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Effects of single and concurrent intermittent administration of human parathyroid hormone and bisphosphonate cimadronate on bone mineral densities of femur in ovariectomized rats

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Abstract

This study compared the single administration of human parathyroid hormone [hPTH(1-34)] or bisphosphonate cimadronate (YM-175), and concurrent therapy with both of these agents for restoration of lost bone mineral density (BMD) in ovariectomized (OVX) rats. Animals were untreated for 4 weeks after surgery, and then injected s.c. with vehicle (OVX+V), hPTH(l-34) (30μg/kg) (OVX+P), YM-175 (5μg/kg) (OVX+Y), or a combination of these two (OVX+P+Y), 3 days a week, for 8 weeks, and killed. BMD of distal, middle, and total femur were determined by dual-energy X-ray absorptiometry (DXA). BMD of distal and total femur, but not of midfemur, decreased at both 4 weeks and 12 weeks after ovariectomy. In the distal femoral BMD, although OVX+Y failed to restore lost BMD in OVX rats, either OVX+P or OVX+P+Y could reverse BMD lost due to OVX. Midfemoral BMD was unchanged through OVX or both single treatments, whereas this parameter was increased only in OVX+P+Y. These results suggest that concurrent treatment with PTH and YM-175 results in a bone anabolic effect not only in cancellous bone but also in cortical bone.

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References

  1. Tam CS, Heersche JNM, Murray TM, Parsons JA (1982) Parathyroid hormone stimulates the bone apposition rate independently of its resorptive action: differential effects of intermittent and continuous administration. Endocrinology 110:506–512

    PubMed  Google Scholar 

  2. Gunness-Hey M, Hock JM (1984) Increased trabecular bone mass in rats treated with synthetic human parathyroid hormone. Metab Bone Dis 5:177–181

    Google Scholar 

  3. Hock JM, Gera I (1992) Effects of continuous and intermittent administration and inhibition of resorption on the anabolic response of bone to parathyroid hormone. J Bone Miner Res 7:65–72

    PubMed  Google Scholar 

  4. Jerome CP (1994) Anabolic effect of high doses of human parathyroid hormone (1-38) in mature intact female rats. J Bone Miner Res 9:933–942

    PubMed  Google Scholar 

  5. Oxlund H, Ejersted C, Andreassen TT, Torring O, Nilsson MHL (1993) Parathyroid hormone (1-34) and (1-84) stimulate bone formation both periosteum and endosteum. Calcif Tissue Int 53:394–399

    PubMed  Google Scholar 

  6. Reeve J, Meunier PJ, Parsons JA, Bernard M, Buvoet OLM, Courpron P, Edouard C, Klenerman L, Neer RM, Renier JC, Slovik O, Vismans FJFE, Potts JT (1980) Anabolic effects of human PTH on trabecular bone in involutional osteoporosis: A multicenter trial. Br Med J 280:1340–1344

    PubMed  Google Scholar 

  7. Slovik D, Rosenthal DI, Doppelt SH, Potts JT, Daly MA, Cambell JA, Neer RM (1986) Restoration of spinal bone in osteoporotic men by treatment with human PTH (1-34) and 1,25-dihydroxyvitamin D. J Bone Miner Res 1:377–382

    PubMed  Google Scholar 

  8. Hesch RD, Prokop M, Busch U, Delling G, Rittinghaus EF (1990) Dramatic increase of bone mass and turnover in osteoporosis by combined 1-38 hPTH and calcitonin therapy. In: Takahashi HE (ed) Bone morphometry. Nishimura, Niigata, p 598

    Google Scholar 

  9. Reeve J, Davies UM, Hesp R, McNally E, Katz D (1990) Treatment of osteoporosis with human parathyroid peptide and observations on effect of sodium fluoride. Br Med J 301:314–318

    Google Scholar 

  10. Reeve J, Bradbeer JN, Arlot ME, Davies UM, Green JR, Hampton L, Edouard C, Hesp R, Hulme P, Ashby JP, Zanelli JM, Meunier PJ (1991) hPTH 1-34 treatment of osteoporosis with added hormone replacement therapy: biomechanical, kinetic and histological responses. Osteoporosis Int 1:162–170

    Google Scholar 

  11. Hori M, Uzawa T, Morita K, Noda T, Takahashi H, Inoue J (1988) Effect of human parathyroid hormone (PTH(1-34)) on experimental osteopenia of rats induced by ovariectomy. Bone Miner 3:193–199

    PubMed  Google Scholar 

  12. Liu CC, Kalu DN (1990) Human PTH prevents bone loss and augments bone formation in sexually mature ovariectomized rats. J Bone Miner Res 3:973–982

    Google Scholar 

  13. Kimmel DB, Bozzato RP, Kronis KA, Kwong P, Recker RR (1993) The effect of recombinant human (1-84) or synthetic human (1-34) parathyroid hormone on the skeleton of adult osteopenic ovariectomized rats. Endocrinology 132:1577–1584

    PubMed  Google Scholar 

  14. Yamamoto N, Takahashi HE, Tanizawa T, Fujimoto R, Hara T, Tanaka S (1993) Maintenance of bone mass by physical exercise after discontinuation of intermittent hPTH(1-34) administration. Bone Mineral 23:333–342

