Female biological resiliency: Differential stress response by sex in human remains from ancient Nubia

This research presents male-female differences in stress response evidenced in human remains from the Medieval site of Kulubnarti in Sudanese Nubia. This analysis is unique in that a direct comparison of subadult males and females is rarely possible using archaeological remains. Rather, such analyses invariably rely on evidence of subadult differences retained in adult (sexable) skeletons. In the case of Kulubnarti, natural mummification has made it possible to measure sex-specific differences among subadults as well as adults following five avenues of investigation: 1) mortality, 2) growth and development, 3) enamel hypoplasia, 4) cribra orbitalia, and 5) cortical bone maintenance. A comparison of mean life expectancy (eox) values for males and females aged 10–55+ years revealed a consistent pattern of greater female survivorship, particularly in childhood (age 10 category) where female life expectancy exceeds that of males by 19%. Measures of growth and development, enamel hypoplasia, cribra orbitalia, and cortical bone loss were subsequently used to test a hypothesis of greater female resiliency based on the mortality data. Male-female differences in skeletal maturation are pronounced with male skeletal ages averaging a significant 2.9 years below their dental age. Females show no significant differences with an average skeletal age 0.75 years ahead of dental age. Males begin hypoplasia formation one year earlier than females and, prior to age four, average 18% more hypoplasias (p<0.05). Also, by age 8, males have on average more than twice the frequency of cribra orbitalia (p<0.05). In contrast to their consistent pattern of reduced childhood stress, adult females lose significantly more cortical bone than their male counterparts and have less cortical bone across the adult age range. Nevertheless, females outnumber males of all ages with a sex-ratio below but parallel to that observed in modern populations. The rapid age-related reduction in males relative to females, even in old age, suggests a continuing female resiliency in spite of their greater rate of osteopenia and may reflect a reproductive advantage to the population through heightened female survival and adaptability.     

Morphometrics of compact bone: an example from Sudanese Nubia.

Morphometric analysis of compact femoral tissue was applied to a prehistoric population from Sudanese Nubia. Microradiographs of thin sections from below the lesser trochanter were examined. A total of 74 adults (40 females, 34 males) from the X-Group population (A.D. 350–550) were used to determine the underlying processes of bone remodeling in skeletal growth and maintenance. The relationship of bone turnover to the age of onset, patterning and frequency of cortical bone loss (osteoporosis) as a function of age and sex was examined. The cortical thickness, cortical area and formation/resorption frequencies were determined. Males exhibit a 4.9% net loss in cortical area, while females show a 10.7% loss. A substantial amount of female loss occurs in the third decade, with a slight gain in the fourth and a steady loss up to the sixth decade. These trends were further explored and refined histologically. The periosteal and endosteal frequencies for males show a variable but definite decrease in mineralization (i.e., increased numbers of osteons in the forming stage) and a slight increase in resorption. Third decade females show a marked difference with high frequencies of resorption spaces and forming osteons. It is suggested that in this population, stress related to childbearing and childrearing may be effecting the frequencies of formation foci and resorption spaces.     

Trabecular involution in femoral heads of a prehistoric (X-group) population from Sudanese Nubia

An analysis of trabecular bone in the head of the femur of 33 males and 40 females from a prehistoric X-Group population from Sudanese Nubia indicates that as age increases from 17 to 50+ years loss of trabecular bone in males (16.01%) is greater than loss in females (13.47%). These results differ from previous studies of cortical bone and ash density of femoral head trabeculae which demonstrate a greater loss in females. An analysis of the differential reaction in the two trabecular systems reveals that principal tensile group trabeculae decrease in thickness with age while principal compressive group trabeculae show an increase with age.     

