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

Abstract

Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits bone resorption by binding to receptor activator of nuclear factor kappa 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 beta 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 beta 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.

Circulating Osteoprotegerin and sRANKL Concentrations in the Perinatal Period at Term

“…Previous studies suggest that maternal levels of OPG gradually increase throughout gestation and are significantly elevated immediately before delivery [26][27][28][29] . The tissue source of OPG in pregnant women is unknown [29] ; however, the rapid postpartum OPG decline in maternal serum [28,29] , the documented expression of OPG in placental tissue [12] and the lower serum OPG levels in neonates compared with their mothers -as reported in the present study -point to a placental origin of OPG.…”

Influence of Antenatal Glucocorticosteroid Exposure on Osteoprotegerin and Receptor Activator of Nuclear Factor &#954;B Ligand Levels in Newborn Infants

“…Therefore, one could assume that OPG levels in neonates reflect maternal OPG levels or are of placental origin. However, it has been shown that OPG in umbilical cord blood was not markedly elevated compared with that in maternal serum, suggesting that the fetus is not a source of OPG in maternal circulation [15]. Human placental microvessels are characterised by endothelial paracellular junctions that are fairly tight and generally impermeable to macromolecules larger than 40,000 Da [39], while OPG is a monomer with a molecular weight of 60,000 Da [40].…”

“…Coronary atherosclerosis is associated with high serum OPG levels in humans, but the exact mechanisms are not yet elucidated [9,10,11,12,13]. Currently, there is little information regarding OPG and RANKL concentrations and their potential role in the human fetus and neonate [14,15]. …”

Maintained malnutrition produces a progressive decrease in (OPG)/RANKL ratio and leptin levels in patients with anorexia nervosa

“…The changes measured in serum may in fact underestimate changes occurring in bone because of non-skeletal sources of OPG and RANKL production that may mask what is occurring in bone tissue. Moreover, OPG is expressed in several tissues other than bone, including lung, heart, kidney and placenta [14].…”