The relative importance of genetics and phenotypic plasticity in dictating bone morphology and mechanics in aged mice: evidence from an artificial selection experiment

Both genetic and environmental factors are known to influence the structure of bone, contributing to its mechanical behavior during, and adaptive response to, loading. We introduce a novel approach to simultaneously address the genetically mediated, exercise-related effects on bone morphometrics and strength, using mice that had been selectively bred for high levels of voluntary wheel running (16 generations). Female mice from high running and control lines were either allowed (n=12, 12, respectively) or denied (n=11, 12, respectively) access to wheels for 20 months. Femoral shaft, neck, and head were measured with calipers and via micro-computed tomography. Fracture characteristics of the femoral head were assessed in cantilever bending. After adjusting for variation in body mass by two-way analysis of covariance, distal width of the femur increased as a result of selective breeding, and mediolateral femoral diameter was reduced by wheel access. Cross-sectional area of the femoral mid-shaft showed a significant linetype x activity effect, increasing with wheel access in high-running lines but decreasing in control lines. Body mass was significantly positively correlated with many of the morphometric traits studied. Fracture load of the femoral neck was strongly positively predicted by morphometric traits of the femoral neck (r2>0.30), but no significant effects of selective breeding or wheel access were found. The significant correlations of body mass with femoral morphometric traits underscore the importance of controlling for body size when analyzing the response of bone size and shape to experimental treatments. After controlling for body mass, measures of the femoral neck remain significant predictors of femoral neck strength.     

Whole body vibration with rest days could improve bone quality of distal femoral metaphysis by regulating trabecular arrangement

Low-magnitude, high-frequency vibration(LMHFV) with rest days(particularly seven rest days) was considerably effective in improving the morphological and mechanical properties of rat proximal femur. However, current knowledge is limited regarding the possible benefit of this mechanical regimen to other bone sites and whether the optimal rest days are the same. This study followed our previous experiment on LMHFV loading with rest days for three-month-old male Wistar rats. The experiment involved seven groups, namely, vibrational loading for X day followed with X day rest(X=1, 3, 5, 7), daily vibrational loading,tail suspension and baseline control. Micro-computed tomography(micro-CT) scanning was used to evaluate the microarchitecture of the distal femoral trabecular bone. Micro-CT image-based microfinite element analysis was performed for each distal femoral metaphysis. LMHFV with rest days substantially changed the trabecular arrangement from remarkably plate-like to rod-like. Vibrational loading with 1 day rest was substantially effective in improving the architecture and apparent-and tissuelevel mechanical properties of the rat distal femoral metaphysis. This study may provide an improved understanding of the sitespecific responses of bone tissue to LMHFV with rest days for a substantially effective therapy of a targeted bone site.     

Comparative effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats.

The purpose of the present study was to compare the effects of alendronate and alfacalcidol on cancellous and cortical bone mass and bone mechanical properties in ovariectomized rats. Twenty-six female Sprague-Dawley rats, 7 months of age, were randomized by the stratified weight method into four groups: the sham-operated control (Sham) group and the three ovariectomy (OVX) groups, namely, OVX + vehicle, OVX + alendronate (2.5 mg/kg, p.o., daily), and OVX + alfacalcidol (0.5 mug/kg, p.o., daily). At the end of the 8-week experimental period, bone histomorphometric analyses of cancellous bone at the proximal tibial metaphysis and cortical bone at the tibial diaphysis were performed, and the mechanical properties of the femoral distal metaphysis and femoral diaphysis were evaluated. OVX decreased cancellous bone volume per total tissue volume (BV/TV), and the maximum load of the femoral distal metaphysis, as a result of increases in serum osteocalcin (OC) levels, and also the number of osteoclasts (N.Oc), osteoclast surface (OcS) and bone formation rate (BFR) per bone surface (BS), and BFR/BV, without any effect on cortical area (Ct Ar), or maximum load of the femoral diaphysis. Alendronate prevented this decrease in cancellous BV/TV by suppressing increases in N.Oc/BS, OcS/BS, BFR/BS, and BFR/BV, without any apparent effect on Ct Ar, or maximum load of the femoral distal metaphysis and femoral diaphysis. On the other hand, alfacalcidol increased cancellous BV/TV, Ct Ar, and the maximum load of the femoral distal metaphysis and femoral diaphysis, by mildly decreasing trabecular BFR/BV, maintaining trabecular mineral apposition rate and osteoblast surface per BS, increasing periosteal and endocortical BFR/BS, and preventing an increase in endocortical eroded surface per BS. The present study clearly showed the differential skeletal effects of alendronate and alfacalcidol in ovariectomized rats. Alendronate prevented OVX-induced cancellous bone loss by suppressing bone turnover, while alfacalcidol improved cancellous and cortical bone mass and bone strength by suppressing bone resorption and maintaining or even increasing bone formation.     