Changes in femoral morphology during egg-laying in Alligator mississippiensis

Birds and many reptiles are egg-layers. Birds provide calcium for the formation of eggshells by resorbing medullary bone, which is laid down before ovulation. Turtles do not possess this mechanism and resorb structural bone to form eggshells. Femora from three groups of alligators (egg-laying females; quiescent, immature, or barren females; and males) were examined to determine if alligators, which are closely related to birds in evolution, resorb structural bone during the formation of eggshells as do turtles. Microradiographs of cross sections from femoral mid-shafts were analyzed for porosity, and the robusticity index of each femur was determined. Scanning electron micrographs of anorganic endosteal and periosteal femoral surfaces were analyzed to determine numbers of entrances of vascular canals, numbers of lacunae of osteoblasts, and types of femoral surfaces. Femora from egg-laying females were significantly less robust than those of other females or males, and sections of bone from the egg-layers were significantly more porous than those of the other groups. Scanning electron microscopy of anorganic femoral endosteal surfaces from egg-laying females revealed significantly more resorption areas when compared with males or non egg-laying females. Periosteal surfaces from egg-layers had significantly more resting and less bone-forming surface than those from the other groups. Results indicated that apposition of periosteal bone may have been reduced in egg-layers and that egg-laying alligators, like turtles, resorb endosteal structural bone, which may be used as a source of calcium for the formation of eggshells.     

Hand dominance and bilateral asymmetry in the structure of the second metacarpal

Bilateral asymmetry in the structure of the second metacarpal was examined in relation to functional hand dominance in a large, clinically nonselected, healthy population sample from the Baltimore Longitudinal Study of Aging. Bilateral bone measurements were made from anteroposterior hand radiographs of a total of 992 individuals, 609 males and 383 females, with an age range of 19–94 years. Hand dominance was determined on the basis of personal impression. Total width and medullary width at the midshaft of the second metacarpal were measured to 0.05 mm using a Helios caliper. These two measurements were used to derive cortical thickness, cortical bone area, periosteal (total) area, medullary area, percent cortical area, and the second moment of area in the mediolateral plane. In both right and left-handed individuals, statistically significant side differences were found in the calculated bone areas and the second moment of area, with the dominant hand being larger. Cortical thickness did not show significant side-related differences for either handedness. These results show that functional handedness leads to periosteal and endosteal expansion of the second metacarpal cortex on the dominant side, increasing bone strength without increasing cortical thickness. This is the first time this pattern of asymmetry has been reported in left-handers as well as right-handers. Our results argue for the primacy of environmental (mechanical) effects in determining bilateral asymmetry of limb bone structural properties. © 1994 Wiley-Liss, Inc.     

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.     

Preservation of femoral bone thickness in middle age predicts survival in genetically heterogeneous mice

To see whether age-related changes in bone could predict subsequent lifespan, we measured multiple aspects of femur size and shape at 4, 15, and 24 months of age in genetically heterogeneous mice. Mice whose cortical bone became thicker from 4 to 15 months, associated with preservation of the endosteal perimeter, survived longer than mice whose endosteal cavity expanded, at the expense of cortical bone, over this age range. Femur size at age 4 months was also associated with a difference in life expectancy: mice with larger bones (measured by length, cortical thickness, or periosteal perimeter) had shorter lifespans. Femur length, midlife change in cortical bone thickness, and midlife values of CD8 T memory cells each added significant power for longevity prediction. Mice in the upper half of the population for each of these three endpoints lived, on average, 103 days (12%) longer than mice with the opposite characteristics. Thus, measures of young adult bone dimensions, changes as a result of bone remodeling in middle age, and immunological maturation provide partially independent indices of aging processes that together help to determine lifespan in genetically heterogeneous mice.     

Computed tomographic measurement of cortical bone geometry

In this study digital images of bone cross-sections obtained by computed tomography were analyzed with an automated outlining method. It was shown that unbiased cross-sectional geometric measurements of cortical bone could be obtained if the periosteal and endosteal surfaces were defined at separate thresholds. Use of different threshold levels for these two surfaces resulted in errors of 2.6% for periosteal diameters, 7.4% for endosteal diameters and 7.3% for cortical area. If incorrect thresholds were used, cortical thickness measurements can have errors as high as 30%. In addition, simulated variation in medullary fat content did not affect measurement of medullary dimensions.     

