Quantitative trait loci for bone lengths on chromosome 5 using dual energy X-Ray absorptiometry imaging in the Twins UK cohort

Human height is a highly heritable and complex trait but finding important genes has proven more difficult than expected. One reason might be the composite measure of height which may add heterogeneity and noise. The aim of this study was to conduct a genome-wide linkage scan to identify quantitative trait loci (QTL) for lengths of spine, femur, tibia, humerus and radius. These were investigated as alternative measures for height in a large, population-based twin sample with the potential to find genes underlying bone size and bone diseases. 3,782 normal Caucasian females, 18-80 years old, with whole body dual energy X-ray absorptiometry (DXA) images were used. A novel and reproducible method, linear pixel count (LPC) was used to measure skeletal sizes on DXA images. Intraclass correlations and heritability estimates were calculated for lengths of spine, femur, tibia, humerus and radius on monozygotic (MZ; n = 1,157) and dizygotic (DZ; n = 2,594) twins. A genome-wide linkage scan was performed on 2000 DZ twin subjects. All skeletal sites excluding spine were highly correlated. Intraclass correlations showed results for MZ twins to be significantly higher than DZ twins for all traits. Heritability results were as follows: spine, 66%; femur, 73%; tibia, 65%; humerus, 57%; radius, 68%. Results showed reliable evidence of highly suggestive linkage on chromosome 5 for spine (LOD score = 3.0) and suggestive linkage for femur (LOD score = 2.19) in the regions of 105cM and 155cM respectively. We have shown strong heritability of all skeletal sizes measured in this study and provide preliminary evidence that spine length is linked to the chromosomal region 5q15-5q23.1. Bone size phenotype appears to be more useful than traditional height measures to uncover novel genes. Replication and further fine mapping of this region is ongoing to determine potential genes influencing bone size and diseases affecting bone.     

Medieval trabecular bone architecture: the influence of age, sex, and lifestyle

Osteoporosis has become a growing health concern in developed countries and an extensive area of research in skeletal biology. Despite numerous paleopathological studies of bone mass, few studies have measured bone quality in past populations. In order to examine age- and sex-related changes in one aspect of bone quality in the past, a study was made of trabecular bone architecture in a British medieval skeletal sample. X-ray images of 5-mm-thick coronal lumbar vertebral bone sections were taken from a total of 54 adult individuals divided into three age categories (18-29, 30-49, and 50+ years), and examined using image analysis to evaluate parameters related to trabecular bone structure and connectivity. Significant age-related changes in trabecular bone structure (trabecular bone volume (BV/TV), trabecular number (Tb.N), trabecular separation (Tb.Sp), and anisotropic ratio (Tb.An)) were observed to occur primarily by middle age with significant differences between the youngest and two older age groups. Neither sex showed continuing change in trabecular structure between the middle and old age groups. Age-related changes in bone connectivity (number of nodes (N.Nd) and node-to-node strut length (Nd.Nd)) similarly indicated a change in bone connectivity only between the youngest and two older age groups. However, females showed no statistical differences among the age groups in bone connectivity. These patterns of trabecular bone loss and fragility contrast with those generally found in modern populations that typically report continuing loss of bone structure and connectivity between middle and old age, and suggest greater loss in females. The patterns of bone loss in the archaeological samples must be interpreted cautiously. We speculate that while nutritional factors may have initiated some bone loss in both sexes, physical activity could have conserved bone architecture in old age in both sexes, and reproductive factors such as high parity and extended periods of lactation could have played a key role in female bone maintenance in this historic population. The study of qualitative elements (such as trabecular architecture) is vital if we are to understand bone maintenance and fragility in the past.     

