Mechanical behavior of human trabecular bone after overloading.

With the etiology of osteoporotic fractures as motivation, the goal of this study was to characterize the mechanical behavior of human trabecular bone after overloading. Specifically, we quantified the reductions in modulus and strength and the development of residual deformations and determined the dependence of these parameters on the applied strain and apparent density. Forty cylindrical specimens of human L1 vertebral trabecular bone were destructively loaded in compression at 0.5% strain per second to strains of up to 3.0% and then immediately unloaded to zero stress and reloaded. (An ancillary experiment on more readily available bovine bone had been performed previously to develop this testing protocol.) In general, the reloading stress-strain curve had a short initial nonlinear region with a tangent modulus similar to Young's modulus. This was followed by an approximately linear region spanning to 0.7% strain, with a reduced residual modulus. The reloading curve always approached the extrapolated envelope of the original loading curve. Percent modulus reduction (between Young's and residual), a quantitative measure of mechanical damage, ranged from 5.2 to 91.0% across the specimens. It increased with increasing plastic strain (r2 = 0.97) but was not related to modulus or apparent density. Percent strength reduction, in the range of 3.6-63.8%, increased with increasing plastic strain (r2 = 0.61) and decreasing apparent density (r2 = 0.23). The residual strains of up to 1.05% depended strongly on applied strain (r2 = 0.96). Statistical comparisons with previous data for bovine tibial bone lend substantial generality to these trends and provide an envelope of expected behavior for other sites. In addition to providing a basis for biomechanical analysis of the effects of damage in trabecular bone at the organ level, these findings support the concept that occasional overloads may increase the risk of fracture by substantially degrading the mechanical properties of the underlying trabecular bone.     

Trabecular Microfracture Precedes Cortical Shell Failure in the Rat Caudal Vertebra Under Cyclic Overloading

Microscopic tissue damage has been observed in otherwise healthy cancellous bone in humans and is believed to contribute to bone fragility and increased fracture risk. Animal models to study microscopic tissue damage and repair in cancellous bone would be useful, but it is currently not clear how loads applied to a whole animal bone are related to the amount and type of resulting microdamage in cancellous bone. In the current study we determine the relationship between applied cyclic compressive overloading and the resulting amount of microdamage in isolated rat tail vertebrae, a bone that has been used previously for in vivo loading experiments. Rat caudal vertebrae (C7–C9, n = 22) were potted in bone cement and subjected to cyclic compressive loading from 0 to 260 N. Loading was terminated in the secondary and tertiary phases of the creep-fatigue curve using custom data-monitoring software. In cancellous bone, trabecular microfracture was the primary form of microdamage observed with few microcracks. Trabecular microfracture prevalence increased with the amount of cyclic loading and occurred in nine out of 10 specimens loaded into the tertiary phase. Only small amounts of microdamage were observed in the cortical shell of the vertebrae, demonstrating that, under axial cyclic loading, damage occurs primarily in regions of cancellous bone before overt fracture of the bone (macroscopic cracks in the cortical shell). These experiments in isolated rat tail vertebrae suggest that it may be possible to use an animal model to study the generation and repair of microscopic tissue damage in cancellous bone.     

