Age-related changes in iliac crest trabecular microanatomic bone structure in man

Age-related changes in the microanatomic structure of human iliac crest trabecular bone have been investigated in biopsies from 90 subjects, using a new computerised method which automatically identifies and quantifies nodes, free ends and a number of topologically defined struts. In both sexes there was a significant age-related decrease in the number of nodes and of trabecular struts, corrected for section area. In females, there was also a significant age-related decrease in the node to free end ratio (P less than 0.001), and the combined node-to-node and node-to-loop strut length, expressed as a percentage of total strut length (P less than 0.001) and a significant increase in free end to free end strut length (P less than 0.001). In males, the only additional age-related change was a significant increase in the cortex to free end strut length (P less than 0.005). These results indicate that loss of trabeculae resulting in decreased interconnectedness of the normal trabecular bone structural pattern, plays an important role in age-related bone loss in females. Removal of trabeculae also occurs in males but in less prominent, implying that trabecular thinning makes a greater contribution to age-related bone loss in males.     

Measurement of anisotropic vertebral trabecular bone loss during aging by quantitative image analysis

Summary Age-dependent variations in the architecture of vertebral trabeculae in both the vertical and horizontal planes were characterized by quantitative image analysis. Images were obtained from autopsy specimens of the third lumbar vertebrae in 61 subjects (30 men and 31 women) whose ages ranged between 33 and 89 years). All subjects had died acutely either after trauma or illnesses unrelated to the skeleton. Using mathematical morphology techniques, we measured total bone area and perimeter, and the width of trabecular particles and medullary spaces in each slice. Between the age intervals 33–49 and 80–89 years: total bone loss in the vertical and horizontal planes was 51 and 64% for women, and 38 and 29% for men, respectively. Mean trabecular width (MTW) in the vertical plane decreased from 172 to 128 μm in women and from 181 to 144 μm in men; MTW in the horizontal plane fell from 144 to 112 μm in women and remained at 114 μm in men. Maximum trabecular width decreased with age in both planes in both sexes. The mode for trabecular width was 111 μm in both sexes for all ages and in both planes. The total number of trabeculae decreased only for women in the vertical plane. Intertrabecular spaces enlarged reciprocally as the trabeculae became thinner, but the widening of spaces was much greater than that expected with trabecular thinning alone. We conclude that age-related bone loss is comprised of two processes: reduction of MTW and fragmentation and complete loss of some trabeculae. We found no evidence of vertical trabeculae thickening during normal aging.     

Age-related changes in vertebral trabecular bone architecture--assessed by a new method

Cylindrical trabecular bone specimens (d = 7 mm) were drilled in a vertical direction from the central part of the third vertebral body (L3) from 23 normal individuals aged 15-87 years (10 males and 13 females). The bone samples were embedded in methylmetacrylate and sawn in 400 microns thick sections with an arbitrary rotation but a fixed vertical axis. The sections were investigated in polarized light at a magnification of x 8. By using this technique, vertical and horizontal trabeculae were clearly separated due to different colors. Photographs were taken. These were magnified, and trabecular thickness and intertrabecular distance were measured, using a Zeiss-integration plate II. A significant age-related decrease was found in the mean horizontal trabecular thickness (r = -0.71, p less than 0.001), while the mean thickness of the vertical trabeculae was unchanged with age (r = 0.06, n.s.). Furthermore, a significant increase was found both for the mean distance between the horizontal trabeculae (r = 0.79, p less than 0.001) and between the vertical trabeculae (r = 0.75, p less than 0.001). The present study gave a clear and striking visual presentation of both the thinning and disappearance of the horizontal supporting struts in the vertebral trabecular lattice and the total removal of some of the vertical trabeculae--leading to the dramatic loss of bone strength previously demonstrated.     

Primary hyperparathyroidism: iliac crest trabecular bone volume, structure, remodeling, and balance evaluated by histomorphometric methods.