Correlation of bone mineralization in the radius and humerus of well premature neonates over the first 4 months of life

To determine how well mineralization correlates in the radius and humerus of neonates, we have measured with photon absorptiometry the bone mineral content (BMC) and bone width (BW) in the humerus and radius of well premature neonates and in the radius alone of well term neonates at birth, 8 and 16 weeks of age. These data allow (1) the correlation of bone mineralization in the humerus and radius at birth and over the first 4 months of life and (2) the correlation between bone mineralization in the radius or humerus at birth and that measured at 8 and 16 weeks in the same bone site. The BMC of the radius was significantly (P < 0.02) correlated with the BMC of the humerus at birth, 8 and 16 weeks, but the BW of the radius was significantly correlated with the BW of the humerus only at 16 weeks. On the other hand, the BMC of the radius at birth in both term and premature neonates failed to correlate significantly (P = ns) with the BMC of the radius at 8 or 16 weeks. In the humerus, the BMC at birth was significantly (P < 0.001) correlated with that measured at 8 but not at 16 weeks. These data indicate that the humerus and radius increase in mineral content at a similar rate over the first 4 months of life but that one cannot accurately predict from the BMC at birth what the bone mineral content will be at 8 and 16 weeks of age.     

Palaeopathology of human remains from the Roman Imperial Age

The increasing attention of archaeological and anthropological research towards palaeopathological studies has allowed to focus the examination of many skeletal samples on this aspect and to evaluate the presence of many diseases afflicting ancient populations. This paper describes the most interesting diseases observed in skeletal samples from five necropolises found in urban and suburban areas of Rome during archaeological excavations in the last decades, and dating back to the Imperial Age. The diseases observed were grouped into the following categories: articular diseases, traumas, infections, metabolic or nutritional diseases, congenital diseases and tumors, and some examples are reported for each group. Although extensive epidemiological investigation in ancient skeletal records is impossible, palaeopathology allowed highlighting the spread of numerous illnesses, many of which can be related to the life and health conditions of the Roman population.     

A method for estimating age of Danish medieval sub-adults based on long bone length

The preferred method for aging archaeological sub-adult skeletons is by dental examination. In cases where no dental records are available, age estimation may be performed according to epiphyseal union, skeletal elements or diaphyseal lengths. Currently no data have been produced specifically for aging archaeological Danish sub-adults from the medieval period based on diaphyseal lengths. The problem with using data on Danish samples, which have been derived from a different population, is the possibility of skewing age estimates. In this study 58 Danish archaeological sub-adults were examined, aged from approximately six years to twenty-one years. The samples were aged according to two dental methods: Haavikko and Ubelaker. Regression formulae were constructed for aging according to their diaphyseal lengths both for individual long bones and combinations of upper and lower long bones. This study indicated that with the regression formulae developed, estimation of age can be done with reasonable results on Danish sub-adults. The Danish data were then compared to data from a different archaeological sample and a modern sample. It showed that the modern data indicated a consistently lower age compared to this sample which increased until reaching a maximum of nearly five years and six months. When comparing the archaeological data to this study, the growth profile crossed over at 12.5 years with a maximum age difference before the cross point of two years and three months lower for the archaeological data. After the cross point there was a maximum difference of three years and four months higher for the archaeological data. This study has shown the importance of using data for age estimation for archaeological material which has been developed specifically for that population. In addition it has presented a possible solution for Danish sub-adult material when dental material is not available.     

Comparison of child morbidity in two contrasting medieval cemeteries from Denmark

This study compares associations between demographic profiles, long bone lengths, bone mineral content, and frequencies of stress indicators in the preadult populations of two medieval skeletal assemblages from Denmark. One is from a leprosarium, and thus probably represents a disadvantaged group (Naestved). The other comes from a normal, and in comparison rather privileged, medieval community (AEbelholt). Previous studies of the adult population indicated differences between the two skeletal collections with regard to mortality, dental size, and metabolic and specific infectious disease. The two samples were analyzed against the view known as the "osteological paradox" (Wood et al. [1992] Curr. Anthropol. 33:343-370), according to which skeletons displaying pathological modification are likely to represent the healthier individuals of a population, whereas those without lesions would have died without acquiring modifications as a result of a depressed immune response. Results reveal that older age groups among the preadults from Naestved are shorter and have less bone mineral content than their peers from AEbelholt. On average, the Naestved children have a higher prevalence of stress indicators, and in some cases display skeletal signs of leprosy. This is likely a result of the combination of compromised health and social disadvantage, thus supporting a more traditional interpretation. The study provides insights into the health of children from two different biocultural settings of medieval Danish society and illustrates the importance of comparing samples of single age groups.     

