Sexual dimorphism in bone growth as a function of body size in moderately malnourished Guatemalan preschool age children

The sexual dimorphism in second metacarpal bone growth was investigated in 710 malnourished Guatemalan children one to seven years old to determine if the sex differences seen are only the result of differences in stature and weight. The study sample was mixed-longitudinal and consisted of 1,586 annual examinations. Boys have greater mean stature, weight, periosteal diameter, medullary diameter and cortical area than girls the same age, while girls have greater age specific mean cortical thickness and percent cortical area than boys. When the effects of stature, weight and age are removed boys still have significantly larger periosteal and medullary diameters and less cortical thickness and percent cortical area than girls. These differences between boys and girls therefore cannot be explained by sex differences in body size. However, no sex differences in cortical area remain after accounting for differences in stature, weight and age.     

Body size, body proportions, and mobility in the Tyrolean "Iceman"

Body mass and structural properties of the femoral and tibial midshafts of the "Iceman," a late Neolithic (5,200 BP) mummy found in the Tyrolean Alps, are determined from computed tomographic scans of his body, and compared with those of a sample of 139 males spanning the European early Upper Paleolithic through the Bronze Age. Two methods, based on femoral head breadth and estimated stature/bi-iliac (pelvic) breath, yield identical body-mass estimates of 61 kg for the Iceman. In combination with his estimated stature of 158 cm, this indicates a short but relatively wide or stocky body compared to our total sample. His femur is about average in strength compared to our late Neolithic (Eneolithic) males, but his tibia is well above average. His femur also shows adaptations for his relatively broad body (mediolateral strengthening), while his tibia shows adaptations for high mobility over rough terrain (anteroposterior strengthening). In many respects, his tibia more closely resembles those of European Mesolithic rather than Neolithic males, which may reflect a more mobile lifestyle than was characteristic of most Neolithic males, perhaps related to a pastoral subsistence strategy. There are indications that mobility in general declined between the European Mesolithic and late Neolithic, and that body size and shape may have become more variable throughout the continent following the Upper Paleolithic.     

Leptin is a potent stimulator of bone growth in ob/ob mice

Leptin, the product of the obese gene, is a circulating hormone secreted primarily from adipocytes. The lack of leptin in ob/ob mice, who are homozygous for the obese gene, results in hyperglycemia, hyperinsulinemia, hyperphagia, obesity, infertility, decreased brain size and decreased stature. To this end, we investigated the role of leptin as a hormonal regulator of bone growth. Leptin administration led to a significant increase in femoral length, total body bone area, bone mineral content and bone density in ob/ob mice as compared to vehicle treated controls. The increase in total body bone mass was a result of an increase in both trabecular and cortical bone mass. These results suggest that the decreased stature of the ob/ob mouse is due to a developmental defect that is readily reversible upon leptin administration. Our demonstration that the signalling or long form (Ob-Rb) of the leptin receptor is present in both primary adult osteoblasts and chondrocytes suggests that the growth promoting effects of leptin could be direct. In summary, these results indicate a novel role for leptin in skeletal bone growth and development.     

The effects of socioeconomic status on endochondral and appositional bone growth,and acquisition of cortical bone in children from 19th century Birmingham,England

Endochondral growth, appositional growth, and acquisition of cortical bone thickness in the femur are investigated in subadult skeletons (N = 43, dental age range birth to 12 years) from the 19^th‐century AD burial site of St. Martin's churchyard, Birmingham, England. Endochondral growth is monitored using diaphyseal femoral length. Appositional growth is monitored using radiographic midshaft mediolateral width and acquisition of cortical bone using combined mediolateral cortical thickness measured at the midshaft from radiographs. The methodology involves plotting these variables against dental age. Growth is compared in children of differing socioeconomic status. Higher and lower status individuals are identified in the assemblage by their burial in brick vaults in the case of the former and in earth‐cut graves in the case of the latter. The relationships between bone dimensions and dental age are described using a polynomial regression procedure, and analysis of regression residuals is used to evaluate differences in bone dimension‐for‐dental age between the two status groups. Results show that lower socioeconomic status individuals had lower cortical thickness‐for‐dental age than those of higher status. This was interpreted as likely reflecting poorer nutrition in the children of lower socioeconomic backgrounds. There was no patterning with respect to socioeconomic status in femur diaphyseal length or midshaft width. The results support the idea that, for skeletal populations, growth in cortical thickness may be a more sensitive indicator of adverse conditions in childhood than growth in bone length or width. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.     