Iliac bone biopsies from 69 patients (48 females, 21 males; median age 58 years; range 17-79 years) with primary hyperparathyroidism (PHP) were examined, and static histomorphometric parameters compared to 30 age- and sex-matched normal controls. The control group for the dynamic parameters constituted 20 sex-matched younger normal controls. Fractional volume of trabecular bone was normal, but the trabeculae were thinner (p less than 0.05) in PHP. The structural parameters marrow space star volume, intertrabecular distance, and mean trabecular plate density were not significantly different in PHP patients compared to normal controls, but the age-related increase, for females, in marrow space star volume and decrease, for both sexes, in mean plate density observed in the controls were not noticed in the PHP group. Trabecular bone remodeling was found significantly increased in the PHP patients reflected by increased extension of eroded (p less than 0.001), osteoid (p less than 0.001), and labeled surfaces (p less than 0.05). The activation frequency was increased by approximately 50% (p less than 0.001). Neither PHP patients nor controls showed age-related decrease in trabecular thickness, and accordingly in both groups the bone balance per remodeling cycle was very close to and not significantly different from zero. Normal postmenopausal women (age greater than or equal to 50 yr) had lower trabecular bone volume (p less than 0.001) and higher intertrabecular distance than normal pre-menopausal women (age less than 50 yr).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of sodium fluoride on trabecular architecture.

The effect of sodium fluoride therapy on iliac trabecular bone has been studied in 15 patients with primary osteoporosis by comparing bone biopsies taken before and after two years of treatment. A marked increase in bone volume (43%) was observed, which was attributable to an increase in trabecular thickness (46%) rather than their number. Because the trabecular bone surface, the trabecular number, the bone volume/trabecular width ratio, and the trabecular terminus number do not change significantly after fluoride treatment, we conclude that fluoride does not induce the de novo generation of trabeculae, nor does it restore trabecular connectivity despite the restoration of bone mass. These data suggest that the restoration of skeletal mass with fluoride may not lead to a comparable decrease in the risk of future fracture.     

Normal postmenopausal women show iliac crest trabecular thickening on vertical sections

Trabecular thickness and the trabecular star volume were estimated in 49 normal individuals (20 males and 29 females) using an unbiased sampling procedure consisting of anisotropic, vertical sections, and a corresponding anisotropic test system. Eight-microns-thick undecalcified stained vertical sections were obtained from iliac crest specimens. Implying a trabecular plate model mean trabecular thickness (Tb.Th., microns) was estimated by different methods: (a) the ratio between bone volume and bone surface (Tb.Th.ratio); (b) the mean of the orthogonal intercepts multiplied with pi/4 (Tb.Th.l0); and (c) the mean of random linear intercepts divided by 2 (Tb.Th.l1). Trabecular star volume (Vtr*, mm3), a true three-dimensional size parameter independent on any model, was estimated using linear intercepts in random directions. Significant (2p less than 0.001) correlations were found between the different methods with coefficients of correlation ranging from 0.71 to 0.89. The Tb.Th. ratio was overall higher (155 +/- 31 microns, (X, SD), 2p less than 0.001) than the other linear estimates, Tb.Th.l0: 144 +/- 26 microns and Tb.Th.l1: 135 +/- 27 microns. Estimates based on orthogonal intercepts (l0) were slightly higher (2p less than 0.001) than those from random linear intercepts (l1). Among all the individuals no significant age-related changes were seen in the measured parameters. However, postmenopausal women (greater than 50 years of age) had more thick trabeculae than younger women (2p = 0.03). Intra-individual distribution analysis disclosed that this finding could not be explained by preferential perforation and loss of thinner trabeculae during bone remodeling. Therefore, normal postmenopausal women do increase trabecular thickness with age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Deterioration of trabecular plate-rod and cortical microarchitecture and reduced bone stiffness at distal radius and tibia in postmenopausal women with vertebral fractures

