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Alendronate treatment promotes bone formation with a less anisotropic microstructure during intramembranous ossification in rats

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Abstract

There are safety concerns regarding administration of bisphosphonates to children. Little is known about the effects of bisphosphonates on bone matrix organization during bone modeling. The present study examined the effects of alendronate (ALN) on bone matrices formed by intramembranous ossification in the appendicular growing skeleton. ALN was administered to 1-week-old Sprague–Dawley rats at a dose of 0, 35, or 350 µg/kg/week for 4 or 8 weeks. The position of femoral diaphysis formed exclusively by intramembranous ossification was identified, and cross sections of cortical bone at this position were analyzed. Bone mineral density (BMD) and geometric parameters were evaluated using peripheral quantitative computed tomography. The preferential orientation degree of biological apatite (BAp) crystals in the bone longitudinal direction, which shows the degree of bone matrix anisotropy, was evaluated using microbeam X-ray diffraction analysis. We analyzed bone histomorphometrical parameters and performed bone nanomechanical tests to examine the material properties of newly developing cortical bone. The preferential orientation degree of BAp crystals significantly decreased in 35 µg/kg/week ALN-treated groups compared with vehicle-treated groups, although there were no significant differences in BMD between the two groups. The periosteal mineral apposition rate significantly increased in the 35 µg/kg/week ALN-treated group. We found a high negative correlation between bone matrix anisotropy and the regional periosteal mineral apposition rate (r = −0.862, P < 0.001). Nanomechanical tests revealed that 35 µg/kg/week ALN administration caused deterioration of the material properties of the bone microstructure. These new findings suggest that alendronate affects bone matrix organization and promotes bone formation with a less anisotropic microstructure during intramembranous ossification.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Faculty of Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Masafumi Kashii, Jun Hashimoto & Hideki Yoshikawa

  2. Division of Materials & Manufacturing Science, Graduate School of Engineering, Osaka University, Osaka, Japan

    Takayoshi Nakano & Yukichi Umakoshi

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  1. Masafumi Kashii
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  2. Jun Hashimoto
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  3. Takayoshi Nakano
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  4. Yukichi Umakoshi
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  5. Hideki Yoshikawa
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Correspondence to Masafumi Kashii.

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Kashii, M., Hashimoto, J., Nakano, T. et al. Alendronate treatment promotes bone formation with a less anisotropic microstructure during intramembranous ossification in rats. J Bone Miner Metab 26, 24–33 (2008). https://doi.org/10.1007/s00774-007-0782-8

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