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Increased bone resorption precedes increased bone formation in the ovariectomized rat

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Abstract

This study describes an increase in biochemical and histomorphometric markers of bone resorption prior to increased bone formation and trabecular bone loss in the ovariectomized rat. Six-month-old, female Sprague Dawley rats were either sham operated or ovariectomized (Ovx) and killed at 0, 6, 9, 15, 18, 21, and 42 days postOperation when femora were collected and trabecular bone volume (BV/TV) was determined from von Kossa silver-stained sections using the Quantimet 520 image analysis system in the distal region. A number of these sections were also examined unstained for fluorochrome labels, and stained for acid phosphatase to detect osteoclast-like cells (ACP surface). At 18 days postoperation, lumbar vertebrae were examined. Blood and urine specimens were analyzed for bone-related biochemical variables. ACP surface was significantly greater in Ovx rats compared with sham at 6 days postoperation (mean ACP surface (%TS) ± SEM: sham 36.4 ± 1.9; Ovx 40.3 ± 1.2,P < 0.05) as was urinary hydroxyproline excretion. Serum osteocalcin and alkaline phosphatase activity were not elevated in Ovx rats compared with Sham until 9 days postoperation. Mineral apposition rate (MAR) was increased at 12 days after ovariectomy (mean MAR (Μm/day) ± SEM: sham 0.85 ± 0.06; Ovx 1.23 ± 0.06,P < 0.05). Trabecular bone volume (BV/TV) at a specific site in the metaphyseal-diaphyseal core area was significantly lower at 15 days postoperation (mean (%) ± SEM: Sham 7.40 ± 1.23, Ovx 4.25 0 0.65,P < 0.05). There was no difference in lumbar vertebral BV/TV between the two groups at 18 days postoperation, however, ACP surface was elevated in the Ovx rats (P < 0.05). A systemic increase in bone resorption at 6 days postovariectomy precedes increased formation whereas the length of time required for the dissolution of trabeculae postoperation is determined locally.

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References

  1. Heaney RP, Recker RR, Saville PD (1978) Menopausal changes in bone remodeling. J Lab Clin Med 92:964–970

    PubMed  CAS  Google Scholar 

  2. Parfitt AM (1979) Quantum concept of bone remodeling and turnover: implications for the pathogenesis of osteoporosis. Calcif Tissue Int 28:1–5

    Article  PubMed  CAS  Google Scholar 

  3. Kelley PJ, Pocock NA, Sambrook PN, Eisman JA (1989) Age- and menopause-related changes in indices of bone turnover. J Clin Endocrinol Metab 69:1160–1165

    Google Scholar 

  4. Steiniche T, Hasling C, Charles P, Eriksen EF, Mosekilde L, Meisen F (1989) A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone remodeling in postmenopausal osteoporosis. Bone 10:313–320

    Article  PubMed  CAS  Google Scholar 

  5. Nordin BEC, Morris HA (1989) The calcium deficiency model for osteoporosis. Nutr Rev 47:65–72

    Article  PubMed  CAS  Google Scholar 

  6. Kalu DN, Liu C-C, Hardin RR, Hollis BW (1989) The aged rat model of ovarian hormone deficiency bone loss. Endocrinology 124:7–16

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Ismail F, Epstein S, Fallon MD, Thomas SB, Reinhardt TA (1989) Serum bone gla protein and the vitamin D endocrine system in the ovariectomised rat. Endocrinology 122:2624–2630

    Google Scholar 

  9. Morris HA, Porter SJ, Durbridge TC, Moore RJ, Need AG, Nordin BEC (1992) Effects of ovariectomy on biochemical and bone variables in the rat. Bone Miner 18:133–142

    Article  PubMed  CAS  Google Scholar 

  10. 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

    Article  PubMed  CAS  Google Scholar 

  11. Kimmel DB, Wronski TJ (1990) Nondestructive measurement of bone mineral in femurs from ovariectomised rats. Calcif Tissue Int 46:101–110

    Article  PubMed  CAS  Google Scholar 

  12. Dempster DW, Birchman R, Xu R, Lindsay R, Shen V (1995) Temporal changes in cancellous bone structure of rats immediately after ovariectomy. Bone 16:157–161

    Article  PubMed  CAS  Google Scholar 

  13. Bergman I, Loxley R (1970) The determination of hydroxyproline in urine hydrolysates. Clin Chim Acta 17:347–349

    Article  Google Scholar 

  14. Daly JA, Ertinghausen G (1972) Direct method for determining inorganic phosphate in serum with the “Centrifichem.” Clin Chem 18:263–265

    PubMed  CAS  Google Scholar 

  15. Marshall DH (1976) Calcium and phosphate kinetics. In: Nordin BEC (ed) Calcium phosphate and magnesium metabolism. Churchill Livingstone, Edinburgh, pp 257–307

    Google Scholar 

  16. Page K (1977) Bone and preparation of bone sections. In: Bancroft JD, Stevens A (eds) Theory and practice of histological techniques, 1st ed. Churchill Livingstone, London, pp 223–248

    Google Scholar 

  17. Durbridge TC, Morris HA, Parsons AM, Parkinson IH, Moore RJ, Porter SJ, Need AG, Nordin BEC, Vernon-Roberts B (1990) Progressive cancellous bone loss in rats after adrenalectomy and oophorectomy. Calcif Tissue Int 47:383–387

    Article  PubMed  CAS  Google Scholar 

  18. Kimmel DB, Jee WSS (1983) Measurement of area perimeter and distance: details of data collection in bone histomorphometry. In: Recker RR (ed) Bone histomorphometry: techniques and interpretation, 1st ed. CRC Press, Florida, pp 89–108