Cortical bone distribution in the femoral neck of strepsirhine primates

The thickness of the inferior and superior cortices of the femoral neck was measured on X-rays of 181 strepsirhine primate femora representing 24 species. Neck length, neck depth and neck-shaft angle were also measured. The strength of the femoral neck in frontal bending was estimated by modeling the neck as a hollow cylinder, with neck depth as the outer diameter and cortical thickness representing the superior and inferior shell dimensions. Results indicate that the inferior cortex is always thicker than the superior cortex. The ratio of superior to inferior cortical thickness is highly variable but distinguishes two of the three locomotor groups in the sample. Vertical clingers and leapers have higher ratios (i.e., a more even distribution of cortical bone) than quadrupeds. The slow climbers tend to have the lowest ratios, although they do not differ significantly from the leapers and quadrupeds. These results do not confirm prior theoretical expectations and reported data for anthropoid primates that link greater asymmetry of the cortical shell to more stereotypical hip excursions. The ratio of superior to inferior cortical thickness is unrelated to body mass, femoral neck length, and neck-shaft angle, calling into question whether the short neck of strepsirhine primates acts as a cantilever beam in bending. On the other hand, the estimated section moduli are highly correlated with body mass and neck length, a correlation that is driven primarily by body mass. In conclusion, we believe that an alternative interpretation to the cantilever beam model is needed to explain the asymmetry in bone distribution in the femoral neck, at least in strepsirhine primates (e.g., a thicker inferior cortex is required to reinforce the strongly curved inferior surface). As in prior studies of cross-sectional geometry of long bones, we found slightly positive allometry of cortical dimensions with body mass.     

Stature and body mass estimation from skeletal remains in the European Holocene

Techniques that are currently available for estimating stature and body mass from European skeletal remains are all subject to various limitations. Here, we develop new prediction equations based on large skeletal samples representing much of the continent and temporal periods ranging from the Mesolithic to the 20th century. Anatomical reconstruction of stature is carried out for 501 individuals, and body mass is calculated from estimated stature and biiliac breadth in 1,145 individuals. These data are used to derive stature estimation formulae based on long bone lengths and body mass estimation formulae based on femoral head breadth. Prediction accuracy is superior to that of previously available methods. No systematic geographic or temporal variation in prediction errors is apparent, except in tibial estimation of stature, where northern and southern European formulae are necessary because of the presence of relatively longer tibiae in southern samples. Thus, these equations should bebroadly applicable to European Holocene skeletal samples.     