Evolution of hindlimb bone dimensions and muscle masses in house mice selectively bred for high voluntary wheel‐running behavior

We have used selective breeding with house mice to study coadaptation of morphology and physiology with the evolution of high daily levels of voluntary exercise. Here, we compared hindlimb bones and muscle masses from the 11th generation of four replicate High Runner (HR) lines of house mice bred for high levels of voluntary wheel running with four non‐selected control (C) lines. Mass, length, diameter, and depth of the femur, tibia‐fibula, and metatarsal bones, as well as masses of gastrocnemius and quadriceps muscles, were compared by analysis of covariance with body mass or body length as the covariate. Mice from HR lines had relatively wider distal femora and deeper proximal tibiae, suggesting larger knee surface areas, and larger femoral heads. Sex differences in bone dimensions were also evident, with males having thicker and shorter hindlimb bones when compared with females. Several interactions between sex, linetype, and/or body mass were observed, and analyses split by sex revealed several cases of sex‐specific responses to selection. A subset of the HR mice in two of the four HR lines expressed the mini‐muscle phenotype, characterized mainly by an ～50% reduction in hindlimb muscle mass, caused by a Mendelian recessive mutation, and known to have been under positive selection in the HR lines. Mini‐muscle individuals had elongated distal elements, lighter and thinner hindlimb bones, altered 3rd trochanter muscle insertion positions, and thicker tibia‐fibula distal widths. Finally, several differences in levels of directional or fluctuating asymmetry in bone dimensions were observed between HR and C, mini‐ and normal‐muscled mice, and the sexes. This study demonstrates that skeletal dimensions and muscle masses can evolve rapidly in response to directional selection on locomotor behavior.     

Greater efficacy of alfacalcidol in the red than in the yellow marrow skeletal sites in adult female rats

The present study compared the bone anabolic effects of graded doses of alfacalcidol in proximal femurs (hematopoietic, red marrow skeletal site) and distal tibiae (fatty, yellow marrow skeletal site). One group of 8.5-month-old female Sprague-Dawley rats were killed at baseline and 4 groups were treated 5 days on/2 days off/week for 12 weeks with 0, 0.025, 0.05 and 0.1 microg alfacalcidol/kg by oral gavage. The proximal femur, bone site with hematopoietic marrow, as well as the distal tibia bone site with fatty marrow, were processed undecalcified for quantitative bone histomorphometry. In the red marrow site of the proximal femoral metaphysis (PFM), 0.1 microg alfacalcidol/kg induced increased cancellous bone mass, improved architecture (decreased trabecular separation, increased connectivity), and stimulated local bone formation of bone 'boutons' (localized bone formation) on trabecular surfaces. There was an imbalance in bone resorption and formation, in which the magnitude of depressed bone resorption greater than depressed bone formation resulted in a positive bone balance. In addition, bone 'bouton' formation contributed to an increase in bone mass. In contrast, the yellow marrow site of the distal tibial metaphysis (DTM), the 0.1 microg alfacalcidol/kg dose induced a non-significant increased cancellous bone mass. The treatment decreased bone resorption equal to the magnitude of decreased bone formation. No bone 'bouton' formation was observed. These findings indicate that the highest dose of 0.1 microg alfacalcidol/kg for 12 weeks increased bone mass (anabolic effect) at the skeletal site with hematopoietic marrow of the proximal femoral metaphysis, but the increased bone mass was greatly attenuated at the fatty marrow site of the distal tibial metaphysis. In addition, the magnitude of the bone gain induced by alfacalcidol treatment in red marrow cancellous bone sites of the proximal femoral metaphysis was half that of the lumbar vertebral body. The latter data were from a previous report from the same animal and protocol. These findings indicated that alfacalcidol as an osteoporosis therapy is less efficacious as a positive bone balance agent that increased trabecular bone mass in a non-vertebral skeletal site where bone marrow is less hematopoietic.     

