Could use of Selective Serotonin Reuptake Inhibitors During Lactation Cause Persistent Effects on Maternal Bone?

Article

Abstract

The lactating mammary gland elegantly coordinates maternal homeostasis to provide calcium for milk. During lactation, the monoamine serotonin regulates the synthesis and release of various mammary gland-derived factors, such as parathyroid hormone-related protein (PTHrP), to stimulate bone resorption. Recent evidence suggests that bone mineral lost during prolonged lactation is not fully recovered following weaning, possibly putting women at increased risk of fracture or osteoporosis. Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants have also been associated with reduced bone mineral density and increased fracture risk. Therefore, SSRI exposure while breastfeeding may exacerbate lactational bone loss, compromising long-term bone health. Through an examination of serotonin and calcium homeostasis during lactation, lactational bone turnover and post-weaning recovery of bone mineral, and the effect of peripartum depression and SSRI on the mammary gland and bone, this review will discuss the hypothesis that peripartum SSRI exposure causes persistent reductions in bone mineral density through mammary-derived PTHrP signaling with bone.

Keywords

serotonin lactation bone Selective Serotonin Reuptake Inhibitor (SSRI) 

Notes

Acknowledgements

This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1747503. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Support was also provided by the Graduate School and the Office of the Vice Chancellor for Research and Graduate Education at the University of Wisconsin-Madison with funding from the Wisconsin Alumni Research Foundation.

References

  1. 1.
    Oftedal OT. The mammary gland and its origin during synapsid evolution. J Mammary Gland Biol Neoplasia. 2002;7:225–52.CrossRefPubMedGoogle Scholar
  2. 2.
    Capuco AV, Akers RM. The origin and evolution of lactation. J Biol. 2009;8:37.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Liu J, Leung P, Breastfeeding YA. Active Bonding Protects against Children’s Internalizing Behavior Problems. Nutrients. 2014;6:76–89.CrossRefGoogle Scholar
  4. 4.
    Feldman R. The neurobiology of mammalian parenting and the biosocial context of human caregiving. Horm Behav. 2016;77:3–17.CrossRefPubMedGoogle Scholar
  5. 5.
    Goldman AS. Evolution of the mammary gland defense system and the ontogeny of the immune system. J Mammary Gland Biol Neoplasia. 2002;7:277–89.CrossRefPubMedGoogle Scholar
  6. 6.
    Hernandez LL, Gregerson KA, Horseman ND. Mammary gland serotonin regulates parathyroid hormone-related protein and other bone-related signals. Am J Physiol Endocrinol Metab. 2012;302:E1009–15.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Tsapakis EM, Gamie Z, Tran GT, Adshead S, Lampard A, Mantalaris A, et al. The adverse skeletal effects of selective serotonin reuptake inhibitors. Eur Psychiatry. 2012;27:156–69.CrossRefPubMedGoogle Scholar
  8. 8.
    Rapport MM, Green AA, Page IH. Crystalline serotonin. Science. 1948;108:329–30.CrossRefPubMedGoogle Scholar
  9. 9.
    Turlejski K. Evolutionary ancient roles of serotonin: long-lasting regulation of activity and development. Acta Neurobiol Exp. 1996;56:619–36.Google Scholar
  10. 10.
    Côté F, Thévenot E, Fligny C, Fromes Y, Darmon M, Ripoche MA, et al. Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function. Proc Natl Acad U S A. 2003;100:13525–30.CrossRefGoogle Scholar
  11. 11.
    Lesurtel M, Soll C, Humar B, Clavien PA. Serotonin: a double-edged sword for the liver? Surgeon. 2012;10:107–13.CrossRefPubMedGoogle Scholar
  12. 12.
    El-Merahbi R, Löffler M, Mayer A, Sumara G. The roles of peripheral serotonin in metabolic homeostasis. FEBS Lett. 2015;589:1728–34.CrossRefPubMedGoogle Scholar
  13. 13.
    Namkung J, Kim H, Park S. Peripheral serotonin: a new player in systemic energy homeostasis. Mol Cells. 2015;38:1023–8.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Watts SW. Oh the places you’ll go! My many colored serotonin (apologies to Dr. Suess). Am J Physiol Heart Circ Physiol. 2016;311:H1225–33.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Matsuda M, Imaoka T, Vomachka AJ, Gudelsky GA, Hou Z, Mistry M, et al. Serotonin regulates mammary gland development via an autocrine-paracrine loop. Dev Cell. 2004;6:193–203.CrossRefPubMedGoogle Scholar
  16. 16.
    Hernandez LL, Stiening CM, Wheelock JB, Baumgard LH, Parkhurst AM, Collier RJ. Evaluation of serotonin as a feedback inhibitor of lactation in the bovine. J Dairy Sci. 2008;91:1834–44.CrossRefPubMedGoogle Scholar
  17. 17.
    Laporta J, Peters TL, Weaver SR, Merriman KE, Hernandez LL. Feeding 5-hydroxy-l-tryptophan during the transition from pregnancy to lactation increase calcium mobilization from bone in rats. Domest Anim Endocrinol. 2013;44:176–84.CrossRefPubMedGoogle Scholar
  18. 18.
    Vela Hinojosa C, León Galván MA, Tapia Rodríguez M, López Ortega G, Cerbón Cervantes MA, Rodríguez CA, et al. Differential expression of serotonin tryptophan hydroylase and monoamine oxidase A in the mammary gland of the Myotis velifer bat. PLoS One. 2013;8:e75062.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Olendorf WH. Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection. Am J Physiol. 1971;221:1629–39.Google Scholar
  20. 20.
    Wang Q, Liu D, Song P, Zou MH. Tryptophan-kynurenine pathway is dysregulated by inflammation, and immune activation. Front Biosci (Landmark Ed). 2015;20:1116–43.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    van Praag HM, Lemus C. Monoamine precursors in the treatment of psychiatric disorders. In: Wurtman RJ, Wurtman JJ, editors. Nutrition and the brain. New York: Raven Press; 1986. p. 89–139.Google Scholar
  22. 22.
    Richard DM, Dawes MA, Mathias CW, Acheson A, Hill-Kapturczak N, Dougherty DM. L-tryptophan: Basic metabolic functions, behavioral research, and therapeutic indications. Int J Tryptophan Res. 2009;2:45–60.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Rahman MK, Nagatsu T, Sakurai T, Hori S, Abe M, Matsuda M. Effect of pyridoxal phosphate deficiency on aromatic L-amino acid decarboxylase activity with L-DOPA and L-5-hydroxytryptophan as substrates in rats. Jpn J Pharmacol. 1982;32:803–11.CrossRefPubMedGoogle Scholar
  24. 24.
    Mann JJ, McBride PA, Brown RP, Linnoila M, Leon AC, DeMeo M, et al. Relationship between central and peripheral serotonin indexes in depressed and suicidal psychiatric inpatients. Arch Gen Psychiatry. 1992;49:442–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Hannon J, Hoyer D. Molecular biology of 5-HT receptors. Behav Brain Res. 2008;195:198–213.CrossRefPubMedGoogle Scholar
  26. 26.