How cancellous and cortical bones adapt to loading and growth hormone

There is great interest in the relationships between growth hormone (GH), muscle loading and bone, in part, because GH increases muscle mass which provides the largest signals that control bone modeling and remodeling. This study was designed to examine the effects of GH and muscle loading by exercise (EX) independently and in combination on bone and skeletal muscle. Thirteen-month-old female F344 rats were divided into 6 groups: Group 1, baseline controls (B); Group 2, agematched controls (C); Group 3, GH treated (2.5 mg rhGH/kg b. wt/day, 5 days per week); Group 4, voluntary wheel running exercise (EX); Group 5, GH+EX, and rats in Group 6 were food restricted (FR) to lower their body weight and examine the effects of decreased muscle load on bone. All animals, except the baseline controls, were sacrificed after 4.5 months. Growth hormone increased the body weight and tibial muscle mass of the rats markedly, while EX caused a slight decrease in body weight and partially inhibited the increase caused by GH in the GH+EX group. Food restriction greatly decreased body weight below that of age-matched controls but neither FR nor EX had a significant effect on the mass of the muscles around the tibia. Growth hormone and EX independently increased tibial diaphyseal cortical bone area (p<0.0001), cortical thickness (p<0.0001), cortical bone mineral content (p<0.0001), periosteal perimeter (p<0.0001) and bone strength-strain index (SSI) (p<0.0001). The effects of GH were more marked, and the combination of GH and EX produced additive effects on many of the tibial diaphyseal parameters including bone SSI. GH+EX, but not GH or EX alone caused a significant increase in endocortical perimeter (p<0.0001). In the FR rats, cortical bone area and cortical mineral content increased above the baseline level (p<0.0001) but were below the levels for age-matched controls (p<0.0001). In addition, marrow area, endocortical perimeter and endocortical bone formation rate increased significantly in the FR rats (p<0.01, p<0.0001, p<0.0001). Three-point bending test of right tibial diaphysis resulted in maximum force (Fmax) values that reflected the group differences in indices of tibial diaphyseal bone mass except that GH+EX did not produce additive effect on Fmax. The latter showed good correlation with left tibial diaphyseal SSI (r=0.857, p<0.0001) and both indices of bone strength correlated well with tibial muscle mass (r=0.771, Fmax; r=0.700, SSI; p<0.0001). We conclude that the bone anabolic effects of GH with or without EX may relate, in part, to increased load on bone from tibial muscles and body weight, which were increased by the hormone. The osteogenic effects of EX with or without GH may relate, in part, to increased frequency of muscle load on bone as EX decreased body weight (p<0.05) but had no significant effect on tibial muscle mass. The enhanced loss of endocortical bone by FR may relate, in part, to decreased load on bone due to low body weight (p<0.0001) as FR did not cause a significant decrease in tibial muscle mass (p=0.357). The roles of humoral and local factors in the bone changes observed remain to be established.     

Additive effect of vitamin K2 and risedronate on long bone mass in hypophysectomized young rats.

Hypophysectomy (HX) arrests bone growth and induces osteopenia in the long bones of rats. The present study investigated the combined effect of vitamin K(2) and risedronate on long bone mass in HX rats, in order to determine whether treatment with these two agents had an additive effect. Forty female Sprague-Dawley rats were hypophysectomized at 6 weeks of age by the supplier, and were shipped to our laboratory at three days after surgery along with ten intact rats that served as age-matched controls. The study was started on the day when the rats were received. Three HX rats were excluded from the study because of the failure of HX. Forty-seven rats (6 weeks old) were assigned to the following 5 groups by the stratified weight randomization method: intact controls, HX alone, HX + vitamin K(2) (30 mg/kg, p.o., daily), HX + risedronate (2.5 microg/kg, s.c., 5 days a week), and HX + vitamin K(2) + risedronate. The dosing period was 4 weeks. HX resulted in a decrease of the femoral bone area, bone mineral content (BMC) and bone mineral density (BMD), as well as a decrease in the cancellous bone mass of the proximal tibial metaphysis and the total tissue and cortical areas of the tibial diaphysis. These changes were associated with a marked reduction in the serum level of insulin like growth factor (IGF)-I and with elevation of serum alkaline phosphatase (ALP) and pyridinoline. Administration of vitamin K(2) increased the serum ALP level in HX rats, but did not affect any of the other parameters. On the other hand, risedronate ameliorated the decrease of femoral BMD and cancellous bone mass at the proximal tibial metaphysis in HX rats without affecting the serum IGF-I level, as a result of not causing a significant elevation of serum pyridinoline. Vitamin K(2) and risedronate combined had an additive effect on the femoral bone area, BMC and BMD, and the combined treatment group did not show any significant reduction of the total tissue and cortical areas at the tibial diaphysis, as well as a reduced serum pyridinoline level compared with untreated rats and an increased serum ALP level compared with untreated or risedronate-treated rats. These results suggest that risedronate had a positive effect on the BMD and cancellous bone mass of long bones in HX rats. Despite the lack of a significant effect of vitamin K(2) on bone mass parameters, it had an additive effect with risedronate on the BMC, BMD and cortical bone mass of long bones in HX rats.     