Do different locomotor modes during growth modulate trabecular architecture in the murine hind limb?

Vertebrate morphologists often implicate functional adaptationsof bone to mechanical milieus when comparing animals with distinctbehavioral repertoires. Functional morphologists frequentlyuse comparative osteology and locomotor behavior to constructcorrelative form–function relationships. While some experimentalwork has investigated functional adaptations of bone elicitedby specific locomotor behaviors, these studies usually manipulaterepertoires by introducing artificial situations (e.g., treadmills)or creating differences in the level of activity (i.e., exercise),either of which can compromise extrapolations to free-ranginganimals. Here, we present trabecular bone morphology and microarchitecturefrom an inbred mouse model in which components of naturalisticlocomotor repertoires were accentuated. Using inbred mice, wecontrol for genetic variability, further isolating the osteogenicresponses to these behaviors. Single female (BALB/cByJ) mice(n = 10 per group) were housed for 8 weeks beginning at 30 dayspostbirth in custom-designed cages that accentuated either linearquadrupedalism or turning. Concurrently, mice in a control groupwere housed singly in open cages. The distal femoral metaphysiswas scanned by micro-computed tomography at the end of the 8-weekexperiment protocol. The experimental groups, particularly the"linear" group, differed significantly from the control group(simulated "free-ranging" condition) in several variables: bonevolume fraction ("linear" 42% less than controls; "turning"24% less than controls), trabecular number ("linear" 12% lessthan controls; "turning" 9% less than controls), connectivitydensity ("linear" 43% less than controls; "turning" 35% lessthan controls), and a characterization of trabecular surfaces("linear" 15% greater than controls; "turning" 11% greater thancontrols). No differences in the degree of anisotropy were observedamong groups, and generally, "linear" and "turning" groups didnot differ significantly from one another in any measures oftrabecular microarchitecture. Considering the distinct differencesin locomotor behaviors between the "linear" quadrupedalism and"turning" groups, these data suggest that comparisons at thedistal femoral metaphysis of trabecular microarchitecture ororientation between different groups of animals may be somewhatlimited in accurately reconstructing the loading conditionsassociated with different locomotor modes.     

A comparison of the femoral head and neck trabecular architecture of Galago and Perodicticus using micro-computed tomography (microCT)

Innovations in micro-computed tomography (microCT) in the medical field have resulted in the development of techniques that allow the precise quantification of bone density and fabric related parameters of trabecular bone. For the purpose of this study, the technique was applied to a small sample of Perodicticus potto and Galago senegalensis femora to see if differences in loading environment elicit the predicted effects on trabecular structure. While the overall bone volume was approximately three times larger in the potto, there was no significant difference in the apparent volume density in the two taxa. When regional differences in the proximal femur were examined, the cancellous bone of the femoral head of Perodicticus potto and Galago senegalensis, while not differing in volume density, showed differences in trabecular orientation, with the potto having more randomly oriented trabeculae than the bushbaby. This was as hypothesized, given that the bushbaby submits its femora to more stereotypical loading environments than the potto. In the femoral neck, the cancellous bone was not only more randomly oriented, it was also denser in the potto compared with the bushbaby. This suggests that trabecular morphology may be extremely sensitive to certain differences in the loading environment and that this information, combined with information on cortical bone structure and external geometry, will result in a more complete understanding of how bone shape and composition correspond to loading and locomotor patterns. Ultimately, a synthesis of these different lines of evidence may have considerable applications in paleontological studies that attempt to reconstruct bone use from morphology.     