Cortical bone remodeling rates in a sample of African American and European American descent groups from the American Midwest: comparisons of age and sex in ribs

This study employs regression analysis to explore population and sex differences in the pattern of age-associated bone loss, as reflected by histomorphometric variables that are measures of intracortical and endocortical bone remodeling. A comparison of an African American sample from the Washington Park Cemetery in St. Louis, Missouri, and a European American rib sample composed of cadavers, autopsies, and forensic cases from Missouri reveals the existence of complex age-associated patterns for differences in measures of intracortical remodeling and cortical area. Females from the two samples express similar bone dimensions and dynamics. The African American females appear to lose more bone than their male counterparts, but this difference is absent in the European American sample. When age-associated patterns are considered, it is in the younger cohorts that African Americans exhibit greater relative cortical area than European Americans, but this is reversed in the older ages, when the latter group manifests greater bone mass. The European American males consistently differ in the slopes and intercepts for the variables compared to the other groups, and differences are highly significant with African American females, with the former group maintaining bone mass while the latter exhibit a more rapid bone loss. Achieving larger relative cortical area due to smaller endosteal area, coupled with better bone quality due to lower intracortical porosity early in life, may be a mechanism by which African Americans, especially females, maintain adequate bone mass in older ages, which buffers them from bone loss and related fragility fractures despite higher rates of intracortical remodeling and endosteal expansion later in life. These results suggest that both genetic and environmental factors are responsible for the differences in bone remodeling and bone mass observed between these samples.     

Size, structure and gender: lessons about fracture risk

The differences in age-related fracture risks among men and women must reflect gender differences in the relevant variables. We are concerned here with gender differences in structural variables that relate to the size and shape of bones. As children grow, their bones grow in diameter through periosteal modeling. Studies show that radial growth is driven by mechanical forces and is not just "genetically programmed". Moving bone mass farther from the center of the diaphysis makes it more effective in resisting bending and twisting forces, and disproportionately so in comparison to changes in bone mass. Gender differences in long bone structure appear to arise because the bone cells of males and females function in different hormonal environments which affect their responses to mechanical loading. In girls, bone formation on the metacarpal periosteal surface essentially stops at puberty, and is replaced by formation on the endosteal surface, reducing endosteal diameter until about age 20. Bone strength is 60% greater in male metacarpals than in those of females because bone is added periosteally in boys and endosteally in girls. At menopause endosteal resorption resumes, accompanied by slow periosteal apposition, weakening cortical structure. Similar phenomena occur in such critical regions as the femoral neck. Another fundamental gender difference in skeletal development is that whole body bone mineral content increases in linear proportion to lean body mass throughout skeletal maturation in boys, but in girls there is a distinct increase in the slope of this relationship at puberty, when estrogen rises. Frost's hypothesis is that this reflects an effect of estrogen on bone's mechanostat set point, and this is increasingly supported by data showing that estrogen and mechanical strain act through a common pathway in osteoblast-like cells. If Frost's hypothesis is correct, the mechanostat is set for maximal effect of mechanical loading on bone gain during the 2-3 years preceding menarche. During the childbearing years, the set point is at an intermediate level, and at menopause, it shifts again to place the skeleton into the metabolic equivalent of a disuse state. The most direct approach to resolving this problem would be to simulate the putative effect of estrogen on the set point itself.     

Patterns of femoral bone remodeling dynamics in a medieval Nubian population

The relationship between age, sex and histomorphometry in femoral cortical bone was examined in a skeletal population of late Medieval antiquity (AD 1250–1450) from Kulubnarti, in Sudanese Nubia. These skeletal remains are naturally mummified and in an excellent state of preservation. The study sample consisted of femoral cross sections from 24 females and 19 males ranging in age from 20 to 50+ years. Femoral cross sections were examined using an image analysis system. Numbers of secondary osteons and osteon fragments were counted, osteon area and Haversian canal area were measured, and several variables were calculated to assess differences between sexes and among age groups in bone remodeling variables. The results indicate significant differences between the sexes in osteon number and size. Males had significantly more intact osteons than females, whereas females had significantly larger osteons than males. Haversian canal dimensions were not statistically significant between the sexes. Sex differences in activity patterns in which males were involved in more physically strenuous tasks may have contributed to differences in remodeling variables. Interpopulational comparisons suggest that mechanical strain affects the microstructural features examined in this study. In particular, small Haversian canals in some archaeological skeletal populations are associated with higher bone volume, which may result from high levels of mechanical strain. Am J Phys Anthropol 104:133–146, 1997. © 1997 Wiley-Liss, Inc.     

