During pregnancy and lactation, novel regulatory sys- tems specific to these settings complement the usual regulators of calcium homeostasis. The fetal calcium demand is met in large part by a doubling of intestinal calcium absorption, an adaptation that may not be fully explained by an observed increase in 1,25(OH)2D3 con- centrations. In comparison, skeletal calcium resorption is a dominant mechanism by which calcium is supplied to the breast milk, aided by renal calcium conservation.
These changes during lactation appear to be driven by PTHrP in association with estrogen deficiency, and are independent of calcium intake.
The rapidity of calcium regain by the skeleton of the lactating woman occurs through a mechanism that is not understood. Although it is apparent that some women can experience fragility fractures as a consequence of pregnancy or lactation, for most women these adapta- tions in calcium and bone metabolism occur silently and without apparent long‐term adverse consequences.
REFERENCES
1. Kovacs CS. Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post‐Weaning Recovery.
Physiol Rev. 2016;96(2):449–547.
2. Trotter M, Hixon BB. Sequential changes in weight, density, and percentage ash weight of human skeletons from an early fetal period through old age. Anat Rec.
1974;179(1):1–18.
3. Turner M, Barre PE, Benjamin A, et al. Does the maternal kidney contribute to the increased circulating 1,25‐
dihydroxyvitamin D concentrations during pregnancy?
Miner Electrolyte Metab. 1988;14:246–52.
4. Halloran BP, DeLuca HF. Calcium transport in small intestine during pregnancy and lactation. Am J Physiol.
1980;239:E64–E8.
5. Brommage R, Baxter DC, Gierke LW. Vitamin D‐ independent intestinal calcium and phosphorus absorp- tion during reproduction. Am J Physiol. 1990;259:G631–G8.
6. Fudge NJ, Kovacs CS. Pregnancy up‐regulates intestinal calcium absorption and skeletal mineralization inde- pendently of the vitamin D receptor. Endocrinology.
2010;151(3):886–95.
7. Pahuja DN, DeLuca HF. Stimulation of intestinal calcium transport and bone calcium mobilization by prolactin in vitamin D‐deficient rats. Science. 1981;214:1038–9.
8. Mainoya JR. Effects of bovine growth hormone, human pla- cental lactogen and ovine prolactin on intestinal fluid and ion transport in the rat. Endocrinology. 1975;96:1165–70.
9. Heaney RP, Skillman TG. Calcium metabolism in normal human pregnancy. J Clin Endocrinol Metab.
1971;33(4):661–70.
10. Woodrow JP, Sharpe CJ, Fudge NJ, et al. Calcitonin plays a critical role in regulating skeletal mineral metabolism during lactation. Endocrinology. 2006;147(9):4010–21.
11. Kirby BJ, Ardeshirpour L, Woodrow JP, et al. Skeletal recovery after weaning does not require PTHrP. J Bone Miner Res. 2011;26(6):1242–51.
12. Purdie DW, Aaron JE, Selby PL. Bone histology and min- eral homeostasis in human pregnancy. Br J Obstet Gynaecol. 1988;95(9):849–54.
13. Kovacs CS, Ralston SH. Presentation and management of osteoporosis presenting in association with pregnancy or lactation. Osteoporos Int. 2015;26(9):2223–41.
14. Kovacs CS. Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones. Physiol Rev. 2014;94(4):
1143–218.
15. Schnatz PF, Curry SL. Primary hyperparathyroidism in pregnancy: evidence‐based management. Obstet Gynecol Surv. 2002;57(6):365–76.
16. Thomas AK, McVie R, Levine SN. Disorders of maternal calcium metabolism implicated by abnormal calcium metabolism in the neonate. Am J Perinatol. 1999;16(10):
515–20.
17. Walker A, Fraile JJ, Hubbard JG. “Parathyroidectomy in pregnancy”—a single centre experience with review of evidence and proposal for treatment algorithim. Gland Surg. 2014;3(3):158–64.
18. Morton A. Altered calcium homeostasis during pregnancy may affect biochemical differentiation of hypercalcaemia. Intern Med J. 2004;34(11):655–6; author reply 6–7.
19. Breslau NA, Zerwekh JE. Relationship of estrogen and pregnancy to calcium homeostasis in pseudohypopar- athyroidism. J Clin Endocrinol Metab. 1986;62:45–51.
20. Koo WW, Walters JC, Esterlitz J, et al. Maternal calcium supplementation and fetal bone mineralization. Obstet Gynecol. 1999;94(4):577–82.
21. VanHouten JN, Dann P, Stewart AF, et al. Mammary‐
specific deletion of parathyroid hormone‐related protein preserves bone mass during lactation. J Clin Invest.
2003;112(9):1429–36.
22. Mamillapalli R, VanHouten J, Dann P, et al. Mammary‐
specific ablation of the calcium‐sensing receptor during lactation alters maternal calcium metabolism, milk calcium transport, and neonatal calcium accrual.
Endocrinology. 2013;154(9):3031–42.
23. Kovacs CS, Chik CL. Hyperprolactinemia caused by lac- tation and pituitary adenomas is associated with altered serum calcium, phosphate, parathyroid hormone (PTH), and PTH‐related peptide levels. J Clin Endocrinol Metab.
1995;80(10):3036–42.
