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Serum Osteoprotegerin as a Determinant of Bone Metabolism in a Longitudinal Study of Human Pregnancy and Lactation

Bone Metabolism Group (K.E.N., A.R., R.E., A.B.) and Department of Obstetrics and Gynecology (R.B.F., V.H.), University of Sheffield, Sheffield, United Kingdom S5 7AU

Address all correspondence and requests for reprints to: Dr. A. Blumsohn, University of Sheffield, Bone Metabolism Group, Clinical Sciences Center (North), Northern General Hospital, Herries Road, Sheffield, United Kingdom S5 7AU. E-mail: ablumsohn{at}sheffield.ac.uk.

Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits bone resorption by binding to receptor activator of nuclear factor B ligand. Murine studies suggest that OPG is elevated in pregnancy, but its role in human pregnancy is unknown. We evaluated the relationship among OPG, bone turnover, and bone density in a longitudinal study of planned human pregnancy and lactation (n = 17; age, 20–36 yr). Samples were collected before conception; at 16, 26, and 36 wk gestation; and at 2 and 12 wk postpartum. Indexes of bone resorption included serum ß C-terminal and urinary N-terminal (uNTX) telopeptides of type I collagen. OPG increased by 110 ± 16% (mean ± SEM) at 36 wk (P < 0.001), followed by a rapid postpartum decline in both lactating and nonlactating women. Bone resorption was elevated at 36 wk (serum ß C-terminal telopeptides by 76 ± 17%; urinary N-terminal telopeptides by 219 ± 41%; P < 0.001). The tissue source of OPG in pregnancy is unknown. Human breast milk contains large amounts of OPG (162 ± 58 ng/ml in milk vs. 0.42 ± 0.03 ng/ml in nonpregnant serum). However, the rapid postpartum decline in serum OPG and the low serum OPG in neonates suggest a placental source. There was no correlation between change in OPG and bone turnover or bone mineral density (P > 0.05), and the physiological importance of elevated OPG in human pregnancy remains uncertain.

This work was supported in part by a research grant from WellBeing.

Abbreviations: BMD, Bone mineral density; CV, coefficient of variation; E₂, estradiol; OPG, osteoprotegerin; RANK, receptor activator of nuclear factor B; RANKL, RANK ligand; sßCTX, serum ß C-terminal telopeptides of type I collagen; uNTX, urinary N-terminal telopeptides of type I collagen.

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