Trabecular microfracture

Healing trabecular microfractures are a common feature in cancellous bone. These lesions, when observed in macerated cancellous bone slices, measure about 500 m in diameter and surround fractures in trabeculae with microcallus. Whether microcallus is a structure acting primarily as a transient brace, preventing relative movement of the fragmented segments and enabling the trabecula to heal, or whether it is a permanent buttress reducing the stress on the fractured strut, preventing the healing process, is not known. Microfractures are the result of normal physical activity. Hence, the widespread occurrence of trabecular microfracture in cancellous bone implies that a reasonable rate of microfracture is physiologically tolerable. There are three putative effects for trabecular microfracture. One is that, in response to impulse loading, cancellous subchondral bone increases its rigidity due to osteosclerosis resulting from bone formed around microfractures. Another hypothesis is that, if sufficient trabecular microfractures occur, they will compromise the trabecular structure of the vertebra and the proximal femur leading to osteoporotic fracture. By inducing remodeling changes, microfractures have an effect on the maintenance of joint structure. There are two histological patterns for microfractures: an early stage, when actively forming woven bone is bridging the fracture; and a more common late stage, when woven bone is inactive. Femoral studies fail to demonstrate that an increasing number of healed or healing microfractures in osteoarthrosis causes the increase of bone in the head of femur. Only one study has reported a significant increase in the number of trabecular microfractures in osteoarthrotic femoral heads compared with normal controls. This significant increase was in patients taking antiinflammatory drugs. In osteoporotic fracture, sufficient trabecular microfracture may lead to femoral fracture. The bone loss in the vertebral bodies is by a loss of horizontal trabeculae. This loss reduces the resistance of vertical elements to deformation under load and creates the conditions for trabecular fracture. Coincident with this observation, microfracture is most prevalent on the vertical structure. The increase of microfractures with increasing age has three possible explanations: (l) the incidence of microfracture increases as trabeculae become thinner; (2) the incidence of microfracture is constant but the rate of healing decreases; or (3) these two factors combine to increase the number of microfractures. The occurrence of trabecular microfracture has been shown to correlate with factors such as physical activity, age, bone viability and remodeling potential, cancellous bone volume, bone mineral content, bone fatigue properties, and the direction of cancellous bone loading. As trabecular microfracture is not an event that initiates a pathological process, a number of important questions need to be addressed. Whatever the answers to these questions, trabecular microfracture is intimately linked to the nature of cancellous bone structure, and the conditions under which microfracture will compromise this structure are fundamental to the question of bone quality.Presented at the NIA Workshop on Aging and Bone Quality, September 3–4, 1992, Bethesda, Maryland     

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.     

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.     

Dependence of trabecular damage on mechanical strain

Trabecular damage may play a role in hip fracture, bone remodeling, and prosthesis loosening. We hypothesized that when trabecular bone is loaded beyond its elastic range, both the type and the amount of damage depend on the applied strains. Thirty specimens of trabecular bone from the bovine tibia underwent compression tests to one of three levels of strain (0.4,1.0, and 2.5%) (n = 10 per group). The 0.4% level was a mechanically nondestructive control group that accounted for any systematic errors. Optical microscopy at magnifications as high as × 200 was then used to quantify the trabecular damage for each group. The amount of damage in the yield group (1.0% strain) did not differ from that in the control group (p = 0.66), whereas damage in the post-ultimate strain group (2.5% strain) increased more than 3-fold (p < 0.0008). Four types of damage were observed: transverse cracks, shear bands, parallel cracks, and complete fractures, of which the first two were dominant. These findings therefore indicate that damage occurs within trabeculae at yield. By comparison with our previous work, it can also be concluded that substantial modulus reductions in trabecular bone (as much as 60%) are caused by damage primarily within trabeculae. The ability to detect such damage clinically may improve in vivo estimates of whole-bone strength by identifying regions of densito metrically normal but mechanically compromised trabecular bone.     

A non-invasive in vitro technique for the three-dimensional quantification of microdamage in trabecular bone

An accurate analysis and quantification of microdamage is critical to understand how microdamage affects the mechanics and biology of bone fragility. In this study we demonstrate the development and validation of a novel in vitro micro-computed tomography (microCT) method that employs lead-uranyl acetate as a radio-opaque contrast agent for automated quantification of microdamage in trabecular bone. Human trabecular bone cores were extracted from the femoral neck, scanned via microCT, loaded in unconfined compression to a range of apparent strains (0.5% to 2.25%), stained in lead-uranyl acetate, and subsequently re-scanned via microCT. An investigation of the regions containing microdamage using the backscatter mode of a scanning electron microscope (BSEM) showed that the lead-uranyl sulfide complex was an effective contrast agent for microdamage in bone. Damaged volume fraction (DV/BV), as determined by microCT, increased exponentially with respect to applied strains and proportionately to mechanically determined modulus reduction (p<0.001). Furthermore, the formation of microdamage was observed to occur before any apparent stiffness loss, suggesting that the localized tissue yielding occurs prior to the structural yielding of trabecular bone. This non-invasive in vitro technique for the detection of microdamage using microCT may serve as a valuable complement to existing morphometric analyses of bone.     

Bisphosphonate treatment affects trabecular bone apparent modulus through micro-architecture rather than matrix properties.

