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.     

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.     

Roentgenographic and direct measurement of femoral cortical involution in a prehistoric Mississippian population

Recent roentgenographic studies suggest that periosteal apposition adds femoral cortical bone faster than it is lost by endosteal involution, so that cortical bone area increases with age. A comparison was made of direct and roentgenographic measurements of femoral cortical bone using femora from 23 females and 20 males of a prehistoric Mississippian population dated at A.D. 1540–1700. The comparison revealed that significant errors existed in the technique of radiographic measurement (p<0.000001), in estimating male and female cortical thickness (p<0.000001), and the changes in thickness with age (p<0.000001). There was no significant interaction of the variables: age, sex, and method. The errors arose partly from the inability of the roentgenograph to reveal clearly endosteal porosity, and partly in the assumption that the medial and lateral cortical wall thickness would be representative of the mean cortical thickness. The reduction in cortical thickness (11.3% males and 29.3% females) with age as measured directly is comparable with loss in modern populations.     

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.     

Cortical bone growth and dietary stress among subadults from Nubia's Batn el Hajar

Cortical bone growth is analyzed for 174 children from a Medieval Christian population at Kulubnarti in the Batn el Hajar of Sudanese Nubia (550–1450 AD ). Using the tibia as a representative long bone, total subperiosteal area, cortical area, medullary area, and percent cortical area at midshaft were calculated. While growth in total and cortical areas, as well as in length, appear to be fairly well maintained, percent cortical area reveals unusual growth patterns which reflect excessive endosteal resorption. Compared to the relative reduction in bone mass which has been observed in malnourished living children, as well as with previously reported evidence for stress in the Kulubnarti population, the present data support an interpretation of nutritionally related stress and of no major diachronic dietary change.     

Brief communication: Reevaluating osteoporosis in human ribs: the role of intracortical porosity

Osteoporosis is a major health concern in modern society and is continually being evaluated in past populations by quantifying bone loss. Cortical area measures are commonly used in anthropological analyses to assess bone loss in the ribs, but these values are typically based on endosteal expansion and do not account for intracortical bone loss. The objective of this study is to evaluate the effectiveness of using absolute cortical area, compared to traditional cortical area measures to describe global bone loss in elderly ribs. Transverse sections were prepared from sixth ribs of ten elderly subjects, and bone area measurements were made from 100× magnification composites of each rib for calculation of cortical area (Ct.Ar) and percent cortical area (% C/T). In addition, all areas of intracortical porosity were measured and percent porosity area (% Po.Ar) calculated. Absolute cortical area (Ct.Ar(A)) was calculated by subtracting porosity area from cortical area, and a percent absolute cortical area (% C(A)/T) calculated. ANOVA results reveal significant interindividual variation in percent porosity area (% Po.Ar). Percent cortical area and percent absolute cortical area values were compared and results show a mean difference of 4.08% exists across all subjects, with a range of 1.19-11.73%. This suggests that intracortical porosity is variable and does play a role in age-associated bone loss in the rib. All future investigations of osteoporosis should account for intracortical porosity in bone loss.     

Continuing periosteal apposition. II: The significance of peak bone mass, strain equilibrium, and age-related activity differentials for mechanical compensation in human tubular bones

It is generally presumed that compensation for the reduction of bone strength by progressive endosteal bone loss in adults is provided by continuing periosteal apposition (CPA) of new lamellar bone. However, the appropriate magnitude of compensatory bone growth, and the parameters that operate to determine that magnitude, are unknown. This paper examines the mechanical compensation hypothesis in a series of right-circular tubular bone analogues. Under this hypothesis, the stated objective of CPA is maintenance of the cross-sectional geometric properties of the element. These include the second and polar moments of area, as well as the cortical area of the section (I, J, and CA, respectively). This study assumes that, as resorption and apposition proceed, geometric change is isometric (shape preserving). The analysis suggests that for a given rate of endosteal bone loss (the stimulus), the magnitude of periosteal growth (the response) required to maintain geometric strength is determined by the maximum ratio (CT0) of the radial distances from the section centroid to the endosteal and periosteal surfaces (i.e., cortical thickness prior to the onset of progressive endosteal bone loss, or peak bone mass). The analysis also indicates that, for any given individual, the amount of compensatory periosteal gain required may be very small. This is particularly true for individuals having a large CT0 and for whom the magnitude of dynamic loading imparted to the skeleton declines with advancing age. This finding is illustrated in a model that relates concepts of bone surface remodeling equilibria and age-related activity differentials.     

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.     

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.     