Does skeletal anatomy reflect adaptation to locomotor patterns? cortical and trabecular architecture in human and nonhuman anthropoids

Although the correspondence between habitual activity and diaphyseal cortical bone morphology has been demonstrated for the fore- and hind-limb long bones of primates, the relationship between trabecular bone architecture and locomotor behavior is less certain. If sub-articular trabecular and diaphyseal cortical bone morphology reflects locomotor patterns, this correspondence would be a valuable tool with which to interpret morphological variation in the skeletal and fossil record. To assess this relationship, high-resolution computed tomography images from both the humeral and femoral head and midshaft of 112 individuals from eight anthropoid genera (Alouatta, Homo, Macaca, Pan, Papio, Pongo, Trachypithecus, and Symphalangus) were analyzed. Within-bone (sub-articular trabeculae vs. mid-diaphysis), between-bone (forelimb vs. hind limb), and among-taxa relative distributions (femoral:humeral) were compared. Three conclusions are evident: (1) Correlations exists between humeral head sub-articular trabecular bone architecture and mid-humerus diaphyseal bone properties; this was not the case in the femur. (2) In contrast to comparisons of inter-limb diaphyseal bone robusticity, among all species femoral head trabecular bone architecture is significantly more substantial (i.e., higher values for mechanically relevant trabecular bone architectural features) than humeral head trabecular bone architecture. (3) Interspecific comparisons of femoral morphology relative to humeral morphology reveal an osteological "locomotor signal" indicative of differential use of the forelimb and hind limb within mid-diaphysis cortical bone geometry, but not within sub-articular trabecular bone architecture.     

Shape‐shift: Semicircular canal morphology responds to selective breeding for increased locomotor activity

Variation in semicircular canal morphology correlates with locomotor agility among species of mammals. An experimental evolutionary mouse model was used to test the hypotheses that semicircular canal morphology (1) evolves in response to selective breeding for increased locomotor activity, (2) exhibits phenotypic plasticity in response to early‐onset chronic exercise, and (3) is unique in individuals possessing the minimuscle phenotype. We examined responses in canal morphology to prolonged wheel access and selection in laboratory mice from four replicate lines bred for high voluntary wheel‐running (HR) and four nonselected control (C) lines. Linear measurements and a suite of 3D landmarks were obtained from 3D reconstructions of μCT‐scanned mouse crania (μCT is microcomputed tomography). Body mass was smaller in HR than C mice and was a significant predictor of both radius of curvature and 3D canal shape. Controlling for body mass, radius of curvature did not differ statistically between HR and C mice, but semicircular canal shape did. Neither chronic wheel access nor minimuscle affected radius of curvature or canal shape These findings suggest that semicircular canal morphology is responsive to evolutionary changes in locomotor behavior, but the pattern of response is potentially different in small‐ versus large‐bodied species.     

Ultrastructural changes in bones of the senescence-accelerated mouse (SAMP6): a murine model for senile osteoporosis

SAMP6, a substrain of senescence-accelerated mice, was developed as an animal model for senile osteoporosis. In the present study, we investigated the bone morphology, together with serum calcium and bone mineral density (BMD) in SAMP6 and age-matched normal mice SAMR1. We did not find any significant differences between SAMR1 and SAMP6 at 1 month of age with regard to the serum compositions and bone morphology. As compared with SAMR1, BMD, the femoral weight, femoral calcium and phosphorus levels were significantly reduced in SAMP6 at 2 and 5 months of age. The number of osteoblasts in trabecular bones was also significantly reduced. Swollen mitochondria and myelin-like structures were found in osteoblasts and osteocytes of SAMP6 mice at 2 and 5 months of age. There was a greater proportion of resting surface and less forming surface in the femoral endosteal surfaces of SAMP6 mice. The amount of trabecular bone in the lumbar vertebra and the distal metaphysis of the femur was reduced. The number of the mast cells in bone marrow of the tibia significantly increased in SAMP6 mice. These findings indicate that the lower bone mass in SAMP6 was due to the reduction in osteoblast formation and suggested that mast cells in bone marrows play a role in the pathogenesis of senile osteoporosis.     