    Google Scholar 

  19. Parkinson IH, Fazzalari NL, Durbridge TC, Moore RJ (1991) Simplified approach to enzymatic identification of osteoclastic bone resorption. J Histotech 14:81–83

    Google Scholar 

  20. Butcher RI, Collins WE, Fugo NW (1974) Plasma concentration of LH, FSH prolactin progesterone and estradiol-17B throughout the 4-day estrous cycle of the rat. Endocrinology 94:1704–1708

    Article  PubMed  CAS  Google Scholar 

  21. Morris HA, Sims NA, Moore RJ, Duguid SF (1992) The effec of age on ovarian hormone-dependent bone loss in the rat Bone Miner 17 (suppl 1): 143

    Google Scholar 

  22. Sims NA, Morris HA, Moore RJ, Durbridge TC (1994) Para thyroidectomy does not prevent bone loss in the ovariec tomised rat. J Bone Miner Res 9:1859–1864

    Article  PubMed  CAS  Google Scholar 

  23. Westlind KC, Wronski TJ, Evans GL, Turner RT (1994) Evidence that increased bone turnover is insufficient to result in bone loss in ovariectomized (OVX) rats. J Bone Miner Res 9 (suppl 1):S198

    Google Scholar 

  24. Baron R, Tross R, Vignery A (1984) Evidence of sequential remodeling in rat trabecular bone: morphology dynamic histomorphometry and changes during skeletal maturation. Anat Rec 208:137–145

    Article  PubMed  CAS  Google Scholar 

  25. Yoshida S, Yamamuro T, Okumura H, Takahashi H (1991) Microstructural changes of osteopenic trabeculae in the rat Bone 12:185–194

    Article  PubMed  CAS  Google Scholar 

  26. Wronski TJ, Dann LM, Homer SL (1989) Time course of vertebral osteopenia in ovariectomized rats. Bone 10:295–301

    Article  PubMed  CAS  Google Scholar 

  27. Dempster DW, Li X-F, Birchman R, Zu R, Shen V, Lindsay R (1992) On the mechanism of cancellous bone loss in the ovariectomised rat. In: Cohn DV, Bennari C, Tashjian AH (eds) Calcium regulating hormones and bone metabolism. Elsevier Science Publishers BV, New York, pp 460–464

    Google Scholar 

  28. Owen TA, Aronow M, Shalhoub V, Barone LM, Wilming L, Tassinari MS, Kennedy MB, Pockwinse S, Lian JB, Stein GS (1990) Progressive development of the rat osteoblast pheno type in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. J Cell Phys iol 143:420–430

    Article  CAS  Google Scholar 

  29. Hietala EL (1993) The effect of ovariectomy on periosteal bone formation and bone resorption in adult rats. Bone Miner 20:57–65

    PubMed  CAS  Google Scholar 

  30. Lindgren U, DeLuca HF (1982) Role of parathyroid hormone and 1,25-dihydroxyvitamin D3 in the development of osteo penia in ovariectomised rats. Calcif Tissue Int 34:510–514

    Article  PubMed  CAS  Google Scholar 

  31. Kalu DN, Hardin RR, Cockerham R (1984) Evaluation of the pathogenesis of skeletal changes in ovariectomised rats. En docrinology 115:507–512

    CAS  Google Scholar 

  32. Nagae Y, Miayamoto M, Miyamoto H (1991) Effect of estro gen replacement on liver function in ovariectomised rats. Tox Sci 16:87–100

    CAS  Google Scholar 

  33. Stock JL, Coderre JA, Burke EM, Danner DB, Chipman SD Shapiro RJ (1992) Identification of estrogen receptor mRNA and the estrogen modulation of parathyroid hormone stimulated cyclic AMP accumulation in opossum kidney cells. J Cell Physiol 150:517–525

    Article  PubMed  CAS  Google Scholar 

  34. Tabuchi C, Simmons DJ, Fausto A, Russell JE, Binderman 1 Avioli LV (1986) Bone deficit in ovariectomised rats. Func tional contribution of the marrow stromal cell population and the effect of oral dihydrotachysterol treatment. J Clin Invest 78:637–642

    Article  PubMed  CAS  Google Scholar 

  35. Parfitt AM, Mathews C, Rao D, Frame B, Kleerekoper M, Villaneuva AR (1980) Impaired osteoblast function in meta bolic bone disease. In: DeLuca HF, Frost HM, Jee WSS, Johnston Jr CC, Parfitt AM (eds) Osteoporosis: recent ad vances in pathogenesis and treatment. University Park Press, Baltimore, pp 321–330

    Google Scholar 

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Authors and Affiliations

  1. Division of Clinical Biochemistry, Institute of Medical and Veterinary Science, Rundle Mall Post Office, Box 14, 5000, Adelaide, South Australia

    N. A. Sims & H. A. Morris

  2. Division of Tissue Pathology, Institute of Medical and Veterinary Science, Rundle Mall Post Office, Box 14, 5000, Adelaide, South Australia

    R. J. Moore & T. C. Durbridge

  3. Department of Physiology, University of Adelaide, South Australia

    N. A. Sims & H. A. Morris

Authors
  1. N. A. Sims
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  2. H. A. Morris
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  3. R. J. Moore
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  4. T. C. Durbridge
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Sims, N.A., Morris, H.A., Moore, R.J. et al. Increased bone resorption precedes increased bone formation in the ovariectomized rat. Calcif Tissue Int 59, 121–127 (1996). https://doi.org/10.1007/s002239900098

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  • DOI: https://doi.org/10.1007/s002239900098

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