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Objectives: This study tests if femoral and humeral cross-sectional geometry (CSG) and cross-sectional properties (CSPs) in an ontogenetic series of wild-caught chimpanzees (Pan troglodytes ssp.) reflect locomotor behavior during development. The goal is to clarify the relationship between limb bone structure and locomotor behavior during ontogeny in Pan., Materials and Methods: The latex cast method was used to reconstruct cross sections at the midshaft femur and mid-distal humerus. Second moments of area (SMAs) (I x , I y , I max , I min ), which are proportional to bending rigidity about a specified axis, and the polar SMA (J), which is proportional to average bending rigidity, were calculated at section locations. Cross-sectional shape (CSS) was assessed from I x /I y and I max /I min ratios. Juvenile and adult subsamples were compared., Results: Juveniles and adults have significantly greater femoral J compared to humeral J. Mean interlimb proportions of J are not significantly different between the groups. There is an overall decreasing trend in diaphyseal circularity between the juvenile phase of development and adulthood, although significant differences are only found in the humerus., Discussion: Juvenile chimpanzee locomotion includes forelimb- and hindlimb-biased behaviors. Juveniles and adults preferentially load their hindlimbs relative to their forelimbs. This may indicate similar locomotor behavior, although other explanations including a diversity of hindlimb-biased locomotor behaviors in juveniles cannot be ruled out. Different ontogenetic trends in forelimb and hindlimb CSS are consistent with limb bone CSG reflecting functional adaptation, albeit the complex nature of bone functional adaptation requires cautious interpretations of skeletal functional morphology from biomechanical analyses., (© 2024 Wiley Periodicals LLC.)

The increased limb bone density documented previously for aquatic tetrapods has been proposed to be an adaptation to overcome buoyancy during swimming and diving. It can be achieved by increasing the amount of bone deposition or by reducing the amount of bone resorption, leading to cortical thickening, loss of medullary cavity, and compaction of trabecular bone. The present study examined the effects of locomotor habit, body size, and phylogeny on the densitometric, cross-sectional, and biomechanical traits of femoral diaphysis and neck in terrestrial, semiaquatic, and aquatic carnivores, and in terrestrial and semiaquatic rodents (12 species) by using peripheral quantitative computed tomography, three-point bending, and femoral neck loading tests. Groupwise differences were analyzed with the univariate generalized linear model and the multivariate linear discriminant analysis supplemented with hierarchical clustering. While none of the individual features could separate the lifestyles or species adequately, the combinations of multiple features produced very good or excellent classifications and clusterings. In the phocid seals, the aquatic niche allowed for lower femoral bone mineral densities than expected based on the body mass alone. The semiaquatic mammals mostly had high bone mineral densities compared to the terrestrial species, which could be considered an adaptation to overcome buoyancy during swimming and shallow diving. Generally, it seems that different osteological properties at the levels of mineral density and biomechanics could be compatible with the adaptation to aquatic, semiaquatic, or terrestrial niches., (© 2024. The Author(s).)

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., (Copyright © 2020 by the American College of Sports Medicine.)

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., (© 2021 Wiley Periodicals LLC.)

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 (Z p -std) decreased with age., Discussion: The decrease in robusticity (Z p -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., (© 2020 Wiley Periodicals LLC.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., (© 2019 Wiley Periodicals, Inc.)

Objectives: Lower limb diaphyseal geometry is often used to evaluate mobility in past populations. Diaphyseal dimensions such as high shape (I X /I Y ) 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., (© 2019 Wiley Periodicals, Inc.)

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.

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 (Z p ) 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 Z p 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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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 (I max /I min , I x /I y )., 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., (© 2018 Wiley Periodicals, Inc.)

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., (Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

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 (R 2  = 0.76) and stiffness (R 2  = 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 (R 2  = 0.66 for both) and stiffness (R 2  = 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.

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., (© 2018 Wiley Periodicals, Inc.)

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., (© 2018 Wiley Periodicals, Inc.)

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., (© 2018 Wiley Periodicals, Inc.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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 Myh4 Minimsc 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., (© 2017 Wiley Periodicals, Inc.)

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., (© 2017 American Society for Bone and Mineral Research.)

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.

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.

Objectives: We investigated the relationship between loading history and bone biomechanical properties used in physical activity reconstructions. These bone properties included bone bending and torsional strength (J), cortical area (CA), the direction of the major axis (theta angle), and element shape ratios determined from cross sections of standardized bone length. In addition, we explored the applicability of anatomically determined cross sections., Methods: Our material consisted of hip and proximal thigh magnetic resonance images of Finnish female athletes (N = 91) engaged in high-jump, triple-jump, endurance running, swimming, power-lifting, soccer and squash; along with a group of active non-athlete individuals (N = 20). We used regression analysis for size-adjustment, and the extracted residuals were then used to compare differences in the bone properties between groups., Results: We found that triple-jumpers, soccer players, and squash players had the greatest values in CA and J, swimmers and non-athletes had the smallest, whereas high-jumpers, power-lifters, and endurance runners exhibited interim values. No between-the-group differences in element shape ratios or theta angles were found. We found that influences of activity were similar regardless of whether standardized length or anatomically determined cross sections were used., Conclusions: Extreme (triple-jump) and directionally inconsistent loading (soccer and squash) necessitate a more robust skeleton compared to directionally consistent loading (high-jump, power-lifting, and endurance running) or non-impact loading (swimming and non-athletes). However, not all of these relationships were statistically significant. Thus, information gained about physical activity using bone properties is informative but limited. Accounting for the limitations, the method is applicable on fragmented skeletal material as anatomically determined cross sections can be used., (© 2017 Wiley Periodicals, Inc.)