Effects of early‐life exposure to Western diet and wheel access on metabolic syndrome profiles in mice bred for high voluntary exercise

Experimental studies manipulating diet and exercise have shown varying effects on metabolic syndrome components in both humans and rodents. To examine the potential interactive effects of diet, exercise and genetic background, we studied mice from four replicate lines bred (52 generations) for high voluntary wheel running (HR lines) and four unselected control lines (C). At weaning, animals were housed for 60 days with or without wheels and fed either a standard chow or Western diet (WD, 42% kcal from fat). Four serial (three juvenile and one adult) blood samples were taken to measure fasting total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), triglycerides and glucose. Western diet was obesogenic for all mice, even after accounting for the amount of wheel running and kilojoules consumed. Western diet significantly raised glucose as well as TC and HDL‐C concentrations. At the level of individual variation (repeatability), there was a modest correlation (r = 0.3–0.5) of blood lipids over time, which was reduced with wheel access and/or WD. Neither genetic selection history nor wheel access had a statistically significant effect on blood lipids. However, HR and C mice had divergent ontogenetic trajectories for body mass and caloric intake. HR mice also had lower adiposity, an effect that was dependent on wheel access. The environmental factors of diet and wheel access had pronounced effects on body mass, food consumption and fasting glucose concentrations, interacting with each other and/or with genetic strain. These data underscore the importance (and often unpredictable nature) of genotype‐by‐environment and environment‐by‐environment interactions when studying body weight regulation.     

Experimental evolution and phenotypic plasticity of hindlimb bones in high-activity house mice

Studies of rodents have shown that both forced and voluntary chronic exercise cause increased hindlimb bone diameter, mass, and strength. Among species of mammals, "cursoriality" is generally associated with longer limbs as well as relative lengthening of distal limb segments, resulting in an increased metatarsal/femur (MT/F) ratio. Indeed, we show that phylogenetic analyses of previously published data indicate a positive correlation between body mass-corrected home range area and both hindlimb length and MT/F in a sample of 19 species of Carnivora, although only the former is statistically significant in a multiple regression. Therefore, we used an experimental evolution approach to test for possible adaptive changes (in response to selective breeding and/or chronic exercise) in hindlimb bones of four replicate lines of house mice bred for high voluntary wheel running (S lines) for 21 generations and in four nonselected control (C) lines. We examined femur, tibiafibula, and longest metatarsal of males housed either with or without wheel access for 2 months beginning at 25-28 days of age. As expected from previous studies, mice from S lines ran more than C (primarily because the former ran faster) and were smaller in body size (both mass and length). Wheel access reduced body mass (but not length) of both S and C mice. Analysis of covariance (ANCOVA) revealed that body mass was a statistically significant predictor of all bone measures except MT/F ratio; therefore, all results reported are from ANCOVAs. Bone lengths were not significantly affected by either linetype (S vs. C) or wheel access. However, with body mass as a covariate, S mice had significantly thicker femora and tibiafibulae, and wheel access also significantly increased diameters. Mice from S lines also had heavier feet than C, and wheel access increased both foot and tibiafibula mass. Thus, the directions of evolutionary and phenotypic adaptation are generally consistent. Additionally, S-line individuals with the mini-muscle phenotype (homozygous for a Mendelian recessive allele that halves hindlimb muscle mass [Garland et al., 2002, Evolution 56:1,267-1,275]) exhibited significantly longer and thinner femora and tibiafibulae, with no difference in bone masses. Two results were considered surprising. First, no differences were found in the MT/F ratio (the classic indicator of cursoriality). Second, we did not find a significant interaction between linetype and wheel access for any trait, despite the higher running rate of S mice.     

Differential effects of jump versus running exercise on trabecular architecture during remobilization after suspension-induced osteopenia in growing rats