Cortical bone maintenance and geometry of the tibia in prehistoric children from Nubia's Batn el Hajar

The relationship between advancing age in adults and patterns of cortical bone maintenance has been extensively documented for archaeological populations (Dewey, et al., 1969; Van Gerven et al., 1969; Perzigian, 1973). Most recently, this research has been expanded to include a more thorough consideration of the geometric properties of bone in relationship to adult age changes (Martin and Atkinsin, 1977; Ruff and Hayes, 1983). To date, however, few studies have documented subadult patterns of cortical bone maintenance in archaeological populations and none have incorporated the relationship between patterns of cortical bone loss and gain and the changing geometric properties of growing bone. Using a sample of 172 tibias from children excavated from the Medieval Christian site of Kulubnarti, located in Nubia's Batn el Hajar, the present research examines the relationship between percent cortical area, bone mineral content, and cross-sectional moments of inertia. Among these children, bone mineral content increases steadily from birth in spite of a reduction in percent cortical area during early and late childhood. It appears, therefore, that tissue quality of the bone is not adversely affected by the reduction. Furthermore, the reduction in percent cortical area in later childhood corresponds to a dramatic increase in bending strength measured by cross-sectional moments of inertia. Thus, whether this cortical reduction is due entirely or in part to either normal modeling or nutritional stress, the tissue and organ quality of the bone is not adversely affected.     

Cortical bone loss with age in three native American populations

Age-related thinning of cortical bone was investigated in archaeological populations of Eskimos, Pueblos, and Arikaras. Medial-lateral cortical thickness was measured on radiographs of humerus and femur, and thickness of the anterior femoral cortex was measured directly on samples taken for histologic study. Maximum length of the bones was used to calculate indices of relative cortical thickness, in order to minimize differences due to body size and build. Bone loss in the humerus begins before middle age in all three populations and, except for Eskimo males, the same is true of the anterior femoral cortex. In general, overall female loss of cortical bone amounts to two or three times that of the males, and in the case of the humerus and the anterior cortex of the femur, this difference is evident by middle age. The weight-bearing femoral medial-lateral cortex shows less sexual difference but has the greatest number of statistically significant differences between populations and the greatest contrast between populations in pattern of loss with age. It appears that of the cortical regions studied this is the area upon which environmental factors have the greatest effect, whereas areas more subject to tensile stress, the humerus and anterior femoral cortex, are less affected by these factors.     

Estimation of stature and body mass from the skeleton among coastal and mid-altitude Andean populations

Adult stature and body mass represent fundamental biological characteristics of individuals and populations, as they are relevant to a range of problems from assessing nutrition and health to longer term evolutionary processes. Stature and body mass estimation from skeletal dimensions are therefore key to addressing biological and social questions about past populations. Anatomical reconstruction provides the most direct proxy for living stature but is only suitable for well-preserved remains. Regression equations for estimating stature from bone lengths are therefore extremely useful, though it is well recognized that differences in body proportions limit the cross-application of equations between samples. Here, we assess the accuracy of published stature estimation equations from worldwide and New World groups applied to archaeological samples from the central Andean coast and highlands of South America. As no existing equations are clearly appropriate, new sample-specific regression equations are presented. Anatomical stature reconstruction is further complicated by artificial cranial modification (ACM) influencing cranial height in Andean samples, so this problem is investigated in the current sample. Although ACM has minimal impact here, the possibility should be explored in other samples before anatomical stature estimation is attempted. Recommendations are also made for estimating body mass from femoral head diameter. The mean of three previously published equations is shown to offer minimal bias and the most reliable estimate of body mass in the study samples.     