Studies of ancient human skeletal remains frequently proceed from the assumption that individuals with robust limb bones and/or rugose, hypertrophic entheses can be inferred to have been highly physically active during life. Here, we experimentally test this assumption by measuring the effects of exercise on limb bone structure and entheseal morphology in turkeys. Growing females were either treated with a treadmill-running regimen for 10 weeks or served as controls. After the experiment, femoral cortical and trabecular bone structure were quantified with μCT in the mid-diaphysis and distal epiphysis, respectively, and entheseal morphology was quantified in the lateral epicondyle. The results indicate that elevated levels of physical activity affect limb bone structure but not entheseal morphology. Specifically, animals subjected to exercise displayed enhanced diaphyseal and trabecular bone architecture relative to controls, but no significant difference was detected between experimental groups in entheseal surface topography. These findings suggest that diaphyseal and trabecular structure are more reliable proxies than entheseal morphology for inferring ancient human physical activity levels from skeletal remains., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Restoration of native head-shaft angle (HSA) is critical for treatment of proximal humerus fracture. However, HSA has not been properly investigated according to the humeral rotation. This study was designed to analyze the relationship between the humeral rotation and the HSA at 1° increments, and clarify its serial changing pattern according to the humeral rotation., Hypothesis: The angulation of HSA would be undervalued when the humerus is being rotated externally and it would be overvalued when it is being rotated internally., Materials and Methods: Eight dried cadaveric normal humeri were CT scanned. They were analyzed using computer-aided design with a standardized neutral position. HSA was the angle between the humeral shaft axis (SA) and the humeral head axis (HA). SA and HA were the best-fit lines through center of all the best-fitting circles in every cross section along the humeral shaft and within the humeral head, respectively. Each 3D model was rotated 30° internally and 45° externally relatives to the SA at 1° increments with the camera was fixed at antero-posterior view of neutral position. Angulation of HSA in every rotational degree was documented as ratio relatives to the angulation of HSA in neutral position., Results: The average HSA at neutral position was 133±1.93°. HSA was underestimated by 8±1.9% and it was overestimated by 20±5.1% at the maximum external rotation (ER) and internal rotation (IR), respectively. HSA was underestimated by 1% in every 5.8° of ER and overestimated by 1% in every 1.5° of IR. Rotational misalignments within 10° of IR and 18° of ER could be tolerated (P>.05)., Conclusions: HSA was underestimated at ER and was overestimated at IR. This information could be useful for surgeons in restoring the native HSA for treatment of proximal humerus fracture., Type of Study: Basic research study., (Copyright © 2017. Published by Elsevier Masson SAS.)

Objectives: Histomorphological analyses of bones are used to estimate an individual's chronological age, interpret a bone's load history, and differentiate species. Among various histomorphological characteristics that can influence mechanical properties of cortical bone, secondary osteon (Haversian system) population density and predominant collagen fiber orientation are particularly important. Cross-sectional shape characteristics of secondary osteons (On.Cr = osteon circularity, On.El = osteon ellipticality) are considered helpful in these contexts, but more robust proof is needed. We sought to determine if variations in osteon shape characteristics are sufficient for accurately differentiating species, load-complexity categories, and regional habitual strain-mode distributions (e.g., tension vs. compression regions)., Materials and Methods: Circularly polarized light images were obtained from 100-micron transverse sections from diaphyses of adult deer calcanei; sheep calcanei, radii, and tibiae; equine calcanei, radii, and third metacarpals (MC3s); chimpanzee femora; and human femora and fibulae. Osteon cross-sectional area (On.Ar), On.Cr, and On.El were quantified indiscriminately and in the contexts of load-complexity and regional strain-mode distributions., Results: On.Cr and On.El, when examined independently in terms of all data, or mean (nested) data, for each bone, exceeded 80% accuracy in the inter-species comparisons only with respect to distinguishing humans from nonhumans. Correct classification among the nonhuman species was <70%. When On.Cr and On.El were coupled together and with On.Ar in discriminant function analyses (nested and unnested data) there were high misclassifications in all but human vs. nonhuman comparisons., Discussion: Frequent misclassifications in nonhuman comparisons might reflect influences of habitual load complexity and/or strain-mode distributions, or other factors not accounted for by these two considerations., (© 2017 Wiley Periodicals, Inc.)

