Skip to main content
SpringerLink
Log in

Effect of intermittent treatment with human parathyroid hormone 1–34 in SAMP6 senescence-accelerated mice

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

We examined trabecular and cortical bone in the senescence-accelerated mouse prone 6 (SAMP6) murine model of senile osteoporosis after treatment with human PTH 1–34. Sixteen-week-old female SAMP6 mice were assigned to control and PTH groups. PTH (20 μg/kg) was administered sc 3 times a week for 12 weeks. The control mouse strain, senescence-accelerated mouse resistant 1 (SAMR1), was used for comparison. The femoral metaphysis and diaphysis were used to measure bone mineral density (BMD), analyze the trabecular and the cortical structure by micro-computed tomography, and for conducting the bone strength test. PTH significantly attenuated the loss of BMD, improved the trabecular bone microstructure, and increased the bone strength in the femoral metaphysis. We did not find any differences in the bone strength of the femoral diaphysis after PTH treatment, although the cortical bone volume and cortical thickness were improved. Although the cortical thickness increased, the cortical bone density decreased, likely because of the increase of cortical porosity in the distal metaphysis after administration of PTH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Takeda T, Hosokawa M, Takeshita S, et al. A new murine model of accelerated senescence. Mech Ageing Dev 1981, 17: 183–94.

    Article  PubMed  CAS  Google Scholar 

  2. Matsushita M, Tsuboyama T, Kasai R, et al. Age-related changes in bone mass in the senescence-accelerated mouse (SAM). SAM-R/3 and SAM-P/6 as new murine models for senile osteoporosis. Am J Pathol 1986, 125: 276–83.

    PubMed Central  PubMed  CAS  Google Scholar 

  3. Ohnishi K, Tomimoto H, Akiguchi I, et al. Age-related decrease of nerve growth factor-like immunoreactivity in the basal forebrain of senescence-accelerated mice. Acta Neuropathol 1995, 90: 11–6.

    Article  PubMed  CAS  Google Scholar 

  4. Takeda T, Hosokawa M, Higuchi K. Senescence-accelerated mouse (SAM): a novel murine model of senescence. Exp Gerontol 1997, 32: 105–9.

    Article  PubMed  CAS  Google Scholar 

  5. Kasai S, Shimizu M, Matsumura T, et al. Consistency of low bone density across bone sites in SAMP6 laboratory mice. J Bone Miner Metab 2004, 22: 207–14.

    Article  PubMed  Google Scholar 

  6. Jilka RL, Weinstein RS, Takahashi K, Parfitt AM, Manolagas SC. Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence. J Clin Invest 1996, 97: 1732–40.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Shimizu M, Higuchi K, Kasai S, et al. Chromosome 13 locus, Pbd2, regulates bone density in mice. J Bone Miner Res 2001, 16: 1972–82.

    Article  PubMed  CAS  Google Scholar 

  8. Shimizu M, Higuchi K, Kasai S, et al. A congenic mouse and candidate gene at the Chromosome 13 locus regulating bone density. Mamm Genome 2002, 13: 335–40.

    Article  PubMed  CAS  Google Scholar 

  9. Body JJ, Gaich GA, Scheele WH, et al. A randomized double-blind trial to compare the efficacy of teriparatide [recombinant human parathyroid hormone (1–34)] with osteoporosis. J Clin Endocrinol Metab 2002, 87: 4528–35.

    Article  PubMed  CAS  Google Scholar 

  10. Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Eng J Med 2001, 344: 1434–41.

    Article  CAS  Google Scholar 

  11. Greenspan SL, Bone HG, Ettinger MP, et al. Effect of recombinant human parathyroid hormone (1–84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis: a randomized trial. Ann Intern Med 2007, 146: 326–39.

    Article  PubMed  Google Scholar 

  12. Wronski TJ, Yen CF, Qi H, Dann LM. Parathyroid hormone is more effective than estrogen or bisphosphonates for restoration of lost bone mass in ovariectomized rats. Endocrinology 1993, 132: 823–31.