High-impact exercise is considered to be very beneficial for bones. We investigated the ability of jump exercise to restore bone mass and structure after the deterioration induced by tail suspension in growing rats and made comparisons with treadmill running exercise. Five-week-old male Wistar rats (n = 28) were randomly assigned to four body weight-matched groups: a spontaneous recovery group after tail suspension (n = 7), a jump exercise group after tail suspension (n = 7), a treadmill running group after tail suspension (n = 7), and age-matched controls without tail suspension or exercise (n = 7). Treadmill running was performed at 25 m/min, 1 h/day, 5 days/wk. The jump exercise protocol consisted of 10 jumps/day, 5 days/wk, with a jump height of 40 cm. Bone mineral density (BMD) of the total right femur was measured by dual-energy X-ray absorptiometry. Three-dimensional trabecular bone architecture at the distal femoral metaphysis was evaluated using microcomputed tomography. After 5 wk of free remobilization, right femoral BMD, right hindlimb muscle weight, and body weight returned to age-matched control levels, but trabeculae remained thinner and less connected. Although both jump and running exercises during the remobilization period increased trabecular bone mass, jump exercise increased trabecular thickness, whereas running exercise increased trabecular number. These results indicate that restoration of trabecular bone architecture induced by jump exercise during remobilization is predominantly attributable to increased trabecular thickness, whereas running adds trabecular bone mass through increasing trabecular number, and suggest that jumping and running exercises have different mechanisms of action on structural characteristics of trabecular bone.     

Does endurance running before orchidectomy prevent osteopenia in rats?

This experiment was performed to study the effects on femoral bone of endurance training performed during the 3 months before orchidectomy in rats which were then killed 90 days later. A total of 70 male Wistar rats were used at 8 weeks old. One day 0 of the experiment, 10 rats were killed by cervical dislocation and used as first controls. Among the 60 others, 30 were selected for treadmill running (60% maximal oxygen uptake, 1 h x day(-1), 6 days x week(-1) for 90 days). The 30 other rats remained at rest. On day 90, 10 exercised (IE) and resting (IR) rats were killed and used as intermediary controls. Among the 20 other animals of each group, 10 were surgically castrated (CXE, CXR) or 10 sham-operated (SHE, SHR) and killed on day 180. On day 90 femoral failure load (three-point bending test) was greater in IE than in IR. Simultaneously, the deoxypyridinolinuria was lower in IE than in IR. On day 180, femoral bones were thinner in CXR than in CXE. The lowest values for trabecular bone are in the distal femoral metaphysis were measured in CXE and CXR rats, but the value measured in CXE was no different from that measured in SHR. Simultaneously total femoral bone density was lower in CXR than in SHE, while no difference concerning femoral metaphyseal density was observed between CXE and SHR. These results confirmed that endurance running increased femoral bone growth and modelling and femoral trabecular area, and thereby peak bone mass, in 8-month-old male rats. In resting animals, castrated after the training period, androgen deficiency decreased femoral density, mineral content and trabecular area. This decrease was not observed in castrated but previously exercised rats. Thus, by increasing peak bone mass, it was considered that endurance training may have a preventive effect against orchidectomy-induced bone loss.     

Selective breeding as a tool to probe skeletal response to high voluntary locomotor activity in mice

We present a novel mouse-model for the study of skeletal structureand evolution, based on selective breeding for high levels ofvoluntary wheel running. Whereas traditional models (originallyinbred strains, more recently knockouts and transgenics) relyon the study of mutant or laboratory-manipulated phenotypes,we have studied changes in skeletal morphometrics resultingfrom many generations of artificial selection for high activityin the form of wheel running, in which mice engage voluntarily.Mice from the four replicate High Runner (HR) lines run nearlythree times as many revolutions during days 5 and 6 of a 6-dayexposure to wheels (1.12 m circumference). We have found significantchanges in skeletal dimensions of the hind limbs, includingdecreased directional asymmetry, larger femoral heads, and widerdistal femora. The latter two have been hypothesized as evolutionaryadaptations for long-distance locomotion in hominids. Exercise-trainingstudies involving experimental groups with and without accessto wheels have shown increased diameters of both femora andtibiafibulae, and suggest genetic effects on trainability (genotype-by-environmentinteractions). Reanalysis of previously published data on bonemasses of hind limbs revealed novel patterns of change in bonemass associated with access to wheels for 2 months. Withoutaccess to wheels, HR mice have significantly heavier tibiafibulaeand foot bones, whereas with chronic access to wheels, a significantincrease in foot bone mass that was linearly related to increasesin daily wheel running was observed. Mice exhibiting a recentlydiscovered small-muscle phenotype ("mini-muscle," [MM] causedby a Mendelian recessive gene), in which the mass of the tricepssurae muscle complex is 50% lower than in normal individuals,have significantly longer and thinner bones in the hind limb.We present new data for the ontogenetic development of musclemass in Control, HR, and MM phenotypes in mice of 1–7weeks postnatal age. Statistical comparisons reveal highly significantdifferences both in triceps surae mass and mass-corrected tricepssurae mass between normal and MM mice at all but the postnatalage of 1 week. Based on previously observed differences in distributionsof myosin isoforms in adult MM mice, we hypothesize that a reductionof myosin heavy-chain type-IIb isoforms with accounts for ourobserved ontogenetic changes in muscle mass.     