Objective: To describe cortical and trabecular volumetric bone mineral density (vBMD), bone mineral content (BMC), cross-sectional area (CSA), and bone strength indexes (BSIs) in adolescent endurance-trained cyclists (CYC) and compare them with controls (CON)., Design: Descriptive cohort study., Participants: Twenty-five male adolescent CYC and 17 CON., Assessment of Risk Factors: Peripheral quantitative computed tomography was used to evaluate proximal and distal sites of the radius and tibia., Main Outcome Measures: Total, trabecular, and cortical BMC, vBMD, and CSA were measured. Also, cortical thickness, endosteal and periosteal circumferences, and different BSIs were calculated. Unadjusted analysis of variance and body weight-adjusted analysis of covariance tests were applied between cyclist and control groups., Results: Cyclists were almost 12% lighter than CON (P < 0.05). Unadjusted data showed lower distal total vBMD and proximal cortical BMC and vBMD in cyclists compared with CON at the radius (P < 0.05) and lower distal total and trabecular BMC, vBMD and bone area, proximal total and cortical BMC and vBMD, and cortical bone area at the tibia (P < 0.05). Body weight-adjusted data showed the same differences for distal total vBMD at the radius and total and trabecular BMC and vBMD at the tibia, diaphyseal radius cortical vBMD and tibia total vBMD, cortical BMC and area, and also for tibia cortical thickness and BSI. The rest of differences were no longer detectable and bone area at the distal radius become significantly higher in cyclist compared with CON (P < 0.05)., Conclusions: Adolescent CYC in this study showed lower values of BMC and vBMD at determined sites of the radius and tibia than CON, some of these differences were explained in part by their lower body weight. However, even further adjustment, some differences remained, which indicates that further longitudinal studies are needed to better understand if cycling influences these differences.

Purpose: This study aims to assess the outcomes of displaced femoral shaft fractures (DFSFs) treated by antegrade nailing with the assistance of a newly invented intramedullary (IM) reduction device., Methods: From December 2012 to August 2013, 43 adult patients with unilateral DFSFs, including 31 males and 12 females, were enrolled into this study. During the operation, the device was used to adjust the direction of guide wire to insert it into the medullary cavity of distal femur and used as a "joystick" to align the femoral shaft fractures before the insertion of IM nail. The operative time and fluoroscopy time were recorded. Follow-up was conducted to assess the fracture union and functional recovery of the affected limbs., Results: The IM reduction device was used intra-operatively to advance the guide wire into the distal femoral medullary cavity successfully in all 43 cases, with a single attempt in 37 cases and two or three attempts in six cases. The average operative time and fluoroscopy time were 58.3 minutes (40-85 minutes) and 9.2 seconds (4.1-21.8 seconds), respectively. All fractures healed well on an average of 5.4 months post-operatively. No limb-length discrepancy or observable malalignment was noted at the follow ups., Conclusions: The IM reduction device can facilitate the insertion of a guide wire into the distal femoral medullary cavity in a closed and controllable manner, be used as a "joystick" to align the femoral shaft fracture, and subsequently facilitate IM nail insertion in the proper position.

BACKGROUND Understanding the nutrient foramina is critical to clinical practice. An insult to the nutrient foramina can be caused by trauma and/or surgical dissection and lead to devascularization and bad outcomes. Few studies have looked at the humerus, and no studies have described relative information of humeral nutrient foramen related to anatomical structures that might be located by palpable landmarks. In this study, we analyzed the anatomical features of the nutrient foramina of the diaphyseal humerus and provide a discussion of clinical relevance. MATERIAL AND METHODS We dissected 19 cadavers and analyzed the relative positions of the foramina and surrounding muscles, and the number, direction, diameter, and location of the nutrient foramina. Foramina index and a new landmark index were used to calculate the location. We compared the data from both sides and the relationships between transverse and longitudinal locations, diameter and total length, and foramina index and landmark index were also analyzed. RESULTS The humeri had one or two main nutrient foramina located in a small area between the coracobrachialis and brachial muscles and oriented toward the elbow. The mean diameter was 1.11±0.32 mm. The mean index and landmark index were 43.76±4.94% and 42.26±5.35%, respectively. There were no differences between sides in terms of diameter, length, or nutrient foramina index. There were no significant correlations between transverse and longitudinal locations or diameter and total length. The foramina index and landmark index showed strong positive correlation (r=0.994, p<0.0001). CONCLUSIONS Our study provides details about the nutrient foramina that will benefit clinicians who treat injuries and diseases of the humerus. Surgeons should be mindful of soft tissue in the foraminal area during surgical procedures.

Simvastatin, a cholesterol treatment drug, has been shown to stimulate bone regeneration. As such, there has been an increase interest in the development of suitable materials and systems for the delivery of simvastatin. Without the appropriate dosage of simvastatin, the therapeutic effects on bone growth will be significantly reduced. Furthermore, similar to many pharmaceutical compounds, at high concentration simvastatin can cause various adverse side-effects. Given the associated side-effects with the usage of simvastatin, the development of suitable controlled drug release system is pertinent. Calcium phosphate in particularly beta-tricalcium phosphate (β-TCP) has been extensively studied and used as a carrier material for drug delivery system. In this study, Foraminifera exoskeletons were used as calcium carbonate precursor materials, which were hydrothermally converted to β-TCP as a carrier material for simvastatin. Natural marine exoskeletons posses interconnected and uniformly porous network capable of improving drug loading and release rate. To prolong the release of simvastatin, an apatite coating was made around the β-TCP sample and in vitro release studies in simulated body fluid (SBF) showed a significant decrease in release rate. Osteoporotic mice were used to examine the compare therapeutic effectiveness of β-TCP, β-TCP with simvastatin, apatite-coated β-TCP with simvastatin and direct injection of simvastatin near the right femur of the mice. Localized and systemic effect were compared with the femur of the non-implanted side (left) and showed that β-TCP with or without simvastatin was able to induce significant bone formation over 6 weeks. Mechanical analysis showed that apatite-coated β-TCP with simvastatin produced significantly stronger bones compared with other experimental groups. This study shows that natural exoskeletons with the appropriate structure can be successfully used as a drug delivery system for simvastatin and can its release can be prolonged with an apatite coating to significantly promote relevant bone formation., (Copyright © 2013 John Wiley & Sons, Ltd.)