    Hernandez LL, Limesand SW, Collier JL, Horseman ND, Collier RJ. The bovine mammary gland expresses multiple functional isoforms of serotonin receptors. J Endocrinol. 2009;203:123–31.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Pai VP, Marshall AM, Hernandez LL, Buckley AR, Horseman ND. Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival. Breast Cancer Res. 2009;11:R81.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Stull MA, Pai V, Vomachka AJ, Marshall AM, Jacob GA, Horseman ND. Mammary gland homeostasis employs serotonergic regulation of epithelial tight junctions. Proc Natl Acad Sci U S A. 2007;104:16708–13.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Pai VP, Horseman ND. Biphasic regulation of mammary epithelial resistance by serotonin through activation of multiple pathways. J Biol Chem. 2008;283:30901–10.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Pai VP, Hernandez LL, Stull MA, Horseman ND. The type 7 serotonin receptor, 5-HT 7, is essential in the mammary gland for regulation of mammary epithelial structure and function. Biomed Res Int. 2015;2015:364736.CrossRefGoogle Scholar
  31. 31.
    Laporta J, Keil KP, Vezina CM, Hernandez LL. Peripheral serotonin regulates maternal calcium trafficking in mammary epithelial cells during lactation in mice. PLoS One. 2014;9:e110190.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Reiter RJ. Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev. 1991;12:151–80.CrossRefPubMedGoogle Scholar
  33. 33.
    Yamaguchi Y, Hayashi C. Simple determination of high urinary excretion of 5-hydroxyindole-3-acetic acid with ferric chloride. Clin Chem. 1978;24:149–50.PubMedGoogle Scholar
  34. 34.
    Holmsen H, Weiss HJ. Secretable storage pools in platelets. Annu Rev Med. 1979;30:119–34.CrossRefPubMedGoogle Scholar
  35. 35.
    McNicol A, Isreals SJ. Platelet dense granules: Structure, function and implications for haemostasis. Thrombosis Research. 1999;95:1–18.CrossRefPubMedGoogle Scholar
  36. 36.
    Berger M, Gray JA, Roth BL. The expanded biology of serotonin. Ann Rev Med. 2009;60:355–66.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Erspamer V. Occurrence of indolealkylamines in nature. In: Erspamer V, editor. Handbook of experimental pharmacology: 5-hydroxytryptamine and related indolealkylamines. New York: Springer Verlag; 1966. p. 132–81.CrossRefGoogle Scholar
  38. 38.
    Biochemistry GMD, Physiology of serotonergic transmission. In: Brookhart JM, Mountcastle VB, editors. Handbook of physiology: the nervous system. New Jersey: Wiley-Blackwell for the American Physiological Society; 1977. p. 573–623.Google Scholar
  39. 39.
    Weaver SR, Jury NJ, Gregerson KA, Horseman ND, Hernandez LL. Characterization of mammary-specific disruptions for Tph1 and Lrp5 during murine lactation. Sci Rep. 2017;7:15155.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Dupont C, Armant DR, Brenner CA. Epigenetics: Definition, mechanism, and clinical perspective. Semin Reprod Med. 2009;27:351–7.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Berger SL. The complex language of chromatin regulation during transcription. Nature. 2007;447:407–12.CrossRefPubMedGoogle Scholar
  42. 42.
    Borrelli E, Nestler EJ, Allis CD, Sassone-Corsi P. Decoding the epigenetic language of neuronal plasticity. Neuron. 2008;60:961–74.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Antequera F. Structure, function and evolution of CpG island promoters. Cell Mol Life Sci. 2003;60:1647–58.CrossRefPubMedGoogle Scholar
  44. 44.
    Métivier R, Gallais R, Tiffoche C, Le Péron C, Jurkowska RZ, Carmouche RP, et al. Cyclical DNA methylation of a transcriptionally active promoter. Nature. 2008;452:45–50.CrossRefPubMedGoogle Scholar
  45. 45.
    Schwarz JM, Nugent BM, McCarthy MM. Developmental and hormone-induced epigenetic changes to estrogen and progesterone receptor genes in brain are dynamic across the life span. Endocrinology. 2010;151:4871–81.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Crider KS, Yang TP, Berry RJ, Bailey LB. Folate and DNA methylation: A review of molecular mechanisms and the evidence for folate's role. Adv Nutr. 2012;3:21–38.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Uysal F, Akkoyunlu G, Ozturk S. Dynamic expression of DNA methyltransferases (DNMTs) in oocytes and early embryos. Biochimie. 2015;116:103–13.CrossRefPubMedGoogle Scholar
  48. 48.
    Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science. 2009;324:929–30.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324:930–5.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333:1300–3.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Holloway T, González-Maeso J. Epigenetic mechanisms of serotonin signaling. ACS Chem Neurosci. 2015;6:1099–109.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Nikolova YS, Koenen KC, Galea S, Wang CM, Seney ML, Sibille E, et al. Beyond genotype: serotonin transporter epigenetic modification predicts human brain function. Nat Neurosci. 2014;17:1153–5.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Kinnally EL, Capitanio JP, Leibel R, Deng L, LeDuc C, Haghighi F, et al. Epigenetic regulation of serotonin transporter expression and behavior in infant rhesus macaques. Genes Brain Behav. 2010;9:575–82.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Rajasethupathy P, Antonov I, Sheridan R, Frey S, Sander C, Tuschl T, et al. A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity. Cell. 2012;149:693–707.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Blazevic S, Horvaticek M, Kesic M, Zill P, Hranilovic D, Ivanisevic M, et al. Epigentic adaptation of the placental serotonin transporter gene (SLC6A4) to gestational diabetes mellitus. PLoS One. 2017;12:e0179934.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Huang L, Frampton G, Rao A, Zhang KS, Chen W, Lai JM, et al. Monoamine oxidase A expression is suppressed in human cholangiocarcinoma via coordinated epigenetic and IL-6-driven events. Lab Invest. 2010;92:1451–60.CrossRefGoogle Scholar
  57. 57.
    Walther DJ, Peter JU, Winter S, Holtje M, Paulmann N, Grohmann M, et al. Serotonylation of small GTPases is a signal transduction pathway that triggers platelet alpha-granule release. Cell. 2003;115:851–62.CrossRefPubMedGoogle Scholar
  58. 58.
    Paulmann N, Grohmann M, Voigt JP, Bert B, Vowinckel J, Bader M, et al. Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation. PLoS Biol. 2009;7:e1000229.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Watts SW, Priestley JR, Thompson JM. Serotonylation of vascular proteins important to contraction. PLoS One. 2009;4:e5682.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Al-Zoairy R, Pedrini MT, Khan MI, Engl J, Tschoner A, Ebenbichler C, et al. Serotonin improves glucose metabolism by serotonylation of the small GTPase Rab4 in L6 skeletal muscles. Diabetol Metab Syndr. 2017;9:1.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Muma NA, Mi Z. Serotonylation and transamidation of other monoamines. ACS Chem Neurosci. 2015;6:961–9.CrossRefPubMedGoogle Scholar
  62. 62.