Developmental stability and canalization of limb bones of brown haresLepus europaeus with varying levels of heterozygosity

We have studied fluctuating asymmetry (FA), as indicator of developmental stability, and between-individual variation, as surrogate of developmental canalization (DC), in long bones (humerus, ulna, radius, femur, tibia) of 72 wild-living adult-sized brown haresLepus europaeus Pallas, 1778 with variable individual heterozygosity (H).H was calculated from 13 polymorphic allozyme loci. According to the “over-dominance hypothesis”, we expected increased developmental stability and canalization at higherH-levels. But at the individual level we did not find any significant correlation between overall FA (FA_I) andH. Also, standard deviations (SD) of mean length (over both body sides) of bones did not differ between individuals from two intentionally created groups of hares, namely one with high and one with lowH. FA-indices and variances of FA-indices of bone lengths did not differ significantly when compared between two intentionally created groups of hares with high and low SD of bone lengths, respectively. These latter findings suggest that developmental stability and DC are two separate or partly separate mechanisms of developmental homeostasis in the studied appendicular skeleton, and thatH has no traceable effect on develop-mental homeostasis. If there is still such an effect, it should be clearly smaller than a possibly combined effect of (presently uncontrolled) environmental stressors.     

Effects of simulated increases in body weight on the growth of limb bones in hypophysectomized rats

The purpose of this study was to subject groups of hypophysectomized male and female rats each to a simulated specific 10% increase in body weight, to a maximum of a doubling of body weight, in order to study the effects of quantified, increased, intermittent, compressive forces on limb bone growth. Chronic centrifugation was employed. 21-day-old Sprague-Dawley rats were used. After 60 days of centrifugation, the rats were sacrificed. The humerus, radius, ulna, femur and tibia were removed from each animal, cleared of all soft tissues, and the bone lengths measured on Helios calipers with an accuracy of 1/20 mm. The data were corrected for differences due to individual body weight by dividing bone lengths by the cube root of the body weight of the same animal. Tukey's studentized multiple-range test was performed to identify aggregations (sets) of force groups between which there are significant differences. The data suggest that the simulated increases in body weight, within the range used for this study, enhance bone growth in hypophysectomized female and male rats similarly - hypophysectomy being a condition known to inhibit bone growth.     

Differential long bone growth of children between two months and eleven years of age

Diaphyseal lengths of the humerus, radius, femur and tibia of upper-middle class White children between two months and 11 years of age show positive allometric growth, indicating substantial shape or proportional change. The segments of the lower extremity display greater allometric increase than the humerus and radius; variation in relative growth within each extremity is small and inconsistent. Sex differences are consistent, with slightly greater proportional increases demonstrated for boys. The results suggest that absolute intralimb variation in growth, following a disto-proximo growth or maturity gradient, is due to initial differences in size or scale and not to differences in patterns of growth. Developmental variation between extremities is due to scaling plus variation in relative growth patterns.     

Allometry of cetacean forelimb bones

This study examines the allometric scaling relationships of the cetacean humerus, radius, and ulna. Bone lengths and diameters were measured for 20 species of odontocete and three species of mysticete cetaceans, representing eight of the nine extant cetacean families. The scaling of individual bone proportions (bone length vs. cranio-caudal diameter, bone length vs. dorso-ventral diameter), and of individual bone dimensions against estimated body mass, are compared to models of geometric and elastic similarity. The geometric similarity model describes the scaling relationship of bone length vs. cranio-caudal diameter and body mass vs. cranio-caudal diameter for the humerus only; geometric similarity also describes the scaling relationship of body mass vs. bone length for all three bones. None of the scaling relationships fits the elastic similarity model. The scaling relationships of bone length vs. dorso-ventral diameter for all three bones, and bone length vs. cranio-caudal diameter for the radius and ulna, exhibit negative allometry, indicating that large bones are less robust than small bones. Negative allometry of structural support elements has not been previously described for terrestrial mammals or plants. The high relative swimming speeds of small delphinids may generate sufficient stresses to require more robust bones relative to those of larger whales. © 1994 Wiley-Liss, Inc.     