Postmenopausal women with vertebral fractures have abnormal bone microarchitecture at the distal radius and tibia by HR-pQCT, independent of areal BMD. However, whether trabecular plate and rod microarchitecture is altered in women with vertebral fractures is unknown. This study aims to characterize the abnormalities of trabecular plate and rod microarchitecture, cortex, and bone stiffness in postmenopausal women with vertebral fractures. HR-pQCT images of distal radius and tibia were acquired from 45 women with vertebral fractures and 45 control subjects without fractures. Trabecular and cortical compartments were separated by an automatic segmentation algorithm and subjected to individual trabecula segmentation (ITS) analysis for measuring trabecular plate and rod morphology and cortical bone evaluation for measuring cortical thickness and porosity, respectively. Whole bone and trabecular bone stiffness were estimated by finite element analysis. Fracture and control subjects did not differ according to age, race, body mass index, osteoporosis risk factors, or medication use. Women with vertebral fractures had thinner cortices, and larger trabecular area compared to the control group. By ITS analysis, fracture subjects had fewer trabecular plates, less axially aligned trabeculae and less trabecular connectivity at both the radius and the tibia. Fewer trabecular rods were observed at the radius. Whole bone stiffness and trabecular bone stiffness were 18% and 22% lower in women with vertebral fractures at the radius, and 19% and 16% lower at the tibia, compared with controls. The estimated failure load of the radius and tibia were also reduced in the fracture subjects by 13% and 14%, respectively. In summary, postmenopausal women with vertebral fractures had both trabecular and cortical microstructural deterioration at the peripheral skeleton, with a preferential loss of trabecular plates and cortical thinning. These microstructural deficits translated into lower whole bone and trabecular bone stiffness at the radius and tibia. Our results suggest that abnormalities in trabecular plate and rod microstructure may be important mechanisms of vertebral fracture in postmenopausal women.     

Age-related changes in trabecular bone microdamage initiation

With age, alterations occurring in bone quality, quantity, and microarchitecture affect the resistance of trabecular bone to local failure. The clinical implications of these changes are evident by the observed exponential increase in fracture incidence with age. Although age-related development of skeletal fragility is well established, it is unclear how the local failure properties of bone change with age. We previously reported a specimen-specific technique to assess microstructural stresses and strains associated with microdamage initiation but did not assess age-related changes. In this study, we compared younger (average age 2 years) and older (average age 10 years) bovine trabecular bone to evaluate how alterations in bovine bone quantity and quality with age affect the local mechanical environment associated with microdamage formation. The results show strong positive correlations between microdamage and local stresses and strains for both younger and older bovine trabecular bone. Correlation strength was slightly improved (<8%) for some parameters by incorporating heterogeneous local material properties based on mineral density into the finite element models. Within individual trabeculae, average stresses and strains were significantly higher in microdamaged trabeculae compared to randomly selected undamaged trabeculae, regardless of age. However, damaged trabeculae in older bone were found to have higher stresses and lower strains than those from younger bone. Corresponding differences in mineral density, microarchitecture, and FEM-determined local material properties were also observed between the two groups. Taken together, these data suggest marked age-related changes in the mechanics of microdamage initiation at the trabecular level. The combined experimental, computational, and histochemical approaches used in this study provide an improved understanding of microdamage initiation and bone quality.     

A stochastic analysis of iliac trabecular bone dynamics

Published normal histomorphometric data were used to derive distributions of thicknesses of trabecular plates and completed bone remodelling units (the basic multicellular unit carrying out bone remodelling, the BMU, when completed is termed a structural unit BSU). A stochastic model was set up to investigate the predictions of current BMU theory. Each of 100 trabecular "thicknesses" was drawn from the appropriate normal distribution using a pseudorandom number generator. Each day, each of its two surfaces when quiescent was assumed to have a 1:900 chance of initiating a remodelling cycle. Resorption (active, 12 days; reversal phase, 27 days) was followed by formation (94 +/- 35 days) and resulted in BMU balance when resorption depth was 36.8 +/- 9.2 micron. Fenestration (thickness less than 0) was assumed to lead to permanent loss of the trabecula. The original model unrealistically increased its mean trabecular thickness as thin trabeculae were lost. This was corrected by assuming that thin trabeculae had greater osteoblastic stimulation and a consequent tendency to thicken, perhaps due to higher mechanical loading. Over 20 years, 14% of trabeculae were lost when the BMU balance was exact and the distribution of trabecular thicknesses was unchanged. About one-half of fenestrations were due to deeper-than-average resorption cavities developing in thin trabeculae, and the remainder to coincident remodelling on both surfaces. A 10% fall in osteoblast lifespan resulted in an additional 36.7% loss of trabecular bone volume and mean trabecular thickness fell to 83.1 micron, compatible with Courpron's data. Simulating more rapid mechanisms of bone loss, approximately 50% of trabeculae could be lost after ten years by the arrest of bone formation; the doubling of resorption depth with unchanged bone formation; and a doubling in the rate of initiation of new BMUs with unchanged bone formation rate, all three followed by complete recovery of BMU balance after only two years. In each case, mean trabecular thickness fell only transiently but trabeculae continued to be lost after recovery. Prolonged osteoblast life span was the most likely explanation for the increased mean trabecular thicknesses and trabecular bone volumes seen in patients with osteoporosis, when treated with sodium fluoride plus calcium supplements or daily injections of parathyroid peptide hPTH 1-34.     

