Lactation and bone turnover: a conundrum of marked bone loss in the setting of coupled bone turnover

Abstract

Context: Mothers who exclusively breastfeed lose up to 10% of their bone mass. This is primarily mediated by PTHrP, in combination with low estrogen levels. The mechanisms underlying this marked bone loss are unknown. Uncoupling of bone turnover, which is seen in other prototypical states of bone loss, would seem the likely explanation. However, the most current markers of bone turnover have not been studied in human lactation.

Objectives: The purpose of this study was to assess bone formation in lactating humans using the most current bone turnover markers.

Design and participants: We conducted a prospective cohort study with repeated measures of bone metabolism in a volunteer sample of 49 women, recruited into three study groups: lactating, bottle feeding, and healthy controls. The postpartum women were studied at 6-8 and 12-14 wk postpartum, whereas the controls were studied at the follicular phase of their menstrual cycles.

Outcome measures: Biochemical markers of bone turnover were assessed.

Results: Mean serum C-telopeptide of type I collagen, a sensitive marker of bone resorption, was approximately 2-fold higher in lactating women as compared with bottle-feeding and healthy controls (P = 0.037 and P < 0.001, respectively). Surprisingly, amino-terminal telopeptides of procollagen 1, the most current marker of bone formation, bone-specific alkaline phosphatase, and osteocalcin were all significantly higher in the lactating group as compared with controls (P < 0.001, P = 0.002, and P < 0.001, respectively).

Conclusions: In contrast to prototypical states of rapid bone loss (myeloma, cancer, and immobilization) in which markers of bone turnover display marked uncoupling, lactational bone loss, as assessed in this small exploratory study, is distinct, showing comparably rapid bone loss in the face of apparent osteoclast-osteoblast coupling.

Figure 1

Estradiol and total and ionized calcium concentrations in lactating, bottle-feeding, and control women at two different time points. The first bar represents the mean and se for each group during the first study visit (6–8 wk postpartum for the lactation and bottle-feeding groups and follicular phase of the menstrual cycle for controls), and the second bar represents the second visit (12–14 wk postpartum or 6–8 wk after visit 1). A, Estradiol levels were significantly lower in the lactation group compared with the other two groups at both time points. B, There were no statistical differences among groups at visit 1 with regard to serum total calcium. When comparing the change in serum calcium from visit 1 to visit 2, there was a minimal but significant increase in serum calcium in the lactation group compared with bottle-feeding and controls. C, There were no statistical differences among groups or time points with regard to ionized calcium levels.

Figure 2

PTH, 25-OHD, 1,25(OH)₂D, and FECa in the three groups. The two bars for each group represent study visits 1 and 2 as previously described. Means and sebars are shown. A and B, There were no statistical differences among groups or time points in regard to PTH or plasma 25-OHD; C, plasma 1,25(OH)₂D was significantly lower in the bottle-feeding group compared with both lactation and control groups at baseline; D, There were no statistical differences among groups in regard to FECa at baseline, but in the time period between the two study visits, FECa significantly increased in the lactation group (P = 0.023). FECa remained stable in the control and bottle-feeding groups.

Figure 3

Serum creatinine, serum phosphorus, and the TmP/GFR for each group at two different time points. The two bars for each group represent study visits 1 and 2 as previously described. Means and sebars are shown. A, There were no statistical differences between groups or time points for serum creatinine; B, serum phosphorus was significantly higher in the lactating group at visit 1 compared with controls; C, TmP/GFR was statistically higher in the lactating group at visit 1 compared with controls.

Figure 4

Markers of bone resorption in the three study groups at two different time points. The two bars for each group represent study visits 1 and 2 as previously described. Means and sebars are shown. A, Bone resorption appeared increased in both the lactating and bottle-feeding groups as assessed by NTX, but this did not achieve statistical significance; B, CTX was significantly higher in the lactating group as compared with the other two groups.

Figure 5

Markers of bone formation in the three study groups at two different time points. The two bars for each group represent study visits 1 and 2 as previously described. Means and sebars are shown. A, BSAP was significantly higher in the lactation group compared with controls at both visits (P = 0.002 for visit 1, and P < 0.001 for visit 2). B, Osteocalcin was significantly increased in the lactation and bottle-feeding groups compared with controls at both visits (P < 0.001 for visits 1 and 2). In the time period between the two study visits, osteocalcin levels significantly decreased in the bottle-feeding women and increased in the lactating women (P = 0.038). C, P1NP, the most current marker of bone formation, was significantly increased in the lactation and bottle-feeding groups compared with controls at both visits (P < 0.001 for both visits 1 and 2). In the time period between the two study visits, P1NP levels significantly decreased in the bottle-feeding women and increased in the lactating women (P = 0.029).