In vivo calvarial bone cell responses to dietary perturbations and the implications for mineral homeostasis

Calvariae from small animals have been an important source for in vitro studies of bone. However, few in vivo studies have been undertaken on quantitative cell changes in calvariae. In the present study of mineral perturbations, rats were first deprived of calcium. After 18 days endosteal osteoclasts and nuclei/osteoclast in the parietal bone had increased 120% (P less than 0.001) and 26% (P less than 0.001), respectively, the marrow space had increased 141% (P less than 0.001), and the bone area experienced a 49% decrease (P less than 0.001). This thinning and weakening of the calvaria was accompanied by a compensatory increase in the number of endosteal osteoblasts (297%, P less than 0.001). These rats were then replenished with calcium, and after 14 days the number of endosteal osteoclasts had decreased to 86% (P less than 0.001) below the control and the endosteal surface was almost completely covered by osteoblasts (866% above the control, P less than 0.001). Bone area was increased by 51% (P less than 0.01). Similarly, in calcium-deficient rats in the tibial diaphysis at the fibular junction, the number of endosteal osteoclasts and the medullary space increased 1606% (P less than 0.001) and 63% (P less than 0.001), respectively, which were accompanied by a 32% decrease (P less than 0.001) in cortical bone area. After calcium replenishment, most endosteal osteoclasts in the tibial diaphysis disappeared from the endosteal surface and were replaced by osteoblasts (increased 487%, P less than 0.001). These results indicate that changes in bone cell activity in response to calcium deficiency are similar in calvariae and long bones, and that mobilization of calcium from the calvaria during calcium deficiency occurs at the expense of the protective action of the calvaria. Therefore, long bones as well as membranous bones are apparently important for the maintenance of mineral homeostasis.     

Cortical remodeling data are affected by sampling location

It has been argued that techniques for estimating adult ageat-death from cortical histology are deleteriously affected by sampling location. This study uses nine complete femoral midshaft cross-sections to test the effect of sampling site on measurement of a standard histological variable, percent remodeled bone. Circumferential periosteal fields from four anatomically defined locations (anterior, posterior, medial, lateral) and four mechanically defined locations (maximum and minimum moments of area) were evaluated. Locations deviating from the periosteal surface toward the endosteal surface were also compared. Significant differences were found for both location and field placement. The anatomical axes exhibited greater variability than the mechanical axes, in particular the anterior location, a standard sampling site for age-at-death estimation techniques. More endosteal fields tended to show elevated levels of percent remodeled bone. This study demonstrates that circumferential and radial sampling locations are important considerations in deriving and applying predictive equations based on cortical remodeling. © 1995 Wiley-Liss, Inc.     

Population frequencies and altered remodeling mechanisms in normal medullary stenosis

As shown in 2065 women aged 18 to 45 years from seven countries of Central and North America, the population frequency of normal medullary stenosis ranges from under 2% to nearly 7%. In this condition, endosteal apposition may begin in infancy and continue through the fourth decade with a compensatory reduction in the rate of subperiosteal apposition, leading to an approximately normal cortical cross-sectional area contained in a smaller subperiosteal envelope.     

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.     

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.     

The Lichfield bone study: the skeletal response to exercise in healthy young men

The skeletal response to short-term exercise training remains poorly described. We thus studied the lower limb skeletal response of 723 Caucasian male army recruits to a 12-wk training regime. Femoral bone volume was assessed using magnetic resonance imaging, bone ultrastructure by quantitative ultrasound (QUS), and bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) of the hip. Left hip BMD increased with training (mean ± SD: 0.85 ± 3.24, 2.93 ± 4.85, and 1.89 ± 2.85% for femoral neck, Ward's area, and total hip, respectively; all P < 0.001). Left calcaneal broadband ultrasound attenuation rose 3.57 ± 0.5% (P < 0.001), and left and right femoral cortical volume by 1.09 ± 4.05 and 0.71 ± 4.05%, respectively (P = 0.0001 and 0.003), largely through the rise in periosteal volume (0.78 ± 3.14 and 0.59 ± 2.58% for right and left, respectively, P < 0.001) with endosteal volumes unchanged. Before training, DXA and QUS measures were independent of limb dominance. However, the dominant femur had higher periosteal (25,991.49 vs. 2,5572 mm(3), P < 0.001), endosteal (6,063.33 vs. 5,983.12 mm(3), P = 0.001), and cortical volumes (19,928 vs. 19,589.56 mm(3), P = 0.001). Changes in DXA, QUS, and magnetic resonance imaging measures were independent of limb dominance. We show, for the first time, that short-term exercise training in young men is associated not only with a rise in human femoral BMD, but also in femoral bone volume, the latter largely through a periosteal response.     

