Ibandronate Suppresses Changes in Apatite Orientation and Young's Modulus Caused by Estrogen Deficiency in Rat Vertebrae

Abstract

Bone material quality is important for evaluating the mechanical integrity of diseased and/or medically treated bones. However, compared to the knowledge accumulated regarding changes in bone mass, our understanding of the quality of bone material is lacking. In this study, we clarified the changes in bone material quality mainly characterized by the preferential orientation of the apatite c-axis associated with estrogen deficiency-induced osteoporosis, and their prevention using ibandronate (IBN), a nitrogen-containing bisphosphonate. IBN effectively prevented bone loss and degradation of whole bone strength in a dose-dependent manner. The estrogen-deficient condition abnormally increased the degree of apatite orientation along the craniocaudal axis in which principal stress is applied; IBN at higher doses played a role in maintaining the normal orientation of apatite but not at lower doses. The bone size-independent Young's modulus along the craniocaudal axis of the anterior cortical shell of the vertebra showed a significant and positive correlation with apatite orientation; therefore, the craniocaudal Young's modulus abnormally increased under estrogen-deficient conditions, despite a significant decrease in volumetric bone mineral density. However, the abnormal increase in craniocaudal Young's modulus did not compensate for the degradation of whole bone mechanical properties due to the bone loss. In conclusion, it was clarified that changes in the material quality, which are hidden in bone mass evaluation, occur with estrogen deficiency-induced osteoporosis and IBN treatment. Here, IBN was shown to be a beneficial drug that suppresses abnormal changes in bone mechanical integrity caused by estrogen deficiency at both the whole bone and material levels.

Keywords: Apatite orientation; Bone quality; Ibandronate; Material anisotropy; Mechanical integrity; Osteoporosis.

Fig. 1

Protocol of animal experiment

Fig. 2

Microbeam X-ray diffractometer (μXRD) analysis of the degree of apatite c-axis orientation. a Schematic drawing of optical system with bone specimen and b a typical obtained μXRD pattern (Debye rings)

Fig. 3

Change in body weight throughout experimental period (n = 7). *: p < 0.05 vs sham for all of OVX groups

Fig. 4

Change in bone mass of the fourth lumbar (L4) vertebral body. a Cross-sectional micro-computed tomography (μCT) images and b cross-sectional area of cortex at the center of the L4 vertebral body (n = 7). a p < 0.05 vs sham; b p < 0.05 vs vehicle; *p < 0.05

Fig. 5

Architectural analysis of trabecular bone in the fourth lumbar (L4) vertebral body (n = 7). a p < 0.05 vs sham; b p < 0.05 vs vehicle; *p < 0.05

Fig. 6

Variations in material properties analyzed in the fourth lumbar (L4) vertebral body cortex (n = 7). a p < 0.05 vs sham; b p < 0.05 vs vehicle

Fig. 7

Correlation analyses between Young’s modulus and volumetric BMD (vBMD), apatite crystalline size, and degree of apatite c-axis orientation

Fig. 8

Variations in whole bone mechanical properties of fifth lumber (L5) vertebral body (n = 7). a p < 0.05 vs sham; b p < 0.05 vs vehicle; *p < 0.05