Who's afraid of the big bad Wolff?: “Wolff's law” and bone functional adaptation

"Wolff's law" is a concept that has sometimes been misrepresented, and frequently misunderstood, in the anthropological literature. Although it was originally formulated in a strict mathematical sense that has since been discredited, the more general concept of "bone functional adaptation" to mechanical loading (a designation that should probably replace "Wolff's law") is supported by much experimental and observational data. Objections raised to earlier studies of bone functional adaptation have largely been addressed by more recent and better-controlled studies. While the bone morphological response to mechanical strains is reduced in adults relative to juveniles, claims that adult morphology reflects only juvenile loadings are greatly exaggerated. Similarly, while there are important genetic influences on bone development and on the nature of bone's response to mechanical loading, variations in loadings themselves are equally if not more important in determining variations in morphology, especially in comparisons between closely related individuals or species. The correspondence between bone strain patterns and bone structure is variable, depending on skeletal location and the general mechanical environment (e.g., distal vs. proximal limb elements, cursorial vs. noncursorial animals), so that mechanical/behavioral inferences based on structure alone should be limited to corresponding skeletal regions and animals with similar basic mechanical designs. Within such comparisons, traditional geometric parameters (such as second moments of area and section moduli) still give the best available estimates of in vivo mechanical competence. Thus, when employed with appropriate caution, these features may be used to reconstruct mechanical loadings and behavioral differences within and between past populations.     

Declining tibial curvature parallels ∼6150 years of decreasing mobility in central european agriculturalists

Long bones respond to mechanical loading through functional adaptation in a suite of morphological characteristics that together ensure structural competence to in vivo loading. As such, adult bone structure is often used to make inferences about past behavior from archaeological remains. However, such biomechanical approaches often investigate change in just one aspect of morphology, typically cross‐sectional morphology or trabecular structure. The relationship between longitudinal bone curvature and mobility patterns is less well understood, particularly in the tibia, and it is unknown how tibial curvature and diaphyseal cross‐sectional geometry interact to meet the structural requirements of loading. This study examines tibial curvature and its relationship with diaphyseal cross‐sectional geometry (CSG) and body size in preindustrial Central Europeans spanning ～6150 years following the introduction of agriculture in the region. Anteroposterior centroid displacement from the proximo‐distal longitudinal axis was quantified at nine diaphyseal section locations (collectively representative of diaphyseal curvature) in 216 tibial three‐dimensional laser scans. Results documented significant and corresponding temporal declines in midshaft centroid displacement and CSG properties. Significant correlations were found between mid‐diaphyseal centroid displacement and all mobility‐related CSG properties, while the relationship weakened toward the diaphyseal ends. No significant relationship was found between centroid displacement and body size variables with the exception of the most distal section location. Results support a relationship between tibial curvature and cross‐sectional geometry among prehistoric Central European agricultural populations, and suggest that changes in mechanical loading may have influenced a suite of morphological features related to bone adaptation in the lower limb. Am J Phys Anthropol 157:260–275, 2015. © 2015 Wiley Periodicals, Inc.     