Body mass and stature estimation based on the first metatarsal in humans

Archaeological assemblages often lack the complete long bones needed to estimate stature and body mass. The most accurate estimates of body mass and stature are produced using femoral head diameter and femur length. Foot bones including the first metatarsal preserve relatively well in a range of archaeological contexts. In this article we present regression equations using the first metatarsal to estimate femoral head diameter, femoral length, and body mass in a diverse human sample. The skeletal sample comprised 87 individuals (Andamanese, Australasians, Africans, Native Americans, and British). Results show that all first metatarsal measurements correlate moderately to highly (r = 0.62-0.91) with femoral head diameter and length. The proximal articular dorsoplantar diameter is the best single measurement to predict both femoral dimensions. Percent standard errors of the estimate are below 5%. Equations using two metatarsal measurements show a small increase in accuracy. Direct estimations of body mass (calculated from measured femoral head diameter using previously published equations) have an error of just over 7%. No direct stature estimation equations were derived due to the varied linear body proportions represented in the sample. The equations were tested on a sample of 35 individuals from Christ Church Spitalfields. Percentage differences in estimated and measured femoral head diameter and length were less than 1%. This study demonstrates that it is feasible to use the first metatarsal in the estimation of body mass and stature. The equations presented here are particularly useful for assemblages where the long bones are either missing or fragmented, and enable estimation of these fundamental population parameters in poorly preserved assemblages.     

Body size prediction from juvenile skeletal remains

There are currently no methods for predicting body mass from juvenile skeletal remains and only a very limited number for predicting stature. In this study, stature and body mass prediction equations are generated for each year from 1 to 17 years of age using a subset of the Denver Growth Study sample, followed longitudinally (n = 20 individuals, 340 observations). Radiographic measurements of femoral distal metaphyseal and head breadth are used to predict body mass and long bone lengths are used to predict stature. In addition, pelvic bi-iliac breadth and long bone lengths are used to predict body mass in older adolescents. Relative prediction errors are equal to or smaller than those associated with similar adult estimation formulae. Body proportions change continuously throughout growth, necessitating age-specific formulae. Adult formulae overestimate stature and body mass in younger juveniles, but work well in 17-year-olds from the sample, indicating that in terms of body proportions they are representative of the general population. To illustrate use of the techniques, they are applied to the juvenile Homo erectus (ergaster) KNM-WT 15000 skeleton. New body mass and stature estimates for this specimen are similar to previous estimates derived using other methods. Body mass estimates range from 50 to 53 kg, and stature was probably slightly under 157 cm, although a precise stature estimate is difficult to determine due to differences in linear body proportions between KNM-WT 15000 and the Denver reference sample.     

Body size estimation of small‐bodied humans: Applicability of current methods

Body size (stature and mass) estimates are integral to understanding the lifeways of past populations.Body size estimation of an archaeological skeletal sample can be problematic when the body size or proportions of the population are distinctive. One such population is that of the Holocene Later Stone Age (LSA) of southern Africa, in which small stature (mean femoral length = 407 mm, n = 52) and narrow pelves (mean bi‐iliac breadth = 210 mm, n = 50) produce a distinctive adult body size/shape, making it difficult to identify appropriate body size estimation methods. Material culture, morphology, and culture history link the Later Stone Age people with the descendant population collectively known as the Khoe‐San. Stature estimates based on skeletal “anatomical” linear measures (the Fully method) and on long bone length are compared, along with body mass estimates derived from “morphometric” (bi‐iliac breath/stature) and “biomechanical” (femoral head diameter) methods, in a LSA adult skeletal sample (n = 52) from the from coastal and near‐coastal regions of South Africa. Indices of sexual dimorphism (ISD) for each method are compared with data from living populations. Fully anatomical stature is most congruent with Olivier's femur + tibia method, although both produce low ISD. McHenry's femoral head body mass formula produces estimates most consistent with the bi‐iliac breadth/staturemethod for the females, although the males display higher degrees of disagreement among methods. These results highlight the need for formulae derived from reference samples from a wider range of body sizes to improve the reliability of existing methods. Am J Phys Anthropol, 2010. © 2009 Wiley‐Liss, Inc.     