Cortical bone maintenance in an historic Afro-American cemetery sample from Cedar Grove, Arkansas

The relocation and analysis of 80 skeletons from the Cedar Grove Cemetery, located in southwest Arkansas, provides an opportunity to examine the level of health and nutrition experienced by Afro-Americans in the post-Reconstruction South (1878-1930). The demographic profile lends support to the interpretation that Cedar Grove participated in the nationwide decline in Afro-American health. The high frequencies of skeletal lesions indicative of dietary deficiencies and infectious disease demonstrate that this was a highly stressed population. For this analysis, adult femoral thin sections (15 females and 14 males) are examined histologically. These data provide support to the assertion that the Cedar Grove population experienced poor health. Measures taken from the sections include cortical thickness, percent cortical area, and mean number of resorption spaces and forming osteons per square millimeter of bone. As a group, they demonstrate low percent cortical area compared with well-nourished normals. They also show high rates of resorption to formation, thereby disrupting the balance necessary for normal cortical bone maintenance. The pattern established for bone porosity in this group is not a function of age but rather is due to other factors, most likely nutrition and disease stress. What may be unique about this group is that males, as well as females, experienced problems with calcium homeostasis and normal maintenance and repair of bone. Taken together, these data support the interpretation that diet and health were substandard in the post-Reconstruction South.     

Effects of age and occupation on cortical bone in a group of 18th-19th century British men

The effects of age and occupation on cortical bone in a group of adult males from the 18th-19th century AD skeletal collection from Christ Church Spitalfields, London, were investigated. Cortical bone was monitored using metacarpal radiogrammetry. Individual age at death was known exactly from coffin plates. Occupation for individuals was known from historical sources. Results showed that continued periosteal apposition was evident throughout adult life, but from middle age onwards this was outstripped by about 2:1 by endosteal resorption, so that there was net thinning of cortical bone. The rate of cortical thinning resembled that seen in modern European males. Cross-sectional properties, as measured by second moments of area, bore no relationship to occupation. The results may suggest that, firstly, patterns of loss of cortical bone have remained unchanged in males for at least two centuries in Britain, and secondly, that biomechanical analyses of metacarpal cortical bone may be rather insensitive indicators of intensity of manual activity.     

Plasma Cortisol Levels Increase with Age in Obese Subjects

In order to assess the influence of age, sex, and body mass on plasma cortisol concentrations, we measured the 24-hour Integrated Concentration (IC) of cortisol (F) in 36 obese subjects (16 males, 20 females) aged 5.3–56.4 years, BMI=35.5 ± 7.3 kg/m² and compared with 119 nonobese subjects, body mass indices (BMI) 21.2 ± 2.7 kg/m², aged 8.8–66.2 years (55 males, 64 females). Subjects were nondiabetic, normotensive, without history of psychiatric illness, and otherwise in good health. IC studies were performed using a continuous blood withdrawal methodology, and IC-F was assayed from the 24 hour pooled sample by a protein binding method. The effect of age and gender on IC-F was analyzed by multivariate regression. In the nonobese group there was no effect of age or sex on IC-cortisol levels, the mean IC-F= 173.8 ± 44.1 nmol/L. A statistically significant but weak negative effect of BMI on IC-cortisol (r = -.18, p<0.05) was present. In the obese subjects there was a significant increase in IC-cortisol levels with age IC-F(nmol/L)=2.76 x age(years) + 85.0 (r²=.36, p<0.0001). IC-cortisol levels tended to be lower in obese males than females when controlled for age (p<0.05). We conclude that in nonobese subjects IC-F levels are independent of age and gender. However, there is a significant increase of IC-cortisol levels with age in obese individuals. The observed increase of IC-cortisol with age may contribute to metabolic complications of obesity.     