Bisphosphonates are emerging as an important treatment for osteoporosis. But whether the reduced fracture risk associated with bisphosphonate treatment is due to increased bone mass, improved trabecular architecture and/or increased secondary mineralization of the calcified matrix remains unclear. We examined the effects of bisphosphonates on both the trabecular architecture and matrix properties of canine trabecular bone. Thirty-six beagles were divided into a control group and two treatment groups, one receiving risedronate and the other alendronate at 5-6 times the clinical dose for osteoporosis treatment. After one year, the dogs were killed, and samples from the first lumbar vertebrae were examined using a combination of micro-computed tomography, finite element modeling, and mechanical testing. By combining these methods, we examined the treatment effects on the calcified matrix and trabecular architecture independently. Conventional histomorphometry and microdamage data were obtained from the second and third lumbar vertebrae of the same dogs [Bone 28 (2001) 524]. Bisphosphonate treatment resulted in an increased apparent Young's modulus, decreased bone turnover, increased calcified matrix density, and increased microdamage. We could not detect any change in the effective Young's modulus of the calcified matrix in the bisphosphonate treated groups. The observed increase in apparent Young's modulus was due to increased bone mass and altered trabecular architecture rather than changes in the calcified matrix modulus. We hypothesize that the expected increase in the Young's modulus of the calcified matrix due to the increased calcified matrix density was counteracted by the accumulation of microdamage.     

In vivo matrix microdamage in a naturally occurring canine fatigue fracture

Greyhound central tarsal bone (CTB) from animals with (n = 11) and without CTB fatigue fracture (n = 15) was examined histologically for the presence, numerical density, and morphology of in vivo microdamage. Complete fracture of the right CTB is a common occurrence during dog racing, because this is the outside limb when running counterclockwise on a circular or oval track. The CTB consisted of both remodeled cortical bone and inner trabecular bone. Thickening and coalescence of trabeculae were observed, particularly dorsally and medially, causing reduction or elimination of the marrow void spaces. A band of tightly packed transverse osteons was also observed adjacent to the concave proximal joint surface. Typical linear microcracks were most often seen in remodeled cortical and trabecular bone and were often observed adjacent to vascular channels. In contrast, ultra-microcracking, represented by diffuse staining with basic fuchsin, was consistently observed in the plantar process around the attachment site for the plantar ligament complex. Dog status (fractured or intact) and side (left or right) both had a significant effect on microcrack density and microcrack surface density (p < 0.05). Microcrack density and microcrack surface density were increased in the right (fractured) CTB from greyhounds with CTB fracture. There was also a trend for side to have a significant effect on microcrack length, with microcrack lengths being higher in the right CTB of both intact and fractured dogs. These data support the general hypothesis that fatigue fracture occurs because of ongoing cyclic stresses after induction of reparative remodeling. Development of methods for biomechanical testing of small cuboidal bones should allow investigation of relationships between accumulation of loading cycles and bone weakening because of microdamage.     

Skeletal Structure in Postmenopausal Women With Osteopenia and Fractures Is Characterized by Abnormal Trabecular Plates and Cortical Thinning

The majority of fragility fractures occur in women with osteopenia rather than osteoporosis as determined by dual‐energy X‐ray absorptiometry (DXA). However, it is difficult to identify which women with osteopenia are at greatest risk. We performed this study to determine whether osteopenic women with and without fractures had differences in trabecular morphology and biomechanical properties of bone. We hypothesized that women with fractures would have fewer trabecular plates, less trabecular connectivity, and lower stiffness. We enrolled 117 postmenopausal women with osteopenia by DXA (mean age 66 years; 58 with fragility fractures and 59 nonfractured controls). All had areal bone mineral density (aBMD) measured by DXA. Trabecular and cortical volumetric bone mineral density (vBMD), trabecular microarchitecture, and cortical porosity were measured by high‐resolution peripheral computed tomography (HR‐pQCT) of the distal radius and tibia. HR‐pQCT scans were subjected to finite element analysis to estimate whole bone stiffness and individual trabecula segmentation (ITS) to evaluate trabecular type (as plate or rod), orientation, and connectivity. Groups had similar age, race, body mass index (BMI), and mean T‐scores. Fracture subjects had lower cortical and trabecular vBMD, thinner cortices, and thinner, more widely separated trabeculae. By ITS, fracture subjects had fewer trabecular plates, less axially aligned trabeculae, and less trabecular connectivity. Whole bone stiffness was lower in women with fractures. Cortical porosity did not differ. Differences in cortical bone were found at both sites, whereas trabecular differences were more pronounced at the radius. In summary, postmenopausal women with osteopenia and fractures had lower cortical and trabecular vBMD; thinner, more widely separated and rodlike trabecular structure; less trabecular connectivity; and lower whole bone stiffness compared with controls, despite similar aBMD by DXA. Our results suggest that in addition to trabecular and cortical bone loss, changes in plate and rod structure may be important mechanisms of fracture in postmenopausal women with osteopenia. © 2014 American Society for Bone and Mineral Research.     