Body size, body shape, and long bone strength in modern humans

To identify behaviorally significant differences in bone structure it is first necessary to control for the effects of body size and body shape. Here the scaling of cross-sectional geometric properties of long bone diaphyses with different "size" measures (bone length, body mass, and the product of bone length and body mass) are compared in two modern human populations with very different body proportions: Pecos Pueblo Amerindians and East Africans. All five major long bones (excluding the fibula) were examined. Mechanical predictions are that cortical area (axial strength) should scale with body mass, while section modulus (bending/torsional strength) should scale with the product of body mass and moment arm length. These predictions are borne out for section moduli, when moment arm length is taken to be proportional to bone length, except in the proximal femoral diaphysis, where moment arm length is proportional to mediolateral body breadth (as would be expected given the predominance of M-L bending loads in this region). Mechanical scaling of long bone bending/torsional strength is similar in the upper and lower limbs despite the fact that the upper limb is not weight-bearing. Results for cortical area are more variable, possibly due to a less direct dependence on mechanical factors. Use of unadjusted bone length alone as a "size" measure produces misleading results when body shape varies significantly, as is the case between many modern and fossil hominid samples. In such cases a correction factor for body shape should be incorporated into any "size" standardization.     

Impact of Long-Term Exposure to the Tyrosine Kinase Inhibitor Imatinib on the Skeleton of Growing Rats

The tyrosine kinase (TK) inhibitor imatinib provides a highly effective therapy for chronic myeloid leukemia (CML) via inhibition of the oncogenic TK BCR-ABL1. However, off-target TKs like platelet-derived growth factor receptors (PDGF-R) and colony-stimulating factor-1 receptor (c-fms), involved in bone remodeling, are also inhibited. Thus, pediatric patients with CML on imatinib exhibit altered bone metabolism, leading to linear growth failure. As TKI treatment might be necessary for a lifetime, long-term effects exerted on bone in children are of major concern. Therefore, we studied the skeletal long-term effects of continuous and intermittent imatinib exposure in a juvenile rat model.Four-weeks-old male Wistar rats were chronically exposed to imatinib via drinking water over a period of 10 weeks. Animals were exposed to a standard and high imatinib dosage continuously and to the high imatinib dose intermittently. Bone mass and strength were assessed using pQCT, micro-computed tomography (μCT), and biomechanical testing at the prepubertal, pubertal, and postpubertal age. Bone length and vertebral height as well as biochemical markers of bone turnover were analyzed.Femoral and tibial bone length were dose-dependently reduced by up to 24% (p<0.0001), femoral and tibial trabecular bone mass density (BMD) were reduced by up to 25% (p<0.01), and femoral breaking strength was lowered by up to 20% (p<0.05). Intermittent exposure mitigated these skeletal effects. Long-term exposure resulted in reduced vertebral height by 15% and lower trabecular BMD by 5%. Skeletal changes were associated with suppressed serum osteocalcin (p<0.01) and non-significantly elevated serum CTX-I and PINP levels.In conclusion, imatinib mainly impaired longitudinal growth of long bones rather than the vertebrae of growing rats. Interestingly, intermittent imatinib exposure has less skeletal side effects, which may be beneficial in pediatric patients taking imatinib.     

Allometry of head and body size in Holocene foragers of the South African Cape

Opportunities to assess morphological allometry in small-bodied human populations are rare. The foragers of the Later Stone Age of the South African Cape are characteristically small-bodied. Previous studies have shown that during the period of ca. 3500 to 2000 years BP (uncalibrated (14) C dates), the regional population shows transient reduced stature, body mass, and cranial size, a pattern that has been tentatively tied to demographic pressure on resources. This study examines the relationships among cranial size (centroid size) and body size (femoral length, femoral head diameter, and bi-iliac breadth) during the second half of the Holocene (N = 62). Reduced major axis regression indicates negative allometry of cranial centroid size with body size. Residuals (from ordinary least squares regression of cranial centroid size on body size) are regressed on radiocarbon date to examine temporal changes in the relationship between cranial and body size. Cranial and pelvic sizes are most conserved through time, while more ancient skeletons possess shorter femora and smaller femoral heads. The relationship between cranial centroid size and femoral length shows larger and more variable residuals at more recent dates, indicating a greater or more variable disassociation between cranial size and stature relative to more ancient skeletons. A similar, but nonsignificant relationship exists between cranial size and bi-iliac breadth. These results provide insights into the use of aspects of body size and proportionality in the assessment of health in past populations.     

