized spatial locations. Hence, intracortical stiffness variability is numerically quantified using a combination of computer vision program and numerical homogenization code. These numerically found stiffness values of the homogenization solution are corroborated experimentally using microhardness indentation measurements taken at the same points that the digital images were taken along a radial distance emanating from the interior (endosteum) surface toward the bone's exterior (periosteum) surface. Good agreement was found between numerically calculated and indentation measured stiffness of Intracortical lamellae. Both indentation measurements and numerical solutions of matrix stiffness showed increasing linear trend of compressive longitudinal modulus (E11) values vs. radial position for both interior and exterior regions. In the interior (exterior) region of cortical bone, stiffness modulus values were found to range from 18.5 to 23.4 GPa (23 to 26.0 GPa) with the aggregate stiffness of the cortical lamella in the exterior region being 12% stiffer than that in the interior region. In order to further validate these findings, experimental and FEM simulation of a mid-diaphysis bone ring under compression is employed. The FEM numerical deflections employed nine concentric regions across the thickness with graded stiffness values based on the digital segmentation and homogenization scheme. Bone ring deflections are found to agree well with measured deformations of the compression bone ring.