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

Takuya Ishimoto,Ryosuke Ozasa,Mitsuru Saito,Yoshihiro Matsumoto,Takayoshi Nakano

doi:10.1007/s00223-021-00940-2

Takuya Ishimoto, Ryosuke Ozasa + Show 3 more

Open Access

https://doi.org/10.1007/s00223-021-00940-2

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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.

Highlights

Osteoporosis is associated with increased fracture risk owing to changes in bone quality and quantity
The volumetric BMD (vBMD) decreased in the vehicle group, whereas the administration of IBN at 30 μg/kg (IBN_30) prevented a decrease in vBMD
Young’s modulus, an important mechanical parameter at the bone material level, showed a similar tendency to the apatite orientation; the modulus was significantly increased in the vehicle group, and showed similar values in the IBN_10and IBN_30-groups to that in the sham group

Summary

Introduction

Osteoporosis is associated with increased fracture risk owing to changes in bone quality and quantity. Bone quality is defined as the material, architectural, and mechanical characteristics, other than quantity, which contribute to bone strength. Despite extensive research on bone quantity, there is limited literature regarding bone quality in osteoporosis. There is a need to investigate bone quality in osteoporosis and its treatments. To prevent and treat osteoporotic disorders, various agents, such as bisphosphonates, parathyroid hormone, selective estrogen receptor modulators, receptor activator of NF-κB ligand inhibitor, and calcitonin, have been developed. Anti-osteoporotic agents have unique functions in controlling bone metabolism depending on their action mechanisms; there may be bone changes that cannot be detected from changes in bone mineral density (BMD), which is used as a gold standard in the diagnosis of

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