Strength of cancellous bone trabecular tissue from normal, ovariectomized and drug-treated rats over the course of ageing

Hormone therapy (HT) drugs and bisphosphonates prevent osteoporosis by inhibiting osteoclastic bone resorption. However, the effects of osteoporosis and anti-resorptive drugs on the mechanical behavior of the bone tissue constituting individual trabeculae have not yet been quantified. In this study, we test the hypothesis that the mechanical properties of bone trabecular tissue will differ for normal, ovariectomized and drug-treated rat bones over the course of ageing. Microtensile testing is carried on individual trabeculae from tibial bone of ovariectomized (OVX) rats, OVX rats treated with tibolone and placebo-treated controls. The method developed minimizes errors due to misalignment and stress concentrations at the grips. The local mineralization of single trabeculae is compared using micro-CT images calibrated for bone mineral content assessment. Our results indicate that ovariectomy in rats increases the stiffness, yield strength, yield strain and ultimate stress of the mineralized tissue constituting trabecular bone relative to normal; we found significant differences (P < 0.05) at 14, 34 and 54 weeks of treatment. These increases are complemented by a significant increase in the mineral content at the tissue level, although overall bone mineral density and mass are reduced. With drug treatment, the properties remain at, or slightly below, the placebo-treated controls levels for 54 weeks. The higher bone strength in the OVX group may cause the trabecular architecture to adapt as seen during osteopenia/osteoporosis, or alternately it may compensate for loss of trabecular architecture. These findings suggest that, in addition to the effects of osteoporosis and subsequent treatment on bone architecture, there are also more subtle processes ongoing to alter bone strength at the tissue level.     

Mechanical consequence of trabecular bone loss and its treatment: a three-dimensional model simulation

Age-related changes in the microstructure of trabecular bone, such as decreases in trabecular number and trabecular thickness, lead to reductions in mechanical properties, such as Young's modulus and strength. Current drug therapy, such as bisphosphonate or parathyroid hormone, improves the mechanical properties of bone mainly by increasing the trabecular thickness, but not increasing the trabecular number. However, the mechanical efficacy of these treatments has not been fully quantified using trabecular bone models. In this study, we used an idealized three-dimensional (3D) microstructural model of trabecular bone to create bone loss either through trabeculae thinning or random removal of trabeculae, and simulated treatment by increasing the trabeculae thickness of the remaining trabeculae. The reduction in either the Young's modulus or the strength due to trabeculae loss was proportional to a much higher power of reduction in bone volume fraction than due to trabeculae thinning. This indicates that bone loss due to trabeculae loss is much more detrimental to Young's modulus and strength of trabecular bone than due to trabeculae thinning, indicating the importance of trabecular number and connectivity in the mechanical integrity of trabecular bone. In general, treatments by increasing the trabecular thickness of remaining trabeculae after trabeculae loss cannot fully recover the initial mechanical properties of intact bone, even if bone loss is fully recovered, whereas trabecular thickening can fully restore the mechanical properties after bone loss by trabeculae thinning. The results also show that the residual loss in mechanical properties is dependent on the extent of trabeculae loss.     