Cortical bone tissue is an anisotropic material characterized by typically five independent elastic coefficients (for transverse isotropy) governing shear and longitudinal deformations in the different anatomical directions. It is well established that the Young's modulus in the direction of the bone axis of long bones has a strong relationship with mass density. It is not clear, however, whether relationships of similar strength exist for the other elastic coefficients, for they have seldom been investigated, and the results available in the literature are contradictory. The objectives of the present work were to document the anisotropic elastic properties of cortical bone at the tibia mid-diaphysis and to elucidate their relationships with mass density. Resonant ultrasound spectroscopy (RUS) was used to measure the transverse isotropic stiffness tensor of 55 specimens from 19 donors. Except for Poisson's ratios and the non-diagonal stiffness coefficient, strong linear correlations between the different elastic coefficients (0.7 < r(2) < 0.99) and between these coefficients and density (0.79 < r(2) < 0.89) were found. Comparison with previously published data from femur specimens suggested that the strong correlations evidenced in this study may not only be valid for the mid-tibia. RUS also measures the viscous part of the stiffness tensor. An anisotropy ratio close to two was found for damping coefficients. Damping increased as the mass density decreased. The data suggest that a relatively accurate estimation of all the mid-tibia elastic coefficients can be derived from mass density. This is of particular interest (1) to design organ-scale bone models in which elastic coefficients are mapped according to Hounsfield values from computed tomography scans as a surrogate for mass density and (2) to model ultrasound propagation at the mid-tibia, which is an important site for the in vivo assessment of bone status with axial transmission techniques.

Peripheral quantitative computed tomography (pQCT) is a popular tool for noninvasively estimating bone mechanical properties. Previous studies have demonstrated that pQCT provides precise estimates that are good predictors of actual bone mechanical properties at popular distal imaging sites (tibia and radius). The predictive ability and precision of pQCT at more proximal sites remain unknown. The aim of the present study was to explore the predictive ability and short-term precision of pQCT estimates of mechanical properties of the midshaft humerus, a site gaining popularity for exploring the skeletal benefits of exercise. Predictive ability was determined ex vivo by assessing the ability of pQCT-derived estimates of torsional mechanical properties in cadaver humeri (density-weighted polar moment of inertia [I(P)] and polar strength-strain index [SSI(P)]) to predict actual torsional properties. Short-term precision was assessed in vivo by performing 6 repeat pQCT scans at the level of the midshaft humerus in 30 young, healthy individuals (degrees of freedom = 150), with repeat scans performed by the same and different testers and on the same and different days to explore the influences of different testers and time between repeat scans on precision errors. IP and SSI(P) both independently predicted at least 90% of the variance in ex vivo midshaft humerus mechanical properties in cadaveric bones. Overall values for relative precision error (root mean squared coefficients of variation) for in vivo measures of IP and SSI(P) at the midshaft humerus were <1.5% and were not influenced by pQCT assessments being performed by different testers or on different days. These data indicate that pQCT provides very good prediction of midshaft humerus mechanical properties with good short-term precision, with measures being robust against the influences of different testers and time between repeat scans., (Copyright © 2015 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Anthropologists frequently use the shaft bending strength index to infer the physical activity levels of humans living in the past from their lower limb bone remains. This index is typically calculated as the ratio of bone shaft second moments of area about orthogonal principal axes (i.e. I(max)/I(min)). Individuals with high I(max)/I(min) values are inferred to have been very active, whereas individuals with low values are inferred to have been more sedentary. However, there is little direct evidence that activity has a causal and predictable effect on the shaft bending strength index. Here, we report the results of two experiments that were designed to test the model within which anthropologists commonly interpret the shaft bending strength index. In the first experiment, mice were treated daily with treadmill exercise for 1 month to simulate a high-activity lifestyle. In the second experiment, in an attempt to simulate a low-activity lifestyle, functional weight-bearing was removed from the hindlimbs of mice for 1 month. Femoral mid-shaft structure was determined with μCT. We found that while exercise resulted in significant enhancement of I(max) and I(min) compared with controls, it failed to significantly increase the I(max)/I(min)index. Similarly, stunted bone growth caused by unloading resulted in significantly diminished I(max) and I(min) compared with controls, but low activity did not lead to significantly decreased I(max)/I(min)compared with normal activity. Together, these results suggest that caution is required when the bone shaft bending strength index is used to reconstruct the activity levels of past humans., (© 2015 Anatomical Society.)

