Comparison of bone loss induced by ovariectomy and neurectomy in rats analyzed by in vivo micro‐CT

Abstract

ABSTRACT:We hypothesized that osteoporosis due to estrogen deficiency progresses faster than due to disuse and that at the same amount of bone loss, disuse leads to less favorable bone structure and mechanical properties than estrogen deficiency. Adult rats were either ovariectomized (OVX) (n ¼ 9) or neurectomized (NX) (n ¼ 8). At week 0, 1, 2, 3, and 4, in vivo micro-CT scans were made of the proximal tibia. Segmented CT-scans at weeks 0 and 4 were used to build a 3D voxel-based micro finite element model (FEM). Displacement in the longitudinal direction was prescribed at the proximal end leading to a compression step of 1%. The severe reduction in metaphyseal bone volume fraction was not significantly different between OVX and NX. Epiphyseal bone loss was less severe in both groups, and BV/TV was significantly lower after NX. Trabecular separation and degree of anisotropy in the metaphysis and connectivity and trabecular number in the epiphysis were significantly more deteriorated after NX. FEM-derived stiffness decreased in both groups, but more after NX. Osteoporosis due to estrogen-deficiency progressed overall at a rate similar to osteoporosis due to disuse. At the same amount of induced bone loss, disuse led to more deteriorated bone structure and mechanical properties than estrogen deficiency. Keywords: estrogen deficiency; disuse; osteoporosis; rats; in vivo micro-CT Osteoporosis is a degenerative bone disease that can develop with reduced estrogen levels during and after menopause and after long periods of disuse. The rat has been used to study osteoporosis, with estrogen deficiency-associated bone loss induced by ovariectomy (OVX), 1-4 and disuse-associated bone loss induced by sciatic neurectomy (NX), tail suspension, or leg taping. 5,6 Both can severely deteriorate bone structure in these models. Differences exist in cellular activity with these forms of bone loss. 7,8 OVX leads to an increased bone formation and resorption rate, disuse leads to decreased turnover rates and increased bone resorption. [9][10][11] This would suggest that bone loss after OVX might proceed faster than that resulting from disuse.Differences also exist in the resulting deterioration of bone mass and microstructure. 9-17 After estrogen deficiency, bone loss is concentrated in the central part of the metaphysis, whereas disuse leads to overall bone loss. 11,13,17 This finding supports the hypothesis that OVX-induced estrogen deficiency increases the mechanostat threshold, 9 leading to low loaded regions being resorbed first, whereas the main loaded structures would remain. With disuse, however, all bone tissue is unloaded, so a more random pattern of bone loss would be expected. 9 This would suggest that disuse-induced osteoporosis would lead to a more severe loss of the main trabecular structures and thus a more severe loss of stiffness and strength in the main loading direction. Upon reloading, distribution of loads in immobilized bones would be very inhomogeneous, because the adaptation to the loading direction is lost. ...

Characterising Bone Material Composition and Structure in the Ovariectomized (OVX) Rat Model of Osteoporosis

“…Our observed declines in BV/TV and Tb.N, and a shift from plate-like trabeculae to rod-like trabeculae are in line with previous publications and confirms the onset of ovariectomy-induced osteoporosis [26][27][28]. One exception to the published literature is the finding of an increase in the Tb.Th parameter in one of the three analyzed regions, i.e.…”

“…Morphological changes and their time-dependence in the trabecular bone structure as a consequence of OVX have been extensively documented based on µCT analysis for both the vertebrae and tibia in rats [26][27][28]. Our observed declines in BV/TV and Tb.N, and a shift from plate-like trabeculae to rod-like trabeculae are in line with previous publications and confirms the onset of ovariectomy-induced osteoporosis [26][27][28].…”

Longitudinal Assessment of In Vivo Bone Dynamics in a Mouse Tail Model of Postmenopausal Osteoporosis

“…Fragility fractures are uncommon in rodents [24], but the strength of the bone must decrease. Therefore, it has been established that bone strength or stiffness can be assessed with mechanical testing [25,26] or finite element analysis [27] as a surrogate for bone fragility.…”

Biomechanical Study of the Effects of Balloon Kyphoplasty on the Adjacent Vertebrae

“…Construction of 3D FE model. Bone geometrical features were extracted from CT DICOM by using Mechanical Finder (MF) software [9]. used to construct heterogeneous 3-dimensional (3D) finite element (FE) models (T11-L3) (Figure 2).…”