Microstructure Determines Apparent-Level Mechanics Despite Tissue-Level Anisotropy and Heterogeneity of Individual Plates and Rods in Normal Human Trabecular Bone

Trabecular plates and rods determine apparent elastic modulus and yield strength of trabecular bone, serving as important indicators of bone's mechanical integrity in health and disease. Although trabecular bone's apparent-level mechanical properties have been widely reported, tissue mechanical properties of individual trabeculae have not been fully characterized. We systematically measured tissue mineral density (TMD)–dependent elastic modulus of individual trabeculae using microindentation and characterized its anisotropy as a function of trabecular type (plate or rod), trabecular orientation in the global coordinate (longitudinal, oblique, or transverse along the anatomic loading axis), and indentation direction along the local trabecular coordinate (axial or lateral). Human trabecular bone samples were scanned by micro-computed tomography for TMD and microstructural measurements. Individual trabecula segmentation was used to decompose trabecular network into individual trabeculae, where trabecular type and orientation were determined. We performed precise, selective indentation of trabeculae in each category using a custom-built, microscope-coupled microindentation device. Co-localization of TMD at each indentation site was performed to obtain TMD-to-modulus correlations. We found significantly higher TMD and tissue modulus in trabecular plates than rods. Regardless of trabecular type and orientation, axial tissue modulus was consistently higher than lateral tissue modulus, with ratios ranging from 1.13 to 1.41. Correlations between TMD and tissue modulus measured from axial and lateral indentations were strong but distinct: axial correlation predicted higher tissue modulus than lateral correlation at the same TMD level. To assess the contribution of experimentally measured anisotropic tissue properties of individual trabeculae to apparent-level mechanics, we constructed non-linear micro-finite element models using a new set of trabecular bone samples and compared model predictions to mechanical testing measurements. Heterogeneous anisotropic models accurately predicted apparent elastic modulus but were no better than a simple homogeneous isotropic model. Variances in tissue-level properties may therefore contribute nominally to apparent-level mechanics in normal human trabecular bone. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Decreased trabecular width and increased trabecular spacing contribute to bone loss with aging

Resistance to fracture depends not only on the total amount of trabecular bone but also on the size and distribution of the trabeculae. We used an image analysis computer to make direct measurements of trabecular width and separation in 33 normal subjects, aged 20 to 80 years. Multiple regression analysis showed that an increase in the distance between adjacent trabeculae accounted for 67.6% of the reduction in trabecular bone area in normal subjects with advancing age, with an additional 23.2% attributed to decreased trabecular width (P less than 0.001). The role of trabecular atrophy in the loss of bone with age was clearly established from the direct relationship between trabecular bone area and the independently measured trabecular width (r = 0.763, P less than 0.001). Effective treatment could increase trabecular bone by thickening the remaining trabeculae. It is, however, unlikely that treatment would replace trabeculae that have been removed or would restore biomechanical strength to the skeleton.     

