Research Article| Volume 23, SUPPLEMENT , S65-S69, May 1996

Estrogen and bone metabolism

      This paper is only available as a PDF. To read, Please Download here.


      Estrogen plays an important role in the growth and maturation of bone as well as in the regulation of bone turnover in adult bone. During bone growth estrogen is needed for proper closure of epiphyseal growth plates both in females and in males. Also in young skeleton estrogen deficiency leads to increased osteoclast formation and enhanced bone resorption. In menopause estrogen deficiency induces cancellous as well as cortical bone loss. Highly increased bone resorption in cancellous bone leads to general bone loss and destruction of local architecture because of penetrative resorption and microfractures. In cortical bone the first response of estrogen withdrawal is enhanced endocortical resorption. Later, also intracortical porosity increases. These lead to decreased bone mass, disturbed architecture and reduced bone strength. At cellular level in bone estrogen inhibits differentiation of osteoclasts thus decreasing their number and reducing the amount of active remodeling units. This effect is probably mediated through some cytokines, IL-1 and IL-6 being strongest candidates. Estrogen regulates the expression of IL-6 in bone marrow cells by a so far unknown mechanism. It is still uncertain if the effects of estrogen on osteoblasts is direct or is due to coupling phenomenon between bone formation to resorption.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Maturitas
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Smith EP
        • Boyd J
        • Frank GR
        • Takahashi H
        • Cohen R
        • Specker B
        • Williams TC
        • Lubahn DB
        • Korach KS
        Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man.
        N Engl J Med. 1994; 331: 1056-1061
        • Kanis JA
        Blackwell Science Ltd, London1994
        • Law MR
        • Wald NJ
        • Meade TW
        Strategies for prevention of osteoporosis and hip fracture.
        Br Med J. 1991; 303: 453-459
        • Christiansen C
        • Christensen MS
        • Larsen NE
        • Transbol I
        Pathophysiology mechanisms of estrogen effect on bone metabolism.
        J Clin Endocrinol Metab. 1982; 55: 1124-1130
        • Lindsay R
        • Hart DM
        • Baird C
        Prevention of spinal osteoporosis in oophorectomized women.
        Lancet. 1980; 2: 1151-1154
        • Stevenson JC
        • Kanis JA
        • Christiansen C
        Bone density measurements.
        Lancet. 1992; 339: 370-371
        • Peng Z
        • Tuukkanen J
        • Väänänen HK
        Exercise can provide protection against bone loss and prevent the decrease in mechanical strength of femoral neck in ovarietomized rats.
        J Bone Miner Res. 1994; 9: 1559-1564
        • Parfitt AM
        The physiological and clinical significance of bone histomorphometric data.
        in: Recker RR Bone Histomorphometry, Techniques and Interpretation. CRC Press, Boca Raton1983: 143-223
        • Eriksen EF
        • Colvard DS
        • Berg NJ
        • Graham ML
        • Mann KG
        • Spelsberg TC
        • Riggs BL
        Evidence of estrogen receptors in normal human osteoblast-like osteosarcoma cells.
        Science. 1988; 241: 84-86
        • Komm BS
        • Terpening CM
        • Benz DJ
        • Graeme KA
        • O'Malley BW
        • Haussler MR
        Estrogen binding receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells.
        Science. 1988; 257: 81-84
        • Oursler M
        • Osdoby P
        • Pyfferoen J
        • Riggs BL
        • Spelsberg TC
        Avian osteoclasts as estrogen target cells.
        in: Proc Natl Acad Sci USA. 88. 1991: 6613-6617
        • Turner RT
        • Riggs BL
        • Spelsberg TC
        Skeletal effects of estrogen.
        Endocrin Rev. 1994; 15: 275-300
        • Jilka RL
        • Hankoc G
        • Girasole G
        • Passeri G
        • Williams DC
        • Abrams JS
        • Boyce B
        • Broxmeyer H
        • Manolagos SC
        Increased osteoclast development after estrogen loss: mediation by interleukin-6.
        Science. 1992; 257: 88-91
        • Ouesler M
        • Peserson L
        • Fitzpatrick L
        • Riggs BL
        • Spelsberg T
        Human giant cell tumor of the bone (osteoclastomas) are estrogen target cells.
        in: Proc Natl Acad Sci USA. 91. 1994: 5227-5231
        • Migliaccio S
        • Newbold RR
        • Cynthia S
        • Korach KS
        • Toverud S
        Decreased tartrate-resistant acid phosphatase activity in bone tissue of animals developmentally treated with estrogens.
        Bone Miner. 1994; 25: S47
        • Lubahn DB
        • Moyer JS
        • Golding TS
        • Couse JF
        • Korach KS
        • Smithies O
        Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene.
        in: Proc Natl Acad Sci USA. 90. 1993: 11162-11166
        • Korach KS
        Insight from the study of animals lacking functional estrogen receptor.
        Science. 1994; 266: 1524-1527
        • Horowitz MC
        Cytokines and estrogen in bone: antiosteoporotic effects.
        Science. 1993; 260: 626-627
        • Girasole G
        • Jilka RL
        • Passeri G
        • Boswell S
        • Boder G
        • Williams DC
        • Manolagos SC
        17β-Estradiol inhibits interleukin-6 production by bone marrow-derived stromal cells and osteobalasts in vitro. A potential mechanism for the antiosteoporotic effect of estrogens.
        J Clin Invest. 1992; 89: 883-891
        • Poli V
        • Balena R
        • Fattori E
        • Markatos A
        • Yamamoto M
        • Tanaka H
        • Ciliberto G
        • Rodan GA
        • Constantini F
        Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion.
        EMBO J. 1994; 13: 1189-1196
        • Keeting PEE
        • Scoff RE
        • Colvard DS
        • Han IK
        • Spelsberg TC
        • Riggs BL
        Lack of a direct estrogen effect on proliferation and differentiation of normal human osteoblast like cells.
        J Bone Miner Res. 1991; 6: 297-304
        • Ernst M
        • Heath JK
        • Rodan GA
        Estradiol effects on proliferation, messenger ribonucleic acid for collagen and insulin-like growth factor-1, and parathyroid hormone-stimulated adenylate cyclase activity in osteoblastic cells from calvariae and long bones.
        Endocrinology. 1989; 125: 825-833
        • Parker MG
        Steroid and related receptors.
        Curr Opin Cell Biol. 1993; 5: 499-504
        • Phahl M
        Nuclear receptor/AP-1 interaction.
        Endocrinol Rev. 1993; 14: 651-658
        • Jeng MH
        • Ten-Dijke P
        • Iwata KK
        • Jordan VC
        Regulation of the levels of three transforming growth factor β mRNAs by estrogen and their effects on the proliferation of human breast cancer cells.
        Mol Cell Endocrinol. 1993; 97: 115-123
        • Pottratz ST
        • Bellido T
        • Mocharla H
        • Crabb D
        • Manolagos SC
        17β-Estradiol inhibits expression of human interleukin-6 promoter-reporter constructs by a receptor dependent mechanism.
        J Clin Invest. 1994; 93: 944-950
        • Yang NN
        • Hardikar S
        • Venugopalan M
        Estrogen receptor: one transcription factor, two genomic pathways.
        in: Abstract B-23 in Mechanisms of Action of Retinoids, Vitamin D, and Steroid Hormones. AACR Special Conference, Whistler, BC, Canada. 1995