Changes in the Architecture of Cancellous Bone in the Femora of Developing Mice as a Result of Short Duration Hypergravity

SYNOPSIS. Mice were used as a model system to demonstrate theeffects of increased loading on the trabecular bone in the developingproximal femur. A two-dimensional free body diagram revealedthat because the femur is normally held in a horizontal positionduring support, functional loading resulted in a net posteriorbending moment and a muscle generated axial compressive loadthat was 7.7 times the normal support weight for that limb.Experimental treatment consisted of four times normal gravityfor 10 min, six times per day for 30 days in addition to unrestrainednormal exercise. Unrestrained normal exercise served as thecontrol. An animal whose foot was amputated by his mother shortlyafter birth was used as a less than normal load example forcomparison with the hypergravity and control groups. All groupswere treated for 30 days. Two areas of trabecular bone wereexamined: a proximal central webbing area that may be underpredominantly tensile loading much of the time, and a more distalarea near the third trochanter that presumably experiences bendingstresses when the animal is exposed to normal activity or hypergravity.Results indicate that: 1) The central webbing area appears tohave a similar mass of bone regardless of loading conditions;however, with increased loading the trabeculae become orientedin directions that approximate directions of presumed principaltensile stresses. 2) There is no genetically predetermined amountof bony tissue in the third trochanter area; when the limb isrelatively unloaded no trabeculae are present, as the loadingincreases trabecular bone is formed. In the hypergravity group,trabeculae in the area of the third trochanter increased inlength and complexity and became more centrally positioned inthe lumen of the femur, a position that presumably would allowthe femur to better resist bending moments. These results demonstratethat short duration, high intensity functional loading can stimulategrowth of trabecular bone, and further, specific types of functionalloading can be correlated with specific architectural changes.     

Articular constraint, handedness, and directional asymmetry in the human second metacarpal

The hypothesis that functional adaptation of joint surfaces to mechanical loading occurs primarily through change in mass, density, and structure of subarticular trabeculae (the "articular constraint" model) is investigated through an analysis of directional asymmetry among three separate bone compartments in the human second metacarpal. Measures of midshaft cross-sectional geometry, osteometry of the distal epiphysis, and subarticular trabecular microarchitecture of the distal epiphysis (assessed by high-resolution microcomputed tomography) were determined for 29 paired male and female metacarpals from a well-preserved nineteenth-century Euro-Canadian historic cemetery sample. For each measure, asymmetry was quantified using both mean-difference and confidence-interval methods. Both methods found a significant right-hand bias for measures of structural strength in midshaft geometry, as has been previously noted for this sample. Articular size, however, exhibits a right-hand bias only with regard to mediolateral, and not dorsopalmar, dimensions, a result that may reflect directional asymmetry in hand breadth at the distal palmar arch. The most striking asymmetries occur for subarticular trabecular microarchitecture. The right metacarpal head exhibits greater bone volume fraction, bone surface density, trabecular number, connectivity, and a more platelike rather than rodlike structure. These outcomes confer greater resistance to both axial compressive and shear strains for the metacarpal head at the metacarpophalangeal arthrosis. In all, these results confirm and extend previous research documenting structural asymmetries and limb dominance and are consistent with the concept of articular constraint. They also suggest a morphological signal through which functional asymmetry associated with handedness in fossil hominins may be investigated.     

A micro-computed tomography study of the trabecular bone structure in the femoral head

The goal of this study was to characterize the trabecular microarchitecture of the femoral head using micro-computed tomography (ICT). Femoral head specimens were obtained from subjects following total hip replacement. Cylindrical cores from the specimens were scanned to obtain 3-D images with an isotropic resolution of 26 Im. Bone structural parameters were evaluated on a per millimeter basis: relative bone volume (BV/TV), trabecular number (Tb.N), thickness (Tb.Th) and separation (Tb.Sp), structure model index (SMI), and connectivity (Conn.D). The ICT data show that the first two millimeters, starting at the joint surface, are characterized by more plate-like trabeculae, and are significantly denser than the underlying trabecular bone. Regional differences in the trabecular architecture reveal that the superior pole has significantly higher BV/TV, Tb.N and Tb.Th values, with lower Tb.Sp compared to the inferior and side poles. Because subchondral bone is essential in the load attenuation of joints, the difference in bone structure between the subchondral and trabecular bone might arise from the different functions each have within joint-forming bones. The denser trabecular structure of the superior pole as compared to the inferior pole can be interpreted as a functional adaptation to higher loading in this area.