    PubMed  CAS  Google Scholar 

  13. Zhang L, Endo N, Yamamoto N, Tanizawa T, Takahashi HE. Effects of single and concurrent intermittent administration of human PTH (1–34) and incadronate on cancellous and cortical bone of femoral neck in ovariectomized rats. Tohoku J Exp Med 1998, 186: 131–41.

    Article  PubMed  CAS  Google Scholar 

  14. Jerome CP, Burr DB, Van Bibber T, Hock JM, Brommage R. Treatment with human parathyroid hormone (1–34) for 18 months increases cancellous bone volume and improves trabecular architecture in ovariectomized cynomolgus monkeys (Macaca fascicularis). Bone 2001, 28: 150–9.

    Article  PubMed  CAS  Google Scholar 

  15. Washimi Y, Ito M, Morishima Y, et al. Effect of combined human PTH (1–34) and calcitonin treatment in ovariectomized rats. Bone 2007, 41: 786–93.

    Article  PubMed  CAS  Google Scholar 

  16. Okimoto N, Tsurukami H, Okazaki Y, et al. Effects of a weekly injection of human parathyroid hormone (1–34) and withdrawal on bone mass, strength, and turnover in mature ovariectomized rats. Bone 1998, 22: 523–31.

    Article  PubMed  CAS  Google Scholar 

  17. Hahn M, Vogel M, Pompesius-Kempa M, Delling G. Trabecular bone pattern factor—a new parameter for simple quantification of bone microarchitecture. Bone 1992, 13: 327–30.

    Article  PubMed  CAS  Google Scholar 

  18. Laib A, Kumer JL, Majumdar S, Lane NE. The temporal changes of trabecular architecture in ovariectomized rats assessed by microCT. Osteoporos Int 2001, 12: 936–41.

    Article  PubMed  CAS  Google Scholar 

  19. Silva MJ, Brodt MD, Ettner SL. Long bones from the senescence accelerated mouse SAMP6 have increased size but reduced wholebone strength and resistance to fracture. J Bone Miner Res 2002, 17: 1597–603.

    Article  PubMed  Google Scholar 

  20. Akhter MP, Cullen DM, Gong G, Recker RR. Bone biomechanical properties in prostaglandin EP1 and EP2 knockout mice. Bone 2001, 29: 121–5.

    Article  PubMed  CAS  Google Scholar 

  21. Kodama Y, Takeuchi Y, Suzawa M, et al. Reduced expression of interleukin-11 in bone marrow stromal cells of senescence-accelerated mice (SAMP6): relationship to osteopenia with enhanced adi-pogenesis. J Bone Miner Res 1998, 13: 1370–7.

    Article  PubMed  CAS  Google Scholar 

  22. Kim GS, Kim CH, Choi CS, Park JY, Lee KU. Involvement of different second messengers in parathyroid hormone-and interleukin-1-induced interleukin-6 and interleukin-11 production in human bone marrow stromal cells. J Bone Miner Res 1997, 12: 896–902.

    Article  PubMed  CAS  Google Scholar 

  23. Jilka RL. Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone 2007, 40: 1434–46.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Ophoff J, Venken K, Callewaert F, Boonen S, Bouillon R, Vanderschueren D. Sex steroids during bone growth: a comparative study between mouse models for hypogonadal and senile osteoporosis. Osteoporos Int 2009, 20: 1749–57.

    Article  PubMed  CAS  Google Scholar 

  25. Sato M, Westmore M, Ma YL, et al. Teriparatide [PTH(1–34)] strengthens the proximal femur of ovariectomized nonhuman primates despite increasing porosity. J Bone Miner Res 2004, 19: 623–9.

    Article  PubMed  CAS  Google Scholar 

  26. Jiang Y, Zhao JJ, Mitlak BH, Wang O, Genant HK, Eriksen EF. Recombinant human parathyroid hormone (1–34) [teriparatide]improves both cortical and cancellous bone structure. J Bone Miner Res 2003, 18: 1932–41.