Load distribution and the predictive power of morphological indices in the distal radius and tibia by high resolution peripheral quantitative computed tomography

A 3D high resolution peripheral quantitative computed tomography scanner (HR-pQCT) (XtremeCT, Scanco Medical, voxel size 82 microm) has been recently developed that can perform in vivo human measurements on peripheral sites, including the wrist and tibia. The goals of this study were to use HR-pQCT measurements to determine the ability of morphological and density measurements to predict bone apparent stiffness and apparent Young's modulus in the distal radius and tibia, to determine the relative importance of cortical and trabecular bone in carrying load in the human distal radius and tibia. Furthermore, the ability of a sub-volume of trabecular bone apparent Young's modulus to predict the Young's modulus of a whole radius and tibia section was determined. A total of 25 measurements of the radius and 12 measurements of the tibia were used for morphological and finite element analyses of sections, and sub-volume cubes of trabecular bone from the distal radius and tibia. The subjects were chosen to obtain a large variation in age ranges and bone architecture and density. By combining multiple measurements, a strong ability to predict bone apparent stiffness and apparent Young's modulus was found for morphological and density measurements in the radius and tibia (R(2)>0.80). The relative importance of the trabecular and cortical bone in carrying load was also found to vary consistently with location in the sample for both the radius and the tibia. This indicates that measurements of the cortical and trabecular bone are required for assessing fracture risk. A cubic section of trabecular bone was found to be insufficient to accurately represent the apparent bone Young's modulus of a radius or tibia section. Morphological and density measurements of the distal radius and tibia have been shown in this study to predict bone apparent Young's modulus and apparent stiffness, and may indicate when a more time consuming finite element analysis is warranted. It should be noted that these results may be an overestimation of the predictive ability of structural parameters, as the influence of bone density is removed from the finite element analyses, and the results were only influenced by bone structure. A measurement of bone apparent Young's modulus is independent of subject size (as opposed to reaction force), and may provide the ability to distinguish between two patients that have similar mean morphological and density measurements; but different overall structures, and therefore, different fracture risk.     

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.     

Fatigue-induced microdamage in cancellous bone occurs distant from resorption cavities and trabecular surfaces

Impaired bone toughness is increasingly recognized as a contributor to fragility fractures. At the tissue level, toughness is related to the ability of bone tissue to resist the development of microscopic cracks or other tissue damage. While most of our understanding of microdamage is derived from studies of cortical bone, the majority of fragility fractures occur in regions of the skeleton dominated by cancellous bone. The development of tissue microdamage in cancellous bone may differ from that in cortical bone due to differences in microstructure and tissue ultrastructure. To gain insight into how microdamage accumulates in cancellous bone we determined the changes in number, size and location of microdamage sites following different amounts of cyclic compressive loading. Human vertebral cancellous bone specimens (n = 32, 10 male donors, 6 female donors, age 76 ± 8.8, mean ± SD) were subjected to sub-failure cyclic compressive loading and microdamage was evaluated in three-dimensions. Only a few large microdamage sites (the largest 10%) accounted for 70% of all microdamage caused by cyclic loading. The number of large microdamage sites was a better predictor of reductions in Young’s modulus caused by cyclic loading than overall damage volume fraction (DV/BV). The majority of microdamage volume (69.12 ± 7.04%) was located more than 30 μm (the average erosion depth) from trabecular surfaces, suggesting that microdamage occurs primarily within interstitial regions of cancellous bone. Additionally, microdamage was less likely to be near resorption cavities than other bone surfaces (p < 0.05), challenging the idea that stress risers caused by resorption cavities influence fatigue failure of cancellous bone. Together, these findings suggest that reductions in apparent level mechanical performance during fatigue loading are the result of only a few large microdamage sites and that microdamage accumulation in fatigue is likely dominated by heterogeneity in tissue material properties rather than stress concentrations caused by micro-scale geometry.     

Risedronate treatment does not increase microdamage in the canine femoral neck

Cortical and trabecular bone from the femoral neck of 24 adult female beagle dogs was examined for microdamage following 2 years of treatment with risedronate (NE-58095). Specimens of the femoral neck, sectioned between the femoral head and the intertrochanteric groove, were bulk stained in 1 % basic fuchsin in graded alcohols and embedded in methylmethacrylate. Five transverse sections of 100 μm from each specimen were examined for microdamage and measurement of cortical and trabecular area, and three sections from each specimen were measured for calculation of trabecular and cortical bone activation frequency (Ac.f) and bone formation rate (BFR/BV) in the superior and anterior regions of the femoral neck. Although no statistical differences were observed among groups for numerical density or length of microcracks, Kruskal-Wallis analysis showed differences among groups for both cortical and trabecular bone area (p < 0.05). Ac.f was significantly lower in both cortical bone (p < 0.05) and trabecular bone (p < 0.005) of the femoral neck at all dosage levels. No significant difference was observed among groups for trabecular mean wall thickness. The hypothesis that microdamage accumulation increases following reduction in Ac.f was not supported for the canine femoral neck in this experiment. This result could be explained by the fact that microdamage does not accumulate following treatment; that transient increases in microdamage at the beginning of the study period had been repaired; or finally, that the canine femoral neck does not reflect weight-bearing conditions of clinical relevance to humans for assessment of microdamage.     