    Lewis MT, Ross S, Strickland PA, Sugnet CW, Jimenez E, Scott MP, et al. Defects in mouse mammary gland development caused by conditional haploinsufficiency of Patched-1. Development. 1999;126:5181–93.PubMedGoogle Scholar
  63. 63.
    Lewis MT, Ross S, Strickland PA, Sugnet CW, Jimenez E, Hui C, et al. The Gli2 transcription factor is required for normal mouse mammary gland development. Dev Biol. 2001;238:133–44.CrossRefPubMedGoogle Scholar
  64. 64.
    Sterling JA, Oyajobi BO, Grubbs B, Padalecki SS, Munoz SA, Gupta A, et al. The hedgehog signaling molecule Gli2 induces parathyroid hormone-related peptide expression and osteolysis in metastatic human breast cancer cells. Cancer Res. 2006;66:7548–53.CrossRefPubMedGoogle Scholar
  65. 65.
    Nwabo Kamdje AH, Seke Etet PF, Vecchio L, Muller JM, Krampera M, Lukong KE. Signaling pathways in breast cancer: therapeutic targeting of the microenvironment. Cell Signal. 2014;26:2843–56.CrossRefPubMedGoogle Scholar
  66. 66.
    Lipinski RJ, Gipp JJ, Zhang J, Doles JD, Bushman W. Unique and complimentary activities of the Gli transcription factors in Hedgehog signaling. Exp Cell Res. 2006;312:1925–38.CrossRefPubMedGoogle Scholar
  67. 67.
    VanHouten JN, Wysolmerski JJ. Low estrogen and high parathyroid hormone-related peptide levels contribute to accelerated bone resorption and bone loss in lactating mice. Endocrinology. 2003;144:5521–9.CrossRefPubMedGoogle Scholar
  68. 68.
    Laporta J, Keil KP, Weaver SR, Cronick CM, Prichard AP, Crenshaw TD, et al. Serotonin regulates calcium homeostasis in lactation by epigenetic activation of hedgehog signaling. Mol Endocrinol. 2014;28:1866–74.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Marcus SM, Flynn HA, Blow FC, Barry KL. Depressive symptoms among pregnant women screened in obstetrics screenings. J Womens Health (Larchmt). 2003;12:373–80.CrossRefGoogle Scholar
  70. 70.
    Davanzo R, Copertino M, De Cunto A, Minen F, Amaddeo A. Antidepressant drugs and breastfeeding: a review of the literature. Breastfeed Med. 2011;6:89–98.CrossRefPubMedGoogle Scholar
  71. 71.
    Tran H, Robb AS. SSRI use during pregnancy. Semin Perinatol. 2015;39:545–7.CrossRefPubMedGoogle Scholar
  72. 72.
    Walther DJ, Peter JU, Bashammakh S, Hortnagl H, Voits M, Fink H, et al. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science. 2003;299:76.CrossRefPubMedGoogle Scholar
  73. 73.
    Schraenen A, Lemaire K, de Faudeur G, Hendrickx N, Granvik M, Van Lommel L, et al. Placental lactogens induce serotonin biosynthesis in a subset of mouse beta cells. Diabetologia. 2010;53:2589–99.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Kim H, Toyofuku Y, Lynn FC, Chak E, Uchida T, Mizukami H, et al. Serotonin regulates pancreatic beta cell mass during pregnancy. Nat Med. 2010;16:804–8.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Iida H, Ogihara T, Min MK, Hara A, Kim YG, Fujimaki K, et al. Expression mechanism of tryptophan hydroxylase 1 in mouse islets during pregnancy. J Mol Endocrinol. 2015;55:41–53.PubMedGoogle Scholar
  76. 76.
    Ohara-Imaizumi M, Kim H, Yoshida M, Fujiwara T, Aoyagi K, Toyofuku Y, et al. Serotonin regulates glucose-stimulated insulin secretion from pancreatic beta cells during pregnancy. Am Proc Natl Acad Sci U S A. 2013;110:19420–5.CrossRefGoogle Scholar
  77. 77.
    Park H, Oh CM, Park J, Park H, Cui S, Kim HS, et al. Deletion of the serotonin receptor type 3A in mice leads to sudden cardiac death during pregnancy. Circ J. 2015;79:1807–15.CrossRefPubMedGoogle Scholar
  78. 78.
    Jeffrey JJ, Ehlich LS, Roswit WT. Serotonin – an inducer of collagenase in myometrial smooth-muscle cells. J Cell Physiol. 1991;146:399–406.CrossRefPubMedGoogle Scholar
  79. 79.
    Ontsouka EC, Reist M, Graber H, Blum JW, Steiner A, Hirsbrunner G. Expression of messenger RNA coding for 5-HT receptor, alpha and beta adrenoreceptor (subtypes) during oestrus and dioestrus in the bovine uterus. J Vet Med A Physiol Pathol Clin Med. 2004;51:385–93.CrossRefPubMedGoogle Scholar
  80. 80.
    Weiner CP, Thompson LP, Liu KZ, Herrig JE. Pregnancy reduces serotonin-induced contraction of guinea pig uterine and carotid arteries. Am J Physiol. 1992;263:H1764–9.PubMedGoogle Scholar
  81. 81.
    Middelkoop CM, Dekker GA, Kraayenbrink AA, Popp-Snijders C. Platelet-poor plasma serotonin in normal and preeclamptic pregnancy. Clin Chem. 1993;39:1675–8.PubMedGoogle Scholar
  82. 82.
    Bolte AC, van Geijn JP, Dekker GA. Pathophysiology of preeclampsia and the role of serotonin. Eur J Obstet Gynecol Reprod Biol. 2001;95:12–21.CrossRefPubMedGoogle Scholar
  83. 83.
    Cengiz H, Dagdeviren H, Caypinar SS, Kanawati A, Yildiz S, Ekin M. Plasma serotonin levels are elevated in pregnant women with hyperemesis gravidarum. Arch Gynecol Obstet. 2015;291:1271–6.CrossRefPubMedGoogle Scholar
  84. 84.
    Laporta J, Peters TL, Merriman KE, Vezina CM, Hernandez LL. Serotonin (5-HT) affects expression of liver metabolic enzymes and mammary gland glucose transporters during the transition from pregnancy to lactation. PLoS One. 2013;8:e57847.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Laporta J, Hernandez LL. Serotonin receptor expression is dynamic in the liver during the transition period in Holstein dairy cows. Domest Anim Endocrinol. 2015;51:65–73.CrossRefPubMedGoogle Scholar
  86. 86.
    Laporta J, Gross JJ, Crenshaw TD, Bruckmaier RM, Hernandez LL. Short communication: Timing of first milking affects serotonin (5-HT) concentrations. J Dairy Sci. 2014;97:2944–8.CrossRefPubMedGoogle Scholar
  87. 87.
