Abstract
Bone loss following menopause can be prevented or reduced by estrogen replacement therapy (ERT). The primary action of estrogen on bone is generally considered to be antiresorptive, but some evidence would also suggest a stimulatory effect on bone formation. The aim of this study was to assess the effect of ERT on biochemical markers of bone resorption (urinary pyridinoline and deoxypyridinoline), and of bone formation (bone-specific alkaline phosphatase — B-ALP, and the C-terminal propeptide of type I collagen — CICP) in a group of 25 postmenopausal women with no evidence of osteoporosis. Since the suggested anabolic effect of estrogen seems to take place in the early period of ERT, we measured the response of markers immediately before and after the start of treatment (30, 60, 120 and 180 days). The markers of bone resorption started to decrease at 30 days and remained low thereafter. We also observed a similar decrease in serum levels of B-ALP and CICP, reflecting a reduction of bone formation rate. Our data would indicate that ERT at the given dose does not have early anabolic effects on bone, in addition to its recognized suppressive effect on bone resorption.
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Ettinger B., Genant H.K., Cann C.E. Long-term estrogen replacement therapy prevents bone loss and fractures. Ann. Intern. Med. 1985, 102: 319–324.
Munk-Jensen N., Nielsen S.P., Obel E.B., Epikse P.B. Reversal of postmenopausal bone loss by oestrogen and progestagen: A double-blind placebo controlled study. Br. Med. J. 1988, 296: 1150–1152.
Eriksen E.F. Normal and pathological remodeling of human trabecular bone: Three dimensional reconstruction of the remodeling sequence in normal and in metabolic bone disease. Endocr. Rev. 1986, 7: 379–407.
Steinicke T., Hasling C., Charles P., Eriksen E.F., Mosekilde L., Melsen F. A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone remodeling in postmenopausal osteoporosis. Bone 1989, 10: 313–320.
Eriksen E.F., Colvard D.S., Berg N.J. Graham M.L., Mann K.G., Spelsberg T.C., Riggs B.L. Evidence of estrogen receptors in normal human osteoblast-like cells. Science 1988, 241: 84–86.
Braidman I.P., Davenport L.K., Carter D.H., Selby P.L., Mawer E.B., Freemont A.J. Preliminary in-situ identification of estrogen target cells in bone. J. Bone Miner. Res. 1995, 16: 74–80.
Samuels A., Perry M.J., Tobias J.H. High-dose estrogen induces de novo medullary bone formation in female mice. J. Bone Miner. Res. 1999, 14: 178–186.
Tobias J.H., Compston J.E. Does estrogen stimulate osteoblast function in postmenopausal women? Bone 1999, 24: 121–124.
Gomez B., Ardakani S., Ju J., Jenkins D., Cerelli M.J., Daniloff G.Y., Kung V.T. Monoclonal antibody assay for measuring bone-specific alkaline phosphatase activity in serum. Clin. Chem. 1995, 41: 1560–1566.
Seyedin S.M., Kung V.T., Daniloff Y.N., Hesley R.P., Gomez B., Nielsen L.A., Rosen H.N., Zuk R.F. Immunoassay for urinary pyridinoline: the new marker of bone resorption. J. Bone Miner. Res. 1993, 5: 635–641.
Robbius S.P., Woitge H., Hessley R., Ju J., Seyedin S.M., Seibel M.J. Direct enzyme-limited immunoassay for urinary deoxypyridinoline as a specific marker for measuring bone resorption. J. Bone Miner. Res. 1994, 9: 1643–1649.
Qu Q., Perala-Heape M., Kapanen A., Dahllund J., Salo J., Vaananen H.K., Harkonen P. Estrogen enhances differentiation of osteoblasts in mouse bone marrow culture. Bone 1998, 22: 201–209.
Garnett T., Studd J., Watson N., Savvas M.A. A cross-sectional study of the effects of long-term percutaneous hormone replacement therapy on bone density. Obstet. Gynecol. 1991, 78: 1002–1007.
Wahab M., Ballard P., Purdie D.W., Cooper A., Wilson J.C. The effect of long-term oestradiol implantation on bone mineral density in postmenopausal women who have undergone hysterectomy and bilateral oophorectomy. Br. J. Obstet. Ginaecol. 1997, 104: 728–731.
Westerlind K.C., Wakley G.K., Evans G.L., Turner R.T. Estrogen does not increase bone formation in growing rats. Endocrinology 1993, 133: 2924–2934.
Hannon R., Blumson A., Naylor K., Eastell R. Response of biochemical markers of bone turnover to hormone replacement therapy: impact of biological variability. J. Bone Miner. Res. 1998, 13: 1124–1133.
Tobias J.H., Laversuch C.J., Chambers T.J., Gallagher A.C. Aminohexane bisphosphonate suppresses bone turnover in postmenopausal women more rapidly than oestrogen-gestagen therapy. Br. J. Rheumatol. 1996, 35: 636–641.
Abe T., Chow J.W.M., Lean J.M., Chambers T.J. Estrogen does not restore bone lost after ovariectomy in the rat. J. Bone Miner. Res. 1983, 8: 831–838.
Patel S., Pazianas M., Tobias J., Chambers J.J., Fox S., Chow J. Early effects of hormone replacement therapy on bone. Bone 1999, 24: 245–248.
McKane W.R., Khosla S., Peterson J.M., Egan K., Riggs B.L. Circulating levels of cytokines that modulate bone resorption: effects of age and menopause in women. J. Bone Miner. Res. 1994, 9: 1313–1318.
Girasole G., Jilka R.L., Passeri G., Boswell S., Boder G., Williams D.C., Manolagas S.C. 17ß-estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteoblasts in vitro: a potential mechanism for the antiosteoporotic effect of estrogens. J. Clin. Invest. 1992, 89: 883–891.
Abrahamsen B., Bonnevie-Nielsen V., Nils Ebbesen E., Gram J., Beck-Nielsen H. Cytokines and bone loss in a 5-year longitudinal study. Hormone replacement therapy suppresses serum soluble interleukin-6 receptor and increases interleukin-1-receptor antagonist: the Danish Osteoporosis Prevention study. J. Bone Miner. Res. 2000, 15: 1545–1554.
Bismar H., Kloppinger T., Schuster E.M., Balbach S., Diel I., Ziegler R., Pfeilschifter J. Transforming growth factor ß (TGFß) levels in the conditioned media of human bone cells: relationship to donor age, bone volume, and concentration of TGFß in human bone matrix in vivo. Bone 1999, 24: 565–569.
Jilka R.L. Cytokines, bone remodeling, and estrogen deficiency: a 1998 update. Bone 1998, 23: 75–81.
Yang N.N., Bryant H.U., Hardikar S., Sato M., Galvin R.J., Glaserbrook A.L., Termine J.D. Estrogen and raloxifene stimulate transforming growth factor-ß3 gene expression in rat bone: a potential mechanism for estrogen- or raloxifene-mediated bone maintenance. Endocrinology 1996, 137: 2075–2084.
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Fiore, C.E., Pennisi, P., Tandurella, F.G. et al. Response of biochemical markers of bone turnover to estrogen treatment in post-menopausal women: Evidence against an early anabolic effect on bone formation. J Endocrinol Invest 24, 423–429 (2001). https://doi.org/10.1007/BF03351042
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DOI: https://doi.org/10.1007/BF03351042