Noninvasive methods to apply controlled, cyclic loads to the living skeleton are used as anabolic procedures to stimulate new bone formation in adults and enhance bone mass accrual in growing animals. These methods are also invaluable for understanding bone signaling pathways. Our focus here is on a particular loading model: in vivo axial compression of the mouse tibia. An advantage of loading the tibia is that changes are present in both the cancellous envelope of the proximal tibia and the cortical bone of the tibial diaphysis. To load the tibia of the mouse axially in vivo, a cyclic compressive load is applied up to five times a week to a single tibia per mouse for a duration lasting from 1 day to 6 weeks. With the contralateral limb as an internal control, the anabolic response of the skeleton to mechanical stimuli can be studied in a pairwise experimental design. Here, we describe the key parameters that must be considered before beginning an in vivo mouse tibial loading experiment, including methods for in vivo strain gauging of the tibial midshaft, and then we describe general methods for loading the mouse tibia for an experiment lasting multiple days.

High-dose glucocorticoids reduce cortical bone gain in rats. The aim of the present study was to examine the effect of the intermittent administration of human parathyroid hormone (1-34) (hPTH[1-34]) on cortical bone in rats treated with high-dose prednisolone (PSL). Twenty-five female Sprague-Dawley rats (6 weeks old) were randomized into the following three groups: a vehicle administration (control) group, a PSL (10 mg/kg s.c., 5 times a week) administration group, and a PSL + hPTH(1-34) (30 μg/kg s.c., 3 times a week) administration group. After 8 weeks of treatment, the bone mineral density (BMD) of the femoral diaphysis was determined using peripheral quantitative computed tomography, and a static bone histomorphometric analysis was performed on the tibial diaphysis. PSL administration induced a decrease in the BMD of the femoral diaphysis, compared with the control group, as well as decreases in the total tissue area, cortical area, percent cortical area, and periosteal perimeter and increases in the marrow area, percent marrow area, and endocortical perimeter of the tibial diaphysis, compared with the control group. The intermittent administration of hPTH(1-34) to PSL-treated rats attenuated PSL-related changes in the BMD of the femoral diaphysis and the percent cortical area, marrow area, percent marrow area, and endocortical perimeter of the tibial diaphysis. The findings of the present study suggest that the intermittent administration of hPTH(1-34) improves cortical BMD, acts on the endocortical bone surface, and improves cortical bone geometry, in rats treated with highdose PSL.

Reference point indentation (RPI) has emerged as a novel tool to measure material-level biomechanical properties in vivo. Human studies have been able to differentiate fracture versus non-fracture patients while a dog study has shown the technique can differentiate drug treatment effects. The goal of this study was to extend this technology to the in vivo measurement of rats, one of the most common animal models used to study bone, with assessment of intra- and inter-animal variability. Seventy-two skeletally mature male Sprague-Dawley rats were subjected to in vivo RPI on the region between the tibial diaphysis and proximal metaphysis. RPI data were assessed using a custom MATLAB program to determine several outcome parameters, including first cycle indentation distance (ID-1st), indentation distance increase (IDI), total indentation distance (TID), first cycle unloading slope (US-1st), and first cycle energy dissipation (ED-1st). Intra-animal variability ranged from 13% to 21% with US-1st and Tot Ed 1st-L being the least variable properties and IDI the most highly variable. Inter-animal variability ranged from 16% (US-1st) to 25% (ED-1st and IDI). Based on these data, group size estimates would need to range from 9 to 18/group to achieve sufficient power for detecting a 25% difference in a two-group experiment. Repeat tests on the contralateral limb of a small cohort of animals (n=17) showed non-significant differences over 28 days ranging from -6% to -18%. These results provide important data on RPI variability (intra- and inter-animal) in rats that can be used to properly power future experiments using this technique., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Studies comparing phenotypic variation with neutral genetic variation in modern humans have shown that genetic drift is a main factor of evolutionary diversification among populations. The genetic population history of our closest living relatives, the chimpanzees and bonobos, is now equally well documented, but phenotypic variation among these taxa remains relatively unexplored, and phenotype-genotype correlations are not yet documented. Also, while the adult phenotype is typically used as a reference, it remains to be investigated how phenotype-genotye correlations change during development. Here we address these questions by analyzing phenotypic evolutionary and developmental diversification in the species and subspecies of the genus Pan. Our analyses focus on the morphology of the femoral diaphysis, which represents a functionally constrained element of the locomotor system. Results show that during infancy phenotypic distances between taxa are largely congruent with non-coding (neutral) genotypic distances. Later during ontogeny, however, phenotypic distances deviate from genotypic distances, mainly as an effect of heterochronic shifts between taxon-specific developmental programs. Early phenotypic differences between Pan taxa are thus likely brought about by genetic drift while late differences reflect taxon-specific adaptations.

Axial compression of the mouse tibia is used to study strain-adaptive bone (re)modeling. In some studies, comparisons between mice of different ages are of interest. We characterized the tibial deformation and force-strain relationships in female C57Bl/6 mice at 5-, 12- and 22-months age. A three-gauge experimental method was used to determine the strain distribution at the mid-diaphysis, while specimen-specific finite element analysis was used to examine strain distribution along the tibial length. The peak strains in the tibial mid-diaphyseal cross-section are compressive and occur at the postero-lateral apex. The magnitudes of these peak compressive strains are 1.5 to 2 times those on the opposite, antero-medial face (a site often used for strain gauge placement). For example, -10 N force applied to a 5-months old mouse engenders a peak compressive strain of -2800 µε and a tensile strain on the antero-medial face of +1450 µε. The orientation of the neutral axis at the mid-diaphysis did not differ with age (p=0.46), indicating a similar deformation mode in young and old tibiae. On the other hand, from 5- to 22-months there is a 25% reduction in cortical thickness and moment of inertia (p<0.05), resulting in significantly greater tibial strain magnitudes in older mice for equivalent applied force (p<0.05). We conclude that comparisons of tibial loading responses in young-adult and old C57Bl/6 tibiae are facilitated by similar deformation pattern across ages, but that modest adjustment of force levels is required to engender matching peak strains., (© 2013 Elsevier Ltd. All rights reserved.)