    Côté F, Fligny C, Bayard E, Launay JM, Gershon MD, Mallet J, et al. Maternal serotonin is crucial for murine embryonic development. Proc Natl Acad Sci U S A. 2007;104:329–34.CrossRefPubMedGoogle Scholar
  88. 88.
    Amireault P, Sibon D, Côté F. Life without peripheral serotonin: Insights from tryptophan hydroxylase 1 knockout mice reveal the existence of paracrine/autocrine serotonergic networks. ACS Chem Neurosci. 2013;4:64–71.CrossRefPubMedGoogle Scholar
  89. 89.
    Yavarone MS, Shuey DL, Sadler TW, Lauder JM. Serotonin uptake in the ectoplacental cone and placenta of the mouse. Placenta. 1993;14:149–61.CrossRefPubMedGoogle Scholar
  90. 90.
    Huang WQ, Zhang CL, Di XY, Zhang RQ. Studies on the localization of 5-hydroxytryptamine and its receptors in human placenta. Placenta. 1998;19:655–61.CrossRefPubMedGoogle Scholar
  91. 91.
    Viau M, Lafond J, Vaillancourt C. Expression of placental serotonin transporter and 5-HT 2A receptor in normal and gestational diabetes mellitus pregnancies. Reprod Biomed Online. 2009;19:207–15.CrossRefPubMedGoogle Scholar
  92. 92.
    Bonnin A, Peng W, Hewlett W, Levitt P. Expression mapping of 5-HT1 receptor subtypes during fetal and early postnatal mouse forebrain development. Neuroscience. 2006;141:781–94.CrossRefPubMedGoogle Scholar
  93. 93.
    Anderson GM, Gutknecht L, Cohen DJ, Brailly-Tabard S, Cohen JH, Ferrari P, et al. Serotonin transporter promoter variants in autism: functional effects and relationship to platelet hyperserotonemia. Mol Psychiatry. 2002;7:831–6.CrossRefPubMedGoogle Scholar
  94. 94.
    Gaspar P, Cases O, Maroteaux L. The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci. 2003;4:1002–12.CrossRefPubMedGoogle Scholar
  95. 95.
    Bonnin A, Goeden N, Chen K, Wilson ML, King J, Shih JC, et al. A transient placental source of serotonin for the fetal forebrain. Nature. 2011;472:347–50.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Toda T, Homma D, Tokuoka H, Hayakawa I, Sugimoto Y, Ichinose H, et al. Birth regulates the initiation of sensory map formation through serotonin signaling. Dev Cell. 2013;27:32–46.CrossRefPubMedGoogle Scholar
  97. 97.
    Schneider ML, Moore CF, Barr CS, Larson JA, Kraemer GW. Moderate prenatal alcohol exposure and serotonin genotype interact to alter CNS serotonin function in rhesus monkey offspring. Alcohol Clin Exp Res. 2011;35:912–20.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Sullivan EL, Grayson B, Takahashi D, Robertson N, Maier A, Bethea CL, et al. J Neurosci. 2010;30:3826–30.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Weaver SR, Bohrer JC, Prichard AS, Perez PK, Streckenbach LJ, Olson JM, et al. Serotonin deficiency rescues lactation on day 1 in mice fed a high fat diet. PLoS One. 2016;11:e0162432.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Raymond JR, Mukhin YV, Gelasco A, Turner J, Collinsworth G, Gettys TW, et al. Multiplicity of mechanisms of serotonin receptor signal transduction. Pharmacol Ther. 2001;92:179–212.CrossRefPubMedGoogle Scholar
  101. 101.
    Collier RJ, Hernandez LL, Horseman ND. Serotonin as a homeostatic regulator of lactation. Domest Anim Endocrinol. 2012;43:161–70.CrossRefPubMedGoogle Scholar
  102. 102.
    Hernandez LL, Collier JL, Vomachka AJ, Collier RJ, Horseman ND. Suppression of lactation and acceleration of involution in the bovine mammary gland by a selective serotonin reuptake inhibitor. J Endocrinol. 2011;209:45–54.CrossRefPubMedGoogle Scholar
  103. 103.
    Zhang CL, Chen H, Wang YH, Zhang RF, Lan XY, Lei CZ, et al. Serotonin receptor 1B (HTR1B) genotype associated with milk production traits in cattle. Res Vet Sci. 2008;85:265–8.CrossRefPubMedGoogle Scholar
  104. 104.
    Qanbari S, Pimentel EC, Tetens J, Thaller G, Lichtner P, Sharifi AR, et al. A genome-wide scan for signatures of recent selection in Holstein cattle. Anim Genet. 2010;41:377–89.PubMedGoogle Scholar
  105. 105.
    Nguyen DA, Neville MC. Tight junction regulation in the mammary gland. J Mammary Gland Biol Neoplasia. 1998;3:233–46.CrossRefPubMedGoogle Scholar
  106. 106.
    Bornstein S, Brown SA, Le PT, Wang X, DeMambro V, Horowitz MC, et al. FGF-21 and skeletal remodeling during and after lactation in C57BL/6J mice. Endocrinology. 2014;155:3516–26.CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Jury NJ, McCormick BA, Horseman ND, Benoit SC, Gregerson KA. Enhanced responsiveness to selective serotonin reuptake inhibitors during lactation. PLoS One. 2015;10:e0117339.CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Davis FM, Janoshazi A, Janardhan KS, Steinckwich N, D'Agostin DM, Petranka JG, Desai PN, Roberts-Thomson SJ, Bird GS, Tucker DK, Fenton SE, Feske S, Monteith GR, Putney JW Jr. Essential role of Orai1 store-operated calcium channels in lactation. Proc Natl Acad Sci U S A. 2015;112:5827-5832.Google Scholar
  109. 109.
    Reinhardt TA, Lippolis JD, Shull GE, Horst RL. Null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2 impairs calcium transport into milk. J Biol Chem. 2004;279:42369–73.CrossRefPubMedGoogle Scholar
  110. 110.
    VanHouten JN, Neville MC, Wysolmerski JJ. The calcium-sensing receptor regulates plasma membrane calcium adenosine triphosphatase isoform 2 activity in mammary epithelial cells: a mechanism for calcium-regulated calcium transport into milk. Endocrinology. 2007;148:5943–54.CrossRefPubMedGoogle Scholar
  111. 111.
    VanHouten JN. Calcium sensing by the mammary gland. J Mammary Gland Biol Neoplasia. 2005;10:129–39.CrossRefPubMedGoogle Scholar
  112. 112.
    Laporta J, Moore SA, Peters MW, Hernandez LL. Short communication: circulating serotonin (5-HT) concentrations on day 1 of lactation as a potential predictor of transition-related disorders. J Dairy Sci. 2013;96:5146–50.CrossRefPubMedGoogle Scholar
  113. 113.