    Google Scholar 

  15. Shen V, Dempster DW, Mellish RWE, Birchman R, Horbet W, Lindsay R (1992) Effects of combined and separate intermittent administration of low-dose parathyroid hormone fragment (1-34) and 17β-estradiol on bone histomorphometry in ovariectomized rats with established osteopenia. Calcif Tissue Int 50:214–220

    PubMed  Google Scholar 

  16. Wronski TJ, Yen C-F, Qi H, Dann LM (1993) Parathyroid hormone is more effective than estrogen or bisphosphonates for restoration of lost bone mass in ovariectomized rats. Endocrinology 132:823–831

    PubMed  Google Scholar 

  17. Wronski TJ, Yen CF (1994) Anabolic effects of parathyroid hormone on cortical bone in ovariectomized rats. Bone 15:51–58

    PubMed  Google Scholar 

  18. Wronski TJ, Yen CF, Scott KS (1991) Estrogen and diphosphonate treatment provide long-term protection against osteopenia in ovariectomized rats. J Bone Miner Res 6:387–394

    PubMed  Google Scholar 

  19. Seedor JG, Quartuccio HA, Thompson DD (1991) The bisphosphonate alendronate (MK-217) inhibits bone loss due to ovariectomy in rats. J Bone Miner Res 6:339–346

    PubMed  Google Scholar 

  20. Jee WSS, Tang LY, Ke HZ, Setterberg RB, Kimmel DB (1993) Maintaining restored bone with bisphosphonate in the ovariectomized rat skeleton: Dynamic histomorphometry of changes in bone mass. Bone 14:493–498

    PubMed  Google Scholar 

  21. Hodsmann AB (1989) Effects of cyclical therapy for osteoporosis using an oral regimen of inorganic phosphate and sodium etidronate: A clinical and bone histomorphometric study. Bone Miner 5:201–212

    PubMed  Google Scholar 

  22. Smith ML, Fogelman I, Hart DM, Scott E, Bevan J, Leggate L (1989) Effect of etidronate disodium on bone turnover following surgical menopause. Calcif Tissue Int 44:74–79

    PubMed  Google Scholar 

  23. Storm T, Thamsborg G, Steiniche T, Genant HK, Sorensen OH (1990) Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 322:1265–1271

    PubMed  Google Scholar 

  24. Watts NB, Harris ST, Genant HK, Wasnich RD, Miller PD, Jackson RD, Licata AA, Ross P, Woodson GC, Janover MJ, Mysiw JW, Kohse. L, Rao MB, Steiger P, Richmond B, Chesnut CH (1990) Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med 323:73–79

    PubMed  Google Scholar 

  25. Fleisch H (1993) Actions. In: Fleisch H (ed) Bisphosphonates in bone disease: From the laboratory to the patient. Stampfli, Berne, pp 33–49

    Google Scholar 

  26. Fujimoto R, Nii A (1990) Effect of disodium dihydrogen (cycloheptilamino) methylene bisphosphonate (YM-175) on the bone formation and resorption in rats and dogs. J Bone Min Res 5[Suppl 11]: S157

    Google Scholar 

  27. Wronski TJ, Walsh CC, Ignaszewski LA (1986) Histologic evidence for osteopenia and increased bone turnover in ovariectomized rats. Bone 7:119–123

    PubMed  Google Scholar 

  28. Wronski TJ, Cintron M, Dann LM (1988) Temporal relationship between bone loss and increased bone turnover in ovariectomized rats. Calcif Tissue Int 43:179–183

    PubMed  Google Scholar 

  29. Wronski TJ, Dann LM, Scott KS, Cintron M (1989) Long-term effects of ovariectomy and aging on the rat skeleton. Calcif Tissue Int 45:360–366

    PubMed  Google Scholar 

  30. Danielsen CC, Mosekilde L, Svenstrup B (1993) Cortical bone mass, composition, and mechanical properties in female rats in regulation to age, long-term ovariectomy, and estrogen substitution. Calcif Tissue Int 52:26–33

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Niigata University School of Medicine, Asahimachi-dori, Nigata-city, 951, Niigata, Japan

    Tasuku Mashiba, Tatsuhiko Tanizawa, Hideaki E. Takahashi, Yuichi Takano & Saburo Nishida

  2. Department of Orthopaedic Surgery, Kagawa Medical School, 1750-1 Miki-cho, Kita-gun, 761-07, Kagawa, Japan

    Tasuku Mashiba, Satoshi Mori & Hiromichi Norimatsu

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  1. Tasuku Mashiba
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  2. Tatsuhiko Tanizawa
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  3. Hideaki E. Takahashi
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  4. Yuichi Takano
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  5. Saburo Nishida
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  6. Satoshi Mori
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  7. Hiromichi Norimatsu
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Mashiba, T., Tanizawa, T., Takahashi, H.E. et al. Effects of single and concurrent intermittent administration of human parathyroid hormone and bisphosphonate cimadronate on bone mineral densities of femur in ovariectomized rats. J Bone Miner Metab 13, 17–22 (1995). https://doi.org/10.1007/BF01771800

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  • DOI: https://doi.org/10.1007/BF01771800

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