We examined the interplay between ethnicity and weight-bearing physical activity on the content and volumetric properties of bone in a pre- to early pubertal South African Black and White population. Sixty six children [Black boys, 10.4 (1.4)yrs, n=15; Black girls, 10.1 (1.2)yrs, n=27; White boys, 10.1 (1.1)yrs, n=7; White girls, 9.6 (1.3)yrs, n=17] reported on all their physical activities over the past two years in an interviewer administered physical activity questionnaire (PAQ). All participants underwent a whole body and site-specific DXA scan and we also assessed bone structure and estimated bone strength with pQCT. Children were classified as being either high or low bone loaders based on the cohort's median peak bone strain score estimated from the PAQ. In the low bone loading group, Black children had greater femoral neck bone mineral content (BMC) (2.9 (0.08)g) than White children (2.4 (0.11)g; p=0.05). There were no ethnic differences in the high bone loaders for femoral neck BMC. At the cortical site, the Black low bone loaders had a greater radius area (97.3 (1.3) vs 88.8 (2.6)mm(2); p=0.05) and a greater tibia total area (475.5 (8.7) vs. 397.3 (14.0)mm(2); p=0.001) and strength (1633.7 (60.1) vs. 1271.8 (98.6)mm(3); p=0.04) compared to the White low bone loaders. These measures were not different between the Black low and high bone loaders or between the Black and White high bone loaders. In conclusion, the present study shows that there may be ethnic and physical activity associations in the bone health of Black and White pre-pubertal children and further prospective studies are required to determine the possible ethnic specific response to mechanical loading., (© 2013.)

Behavioral studies indicate that adult mountain gorillas (Gorilla beringei) are the most terrestrial of all nonhuman hominoids, but that infant mountain gorillas are much more arboreal. Here we examine ontogenetic changes in diaphyseal strength and length of the femur, tibia, humerus, radius, and ulna in 30 Virunga mountain gorillas, including 18 immature specimens and 12 adults. Comparisons are also made with 14 adult western lowland gorillas (Gorilla gorilla gorilla), which are known to be more arboreal than adult mountain gorillas. Infant mountain gorillas have significantly stronger forelimbs relative to hind limbs than older juveniles and adults, but are nonsignificantly different from western lowland gorilla adults. The change in inter-limb strength proportions is abrupt at about two years of age, corresponding to the documented transition to committed terrestrial quadrupedalism in mountain gorillas. The one exception is the ulna, which shows a gradual increase in strength relative to the radius and other long bones during development, possibly corresponding to the gradual adoption of stereotypical fully pronated knuckle-walking in older juvenile gorillas. Inter-limb bone length proportions show a contrasting developmental pattern, with hind limb/forelimb length declining rapidly from birth to five months of age, and then showing no consistent change through adulthood. The very early change in length proportions, prior to significant independent locomotion, may be related to the need for relatively long forelimbs for climbing in a large-bodied hominoid. Virunga mountain gorilla older juveniles and adults have equal or longer forelimb relative to hind limb bones than western lowland adults. These findings indicate that both ontogenetically and among closely related species of Gorilla, long bone strength proportions better reflect actual locomotor behavior than bone length proportions., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Unlabelled: Osteoporotic fracture rates differ according to race with Blacks having up to half the rate of Whites. The current study demonstrates that racial divergence in cortical bone properties develops in early childhood despite lower serum 25-hydroxyvitamin D in Blacks., Introduction: Racial differences in bone structure likely have roots in childhood as bone size develops predominantly during growth. This study aimed to compare cortical bone health within the tibial diaphysis of Black and White children in the early stages of puberty and explore the contributions of biochemical variables in explaining racial variation in cortical bone properties., Methods: A cross-sectional study was performed comparing peripheral quantitative computed tomography-derived cortical bone measures of the tibial diaphysis and biochemical variables in 314 participants (n = 155 males; n = 164 Blacks) in the early stages of puberty., Results: Blacks had greater cortical volumetric bone mineral density, mass, and size compared to Whites (all p < 0.01), contributing to Blacks having 17.0 % greater tibial strength (polar strength-strain index (SSIP)) (p < 0.001). Turnover markers indicated that Blacks had higher bone formation (osteocalcin (OC) and bone-specific alkaline phosphatase) and lower bone resorption (N-terminal telopeptide) than Whites (all p < 0.01). Blacks also had lower 25-hydroxyvitamin D (25(OH)D) and higher 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) (all p < 0.05). There were no correlations between tibial bone properties and 25(OH)D and PTH in Whites (all p ≥ 0.10); however, SSIP was negatively and positively correlated with 25(OH)D and PTH in Blacks, respectively (all p ≤ 0.02). Variation in bone cross-sectional area and SSIP attributable to race was partially explained by tibial length, 25(OH)D/PTH, and OC., Conclusions: Divergence in tibial cortical bone properties between Blacks and Whites is established by the early stages of puberty with the enhanced cortical bone properties in Black children possibly being explained by higher PTH and OC.

