The effects of bone remodeling inhibition by alendronate on three-dimensional microarchitecture of subchondral bone tissues in guinea pig primary osteoarthrosis.
ABSTRACT We assessed whether increase of subchondral bone density enhances cartilage stress during impact loading, leading to progressive cartilage degeneration and accelerated osteoarthrosis (OA) progression. Sixty-six male guinea pigs were randomly divided into six groups. During a 9-week treatment period, four groups received twice-weekly subcutaneous injections of alendronate (ALN) in two doses: two groups received 10 microg/kg and two groups received 50 microg/kg. The two control groups received vehicle. After 9 weeks, one 10 microg/kg ALN group, one 50 microg/kg ALN group, and one control group were killed. The remaining three groups (17-week groups) were left for an additional 8 weeks, receiving the same treatment regimen before death. The left proximal tibiae were scanned by micro-computed tomography to quantify the microarchitecture of subchondral bone, followed by mechanical testing and determination of collagen and mineral. The control groups had typical OA-related cartilage degeneration at 9 and 17 weeks, whereas the 50 microg/kg ALN group had even worse degeneration in the medial condyle. It is unclear whether there is a direct or a secondary effect of ALN on the cartilage. The 9-week ALN group had significantly greater subchondral plate thickness. The 9- and 17-week groups had similar changes of cancellous bone microarchitecture, with greater volume fraction and connectivity and an extremely plate-like structure. The 9-week ALN group had greater bone mineral concentration, and the 17-week ALN group had reduced collagen concentration and greater mineral concentration. Treatment with ALN did not significantly change the mechanical properties of the cancellous bone.
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ABSTRACT: Recent development in three-dimensional (3-D) imaging of cancellous bone has made possible true 3-D quantification of trabecular architecture. This provides a significant improvement of the tools available for studying and understanding the mechanical functions of cancellous bone. This article reviews the different techniques for 3-D imaging, which include serial sectioning, X-ray tomographic methods, and NMR scanning. Basic architectural features of cancellous bone are discussed, and it is argued that connectivity and architectural anisotropy (fabric) are of special interest in mechanics-architecture relations. A full characterization of elastic mechanical properties is, with traditional mechanical testing, virtually impossible, but 3-D reconstruction in combination with newly developed methods for large-scale finite element analysis allow calculations of all elastic properties at the cancellous bone continuum level. Connectivity has traditionally been approached by various 2-D methods, but none of these methods have any known relation to 3-D connectivity. A topological approach allows unbiased quantification of connectivity, and this further allows expressions of the mean size of individual trabeculae, which has previously also been approached by a number of uncertain 2-D methods. Anisotropy may be quantified by fundamentally different methods. The well-known mean intercept length method is an interface-based method, whereas the volume orientation method is representative of volume-based methods. Recent studies indicate that volume-based methods are at least as good as interface-based methods in predicting mechanical anisotropy. Any other architectural property may be quantified from 3-D reconstructions of cancellous bone specimens as long as an explicit definition of the property can be given. This challenges intuitive and vaguely defined architectural properties and forces bone scientists toward 3-D thinking.Bone 05/1997; 20(4):315-28. · 3.82 Impact Factor
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ABSTRACT: The “mature rat model” is an effective and often-used surrogate for studying mechanisms and characteristics of estrogen-deficient osteopenia. The purpose of this study was to extend our understanding of this animal model to include the mechanical properties of cancellous bone in the proximal tibia. Female Sprague–Dawley rats were divided into two groups (n = 13 each) at 14 weeks of age: an ovariectomized group (OVX) and a sham-operated control group (sham). The study terminated after a duration of 5 weeks. Specimens 2 mm long were cut from the proximal tibial metaphysis just below the growth plate and tested using two methods: (1) “whole-slice” compression, in which the entire specimen is loaded between two larger flat platens and (2) “reduced-platen” compression (RPC), which uses platens sized and aligned to load only the cancellous bone in the center of the sample. Three-point bending tests also were conducted on the femur. The short duration of estrogen deficiency yielded only minimal differences (< 10%) in femoral cortical bone but dramatic reductions (∼60%) in cancellous bone properties as determined by the RPC method. Ultimate stress was 7.23 MPa ± 1.97 MPa for OVX versus 18.1 MPa ± 5.21 MPa for sham; and elastic modulus was 252 MPa ± 104 MPa for OVX versus 603 MPa ± 180 MPa for sham. These changes in mechanical properties are similar in many respects to the dramatic effects reported in histomorphometric studies. For the whole-slice method, differences in mechanical properties between the two groups were not as large because the test directly loads both cancellous and cortical bone, and the latter is not affected as severely by estrogen deficiency. In this case, ultimate stress and elastic modulus were only 30% (or less) lower for the OVX group. (J Bone Miner Res 2000;15:284–292)Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2000; 15(2):284 - 292. · 6.04 Impact Factor
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ABSTRACT: Knee joints from cynomolgus monkeys of both genders and a wide range of ages were examined to characterize further the natural history of osteoarthritis (OA) in these animals. The objectives of this study were to characterize better the subchondral bone changes previously noted in this disease, to determine whether the severity of OA in these animals is affected by age or weight, and to determine whether males and females are affected similarly. As had been seen in previous studies, the medial tibial plateau was the most severely affected site. The thickness of the subchondral plate in the medial tibial plateau increased with increasing severity of articular cartilage lesions in both males and females; however, in monkeys with subchondral plate thicknesses less than 400 microns, articular cartilage lesions were essentially absent. Subchondral plate thickness increased with increasing weight in both genders, but females had a higher subchondral plate thickness than males for a given body weight. There was no correlation between bone volume in the proximal tibial epiphysis and articular cartilage lesions of OA. The prevalence and severity of OA in the medial tibial plateau increased with increasing age, but were not affected by gender or weight. Although there was no correlation between articular cartilage lesions and body mass index or weight, the waist/hip circumference ratio and severity of articular cartilage lesions were correlated in the female monkeys. This work provides evidence that thickening of the subchondral bone plate may be more important than the volume of epiphyseal/metaphyseal cancellous bone in determining the biomechanical stresses in the joint and in influencing the development of articular cartilage lesions.Journal of Bone and Mineral Research 10/1996; 11(9):1209-17. · 6.13 Impact Factor