24. Dobnig H, Kainer F, Stepan V, et al. Elevated parathyroid hormone‐related peptide levels after human gestation:
relationship to changes in bone and mineral metabo- lism. J Clin Endocrinol Metab. 1995;80(12):3699–707.
25. Sowers MF, Hollis BW, Shapiro B, et al. Elevated parathyroid hormone‐related peptide associated with lactation and bone density loss. JAMA. 1996;276(7):
549–54.
26. Qing H, Ardeshirpour L, Pajevic PD, et al. Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. J Bone Miner Res. 2012;27(5):1018–29.
27. Kolthoff N, Eiken P, Kristensen B, et al. Bone mineral changes during pregnancy and lactation: a longitudinal cohort study. Clin Sci (Lond). 1998;94(4):405–12.
28. Polatti F, Capuzzo E, Viazzo F, et al. Bone mineral changes during and after lactation. Obstet Gynecol.
1999;94(1):52–6.
29. Kalkwarf HJ, Specker BL, Bianchi DC, et al. The effect of calcium supplementation on bone density during lactation and after weaning. N Engl J Med. 1997;
337(8):523–8.
30. Cross NA, Hillman LS, Allen SH, et al. Changes in bone mineral density and markers of bone remodeling during lactation and postweaning in women consuming high amounts of calcium. J Bone Miner Res. 1995;10(9):
1312–20.
31. Laskey MA, Prentice A, Hanratty LA, et al. Bone changes after 3 mo of lactation: influence of calcium intake, breast‐milk output, and vitamin D‐receptor genotype.
Am J Clin Nutr. 1998;67(4):685–92.
32. Sowers M. Pregnancy and lactation as risk factors for subsequent bone loss and osteoporosis. J Bone Miner Res. 1996;11(8):1052–60.
33. Bjornerem A, Ghasem‐Zadeh A, Wang X, et al.
Irreversible Deterioration of Cortical and Trabecular Microstructure Associated with Breastfeeding. J Bone Miner Res. 2017;32(4):681–7.
34. Brembeck P, Lorentzon M, Ohlsson C, et al. Changes in cortical volumetric bone mineral density and thickness, and trabecular thickness in lactating women postpar- tum. J Clin Endocrinol Metab. 2015;100(2):535–43.
35. Reid IR, Wattie DJ, Evans MC, et al. Post‐pregnancy osteoporosis associated with hypercalcaemia. Clin Endocrinol (Oxf). 1992;37(3):298–303.
36. Phillips AJ, Ostlere SJ, Smith R. Pregnancy‐associated osteoporosis: does the skeleton recover? Osteoporos Int.
2000;11(5):449–54.
37. Caplan RH, Beguin EA. Hypercalcemia in a calcitriol‐
treated hypoparathyroid woman during lactation. Obstet Gynecol. 1990;76(3 Pt 2):485–9.
38. Mather KJ, Chik CL, Corenblum B. Maintenance of serum calcium by parathyroid hormone‐related peptide during lactation in a hypoparathyroid patient. J Clin Endocrinol Metab. 1999;84(2):424–7.
154 Pregnancy and Lactation
39. Kent GN, Price RI, Gutteridge DH, et al. Human lactation:
forearm trabecular bone loss, increased bone turnover, and renal conservation of calcium and inorganic phosphate with recovery of bone mass following weaning. J Bone Miner Res. 1990;5:361–9.
40. Sowers M, Zhang D, Hollis BW, et al. Role of calcio- trophic hormones in calcium mobilization of lactation.
Am J Clin Nutr. 1998;67(2):284–91.
41. Prentice A. Calcium in pregnancy and lactation. Annu Rev Nutr. 2000;20:249–72.
42. Prentice A, Jarjou LM, Cole TJ, et al. Calcium require- ments of lactating Gambian mothers: effects of a cal- cium supplement on breast‐milk calcium concentration, maternal bone mineral content, and urinary calcium excretion. Am J Clin Nutr. 1995;62(1):58–67.
43. Prentice A, Jarjou LM, Stirling DM, et al. Biochemical markers of calcium and bone metabolism during 18 months of lactation in Gambian women accustomed to a low calcium intake and in those consuming a
calcium supplement. J Clin Endocrinol Metab. 1998;
83(4):1059–66.
44. Prentice A, Yan L, Jarjou LM, et al. Vitamin D status does not influence the breast‐milk calcium concentra- tion of lactating mothers accustomed to a low calcium intake. Acta Paediatr. 1997;86(9):1006–8.
45. Bezerra FF, Mendonca LM, Lobato EC, et al. Bone mass is recovered from lactation to postweaning in adolescent mothers with low calcium intakes. Am J Clin Nutr.
2004;80(5):1322–6.
46. Chantry CJ, Auinger P, Byrd RS. Lactation among ado- lescent mothers and subsequent bone mineral density.
Arch Pediatr Adolesc Med. 2004;158(7):650–6.
47. Kovacs CS, Kronenberg HM. Maternal‐fetal calcium and bone metabolism during pregnancy, puerperium, and lactation. Endocr Rev. 1997;18(6):832–72.
48. Kovacs CS. Calcium and bone metabolism during preg- nancy and lactation. J Mammary Gland Biol Neoplasia.
2005;10(2):105–18.
155
Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Ninth Edition. Edited by John P. Bilezikian.
© 2019 American Society for Bone and Mineral Research. Published 2019 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/asbmrprimer