Some pharmacologic effects on bone modeling may not be evident in studies of remodeling skeletons. This study analyzes some effects of olpadronate on cortical bone modeling and post-yield properties in femurs diaphyses (virtually only-modeling bones) of young rats by mid-diaphyseal pQCT scans and bending tests. We studied 20/22 male/female animals traetad orally with olpadronate (45-90 mg/kg/d, 3 months) and 8/9 untreated controls. Both OPD doses enhanced diaphyseal cross-sectional moments of inertia (CSMI) with no change in cortical vBMD and elastic modulus. Yield stiffness and strength were mildly increased. Post-yield strength, deflection and energy absorption were strikingly enhanced. Ultimate strength was enhanced mainly because of effects on bone mass/geometry and post-yield properties. The large improvement of post-yield properties could be explained by improvements in bone geometry. Improvements in bone mass/geometry over weight-bearing needs suggest an enhanced modeling-related response to mechanical stimuli. Effects on tissue microstructural factors (not measured) could not be excluded. Results reveal novel olpadronate effects on bone strength and toughness unrelated to tissue mineralization and stiffness, even at high doses. Further studies could establish whether this could also occur in modeling-remodeling skeletons. If so, they could counteract the negative impact of anti-remodeling effects of bisphosphonates on bone strength.

Ontogenetic growth processes in human long bones are key elements, determining the variability of adult bone structure. This study seeks to identify and describe the interaction between ontogenetic growth periods and changes in femoral and tibial diaphyseal shape. Femora and tibiae (n = 46) ranging developmentally from neonate to skeletally mature were obtained from the Norris Farms No. 36 archeological skeletal series. High-resolution X-ray computed tomography scans were collected. Whole-diaphysis cortical bone drift patterns and relative bone envelope modeling activity across ages were assessed in five cross-sections per bone (total bone length: 20%, 35%, 50%, 65%, and 80%) by measuring the distance from the section centroid to the endosteal and periosteal margins in eight sectors using ImageJ. Pearson correlations were performed to document and interpret the relationship between the cross-sectional shape (Imax /Imin ), total subperiosteal area, cortical area, and medullary cavity area for each slice location and age for both the femur and the tibia. Differences in cross-sectional shape between age groups at each cross-sectional position were assessed using nonparametric Mann-Whitney U tests. The data reveal that the femoral and tibial midshaft shape are relatively conserved throughout growth; yet, conversely, the proximal and distal femoral diaphysis and proximal tibial diaphysis appear more sensitive to developmentally induced changes in mechanical loading. Two time periods of accelerated change are identified: early childhood and prepuberty/adolescence., (Copyright © 2013 Wiley Periodicals, Inc.)

Local insulin delivery has been shown to improve osseous healing in diabetic animals. The purpose of this study was to quantify the effects of local intramedullary delivery of saline or Ultralente insulin (UL) on various fracture healing parameters using an in vivo non-diabetic BB Wistar rat model. Quantitation of local insulin levels showed a rapid release of insulin from the fractured femora, demonstrating complete release at 2 days. RT-PCR analysis revealed that the expression of early osteogenic markers (Col1α2, osteopontin) was significantly enhanced with UL treatment when compared with saline controls (p < 0.05). Significant differences in VEGF + cells and vascularity were evident between the treatment and control groups at day 7 (p < 0.05). At day 21, histomorphometric analysis demonstrated a significant increase in percent mineralized tissue in the UL-treated animals compared with controls (p < 0.05), particularly within the subperiosteal region of the fracture callus. Mechanical testing at 4 weeks showed significantly greater mechanical strength for UL-treated animals (p < 0.05), but healing in control animals caught up at 6 weeks post-fracture. These results suggest that the primary osteogenic effect of UL during the early stages of fracture healing (1-3 weeks) is through an increase in osteogenic gene expression, subperiosteal angiogenesis, and mineralized tissue formation., (Copyright © 2012 Orthopaedic Research Society.)

A significant number of lower extremity fractures result in mal-union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin-dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non-diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high-dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low-dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment., (Copyright © 2012 Orthopaedic Research Society.)

Objectives: To compare the outcome of three different fixation methods and to determine prognostic factors in cats with diaphyseal femoral fractures., Methods: Retrospective analysis of case records of cats with diaphyseal femoral fractures surgically corrected using external fixators, bone plate or plate-rod construct. Outcome was evaluated by estimating the time to bone healing and by calculating the complication rate., Results: In total, an external fixator was used in 30 cases, a bone plate in 20 cases and a plate-rod construct in 56 cases. All methods were successful in achieving bone healing without significant differences. There was a significant difference between the categorized complication rates between the treatment groups. The external fixation group had the most complications overall. When only the major and catastrophic complications were taken into account, it had the fewest complications. The plate-rod construct had the fewest complications overall, with most being major complications. The bone plate group had a complication rate between that of the external fixation and plate-rod construct groups. It had the most catastrophic complications in relative terms., Clinical Significance: There was no statistically significant difference in the time to achieve bone healing but there was a significant difference in categorized complication rates between the groups., (© 2013 British Small Animal Veterinary Association.)