A Computational Model for Cortical Endosteal Surface Remodeling Induced by Mechanical Disuse

In mechanical disuse conditions associated with immobilization and microgravity in spaceflight, cortical endosteal surface moved outward with periosteal surface moving slightly or unchanged, resulting in reduction of cortical thickness. Reduced thickness of the shaft cortex of long bone can be considered as an independent predictor of fractures. Accordingly, it is important to study the remodeling process at cortical endosteal surface. This paper presents a computer simulation of cortical endosteal remodeling induced by mechanical disuse at the Basic Multicellular Units level with cortical thickness as controlling variables. The remodeling analysis was performed on a representative rectangular slice of the cross section of cortical bone volume. The pQCT data showing the relationship between the duration of paralysis and bone structure of spinal cord injured patients by Eser et al. (2004) were used as an example of mechanical disuse to validate the model. Cortical thickness, BMU activation frequency, mechanical load and principal compressive strain for tibia and femur cortical models were simulated. The effects of varying the mechanical load and maximum BMU activation frequency were also investigated. The cortical thicknesses of femur and tibia models were both consistent with the clinical data. Varying the decreasing coefficient in mechanical load equation had little effect on the steady state values of cortical thickness and BMU activation frequency. However, it had much effect on the time to reach steady state. The maximum BMU activation frequency had effects on both the steady state value and the time to reach steady state for cortical thickness and BMU activation frequency. The computational model for cortical endosteal surface remodeling developed in this paper can be further used to quantify and predict the effects of mechanical factors and biological factors on cortical thickness and help us to better understand the relationship between bone morphology and mechanical as well as biological environment.     

Bone mass in Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia

Bone mass, as assessed by measurements of total subperiosteal diameter and medullary width of the second metacarpal bone on hand-wrist radiographs, was evaluated for 31 Guamanian patients (15 males, 16 females) with amyotrophic lateral sclerosis (ALS), 67 patients (39 males, 28 females) with parkinsonism-dementia (PD), and 66 (34 males, 32 females) nonaffected Guamanian controls. Comparisons between the two disease groups and between each disease group and the nonaffected controls were made taking into account the sex, age, and disability status of each participant. At all ages, ALS patients of both sexes had significantly lower percent cortical areas (PCA) than did nonaffected controls. The ALS males also had significantly lower PCA than PD males, although no significant differences were observed between female ALS and PD patients. The PD patients of either sex had a lower PCA when compared to controls, but the differences were not statistically significant. The observed differences in PCA were due solely to increased medullary width, suggesting that the diminished cortical bone thickness resulted from greater bone resorption rather than differential bone growth. Longitudinal studies support the cross-sectional findings of accelerated bone loss among ALS patients. It is not possible to determine from the present data whether the observed differences in PCA of the second metacarpal of the ALS patients are due to atrophy of the first interosseous muscle, to a generalized resorption process inherently associated with the development and progression of ALS, or to factors not accounted for by the present analysis.     

Estimation of bone matrix apparent stiffness variation caused by osteocyte lacunar size and density

The role of osteocyte lacunar size and density on the apparent stiffness of bone matrix was predicted using a mechanical model from the literature. Lacunar size and lacunar density for different bones from different gender and age groups were used to predict the range of matrix apparent stiffness values for human cortical and cancellous tissue. The results suggest that bone matrix apparent stiffness depends on tissue type (cortical versus cancellous), age, and gender, the magnitudes of the effects being significant but small in all cases. Males had a higher predicted matrix apparent stiffness than females for vertebral cancellous bone (p< I0(-7)) and the difference increased with age (p =0.0007). In contrast, matrix apparent stiffness was not different between males and females forfemoral cortical bone and increased with age in both males (p < 0.0001) and females (p < 0.0364). Osteocyte lacunar density and size may cause significant gender and age-related variations in bone matrix apparent stiffness. The magnitude of variations in matrix apparent stiffness was small within the physiological range of lacunar size and density for healthy bone, whereas the variations can be profound in certain pathological cases. It was proposed that the mechanical effects of osteocyte density be uncoupled from their biological effects by controlling lacunar size in normal bone.     