Sex differences in age-related loss of vertebral trabecular bone mass and structure—biomechanical consequences

Density, structure, and biomechanical competence of trabecular bone were analyzed on cylinders from the central part of the third lumbar vertebral body (L₃) from 91 normal individuals aged 15—91 years (48 males and 43 females). A significant and identical age-related decrease (p < 0.001) in bone density (apparent ash-density and trabecular bone volume) was found for both males and females. The structural analyses revealed a marked, age-related increase (p < 0.001) in the distance between the horizontal trabeculae in both sexes. In individuals older than 75 years, this increase was significantly higher for females than for males (p < 0.05). No other significant sex-related differences could be demonstrated in the age-related changes in the trabecular network. The biomechanical compression tests showed a significant and identical age-related decrease (p < 0.001) in stress-values in the vertical direction for both males and females. When horizontal cylinders were compressed, a steady decrease of bone strength was seen in males, while in females there was a tendency to a pronounced loss of bone strength around the age of 40–50 years. The present study demonstrated clearly a sex-related difference in the changes in vertebral trabecular architecture with age, with a higher tendency to perforation of the horizontal supporting struts in females than in males. The biomechanical consequences of this in these normal individuals were minor—but might be very marked in osteoporotic patients.     

One year of alendronate treatment lowers microstructural stresses associated with trabecular microdamage initiation

Alendronate, an anti-remodeling agent, is commonly used to treat patients suffering from osteoporosis by increasing bone mineral density. Though fracture risk is lowered, an increase in microdamage accumulation has been documented in patients receiving alendronate, leading to questions about the potentially detrimental effects of remodeling suppression on the local tissue (material) properties. In this study, trabecular bone cores from the distal femur of beagle dogs treated for one year with alendronate, at doses scaled by weight to approximate osteoporotic and Paget's disease treatment doses in humans, were subjected to uniaxial compression to induce microdamage. Tissue level von Mises stresses were computed for alendronate-treated and non-treated controls using finite element analysis and correlated to microdamage morphology. Using a modified version of the Moore and Gibson classification for damage morphology, we determined that the von Mises stress for trabeculae exhibiting severe and linear microcrack patterns was decreased by approximately 25% in samples treated with alendronate compared with non-treated controls (p<0.01), whereas there was no reduction in the von Mises stress state for diffuse microdamage formation. Furthermore, an examination of the architectural and structural characteristics of damaged trabeculae demonstrated that severely damaged trabeculae were thinner, more aligned with the loading axis, and less mineralized than undamaged trabeculae in alendronate-treated samples (p<0.01). Similar relationships with damage morphology were found only with trabecular orientation in vehicle-treated control dogs. These results indicate that changes in bone's architecture and matrix properties associated with one year of alendronate administration reduce trabecular bone's ability to resist the formation of loading-induced severe and linear microcracks, both of which dissipate less energy prior to fracture than does diffuse damage.     

Quantification of the roles of trabecular microarchitecture and trabecular type in determining the elastic modulus of human trabecular bone.

The roles of microarchitecture and types of trabeculae in determining elastic modulus of trabecular bone have been studied in microCT images of 29 trabecular bone samples by comparing their Young's moduli calculated by finite element analysis (FEA) with different trabecular type-specific reconstructions. The results suggest that trabecular plates play an essential role in determining elastic properties of trabecular bone. INTRODUCTION: Osteoporosis is an age-related disease characterized by low bone mass and architectural deterioration. Other than bone volume fraction (BV/TV), microarchitecture of bone is also believed to be important in governing mechanical properties of trabecular bone. We quantitatively examined the role of microarchitecture and relative contribution of trabecular types of individual trabecula in determining the elastic property of trabecular bone. MATERIALS AND METHODS: Twenty-nine human cadaveric trabecular bone samples were scanned at 21-mum resolution using a microCT system. Digital topological analysis (DTA) consisting of skeletonization and classification was combined with a trabecular type-specific reconstruction technique to extract the skeleton and identify topological type of trabeculae of the original trabecular bone image. Four different microCT-based finite element (FE) models were constructed for each specimen: (1) original full voxel; (2) skeletal voxel; (3) rod-reconstructed, preserving rod volume and plate skeleton; and (4) plate-reconstructed, preserving plate volume and rod skeleton. For each model, the elastic moduli were calculated under compression along each of three image-coordinate axis directions. Plate and rod tissue fractions directly measured from DTA-based topological classification were correlated with the elastic moduli computed from full voxel model. RESULTS: The elastic moduli of skeleton models were significantly correlated with those of full voxel models along all three coordinate axes (r(2) = 0.38 approximately 0.53). The rod-reconstructed model contained 21.3% of original bone mass and restored 1.5% of elastic moduli, whereas the plate-reconstructed model contained 90.3% of bone mass and restored 53.2% of elastic moduli. Plate tissue fraction showed a significantly positive correlation (r(2) = 0.49) with elastic modulus by a power law, whereas rod tissue fraction showed a significantly negative correlation (r(2) = 0.42). CONCLUSIONS: These results quantitatively show that the microarchitecture alone affects elastic moduli of trabecular bone and trabecular plates make a far greater contribution than rods to the bone's elastic behavior.     

