Serum osteoprotegerin/osteoclastogenesis-inhibitory factor during pregnancy and lactation and the relationship with calcium-regulating hormones and bone turnover markers.
Pregnancy and lactation induce dynamic changes in maternal bone and calcium metabolism. A novel cytokine termed osteoprotegerin (OPG)/osteoclastogenesis-inhibitory factor (OCIF) was recently isolated; this cytokine inhibits osteoclast maturation. To define the effects of pregnancy and lactation on circulating OPG/OCIF in mothers, we studied the changes in the levels of OPG/ OCIF as well as those of calcium-regulating hormones and biochemical markers of bone turnover in the maternal circulation during pregnancy (at 8-11 weeks, at 22-30 weeks, at 35-36 weeks and immediately before delivery) and lactation (at 4 days and at 1 month postpartum). Serum intact parathyroid hormone levels did not change and were almost within the normal range in this period. In contrast, serum 1,25-dihydroxyvitamin D levels increased with gestational age and were above the normal range during pregnancy. After delivery, they fell rapidly and significantly (P<0.01) to the normal range. The levels of serum bone-specific alkaline phosphatase, one of the markers of bone formation, increased with gestational age. After delivery, these levels were further increased at 1 month postpartum. The levels at 1 month postpartum were significantly higher than those at 8-11 and 22-30 weeks of pregnancy (P<0.01 and P<0.05 respectively). The levels of serum C-terminal telopeptides of type I collagen, one of the markers of bone resorption, did not change during pregnancy. After delivery, they rapidly and significantly (P<0.01) rose at 4 days postpartum, and had then fallen by 1 month postpartum. Circulating OPG/OCIF levels gradually increased with gestational age and significantly (P<0.01) increased immediately before delivery to 1.40+/-0.53 ng/ml (means+/-S.D.) compared with those in the non-pregnant, non-lactating controls (0.58+/-0.11 ng/ml). After delivery, they fell rapidly to 0.87+/-0.27 ng/ml at 4 days postpartum and had fallen further by 1 month postpartum. These results suggest that the fall in OPG/OCIF levels may be partially connected with the marked acceleration of bone resorption after delivery.
Uemura
H
H
Department of Obstetrics and Gynecology, University of Tokushima, School of Medicine, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan. uemura@clin-med.tokushima-u.ac.jp
Yasui
T
T
Kiyokawa
M
M
Kuwahara
A
A
Ikawa
H
H
Matsuzaki
T
T
Maegawa
M
M
Furumoto
H
H
Irahara
M
M
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001862:Bone Resorption; D002118:Calcium / Q000097:blood; D016022:Case-Control Studies; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007774:Lactation / Q000097:blood*; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000097:blood; D010758:Phosphorus / Q000097:blood; D011247:Pregnancy / Q000097:blood*; D011264:Pregnancy Trimesters; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D012044:Regression Analysis; D012709:Serum Albumin / Q000032:analysis; D018709:Statistics, Nonparametric; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D015415:Biomarkers; D024042:Collagen Type I; D006023:Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D010455:Peptides; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D012709:Serum Albumin; C506030:TNFRSF11B protein, human; C052929:collagen type I trimeric cross-linked peptide; D014807:Vitamin D; D010758:Phosphorus; C097949:1,25-dihydroxyvitamin D; D003094:Collagen; D000469:Alkaline Phosphatase; D002118:Calcium