退行性关节炎与骨质疏松性股骨颈骨小梁的有限元分析

目的以生物力学的观点探讨分析退行性关节炎(OA)及骨质疏松(OP)的临床病变表现。方法建立OA及OP患者股骨颈骨小梁的有限元模型,分别计算指标参数,并利用骨小梁分布密度,配合有限元法计算得到骨小梁组织真正的材料性质,重新模拟破坏的情形,观察不同模型的应变分布,并探讨各指标参数及材料性质对骨小梁强度的影响。结果骨小梁的数量越多、密度越高,达到屈服应变的比例就越低。骨小梁的间隔越大,则达到屈服应变的比例就越高。而骨小梁的表面积比及厚度与结构强度无关。试件的结构刚度、剪切模量及骨小梁组织的弹性模量等材料性质越高,其达到屈服应变的元素的比例就会越低。结论虽然几何外形也是影响材料性质的因素之一,但材料性质对骨小梁强度的影响要比几何外形明显。     

Effects of damage morphology on cortical bone fragility

Despite a general understanding that bone microdamage has distinct strain dependent morphologies, very little information exists on how different damage morphologies develop and participate in bone fracture. In this study, cortical bone beams were subjected to the primary or tertiary phases of bending fatigue followed by either post-hoc fracture toughness tests or microdamage analysis to determine the sequence in which linear microcracks and diffuse damage form during bending fatigue and how they affect the propensity of bone to fracture. The results demonstrate that, following the primary phase, linear microcracks and diffuse damage are formed on the compressive and tensile sides, respectively (p<0.05). Furthermore, this mode of damage formation results in a greater toughness loss if a fracture crack initiates from the tensile side rather than the compressive side (p<0.05). Continued loading of bone specimens to the tertiary phase, however, leads to further accumulation of damage only on the compressive side (p<0.05), and this mode of damage formation results in a further toughness loss if a fracture crack initiates from the compressive side rather than the tensile side (p<0.05). Thus, cortical bone compartmentalizes the damage morphologies in different regions and the sequence of damage production in different phases of cyclic loading to dissipate energy and resist a catastrophic fracture.     

Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures

We recently demonstrated that suppressed bone remodeling allows microdamage to accumulate and causes reductions in some mechanical properties. However, in our previous study, 1 year treatment with high-dose etidronate (EHDP) did not increase microdamage accumulation in most skeletal sites of dogs in spite of complete remodeling suppression and the occurrence of spontaneous fractures of ribs and/or thoracic spinous processes. This study evaluates the effects of EHDP on microdamage accumulation and biomechanical properties before fractures occur. Thirty-six female beagles, 1-2 years old, were treated daily for 7 months with subcutaneous injections of saline vehicle (CNT) or EHDP at 0.5 (E-low) or 5 mg/kg per day (E-high). After killing, bone mineral measurement, histomorphometry, microdamage analysis, and biomechanical testing were performed. EHDP treatment suppressed intracortical and trabecular remodeling by 60%-75% at the lower dose, and by 100% at the higher dose. Osteoid accumulation caused by a mineralization deficit occurred only in the E-high group, and this led to a reduction of mineralized bone mass. Microdamage accumulation increased significantly by two- to fivefold in the rib, lumbar vertebra, ilium, and thoracic spinous process in E-low, and by twofold in the lumbar vertebra and ilium in E-high. However, no significant increase in damage accumulation was observed in ribs or thoracic spinous processes in E-high where fractures occur following 12 months of treatment. Mechanical properties of lumbar vertebrae and thoracic spinous processes were reduced significantly in both E-low and E-high. These findings suggest that suppression of bone remodeling by EHDP allows microdamage accumulation, but that osteoid accumulation reduces production of microdamage.