Bone length and muscle weight in mice subjected to genetic selection for the relative length of the tibia and radius

Mice which had undergone 5 generations of selection for high and low values of the tibia length/radius length ratio were compared with unselected controls at 10 weeks of age. The ratio responded to selection in both directions. The length of the radius was increased in the low line while the response in the high line was due to an increase in the length of the tibia and a small but statistically insignificant decrease in radius length. High and low line mice were heavier than the controls. The responses of the tibia and femur and of the radius and humerus were generally similar, suggesting the existence of an association between the genetic control of the lengths of the bones of a limb. There were also correlated responses in the weight of the tibialis anterior, biceps brachii and sternomastoid, and there is some evidence to suggest that the weight of a muscle may be influenced by the length of a bone to which it is attached.     

Diachronic patterns of change in structural properties of the femur in the prehistoric American Southwest

Diachronic patterns of change in the femoral diaphysis are examined in archaeological skeletal samples from the American Southwest. Three cultural periods differing in subsistence-settlement strategies are represented: Early Villages (A.D. 500-1150), Abandonments (A.D. 1150-1300), and Aggregated Villages (A.D. 1300-1540). Relevant properties of cross-sectional geometry and bone density were obtained using computerized tomography. Temporal trends in geometry suggest that activity levels increased between Early Villages and Abandonments, then declined during Aggregated Villages. In both sexes, femoral shape became more circular, and bending stresses were reduced in the a-p plane through time. Compared to the other periods, bone density was the lowest during Abandonments in both sexes. The reduction in bone density may reflect declining nutritional quality through time that was especially poor during the Abandonments period. Patternings in sexual dimorphism suggest that Abandonments males may have been more sensitive to nutritional stress than contemporary females.     

Skeletal manifestations of hypothyroidism from Switzerland

Hypothyroidism is caused by a deficiency in the synthesis of thyroid hormone. Dwarfism is the most obvious skeletal manifestation, but most people with hypothyroidism do not have any skeletal evidence of the disease. When the skeleton is affected, the severity of this manifestation depends on the degree of the deficiency and age of onset. Endemic hypothyroidism typically is linked to specific ecological settings such as the high mountains where iodine is absent, or else it occurs with very low concentrations in water and soil. In these areas, the prevalence may be as high as 8%. The disease can be expected to occur in archaeological human skeletal samples from endemic regions. Sporadic hypothyroidism is caused by a deficiency in the thyroid gland itself, and is not linked to any specific environmental context. The disease may be the result of a genetic defect, but can also be caused by other pathological conditions that may affect the thyroid gland, including infection and cancer. The skeletal abnormalities of the two variants will be indistinguishable in archaeological human remains. In order to identify hypothyroidism in archaeological skeletal samples, one must be aware of the differences in pathological skeletal changes seen in hypothyroidism in comparison with other diseases, such as achondroplasia, that can cause similar abnormalities. Twelve clinically documented cases of hypothyroidism provide data for understanding the skeletal abnormalities associated with this disease. All 12 are modern documented cases from Switzerland, where endemic hypothyroidism occurred in the iodine-deficient Alpine regions. However, at least one case in the sample was caused by a defect in the thyroid gland itself.     

Scaling of the appendicular skeleton of the giraffe (Giraffa camelopardalis)