    Moore SA, Laporta J, Crenshaw TD, Hernandez LL. Patterns of circulating serotonin and related metabolites in multiparous dairy cows in the peripartum period. J Dairy Sci. 2015;98:3754–65.PubMedGoogle Scholar
  114. 114.
    Laporta J, Moore SA, Weaver SR, Cronick CM, Olsen M, Prichard AP, et al. Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows. J Endocrinol. 2015;226:43–55.CrossRefPubMedGoogle Scholar
  115. 115.
    Hernández-Castellano LE, Hernandez LL, Weaver SR, Bruckmaier RM. Increased serum serotonin improves parturient calcium homeostasis in dairy cows. J Dairy Sci. 2017;100:1580–7.CrossRefPubMedGoogle Scholar
  116. 116.
    Weaver SR, Prichard AP, Endres EL, Newhouse SA, Peters TL, Crump PM, et al. Elevation of circulating seorotnin improves calcium dynamics in the peripartum dairy cow. J Endocrinol. 2016;230:105–23.CrossRefPubMedGoogle Scholar
  117. 117.
    Hernández-Castellano LE, Hernandez LL, Sauerwein H, Bruckmaier RM. Endocrine and metabolic changes in transition dairy cows are affected by pre-partum infusions of a serotonin precursor. J Dairy Sci. 2017;100:5050–7.CrossRefPubMedGoogle Scholar
  118. 118.
    Kovacs CS. Maternal mineral and bone metabolism during pregnancy, lactation, and post-weaning recovery. Physiol Rev. 2016;96:449–547.CrossRefPubMedGoogle Scholar
  119. 119.
    Charoenphandhu N, Krishnamra N. Prolactin is an important regulator of intestinal calcium transport. Can J Physiol Pharmacol. 2007;85:569–81.CrossRefPubMedGoogle Scholar
  120. 120.
    Klein CJ, Moser-Veillon PB, Douglass LW, Ruben KA, Trocki O. A longitudinal study of urinary calcium, magnesium, and zinc excretion in lactating and nonlactating postpartum women. Am J Clin Nutr. 1995;61:779–86.CrossRefPubMedGoogle Scholar
  121. 121.
    Ramberg CF Jr, Mayer GP, Kronfeld DS, Phang JM, Berman M. Calcium kinetics in cows during late pregnancy, parturition, and early lactation. Am J Physiol. 1970;219:1166–77.PubMedGoogle Scholar
  122. 122.
    Goff JP. The monitoring, prevention, and treatment of milk fever and subclinical hypocalcemia in dairy cows. Vet J. 2008;176:50–7.CrossRefPubMedGoogle Scholar
  123. 123.
    Chapinal N, Carson ME, LeBlanc SJ, Leslie KE, Godden S, Capel M, et al. The association of serum metabolites in the transition period with milk production and early-lactation reproductive performance. J Dairy Sci. 2012;95:1301–9.CrossRefPubMedGoogle Scholar
  124. 124.
    Martinez N, Risco CA, Lima FS, Bisinotto RS, Greco LF, Ribeiro ES, et al. Evaluation of peripartal calcium status, energetic profile, and neutrophil function in dairy cows at low or high risk of developing uterine disease. J Dairy Sci. 2012;95:7158–72.CrossRefPubMedGoogle Scholar
  125. 125.
    Massey CD, Wang C, Donovan GA, Beede DK. Hypocalcemia at parturition as a risk factor for left displacement of the abomasum in dairy cows. J Am Vet Med Assoc. 1993;203:852–3.PubMedGoogle Scholar
  126. 126.
    Hammon DS, Evjen IM, Dhiman TR, Goff JP, Walters JL. Neutrophil function and energy status in Holstein cows with uterine health disorders. Vet Immunol Immunopathol. 2006;113:21–9.CrossRefPubMedGoogle Scholar
  127. 127.
    Kimura K, Reinhardt TA, Goff JP. Parturition and hypocalcemia blunts calcium signals in immune cells of dairy cattle. J Dairy Sci. 2006;89:2588–95.CrossRefPubMedGoogle Scholar
  128. 128.
    Martinez N, Sinedino LD, Bisinotto RS, Ribeiro ES, Gomes GC, Lima FS, et al. Effect of induced subclinical hypocalcemia on physiological responses and neutrophil function in dairy cows. J Dairy Sci. 2014;97:874–87.CrossRefPubMedGoogle Scholar
  129. 129.
    Sepúlveda-Varas P, Weary DM, Noro M, von Keyserlingk MA. Transition diseases in grazing dairy cows are related to serum cholesterol and other analytes. PLoS One. 2015;10:e0122317.CrossRefPubMedPubMedCentralGoogle Scholar
  130. 130.
    Rodriguez EM, Aris A, Bach A. Associations between subclinical hypocalcemia and postparturient diseases in dairy cows. J Dairy Sci. 2017;100:7427–34.CrossRefPubMedGoogle Scholar
  131. 131.
    Reinhardt TL, Lippolis JD, McCluskey BJ, Goff JP, Horst RL. Prevalence of subclinical hypocalcemia in dairy herds. Vet J. 2011;188:122–4.CrossRefPubMedGoogle Scholar
  132. 132.
    Martín-Tesoro J, Martens H. Calcium and magnesium physiology and nutrition in relation to the prevention of milk fever and tetany (dietary management of macrominerals in preventing disease). Vet Clin North Am Food Anim Pract. 2014;30:643–70.CrossRefGoogle Scholar
  133. 133.
    Caixeta LS, Ospina PA, Capel MB, Nydam DV. The association of subclinical hypocalcemia, negative energy balance and disease with bodyweight change during the first 30 days post-partum in dairy cows milked with automatic milking systems. Vet J. 2015;204:150–6.CrossRefPubMedGoogle Scholar
  134. 134.
    Charbonneau E, Pellerin D, Oetzel GR. Impact of lowering dietary cation-anion difference in nonlactating dairy cows: A meta-analysis. J Dairy Sci. 2006;89:537–48.CrossRefPubMedGoogle Scholar
  135. 135.
    Weich W, Block E, Litherland NB. Extended negative dietary cation-anion difference feeding does not negatively affect postpartum performance of multiparous dairy cows. J Dairy Sci. 2013;96:5780–92.CrossRefPubMedGoogle Scholar
  136. 136.
    Leno BM, Ryan CM, Stokol T, Kirk D, Zanzalari KP, Chapman JD, et al. Effects of prepartum dietary cation-anion difference on aspects of peripartum mineral and energy metabolism and performance of multiparous Holstein cows. J Dairy Sci. 2017;100:4604–22.CrossRefPubMedGoogle Scholar
  137. 137.
    Goff JP, Horst RL. Role of acid-base physiology on the pathogenesis of parturient hypocalcaemia (milk fever) -- the DCAD theory in principal and practice. Acta Vet Scand Suppl. 2003;97:51–6.PubMedGoogle Scholar
  138. 138.
