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Differences in vertebral, tibial, and iliac cancellous bone metabolism in ovariectomized rats

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Abstract

Bone histomorphometry is usually performed on the iliac bone in humans and the tibia or vertebrae in rats. Bone metabolism differences among skeletal sites may be problematic when translating experimental results from rats to humans, but data on such differences in rats are lacking. Therefore, we examined the differences in bone structure and metabolism among skeletal sites using the lumbar vertebra (LV), tibia, and iliac bone obtained from ovariectomized or sham-operated rats preoperatively and at various times from 3 days to 26 weeks postoperatively. The trabeculae were thicker in the LV, where bone metabolism was less active than at other sites, and numerous fine trabeculae were observed in the tibia, where bone metabolism was more active. The iliac bone structure and metabolism were intermediate between those of the tibia and LV. Ovariectomy induced lower bone volume and higher bone metabolism in all skeletal sites, but the changes were greatest and occurred earliest in the tibia, followed by the iliac bone and then LV. Ovariectomy caused changes in bone metabolic markers, which occurred earlier than those in bone tissue. Activation frequency (Ac.f) increased after ovariectomy. At week 26 in ovariectomized rats, Ac.f was highest in the tibia (3.13 N/year) but similar between iliac bone (0.87 N/year) and LV (1.39 N/year). Ac.f is reportedly 0.3–0.4 N/year in the iliac bone of postmenopausal women, suggesting that bone turnover in rats is several times higher than in humans. The reference values reported here are useful for translating experimental results from rats to humans.

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Acknowledgments

This study was funded by Asahi Kasei Pharma Corporation. The authors thank Hiroshi Kuriyama, VMD., for providing scientific advice; Hideyuki Yamato, Ph.D., from Kureha Corporation for providing technical assistance, and Nicholas Smith, PhD, for providing editorial assistance.

Conflict of interest

Aya Takakura, Ryoko Takao-Kawabata, Yukihiro Isogai, and Toshinori Ishizuya are employees of Asahi Kasei Pharma Corporation. Makoto Kajiwara and Hisashi Murayama are employees of Kureha Special Laboratory. Sadakazu Ejiri has no conflicts of interest to report.

Author information

Authors and Affiliations

  1. Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni, Shizuoka, 410-2321, Japan

    Aya Takakura, Ryoko Takao-Kawabata, Yukihiro Isogai & Toshinori Ishizuya

  2. Pharmaceutical Department, Kureha Special Laboratory, 3-26-2 Hyakunincho, Shinjuku-ku, Tokyo, 169-8503, Japan

    Makoto Kajiwara & Hisashi Murayama

  3. Department of Oral Anatomy, Asahi University School of Dentistry, 1851 Hozumi, Mizuho, Gifu, 501-0296, Japan

    Sadakazu Ejiri

Authors
  1. Aya Takakura
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  2. Ryoko Takao-Kawabata
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  3. Yukihiro Isogai
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  4. Makoto Kajiwara
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  5. Hisashi Murayama
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  6. Sadakazu Ejiri
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  7. Toshinori Ishizuya
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Corresponding author

Correspondence to Aya Takakura.

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774_2015_678_MOESM1_ESM.pptx

Fig. S1. Changes in the structural parameters in the lumbar vertebra, iliac bone, and tibia. (a–c) Trabecular bone volume (BV/TV) changes in the lumbar vertebra (a), iliac bone (b), and tibia (c). (d–f) Trabecular thickness (Tb.Th) changes in the lumbar vertebra (d), iliac bone (e), and tibia (f). (g–i) Trabecular number (Tb.N) changes in the lumbar vertebra (g), iliac bone (h), and tibia (i). (j–l) Trabecular separation (Tb.Sp) changes in the lumbar vertebra (j), iliac bone (k), and tibia (l). Closed circles: sham group; open circles: ovariectomy (OVX) group. *p < 0.05, OVX group vs. sham group (Student’s t test). †p < 0.05, for each time point vs. week 0 (Student’s t-test). Fig. S2. Changes in bone resorption parameters in the lumbar vertebra, iliac bone, and tibia. (a–c) Eroded surface (ES/BS) changes in the lumbar vertebra (a), iliac bone (b), and tibia (c). (d–f) Osteoclast surface (Oc.S/BS) changes in the lumbar vertebra (d), iliac bone (e), and tibia (f). (g–i) Osteoclast number (N.Oc/BS) changes in the lumbar vertebra (g), iliac bone (h), and tibia (i). Closed circles: sham group; open circles: ovariectomy (OVX) group. *p < 0.05, OVX group vs. sham group (Student’s t-test). †p < 0.05, for each time point vs. week 0 (Student’s t-test). Fig. S3. Changes in bone formation parameters in the lumbar vertebra, iliac bone, and tibia. (a–c) Osteoid surface (OS/BS) changes in the lumbar vertebra (a), iliac bone (b), and tibia (c). (d–f) Osteoblast surface (Ob.S/BS) changes in the lumbar vertebra (d), iliac bone (e), and tibia (f). Closed circles: sham group; open circles: ovariectomy (OVX) group. *p < 0.05, OVX group vs. sham group (Student’s t-test). †p < 0.05, for each time point vs. week 0 (Student’s t-test). Fig. S4-1. Changes in kinetic parameters in the lumbar vertebra, iliac bone, and tibia. (a–c) Mineralizing surface (MS/BS) changes in the lumbar vertebra (a), iliac bone (b), and tibia (c). (d–f) Mineral apposition rate (MAR) changes in the lumbar vertebra (d), iliac bone (e), and tibia (f). (g–i) Osteoid maturation time (Omt) changes in the lumbar vertebra (g), iliac bone (h), and tibia (i). (j–l) Bone formation rate (BFR/BV) changes in the lumbar vertebra (j), iliac bone (k), and tibia (l). Closed circles: sham group; open circles: ovariectomy (OVX) group. *p < 0.05, OVX group vs. sham group (Student’s t-test). †p < 0.05, for each time point vs. week 0 (Student’s t-test). Fig. S4-2 Changes in kinetic parameters of lumbar vertebra, iliac bone, and tibia. (a–c) Formation period (FP) changes in lumbar vertebra (a), iliac bone (b), and tibia (c). (d–f) Remodeling period (Pm/P) changes in the lumbar vertebra (d), iliac bone (e), and tibia (f). (g–i) Total period (Tt.P) changes in the lumbar vertebra (g), iliac bone (h), and tibia (i). (j–l) Activation frequency (Ac.f) changes in the lumbar vertebra (j), iliac bone (k), and tibia (l). Closed circles: sham group; open circles: ovariectomy (OVX) group. *p < 0.05, OVX group vs. sham group (Student’s t-test). †p < 0.05, for each time point vs. week 0 (Student’s t-test). (PPTX 701 kb)

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Takakura, A., Takao-Kawabata, R., Isogai, Y. et al. Differences in vertebral, tibial, and iliac cancellous bone metabolism in ovariectomized rats. J Bone Miner Metab 34, 291–302 (2016). https://doi.org/10.1007/s00774-015-0678-y

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  • DOI: https://doi.org/10.1007/s00774-015-0678-y

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