The importance of accounting for the area of the medullary cavity in cross‐sectional geometry: A test based on the femoral midshaft

In cross‐sectional geometric (CSG) studies, both the subperiosteal and endosteal contours are considered important factors in determining bone bending rigidity. Recently, regression equations predicting CSG properties from a section's external dimensions were developed in a world‐wide sample of human long bones. The results showed high correlations between some subperiosteally derived and actual CSG parameters. We present a theoretical model that further explores the influence of endosteal dimensions on CSG properties. We compare two hypothetical femoral midshaft samples with the same total subperiosteal area but with percentages of cortical bone at the opposite ends of published human variation for population sample means. Even in this relatively uncommon scenario, the difference between the samples in the resultant means for predicted femoral polar second moment of area (J) appears to be modest: power analysis indicates that a minimum sample size of 61 is needed to detect the difference 90% of the time via a t‐test. Moreover, endosteal area can be predicted—although with substantial error—from periosteal area. Despite this error, including this relationship in subperiosteally derived estimates of J produces sample mean estimates close to true mean values. Power analyses reveal that when similar samples are used to develop prediction equations, a minimum sample of hundreds or more may be needed to distinguish a predicted mean J from the true mean J. These results further justify the use of regression equations estimating J from periosteal contours when analyzing behaviorally induced changes in bone rigidity in ancient populations, when it is not possible to measure endosteal dimensions. However, in other situations involving comparisons of individual values, growth trends, and senescence, where relative cortical thickness may vary greatly, inclusion of endosteal dimensions is still important. Am J Phys Anthropol, 2010. © 2010 Wiley‐Liss, Inc.     

Supraphysiological testosterone enanthate administration prevents bone loss and augments bone strength in gonadectomized male and female rats

High-dose testosterone enanthate (TE) may prevent hypogonadism-induced osteopenia. For this study, 3-mo-old male and female Fisher SAS rats underwent sham surgery, gonadectomy (GX), or GX plus 28 days TE administration (7.0 mg/wk). GX reduced serum sex hormones (i.e., testosterone, dihydrotestosterone, and estradiol) (P < 0.05) in both sexes and bone concentrations of testosterone (males only), and estradiol (females only). GX also elevated urine deoxypyridinoline/creatinine in both sexes and serum osteocalcin (females only), findings that are consistent with high-turnover osteopenia. GX reduced cancellous bone volume (CBV) and increased osteoid surfaces in tibia of both sexes. GX males also experienced reduced trabecular number and width and increased trabecular separation, whereas GX females experienced increased osteoblast and osteoid surfaces. Bone biomechanical characteristics remained unaffected by GX, except that femoral stiffness was reduced in females. In contrast, TE administration to GX rats elevated serum and bone androgens to supraphysiological concentrations in both sexes but altered neither serum nor bone estradiol in males. Additionally, TE did not prevent GX-induced reductions in serum or bone estradiol in females. TE also reduced markers of high-turnover osteopenia in both sexes. In males, TE prevented GX-induced changes in trabecular number and separation, CBV, and osteoid surfaces while diminishing osteoblast and osteoclast surfaces; however, these changes were not fully prevented in females. In both sexes, TE increased femoral length and femoral maximal strength to above that of Sham and GX animals while preventing the loss of femoral stiffness in females. In conclusion, TE administration appears protective of cancellous bone in male rats and augments cortical bone strength in both sexes.     

Irreversible loss of the substantia compacta in metabolic bone diseases based on roentgenogrammetric data

A study was made of gram roentgenographic indices of the compact substance (CS) in metabolic skeletal diseases: of the cortical layer summary thickness (CST) and a cortical area (CA) of the metacarpal bone II in 310 patients and the femoral cortical index (FCI) in 184 patients. Three components in CS loss were singled out: involution, metabolic and inert. Irreversibility of endocortical loss of the osseous tissue was shown and interpreted as fast developing involution osteoporosis. CST is a more sensitive index of CS loss than FCI though the combination of both indices provides more information on CS loss.