Cosmos 1887: morphology, histochemistry, and vasculature of the growing rat tibia

Light microscopy, electron microscopy, and enzyme histochemistry were used to study the effects of spaceflight on metaphyseal and cortical bone of the rat tibia. Cortical cross-sectional area and perimeter were not altered by a 12.5-day spaceflight in 3-month-old male rats. The endosteal osteoblast population and the vasculature near the periosteal surface in flight rats compared with ground controls showed more pronounced changes in cortical bone than in metaphyseal bone. The osteoblasts demonstrated greater numbers of transitional Golgi vesicles, possibly caused by a decreased cellular metabolic energy source, but no difference in the large Golgi saccules or the cell membrane-associated alkaline phosphatase activity. The periosteal vasculature in the diaphysis of flight rats often showed lipid accumulations within the lumen of the vessels, occasional degeneration of the vascular wall, and degeneration of osteocytes adjacent to vessels containing intraluminal deposits. These changes were not found in the metaphyseal region of flight animals. The focal vascular changes may be due to ischemia of bone or a developing fragility of the vessel walls as a result of spaceflight.     

Reduced bone mineral density and radial bone growth in young rabbits treated with dexamethasone eye drops

OBJECTIVE: To investigate the effect of dexamethasone eye drops on bone metabolism in newborn rabbits. METHODS: Thirty-four 3-week-old rabbits had unilateral clear lens extraction and were randomized into three groups. Postoperatively, group 1 received high-dose and group 2 low-dose dexamethasone eye drops (average doses 0.27 and 0.10 mg/kg body weight/day, respectively). These rabbits also received a postoperative subconjunctival injection of betamethasone. Group 3 (control) received vehicle eye drops only. After 8 weeks of treatment, all animals were killed and the left femurs were isolated and subjected to peripheral quantitative computerized tomography (pQCT) and dual X-ray absorptiometry (DXA) analyses. RESULTS: DXA showed that rabbits treated with either a high or low dose of dexamethasone eye drops had significantly reduced areal bone mineral density (BMD), area and total bone mineral content (BMC) of the femur. Measurements with pQCT demonstrated a dose-dependent reduction in cortical BMC, cortical volumetric BMD and cortical area. These effects were associated with an inhibition of radial femur growth, cortical thickness and periosteal and endosteal circumferences. CONCLUSION: Dexamethasone eye drops have systemic effects affecting several bone parameters in young rabbits. Any long-term systemic effects of ocular glucocorticoids need to be further studied.     

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.     

A novel method to 'exercise' rats: making rats rise to erect bipedal stance for feeding - raised cage model

We employed a novel method to exercise rats: making them rise to bipedal stance for feeding using raised cages. We studied its effects on the skeletons of 6 and 10-month-old intact or orchidectomized (ORX) rats. Body and hindlimb muscle weights, tibial BMC and periosteal cortical bone formation increased after housing in raised cages, but more so in 6-month-old animals than in 10-month-old ones. In 6-month-old orchidectomized rats, raised cages partially prevented ORX-induced bone loss by stimulating periosteal cortical bone (TX) formation and decreased bone resorption next to marrow. In 10-month-old male orchidectomized rats, raised cages also decreased the endosteal and trabecular bone resorption, but not enough to prevent completely ORX-induced net bone losses. Because the osteogenic effects of raised cages alone were only partial, we also studied the interaction between raised cage and prostaglandin E(2) (PGE(2)) in 10-month-old retired female breeders. When treated with combined raised cage and PGE(2), both cortical (TX) and trabecular bone mass of the proximal tibial metaphysis and lumbar vertebral body increased over either raised cages or PGE(2) treatment alone, that was accompanied by dramatic increased bone formation at periosteal and endosteal surfaces. Thus making rats rise to erect bipedal stance for feeding helps to prevent bone loss after orchidectomy; it amplifies the anabolic effects of PGE(2), and it provides an inexpensive, non-invasive and reliable way to increase mechanical loading of certain bones of the rat skeleton.     

Apparent age-related bone loss among adult female Gombe chimpanzees

Apparent age-related bone loss among adult females was observed in a skeletal sample derived from the free-ranging Gombe chimpanzee population of Tanzania. Photon absorptiometric and computed tomographic bone scans indicated that, as in humans, bone was lost from the endosteal surface, but, in contrast to humans, more bone was lost from cortical sites than from cancellous sites. The etiology of this bone loss may be related to a number of factors, including hormonal changes, nutritional inadequacy, and decreased physical activity late in life coupled with the demands of pregnancy and lactation.