Giraffes have remarkably long and slender limb bones, but it is unknown how they grow with regard to body mass, sex, and neck length. In this study, we measured the length, mediolateral (ML) diameter, craniocaudal (CC) diameter and circumference of the humerus, radius, metacarpus, femur, tibia, and metatarsus in 10 fetuses, 21 females, and 23 males of known body masses. Allometric exponents were determined and compared. We found the average bone length increased from 340 ± 50 mm at birth to 700 ± 120 mm at maturity, while average diameters increased from 30 ± 3 to 70 ± 11 mm. Fetal bones increased with positive allometry in length (relative to body mass) and in diameter (relative to body mass and length). In postnatal giraffes bone lengths and diameters increased iso‐ or negatively allometric relative to increases in body mass, except for the humerus CC diameter which increased with positive allometry. Humerus circumference also increased with positive allometry, that of the radius and tibia isometrically and the femur and metapodials with negative allometry. Relative to increases in bone length, both the humerus and femur widened with positive allometry. In the distal limb bones, ML diameters increased isometrically (radius, metacarpus) or positively allometric (tibia, metatarsus) while the corresponding CC widths increased with negative allometry and isometrically, respectively. Except for the humerus and femur, exponents were not significantly different between corresponding front and hind limb segments. We concluded that the patterns of bone growth in males and females are identical. In fetuses, the growth of the appendicular skeleton is faster than it is after birth which is a pattern opposite to that reported for the neck. Allometric exponents seemed unremarkable compared to the few species described previously, and pointed to the importance of neck elongation rather than leg elongation during evolution. Nevertheless, the front limb bones and especially the humerus may show adaptation to behaviors such as drinking posture. J. Morphol. 276:503–516, 2015. © 2014 Wiley Periodicals, Inc.     

Hibernation does not reduce cortical bone density,area or second moments of inertia in woodchucks (Marmota monax)

Long periods of inactivity in most mammals result in bone loss that may not be completely recoverable during an individual's lifetime regardless of future activity. Prolonged inactivity is normal during hibernation, but it remains uncertain whether hibernating mammals suffer decreased bone properties after hibernation that affects survival. We test the hypothesis that relative cortical area (C_A), apparent density, bone area fraction (B.Ar/T.Ar), and moments of inertia do not differ between museum samples of woodchucks (Marmota monax) collected before and after hibernation. We used peripheral quantitative computed tomography to examine bone geometry in the femur, tibia, humerus and mandible. We see little evidence for changes in bone measures with hibernation supporting our hypothesis. In fact, when including subadults to increase sample sizes and controlling age statistically, we observed a trend toward increased bone properties following hibernation. Diaphyses were significantly denser in the humerus, femur, and tibia after hibernation, and relative mandibular cortical area was significantly larger. Similarly, relative mechanical indices were significantly larger in the mandible after hibernation. Although tests of individual measures in many cases were not significantly different prehibernation versus posthibernation, the overall pattern of average increase posthibernation was significant for relative C_A and densities as well as relative diaphyseal mechanical indices when examining outcomes collectively. The exception to this pattern was a reduction in metaphyseal trabecular bone following hibernation. Individually, only humeral B.Ar/T.Ar was significantly reduced, but the average reduction in trabecular measures post‐hibernation was significant when examined collectively. Because the sample included subadults, we suggest that much of the increased bone relates to their continued growth during hibernation. Our results indicate that woodchucks are more similar to large hibernators that maintain skeletal integrity compared to smaller‐bodied hibernators that may lose bone. This result suggests a potential size‐related trend in bone response to hibernation across mammals. J. Morphol., 2012. © 2012Wiley Periodicals, Inc.     

The correlation of bone robusticity with the perforation of the coronoid-olecranon septum in the humerus of man

Hrdli?ka ('32) theorized that the tendency towards perforation of the coronoid-olecranon septum of the humerus was phylogenetic in origin, but its appearance also seemed to be negatively correlated with bone size. By determining the correlation between the occurrence of the perforation and certain standard anthropometric measurements, the present study provides a statistical tool to test Hrdli?ka's hypothesis more rigorously. The minimum middle diameter of the humerus is shown to be significantly related to the occurrence of septal perforation, in samples of archeological skeletal material. Using the minimum middle diameter of the humerus as a quantitative assessment of robusticity, more robust samples were found to have smaller mean percentages of perforation.     

Black rats (Rattus rattus) from medieval Mertola (Baixo Alentejo, Portugal)

This paper is about the analysis and interpretation of micromammal samples from archaeological sites while reporting on a black rat assemblage from XIII^th century Muslim levels in the city of Mertola. Questions concerning skeletal representation, size plus age estimations and bone fragmentation are discussed from a taphonomic standpoint. It is concluded that the tendency to interpret rodent accumulations in anthropic sites as evidence of preybird activities might be an oversimplification in need of substantial revision.