    Article  PubMed  CAS  Google Scholar 

  27. Recker RR, Bare SP, Smith SY, et al. Cancellous and cortical bone architecture and turnover at the iliac crest of postmenopausal osteoporotic women treated with parathyroid hormone 1–84. Bone 2009, 44: 113–9.

    Article  PubMed  CAS  Google Scholar 

  28. Fox J, Miller MA, Newman MK, Recker RR, Turner CH, Smith SY. Effects of daily treatment with parathyroid hormone 1–84 for 16 months on density, architecture and biomechanical properties of cortical bone in adult ovariectomized rhesus monkeys. Bone 2007, 41: 321–30.

    Article  PubMed  CAS  Google Scholar 

  29. Tazawa K, Hoshi K, Kawamoto S, Tanaka M, Ejiri S, Ozawa H. Osteocytic osteolysis observed in rats to which parathyroid hormone was continuously administered. J Bone Miner Metab 2004, 22: 524–9.

    Article  PubMed  CAS  Google Scholar 

  30. Lotinun S, Evans GL, Bronk JT, et al. Continuous parathyroid hormone induces cortical porosity in the rat: effects on bone turnover and mechanical properties. J Bone Miner Res 2004, 19: 1165–71.

    Article  PubMed  CAS  Google Scholar 

  31. Ejersted C, Andreassen TT, Oxlund H, et al. Human parathyroid hormone (1–34) and (1–84) increase the mechanical strength and thickness of cortical bone in rats. J Bone Miner Res 1993, 8: 1097–101.

    Article  PubMed  CAS  Google Scholar 

  32. Hirano T, Burr DB, Cain RL, Hock JM. Changes in geometry and cortical porosity in adult, ovary-intact rabbits after 5 months treatment with LY333334 (hPTH 1–34). Calcif Tissue Int 2000, 66: 456–60.

    Article  PubMed  CAS  Google Scholar 

  33. Burr DB, Hirano T, Turner CH, Hotchkiss C, Brommage R, Hock JM. Intermittently administered human parathyroid hormone(1–34) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgus monkeys. J Bone Miner Res 2001, 16: 157–65.

    Article  PubMed  CAS  Google Scholar 

  34. Fujita T, Inoue T, Morii H, et al. Effect of an intermittent weekly dose of human parathyroid hormone (1–34) on osteoporosis: a randomized double-masked prospective study using three dose levels. Osteoporos Int 1999, 9: 296–306.

    Article  PubMed  CAS  Google Scholar 

  35. Black DM, Bouxsein ML, Palermo L, et al; PTH Once-Weekly Research (POWR) Group. Randomized trial of once-weekly parathyroid hormone (1–84) on bone mineral density and remodeling. J Clin Endocrinol Metab 2008, 93: 2166–72.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedic Surgery, Fujita Health University, 1–98 Dengakugakubo, Kutukake-cho, Toyoake City, Aichi 470-1192, Japan

    Y. Washimi MD, Y. Yamamoto & H. Yamada

  2. Department of Anatomy, Gifu University Graduate School, Gifu City

    Y. Washimi MD & H. Chen

  3. Laboratory for Development Pharmacology, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Izunokuni City, Japan

    A. Ito, R. Takao & T. Uzawa

  4. Department of Physical Therapy, Chubu Gakuin University Faculty of Rehabilitation, Seki City, Japan

    S. Shoumura

Authors
  1. Y. Washimi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Takao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. Uzawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y. Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. Shoumura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. Washimi MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Washimi, Y., Chen, H., Ito, A. et al. Effect of intermittent treatment with human parathyroid hormone 1–34 in SAMP6 senescence-accelerated mice. J Endocrinol Invest 33, 395–400 (2010). https://doi.org/10.1007/BF03346610

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03346610

Keywords

Search

Navigation