Unlabelled: Micro-finite element analysis applied to high-resolution (0.234-mm length scale) MRI reveals greater whole and cancellous bone stiffness, but not greater cortical bone stiffness, in the distal femur of female dancers compared to controls. Greater whole bone stiffness appears to be mediated by cancellous, rather than cortical bone adaptation., Introduction: The purpose of this study was to compare bone mechanical competence (stiffness) in the distal femur of female dancers compared to healthy, relatively inactive female controls., Methods: This study had institutional review board approval. We recruited nine female modern dancers (25.7±5.8 years, 1.63±0.06 m, 57.1±4.6 kg) and ten relatively inactive, healthy female controls matched for age, height, and weight (32.1±4.8 years, 1.6±0.04 m, 55.8±5.9 kg). We scanned the distal femur using a 7-T MRI scanner and a three-dimensional fast low-angle shot sequence (TR/TE=31 ms/5.1 ms, 0.234 mm×0.234 mm×1 mm, 80 slices). We applied micro-finite element analysis to 10-mm-thick volumes of interest at the distal femoral diaphysis, metaphysis, and epiphysis to compute stiffness and cross-sectional area of whole, cortical, and cancellous bone, as well as cortical thickness. We applied two-tailed t-tests and ANCOVA to compare groups., Results: Dancers demonstrated greater whole and cancellous bone stiffness and cross-sectional area at all locations (p<0.05). Cortical bone stiffness, cross-sectional area, and thickness did not differ between groups (>0.08). At all locations, the percent of intact whole bone stiffness for cortical bone alone was lower in dancers (p<0.05). Adjustment for cancellous bone cross-sectional area eliminated significant differences in whole bone stiffness between groups (p>0.07), but adjustment for cortical bone cross-sectional area did not (p<0.03)., Conclusions: Modern dancers have greater whole and cancellous bone stiffness in the distal femur compared to controls. Elevated whole bone stiffness in dancers may be mediated via cancellous, rather than cortical bone adaptation.

Descriptions of Pleistocene activity patterns often derive from comparisons of long bone diaphyseal robusticity across contemporaneous fossilized hominins. The purpose of this study is to augment existing understanding of Pleistocene hominin mobility patterns by interpreting fossil variation through comparisons with a) living human athletes with known activity patterns, and b) Holocene foragers where descriptions of group-level activity patterns are available. Relative tibial rigidity (midshaft tibial rigidity (J)/midshaft humeral rigidity (J)) was compared amongst Levantine and European Neandertals, Levantine and Upper Palaeolithic Homo sapiens, Holocene foragers and living human athletes and controls. Cross-country runners exhibit significantly (p<0.05) greater relative tibial rigidity compared with swimmers, and higher values compared with controls. In contrast, swimmers displayed significantly (p<0.05) lower relative tibial rigidity than both runners and controls. While variation exists among all Holocene H. sapiens, highly terrestrially mobile Later Stone Age (LSA) southern Africans and cross-country runners display the highest relative tibial rigidity, while maritime Andaman Islanders and swimmers display the lowest, with controls falling between. All fossil hominins displayed relative tibial rigidity that exceeded, or was similar to, the highly terrestrially mobile Later Stone Age southern Africans and modern human cross-country runners. The more extreme skeletal structure of most Neandertals and Levantine H. sapiens, as well as the odd Upper Palaeolithic individual, appears to reflect adaptation to intense and/or highly repetitive lower limb (relative to upper limb) loading. This loading may have been associated with bipedal travel, and appears to have been more strenuous than that encountered by even university varsity runners, and Holocene foragers with hunting grounds 2000-3000 square miles in size. Skeletal variation among the athletes and foraging groups is consistent with known or inferred activity profiles, which support the position that the Pleistocene remains reflect adaptation to extremely active and mobile lives., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Bone overgrowth is a known phenomenon occurring after fracture of growing long bones with possible long-term physical consequences for affected children. Here, the physeal expression of bone morphogenetic proteins (BMPs) was investigated in a fracture-animal model to test the hypothesis that a diaphyseal fracture stimulates the physeal expression of these known key regulators of bone formation, thus stimulating bone overgrowth. Sprague-Dawley rats (male, 4 weeks old), were subjected to a unilateral mid-diaphyseal tibial fracture. Kinetic expression of physeal BMP-2, -4, -6, -7, and BMP receptor-1a (BMPR-1a) was analyzed in a monthly period by quantitative real time-polymerase chain reaction and immunohistochemistry. On Days 1, 3, 10, and 14 post-fracture, no changes in physeal BMPs gene-expression were detected. Twenty-nine days post-fracture, when the fracture was consolidated, physeal expression of BMP-6 and BMPR-1a was significantly upregulated in the growth plate of the fractured and contra-lateral intact bone compared to control (p<0.005). This study demonstrates a late role of BMP-6 and BMPR-1a in fracture-induced physeal growth alterations and furthermore, may have discovered the existence of a regulatory "cross-talk" mechanism between the lower limbs whose function could be to limit leg-length-discrepancies following the breakage of growing bones., (Copyright © 2012 Orthopaedic Research Society.)