Elevated IGFBP-1 cause high bone turnover in growth-restricted monochorionic twins with discordant birth weight.

Abstract

To test the hypothesis that low birth weight twins have a higher risk of osteoportotic fracture in later life, we investigated the association between fetal IGF axis and type-1 collagen markers of bone turnover in monochorionic (MC) twins with or without discordant birth weight of >or=20%. Maternal and cord bloods were collected from gestational age matched MC twins of discordant (n = 16) and concordant birth weights (n = 16). The samples were assayed for cross linked carboxyl terminal telopeptide (ICTP, a marker of bone resorption) and pro-peptide (PICP, a marker of bone formation) of type I collagen, IGF-1, and IGFBP-1 by radio-immunoassay. The growth-restricted twins (IUGR) of discordant group had higher fetal IGFBP-1 and ICTP (P < 0.001) levels, while PICP (P < 0.001) was lower than the co-twins with normal weight (AGA). In contrast, cord blood levels of IGF-1, IGFBP-1, ICTP, and PICP in concordant twin pairs were comparable to AGA twins. The concordant and AGA twins had a positive correlation between ICTP and PICP levels (y = 23x - 711; r = 0.84; P < 0.001; n = 48) but no such association was found in IUGR twins. Instead, IGFBP-1 levels in IUGR twins had a negative association with PICP (r = 0.81; P < 0.001; n = 16) and a positive correlation with ICTP (r- = 0.51; P < 0.05; n = 16). No such association was found in concordant and AGA twins. These data suggest that growth-restricted twins had high bone turnover, due to elevated IGFBP-1. This association seems to be independent of maternal and genetic factors.