    Goff JP, Liesegang A, Horst RL. 2014. Diet-induced pseudohypoparathyroidism: A hypocalcemia and milk fever risk factor. J Dairy Sci. 2014;97:1520–8.CrossRefPubMedGoogle Scholar
  139. 139.
    Cross NA, Hillman LS, Allen SH, Krause GF, Vieira NE. Calcium homeostasis and bone metabolism during pregnancy, lactation, and postweaning: a longitudinal study. Am J Clin Nutr. 1995;61:514–23.CrossRefPubMedGoogle Scholar
  140. 140.
    Affinito P, Tommaselli GA, di Carlo C, Guida F, Nappi C. Changes in bone mineral density and calcium metabolism in breastfeeding women: a one-year follow up study. J Clin Endocrinol Metab. 1996;81:2314–8.PubMedGoogle Scholar
  141. 141.
    Diaz de Barboza G, Guizzardi S, Tolosa de Talamoni N. Molecular aspects of intestinal calcium absorption. World J Gastroenterol. 2015;21:7142–54.CrossRefPubMedPubMedCentralGoogle Scholar
  142. 142.
    Halloran BP, DeLuca HF. Calcium transport in small intestine during pregnancy and lactation. Am J Physiol. 1980;239:E64–8.PubMedGoogle Scholar
  143. 143.
    Boass A, Toverud SU, Pike JW, Haussler MR. Calcium metabolism during lactation: enhanced intestinal calcium absorption in vitamin D-deprived, hypocalcemic rats. Endocrinology. 1981;109:900–7.CrossRefPubMedGoogle Scholar
  144. 144.
    Kent GN, Price RI, Gutteridge DH, Rosman KJ, Smith M, Allen JR, et al. The efficiency of intestinal calcium absorption is increased in late pregnancy but not in established lactation. Calcif Tissue Int. 1991;48:293–5.CrossRefPubMedGoogle Scholar
  145. 145.
    Ritchie LD, Fung EB, Halloran BP, Turnlund JR, Van Loan MD, Cann CE, et al. A longitudinal study of calcium homeostasis during human pregnancy and lactation and after resumption of menses. Am J Clin Nutr. 1998;67:693–701.CrossRefPubMedGoogle Scholar
  146. 146.
    Ardeshirpour L, Brian S, Dann P, VanHouten J, Wysolmerski J. Increased PTHrP and decreased estrogens alter bone turnover but do not reproduce the full effects of lactation on the skeleton. Endocrinology. 2010;151:5591–601.CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Krebs NF, Reidinger CJ, Robertson AD, Brenner M. Bone mineral density changes during lactation: maternal, dietary, and biochemical correlates. Am J Clin Nutr. 1997;65:1738–46.CrossRefPubMedGoogle Scholar
  148. 148.
    Naveh-Many T, Raue F, Grauer A, Silver J. Regulation of calcitonin gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat. J Bone Miner Res. 1992;7:1233–7.CrossRefPubMedGoogle Scholar
  149. 149.
    Ardeshirpour L, Dann P, Adams DJ, Nelson T, VanHouten J, Horowitz MC, et al. Weaning triggers a decrease in receptor activator of nuclear factor-kappaB ligand expression, widespread osteoclast apoptosis, and rapid recovery of bone mass after lactation in mice. Endocrinology. 2007;148:3875–86.CrossRefPubMedGoogle Scholar
  150. 150.
    Liu XS, Ardeshirpour L, VanHouten JN, Shane E, Wysolmerski JJ. Site-specific changes in bone microarchitecture, mineralization, and stiffness during lactation and after weaning in mice. J Bone Miner Res. 2012;27:865–75.CrossRefPubMedGoogle Scholar
  151. 151.
    Wendelboe MH, Thomsen JS, Henriksen K, Vegger JB, Brüel A. Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice. Bone. 2016;87:27–36.CrossRefPubMedGoogle Scholar
  152. 152.
    Hiyaoka A, Yoshida T, Cho F, Yoshikawa Y. Changes in bone mineral density of lumbar vertebrae after parturition in African green monkeys (Cercopithecus aethiops). Exp Anim. 1996;45:257–9.CrossRefPubMedGoogle Scholar
  153. 153.
    Ott SM, Lipkin EW, Newell-Morris L. Bone physiology during pregnancy and lactation in young macaques. J Bone Miner Res. 1999;14:1779–88.CrossRefPubMedGoogle Scholar
  154. 154.
    Miller MA, Omura TH, Miller SC. Increased cancellous bone remodeling during lactation in beagles. Bone. 1989;10:279–85.CrossRefPubMedGoogle Scholar
  155. 155.
    Giesemann MA, Lewis AJ, Miller PS, Akhter MP. Effects of the reproductive cycle and age on calcium and phosphorus metabolism and bone integrity of sows. J Anim Sci. 1998;76:796–807.CrossRefPubMedGoogle Scholar
  156. 156.
    Liesegang A, Risteli J, Wanner M. The effects of first gestation and lactation on bone metabolism in dairy goats and milk sheep. Bone. 2006;38:794–802.CrossRefPubMedGoogle Scholar
  157. 157.
    Liesegang A, Eicher R, Sassi ML, Risteli J, Kraenzlin M, Riond JL, et al. Biochemical markers of bone formation and resorption around parturition and during lactation in dairy cows with high and low standard milk yields. J Dairy Sci. 2000;83:1773–81.CrossRefPubMedGoogle Scholar
  158. 158.
    Holtenius K, Ekelund A. Biochemical markers of bone turnover in the dairy cow during lactation and the dry period. Res Vet Sci. 2005;78:17–9.CrossRefPubMedGoogle Scholar
  159. 159.
    Laskey MA, Prentice A, Hanratty LA, Jarjou LM, Dibba B, Beavan SR, 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;67:685–92.CrossRefPubMedGoogle Scholar
  160. 160.
    Sowers M, Corton G, Shapiro B, Jannausch ML, Crutchfield M, Smith ML, et al. Changes in bone density with lactation. JAMA. 1993;269:3130–5.CrossRefPubMedGoogle Scholar
  161. 161.
    More C, Bettembuk P, Bhattoa HP, Balogh A. The effects of pregnancy and lactation on bone mineral density. Osteoporos Int. 2001;12:732–7.CrossRefPubMedGoogle Scholar
  162. 162.
    Møller UK, Vio Streym S, Mosekilde L, Rejnmark L. Changes in bone mineral density and body composition during pregnancy and postpartum. A controlled cohort study. Osteoporos Int. 2012;23:1213–23.CrossRefPubMedGoogle Scholar
  163. 163.
    Brembeck P, Lorentzon M, Ohlsson C, Winkvist A, Augustin H. Changes in cortical volumetric bone mineral density and thickness, and trabecular thickness in lactating women postpartum. J Clin Endocrinol Metab. 2015;100:535–43.CrossRefPubMedGoogle Scholar
  164. 164.