Diaphysator: An online application for the exhaustive cartography and user-friendly statistical analysis of long bone diaphyses

The cross-sectional geometry (CSG) of long bone diaphyses is used in bioanthropology to evaluate their resistance to biomechanical constraints and to infer life-history-related patterns such as mobility, activity specialization or intensity, sexual dimorphism, body mass and proportions. First limited by technical analytical constraints to the analysis of one or two cross sections per bone, it has evolved into the analysis of cross sections of the full length of the diaphyseal part of long bones. More recently, researchers have developed analytical tools to map the cortical thickness of entire diaphyses to evaluate locomotor signatures. However, none of these analytical tools are easy to use for scientists who are not familiar with computer programming, and some statistical procedures–such as mapping the correlation coefficients of the diaphyseal thickness with various parameters have yet to be made available. Therefore, we developed an automated and open-source application that renders those analyses (both CSG and cortical thickness) in a semiautomated and user friendly manner. This application, called “Diaphysator”, is associated with another free software (“Extractor”, presented in Dupej et al. (2017). American Journal of Physical Anthropology, 164, 868–876). Diaphysator can be used as an online application ( https://diaphysator.shinyapps.io/maps ) or as a package for R statistical software. Along with the mean maps of cortical thickness and mean CSG parameter graphs, the users can evaluate the correlations and partial correlations of both CSG parameters at every cross section along the diaphyseal length, and cortical thickness data points of the entire diaphysis, with any factor such as age, sex, stature, and body mass.     

A comparison of cortical bone thickness in the femoral midshaft of humans and two non-human mammals

Fragments of bone shafts that lack diagnostic features can be difficult to identify as human or non-human—an important task in forensic science and archaeology. Some workers have found the thickness of cortical bone in the shaft to be a useful distinction, although the sparse literature in the field is contradictory in how this may be applied.The aim of the present study was to determine whether any difference is discernible between humans, kangaroos and sheep (mammals whose remains are commonly confused with those of humans in Australia) at the femoral midshaft, with a view to a larger-scale analysis if differences were discovered. Cross-sections at the midpoint of the shaft were measured to determine the diameter of the whole shaft and the medullary cavity on each bone; an index describing cortical thickness relative to shaft diameter was calculated. Statistically significant differences were found between all three groups, with humans showing the thickest cortical bone, and sheep the thinnest. These differences may be linked to a higher load on the human femur, due to a larger body mass carried on two legs, as opposed to the sheep's four. Further work now needs to be carried out to determine if differences are present when comparing multiple sites on the skeleton, and between non-human mammals of different sizes.     

Bone growth, modeling and remodeling in a supernumerary metatarsal bone associated with segmental gigantism in cutis marmorata telangiectatica congenita

Skeletal structure and processes of bone growth, modeling and remodeling were studied in a supernumerary metatarsal surgically removed from a 3-year-old boy affected by Cutis Marmorata Telangiectatica Congenita (CMTC), associated with hypertrophy of the right upper and lower limbs and postaxial hexadactylism of the homolateral hand and foot. No other anomalies were observed. The excess of periosteal growth, due to congenital anomaly, induced an abnormal development of both modeling and remodeling processes. In bone modeling, osteoblast activity on the periosteal surface was not paralleled by osteoclast resorption along the wall of the medullary canal, and this enormously increased the cortical thickness. In bone remodeling, osteoclastic resorption cavities were not refilled by secondary Haversian systems, thus inducing a severe bone loss. While the alteration of bone growth and modeling can be ascribed to the congenital disease, the unbalanced bone remodeling appears mainly to depend on mechanical disuse of the supernumerary metatarsal.     

Neandertal knees: power lifters in the Pleistocene?

