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Alendronate does not prevent long bone fragility in an inactive rat model

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Abstract

The lack of estrogen and inactivity are both important in the pathogenesis of osteoporosis in elderly women, and there have been no appropriate rodent studies to examine the effects of common bisphosphonates on these two components separately. We compared the efficacy of alendronate (ALN) on the long bones of aged female rats, which were sedentary, estrogen deficient, or both. The rats were either forced to remain in a sitting position or allowed to walk in standard cages with or without ALN administration. The 8-week experimental period began 5 weeks after ovariectomy or sham surgery. Parameters of the hindlimb bones were determined by a three-point bending test, peripheral quantitative computed tomography, microfocus computed tomography, confocal laser Raman microspectroscopy, and dynamic histomorphometry. Regardless of ovariectomy, ALN was ineffective against the deterioration of breaking stress caused by sitting even though the trabecular bone mineral density was significantly higher in the sitting–ALN groups. Toughness was significantly deficient in the ovariectomy sitting–ALN group. This was in agreement with the bone geometry with a greater marrow space. Sitting also increased the mineral-to-matrix ratio and the carbonate-to-phosphate ratio, both indicative of aged bone. A greater loss of proteinaceous amide intensity compared with mineral intensity resulted in an increased mineral-to-matrix ratio in the presence of ALN. Sitting resulted in deficits in the quality and the geometry of cortical bone, resulting in fragility. The use of bisphosphonates, such as ALN, may provide a therapy best suited for osteoporotic individuals whose daily activity is not limited.

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Acknowledgments

C. Shimada and H. Kawabata provided indispensable technical assistance. This study was supported by Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research to K.N., M.I., and Y.M.T.

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Author notes

  1. M. Suto

    Present address: Suto Orthopedic Clinic, Katagama, Japan

Authors and Affiliations

  1. Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan

    K. Naruse, K. Uchida, M. Suto, K. Urabe, M. Takaso & M. Itoman

  2. First Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, Osaka, Japan

    K. Miyagawa

  3. Department of Oral Sciences, Division of Molecular and Cellular Biology of Mineralized Tissues, Kanagawa Dental University Graduate School of Dentistry, 82 Inaokacho, Yokosuka, Kanagawa, 238-8580, Japan

    A. Kawata & Y. Mikuni-Takagaki

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Correspondence to Y. Mikuni-Takagaki.

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K. Naurse and K. Uchida contributed equally to this work.

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Naruse, K., Uchida, K., Suto, M. et al. Alendronate does not prevent long bone fragility in an inactive rat model. J Bone Miner Metab 34, 615–626 (2016). https://doi.org/10.1007/s00774-015-0714-y

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  • DOI: https://doi.org/10.1007/s00774-015-0714-y

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