    Suntornsaratoon P, Wongdee K, Goswami S, Krishnamra N, Charoenphandhu N. Bone modeling in bromocriptine-treated pregnant and lactating rats: possible osteoregulatory role of prolactin in lactation. Am J Physiol Endocrinol Metab. 2010;299:E426–36.CrossRefPubMedGoogle Scholar
  165. 165.
    Boyce BF, Xing L. Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther. 2007;9:S1.CrossRefPubMedPubMedCentralGoogle Scholar
  166. 166.
    Cross NA, Hillman LS, Allen SH, Krause GF. 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;10:1312–20.CrossRefPubMedGoogle Scholar
  167. 167.
    Prentice A, Jarjou LM, Stirling DM, Buffenstein R, Fairweather-Tait S. 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;83:1059–66.PubMedGoogle Scholar
  168. 168.
    Ardeshirpour L, Dumitru C, Dann P, Sterpka J, VanHouten J, Kim W, et al. OPG treatment prevents bone loss during lactation but does not affect milk production or maternal calcium metabolism. Endocrinology. 2015;156:2762–73.CrossRefPubMedPubMedCentralGoogle Scholar
  169. 169.
    Lorget F, Kamel S, Mentaverri R, Wattel A, Naassila M, Maamer M, et al. High extracellular calcium concentrations directly stimulate osteoclast apoptosis. Biochem Biophys Res Commun. 2000;268:899–903.CrossRefPubMedGoogle Scholar
  170. 170.
    Boyce BF. Advances in the regulation of osteoclasts and osteoclast functions. J Dent Res. 2013;92:860–7.CrossRefPubMedPubMedCentralGoogle Scholar
  171. 171.
    Miller SC, Bowman BM. Rapid inactivation and apoptosis of osteoclasts in the maternal skeleton during the bone remodeling reversal at the end of lactation. Anat Rec (Hoboken). 2007;290:65–73.CrossRefPubMedGoogle Scholar
  172. 172.
    Onal M, Galli C, Fu Q, Xiong J, Weinstein RS, Manolagas SC, et al. The RANKL distal control region is required for the increase in RANKL expression, but not the bone loss, associated with hyperparathyroidism or lactation in adult mice. Mol Endocrinol. 2013;26:341–8.CrossRefGoogle Scholar
  173. 173.
    Belanger LF. Osteocytic osteolysis. Calcif Tissue Res. 1969;4:1–12.CrossRefPubMedGoogle Scholar
  174. 174.
    Bonewald LF. The amazing osteocyte. J Bone Miner Res. 2011;26:229–38.CrossRefPubMedGoogle Scholar
  175. 175.
    Wysolmerski JJ. Osteocytes remove and replace perilacunar mineral during reproductive cycles. Bone. 2013;54:230–6.CrossRefPubMedPubMedCentralGoogle Scholar
  176. 176.
    Qing H, Ardeshirpour L, Pajevic PD, Dusevich V, Jähn K, Kato S, et al. Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. J Bone Miner Res. 2012;27:1018–29.CrossRefPubMedPubMedCentralGoogle Scholar
  177. 177.
    Tang SY, Herber RP, Ho SP, Alliston T. Matrix metalloproteinase-13 is required for osteocytic perilacunar remodeling and maintains bone fracture resistance. J Bone Miner Res. 2012;27:1936–50.CrossRefPubMedPubMedCentralGoogle Scholar
  178. 178.
    Macica CM, King HE, Wang M, McEachon CL, Skinner CW, Tommasini SM. Novel anatomic adaptation of cortical bone to meet increased mineral demands of reproduction. Bone. 2016;85:59–69.CrossRefPubMedGoogle Scholar
  179. 179.
    Kaya S, Basta-Pljakic J, Seref-Ferlengez Z, Majeska R, Cardoso L, Bromage T, et al. Lactation-induced changes in the volume of osteocyte lacunar-canalicular space alter mechanical properties in cortical bone tissue. J Bone Miner Res. 2017;32:688–97.CrossRefPubMedGoogle Scholar
  180. 180.
    Vajda EG, Bowman BM, Cancellous MSC. cortical bone mechanical properties and tissue dynamics during pregnancy, lactation, and post-lactation in the rat. Biol Reprod. 2001;65:689–95.CrossRefPubMedGoogle Scholar
  181. 181.
    Hens JR, Wysolmerski JJ. Key stages of mammary gland development: molecular mechanisms involved in the formation of the embryonic mammary gland. Breast Cancer Res. 2005;7:220–4.CrossRefPubMedPubMedCentralGoogle Scholar
  182. 182.
    Lee K, Deeds JD, Segre GV. Expression of parathyroid hormone-related peptide and its receptor messenger ribonucleic acids during fetal development of rats. Endocrinology. 1995;136:453–63.CrossRefPubMedGoogle Scholar
  183. 183.
    Kovacs CS. The role of PTHrP in regulating mineral metabolism during pregnancy lactation, and fetal/neonatal development. Clinic Rev Bone Miner Metab. 2014;12:142–64.CrossRefGoogle Scholar
  184. 184.
    Stewart AF, Insogna KL, Burtis WJ, Aminiafshar A. Wu T, Weir EC, Broadus AE. Frequency and partial characterization of adenylate cyclase-stimulating activity in tumors associated with humoral hypercalcemia of malignancy. J Bone Miner Res. 1986;1:267–76.CrossRefPubMedGoogle Scholar
  185. 185.
    Burtis WJ, Wu T, Bunch C, Wysolmerski JJ, Insogna KL, Weir EC, et al. Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. J Biol Chem. 1987;262:7151–6.PubMedGoogle Scholar
  186. 186.
    Burtis WJ, Brady TG, Orloff JJ, Ersbak JB, Warrell RP, Olson BR, et al. Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. N Engl J Med. 1990;322:1106–12.CrossRefPubMedGoogle Scholar
  187. 187.
    Stiegler C, Leb G, Kleinert R, Warnkross H, Ramschak-Schwarzer S, Lipp R, et al. Plasma levels of parathyroid hormone-related peptide are elevated in hyperprolactinemia and correlated to bone density status. J Bone Miner Res. 1995;10:751–9.CrossRefPubMedGoogle Scholar
  188. 188.
    Washam CL, Byrum SD, Leitzel K, Ali SM, Tackett AJ, Gaddy D, et al. Identification of PTHrP(12-48) as a plasma biomarker associated with breast cancer bone metastasis. Cancer Epidemiol Biomarkers Prev. 2013;22:972–83.CrossRefPubMedPubMedCentralGoogle Scholar
  189. 189.
    Thiébaud D, Janisch S, Koelbl H, Hanzal E, Jacquet AF, Leodolter S, et al. Direct evidence of a parathyroid related protein gradient between the mother and the newborn in humans. Bone Miner. 1993;23:213–21.CrossRefPubMedGoogle Scholar
  190. 190.
    Ardawi MS, Nasrat HA, BA’Aqueel HS. Calcium-regulating hormones and parathyroid hormone-related peptide in normal human pregnancy and postpartum: a longitudinal study. Eur J Endocrinol. 1997;137:402–9.CrossRefPubMedGoogle Scholar
  191. 191.
