Combination treatment with ibandronate and eldecalcitol prevents osteoporotic bone loss and deterioration of bone quality characterized by nano-arrangement of the collagen/apatite in an ovariectomized aged rat model

Ozasa, Ryosuke; Saito, Mitsuru; Ishimoto, Takuya; Matsugaki, Aira; Matsumoto, Yoshihiro; Nakano, Takayoshi

Affiliations

¹Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan

²Department of Orthopaedic Surgery, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan

³Product Research Department, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan

Abstract and keywords

Combination therapy with bisphosphonates and vitamin D3 analogs has been frequently used for the treatment of osteoporosis. However, its effects on bone anisotropies, such as orientations of collagen and apatite at the nanometer-scale, which is a promising bone quality index, and its trabecular architecture at the micrometer scale, are not well understood despite its important mechanical properties and its role in fracture risk. In the present study, we analyzed the effects of ibandronate (IBN), eldecalcitol (ELD), and their combination on the collagen/apatite orientation and trabecular architectural anisotropy using an estrogen-deficiency-induced osteoporotic rat model. Estrogen deficiency caused by ovariectomy (OVX) excessively increased the degree of collagen/apatite orientation or trabecular architectural anisotropy along the craniocaudal axis in the lumbar vertebra compared to that of the sham-operated group. The craniocaudal axis corresponds to the direction of principal stress in the spine. The excessive material anisotropy in the craniocaudal axis contributed to the enhanced Young’s modulus, which may compensate for the reduced mechanical resistance by bone loss to some extent. The solo administration of IBN and ELD prevented the reduction of bone fraction (BV/TV) determined by μ-CT, and combination therapy showed the highest efficacy in BV/TV gain. Furthermore, the solo administration and combination treatment significantly decreased the degree of collagen/apatite orientation to the sham level. Based on the results of bone mass and collagen/apatite orientation, combination treatment is an effective strategy. This is the first report to demonstrate the efficacy of IBN, ELD, and combination treatment with IBN and ELD relative to the bone micro-architectural anisotropy characterized by collagen/apatite orientation.

Keywords: Osteoporosis treatment; Combination therapy; Ibandronate; Eldecalcitol; Bone quality; Collagen/apatite orientation; ECM; extracellular matrix; IBN; ibandronate; ELD; eldecalcitol; OVX; ovariectomy; µ-CT; micro-computed tomography; BV/TV; bone volume fraction; Tb.Th; trabecular thickness; Tb.N; trabecular number; Tb.Sp; trabecular separation; DA; degree of anisotropy; SMI; structure model index; vBMD; volumetric bone mineral density; pQCT; peripheral quantitative computed tomography; µ-XRD; microbeam X-ray diffraction; PSPC; position sensitive proportional counter

Links

DOI: 10.1016/j.bone.2021.116309

PubMed: 34998980

WoS: 000773553100003

History

Received: 2021-11-11

Revised: 2021-12-20

Accepted: 2021-12-20

Online: 2022-01-5

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