The relative contribution of trabecular and cortical bone to the strength of human lumbar vertebrae

An experiment was performed to determine the relative contribution of the cortical shell and of the central trabecular bone to the peak, non-destructive compressive strength of excised human lumbar vertebrae. The vertebral units tested utilized the adjacent intervertebral discs to distribute the loads. Among other results the study indicated that (1) the cortex generally contributes 45–75% of the peak strength, regardless of percent ash or physical density of the trabecular bone; (2) when the ash content of a vertebral trabecular bone is <59%, only 40% or less of the forces are transmitted directly by the central trabecular bone. When the ash content exceeds 59, >40% of the forces are transmitted via the central trabeculae and, as would be expected, (3) less force is transmitted by way of the central trabeculae in older subjects than in those 40 years of age.From the Department of Radiology, Yale University School of Medicine (S.D.R. and E.S.) and the Department of Engineering and Applied Science, Yale University (J.B.). Supported by USPHS Grants AM-09664 and GM-01152     

Biomechanical competence of vertebral trabecular bone in relation to ash density and age in normal individuals

Cylindrical trabecular bone samples from the central part of the first lumbar vertebral body were obtained from 42 normal people (27 females and 15 males) aged 15-87 years and analyzed by a compression test in either vertical or horizontal direction. Maximum stress, maximum stiffness, energy absorption capacity, and strain at maximum stress (compressibility) were calculated from the load-deformation curves. The ash density of the samples was measured after incineration. From age 20 to 80 years, the decline (P less than 0.01) in ash density was 48-50% compared to a 75-80% decrease (P less than 0.001) in vertical stress, stiffness, and energy absorption capacity. Qualitatively similar age-related changes (P less than 0.01) were observed by horizontal compression, but the absolute values were smaller. In both directions, highly significant positive correlations (P less than 0.01) were observed between the biomechanical properties and ash density stress, stiffness and energy absorption capacity still showed significant decreases with age (P less than 0.01). The vertical maximum strain values, which increased (P less than 0.05) with age, were inversely related to the other biomechanical variables (P less than 0.05) and to the ash density (P less than 0.05). It is concluded from the study that the biomechanical competence of vertebral trabecular bone depends not only on bone mass (ash density) but also on the continuity of the trabecular lattice, which changes with increasing age.     

Stochastic simulations of remodeling applied to a two-dimensional trabecular bone structure

In this investigation the stochastic dynamics of trabecular bone remodeling (which is a key concept in a range of remodeling models) is verified. For this purpose, two-dimensional binary images of horizontal histological sections of lumbar vertebral bone (L-3) were collected from young and old subjects. Then the stochastic algorithm of remodeling was applied to the images of young trabecular bone. The resulting images of "simulated" old structures and those of "real" old structures were analyzed to evaluate the following architectural parameters: bone volume/trabecular volume; mean area of marrow cavities; mean trabeculae length; marrow space star volume; Euler number density; trabecular thickness; trabecular number; trabecular separation; mean two-point distance along the skeleton of trabecular structure; probability of disconnection; the ratio of marrow space star volume to geometrical volume and dimensionless ratio of mean area of marrow cavities; and mean trabecular length squared (form factor). Using the parametric t-test, the groups of simulated and real old bone images were compared. It is found that the p value of the t-test is never less than 0.20. For eight parameters the p value is >0.45. It is concluded that, as long as the horizontal sections of lumbar vertebrae are considered (sections perpendicular to the direction of the main spine load), the stochastic algorithm of bone remodeling will properly reproduce the architectural properties of trabecular bone.     