It has been proposed (Trinkaus, 1983 a; Miller & Gross, 1998) that the marked thickness of Neandertal patellae and/or the posterior displacement of their tibial condyles increased their relative M. quadriceps femoris moment arms, thereby making their legs powerful in extension. However, it is necessary to compare these reflections of muscle moment arm length to appropriate measures of the body weight moment arm and body mass estimates, both of which are influenced by ecogeographically determined body proportions. Reassessment of tibial condylar displacement and patellar thickness, as well as patellar height, relative to an appropriate measure of the moment arm for the baseline load on the knee (body weight), to that moment arm times estimated body mass, and to that moment arm times a skeletal reflection of body mass (femoral head diameter) rejects the hypothesis that the Neandertals had exceptionally powerful knee extension. Relative tibial condylar displacement remains above that of a modern industrial society sample, but similar to that of the Broken Hill tibia, Late Pleistocene early modern humans and a recent human nonindustrial sample. Relative patellar thickness is similar to that of early modern humans, who have relatively thick patellae compared to the late Holocene human samples. Consequently, once body proportions are taken into account, there is little difference between the Neandertals and other later Pleistocene humans in knee extensor mechanical advantage, and all of these fossil hominids are similar in the more important proximal tibial proportions to those of nonindustrial recent humans.     

Skeletal growth and the changing genetic landscape during childhood and adulthood

Growth, development, and decline of the human skeleton are of central importance to physical anthropology. All processes of skeletal growth (longitudinal growth as well as gains and losses of bone mass) are subjected to environmental and genetic influences. These influences, and their relative contributions to the phenotype, can be asserted at any stage of life. We present here the gross phenotypic and genetic landscapes of four skeletal traits, and show how they vary across the life span. Phenotypic sex differences are found in bone diameter and cortical index (a ratio of cortical thickness over bone diameter) at a very early age and continue throughout most of life. Sexual dimorphism in summed cortical thickness and bone length, however, is not evident until shortly after the pubertal growth spurt. Genetic contributions (heritability) to these skeletal phenotypes are generally moderate to high. Bone length and bone diameter (which both scale with body size) tend to have the highest heritability, with heritability of bone length fairly stable across ages (with a notable dip in early childhood) and that of bone diameter peaking in early childhood. The bone traits summed cortical thickness and cortical index that may better reflect bone mass, a more plastic phenomenon, have slightly lower genetic influences, on average. Results from our phenotypic and genetic landscapes serve three key purposes: 1) demonstration of the integrated nature of the genetic and environmental underpinnings of skeletal form, 2) identification of periods of bone's relative sensitivity to genetic and environmental influences, 3) and stimulation of hypotheses predicting the effects of exposure to environmental variables on the skeleton, given variation in the underlying genetic architecture. Am J Phys Anthropol, 2013. © 2012 Wiley Periodicals, Inc.     

Gender specific LRP5 influences on trabecular bone structure and strength

A mutation in LRP5 (low-density lipoprotein receptor-related protein 5) has been shown to increase bone mass and density in humans and animals. Transgenic mice expressing the LRP5 mutation (G171V) demonstrate an increase in bone mass as compared to non-transgenic (NTG) littermates. This study evaluated LRP5 gene and gender-related influences on the structural and biomechanical strength properties of trabecular and cortical bone in femurs and vertebrae (L5) of 17-week-old mice. Micro-computed tomography was used to evaluate the trabecular bone structure of distal femurs and vertebrae ex vivo. Mechanical testing of the trabecular bone in the distal femur was done to determine biomechanical strength. Differences due to genotype and gender were tested using two-way ANOVA at a significance level of p<0.05. Trabecular bone structural parameters (BV/TV, trabecular thickness, number, etc.) at the distal femur, femoral neck, and vertebral body sites were greater in the transgenic as compared to the NTG mice. In addition, vertebral cortical thickness and trabecular strength parameters (ultimate and yield loads, stiffness, ultimate and yield stresses) in the distal femur were greater in the transgenic mice as compared to NTG. The increasing trends of cortical thickness were also noted in the transgenic mice as compared to NTG. Within LRP5 (G171V) mutant mice, there were significant gender-related differences in some of the trabecular bone structural parameters at all the sites (distal femur, femoral neck, and vertebral body). However, unlike trabecular structural parameters, the gender-specific differences were not found in the trabecular strength of LRP5 transgenic mice. In summary, these findings suggest that the LRP5 (G171V) mutation results in greater trabecular bone structure and strength at both the distal femurs and vertebral bodies as compared to NTG. In addition, only the trabecular structure parameters were affected by gender within the LRP5 (G171V) mutation.