Age-related changes in resorption cavity characteristics in human trabecular bone

The depth of resorption cavities in trabecular bone is an important determinant of bone structure and has implications relevant to the cellular pathophysiology of bone loss in osteoporosis. However, assessment of resorption depth has proved difficult and few data are available; in this study we report age-related changes in iliac crest trabecular bone obtained from 41 normal healthy subjects (21 female, 20 male) aged 22-80 years. Using 8-microns undecalcified sections stained with toluidine blue, resorption cavities were quantitatively assessed by a computerized technique in which the eroded bone surface is reconstructed and measurements made interactively. Maximum and mean cavity depth showed no significant correlation with age in either sex. The absolute length of eroded surface was unrelated to age but the eroded surface/BS (%) and the number of cavities/BS (/mm) showed a significant positive correlation with age (r = 0.384 and 0.386 respectively, p less than 0.05). No significant correlation was found between age and either cavity area or density. These results suggest that increased resorption depth does not contribute to age-related bone loss, although the possibility that deeper resorption cavities occur which result in trabecular penetration and are therefore unrecognizable cannot be discounted. The age-related increase in eroded surface/BS (%) reflects a decreased available trabecular surface and/or increased number of cavities rather than a greater surface length of individual cavities; alternatively it may indicate an increased resorption period. No evidence of increased resorption depth at the time of the menopause was found in this study.     

An orientation distribution function for trabecular bone

We describe a new method for quantifying the orientation of trabecular bone from three-dimensional images. Trabecular lattices from five human vertebrae were decomposed into individual trabecular elements, and the orientation, mass, and thickness of each element were recorded. Continuous functions that described the total mass (M(phi,theta)) and mean thickness (tau(phi,theta)) of all trabeculae as a function of orientation were derived. The results were compared with experimental measurements of the elastic modulus in three principal anatomic directions. A power law scaling relationship between the anisotropies in mass and elastic modulus was observed; the scaling exponent was 1.41 (R2=0.88). As expected, the preponderance of trabecular mass was oriented along the cranial-caudal direction; on average, there was 3.4 times more mass oriented vertically than horizontally. Moreover, the vertical trabeculae were 30% thicker, on average, than the horizontal trabeculae. The vertical trabecular thickness was inversely related to connectivity (R2=0.70; P=0.07), suggesting a possible organization into either few, thick trabeculae or many thin trabeculae. The method, which accounts for the mechanical connectedness of the lattice, provides a rapid way to both visualize and quantify the three-dimensional organization of trabecular bone.     

Effects of short-term alendronate treatment on the three-dimensional microstructural,physical, and mechanical properties of dog trabecular bone

The bisphosphonate, alendronate, is well known for its potent inhibition of osteoclast-mediated bone resorption. It has been used clinically for the treatment of osteoporosis and has also recently been used to reduce osteolysis around prostheses in a canine revision model of implant loosening (femoral condyle). In this study, the effects of alendronate on trabecular bone properties were assessed in dogs at an oral dose of 0.5 mg/kg per day over a 12 week period, and compared with control dogs. Cubic cancellous bone specimens were produced from lumbar vertebrae (L-1 and L-2) and bilateral proximal humeri. These specimens were scanned using a high-resolution microcomputed tomography (micro-CT) system. From accurate data sets, three-dimensional microstructural properties were calculated and physical and mechanical properties were determined. Treatment with alendronate increased bone volume fraction by 9.5%, 7.7%, 7.4%, and 18.4%, respectively, in L-1, L-2, humeral greater tuberosity, and humeral head trabecular bone. In the lumbar vertebrae, the alendronate-treated trabeculae were thicker and lower in bone surface-to-volume ratio. In the greater tuberosity, the alendronate-treated trabeculae were thicker, lower in bone surface-to-volume ratio, and less anisotropic. In the humeral head, the alendronate-treated trabeculae were thicker, less anisotropic, lower in surface density, and showed decreased trabecular separation. Alendronate significantly increased apparent density and collagen density in the lumbar vertebrae and humeral heads, and significantly decreased collagen concentration in the vertebrae. In the lumbar vertebrae, Young's modulus in the cephalocaudal direction, ultimate stress, and failure energy were significantly increased in the alendronate-treated group. The changes in mechanical properties in the humeral head trabecular bone were similar to those seen in the lumbar vertebrae. Our results demonstrate that alendronate increases the mechanical properties of healthy canine trabecular bone after short-term treatment. The physical and microstructural changes of trabecular bone are consistent with the significantly increased mechanical properties.