    Lippuner K, Zehnder HJ, Casez JP, Takkinen R, Jaeger P. PTH-related protein is released into the mother’s bloodstream during lactation: evidence for beneficial effects on maternal calcium-phosphate metabolism. J Bone Miner Res. 1996;11:1394–9.CrossRefPubMedGoogle Scholar
  192. 192.
    Sowers MF, Hollis BW, Shapiro B, Randolph J, Janney CA, Zhang D, et al. Elevated parathyroid hormone-related peptide associated with lactation and bone density loss. JAMA. 1996;276:549–54.CrossRefPubMedGoogle Scholar
  193. 193.
    Powell GJ, Southby J, Danks JA, Stillwell RG, Hayman JA, Henderson MA, et al. Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res. 1991;51:3059–61.PubMedGoogle Scholar
  194. 194.
    Wang Y, Lei R, Zhuang X, Zhang N, Pan H, Li G, et al. DLC1-dependent parathyroid hormone-like hormone inhibition suppresses breast cancer bone metastasis. J Clin Invest. 2014;124:1646–59.CrossRefPubMedPubMedCentralGoogle Scholar
  195. 195.
    Wysolmerski JJ. Parathyroid hormone-related protein: an update. J Clin Endocrinol Metab. 2012;97:2947–56.CrossRefPubMedPubMedCentralGoogle Scholar
  196. 196.
    Pioszak AA, Parker NR, Gardella TJ, Xu HE. Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides. J Biol Chem. 2009;284:28382–91.CrossRefPubMedPubMedCentralGoogle Scholar
  197. 197.
    Horwitz MJ, Tedesco MB, Sereika SM, Syed MA, Garcia-Ocaña A, Bisello A, et al. Continuous PTH and PTHrP infusion causes suppression of bone formation and discordant effects on 1,25(OH)2 vitamin D. J Bone Miner Res. 2005;20:1792–803.CrossRefPubMedGoogle Scholar
  198. 198.
    Cosman F, Greenspan SL. Parathyroid hormone treatment for osteoporosis. In: Rosen CJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. Washington DC: American Society for Bone and Mineral Research; 2008. p. 244–9.CrossRefGoogle Scholar
  199. 199.
    Karaplis AC, Goltzman. PTH and PTHrP effects on the skeleton. Rev Endocr Metab Disord. 2000;1:331–41.CrossRefPubMedGoogle Scholar
  200. 200.
    Jemtland R, Divieti P, Lee K, Segre GV. Hedgehog promotes primary osteoblast differentiation and increases PTHrP mRNA expression and iPTHrP secretion. Bone. 2003;32:611–20.CrossRefPubMedGoogle Scholar
  201. 201.
    Mak KK, Bi Y, Wan C, Chuang PT, Clemens T, Young M, et al. Hedgehog signaling in mature osteoblasts regulates bone formation and resorption by controlling PTHrP and RANKL expression. Dev Cell. 2008;14:674–88.CrossRefPubMedGoogle Scholar
  202. 202.
    Kiuru M, Solomon J, Ghali B, van der Meulen M, Crystal RG, Hidaka C. Transient overexpression of sonic hedgehog alters the architecture and mechanical properties of trabecular bone. J Bone Miner Res. 2003;24:1598–607.CrossRefGoogle Scholar
  203. 203.
    Budayr AA, Halloran BP, King JC, Diep D, Nissenson RA, Strewler GJ. High levels of parathyroid hormone-like protein in milk. Proc Natl Acad Sci U S A. 1989;86:7183–5.CrossRefPubMedPubMedCentralGoogle Scholar
  204. 204.
    Onda K, Sato A, Yamaguchi M, Matsuki N, Ono K, Wada Y. Parathyroid hormone-related protein (PTHrP) and Ca levels in the milk of lactating cows. J Vet Med Sci. 2006;68:709–13.CrossRefPubMedGoogle Scholar
  205. 205.
    VanHouten JN, Dann P, McGeoch G, Brown EM, Krapcho K, Neville M, et al. The calcium-sensing receptor regulates mammary gland parathyroid hormone–related protein production and calcium transport. J Clin Invest. 2004;113:598–608.CrossRefPubMedPubMedCentralGoogle Scholar
  206. 206.
    Mamillapalli R, VanHouten J, Dann P, Bikle D, Chang W, Brown E, 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;154:3031–42.CrossRefPubMedPubMedCentralGoogle Scholar
  207. 207.
    Reid IR, Wattie DJ, Evans MC, Budayr AA. Postpregnancy osteoporosis associated with hypercalcemia. Clin Endocrinol (Oxf). 1992;37:298–303.CrossRefPubMedGoogle Scholar
  208. 208.
    Segal E, Hochberg I, Weisman Y, Ish-Shalom S. Severe postpartum osteoporosis with increased PTHrP during lactation in a patient after total thyroidectomy and parathyroidectomy. Osteoporos Int. 2011;22:2907–11.CrossRefPubMedGoogle Scholar
  209. 209.
    Ozturk C, Atamaz FC, Akkurt H, Akkoc Y. Pregnancy-associated osteoporosis presenting after severe vertebral fractures. J Obstet Gynaecol Res. 2014;40:288–92.CrossRefPubMedGoogle Scholar
  210. 210.
    Grizzo FM, da Silva Martins J, Pinheiro MM, Jorgetti V, Carvalho MD, Pelloso SM. Pregnancy and lactation-associated osteoporosis: Bone histomorphometric analysis and response to treatment with zoledronic acid. Calcif Tissue Int. 2015;97:421–5.CrossRefPubMedGoogle Scholar
  211. 211.
    Kovacs CS. The skeleton is a storehouse of mineral that is plundered during lactation and (fully?) replenished afterwards. J Bone Miner Res. 2017;32:676–80.CrossRefPubMedGoogle Scholar
  212. 212.
    Pirola CJ, Wang HM, Kaymar A, Wu S, Enomoto H, Sharifi B, et al. Angiotensin II regulates parathyroid hormone-related protein expression in cultured rat aortic smooth muscle cells through transcriptional and post-transcriptional mechanisms. J Biol Chem. 1993;268:1987–94.PubMedGoogle Scholar
  213. 213.
    Zong JC, Wang X, Zhou X, Wang C, Chen L, Yin LJ, et al. Gut-derived serotonin induced by depression promotes breast cancer bone metastasis through the RUNX2/PTHrP/RANKL pathway in mice. Oncol Rep. 2016;35:739–48.CrossRefPubMedGoogle Scholar
  214. 214.
    Kirby BJ, Ardeshirpour L, Woodrow JP, Wysolmerski JJ, Sims NA, Karaplis AC, et al. Skeletal recovery after weaning does not require PTHrP. J Bone Miner Res. 2011;26:1242–51.CrossRefPubMedPubMedCentralGoogle Scholar
  215. 215.
    Laskey MA, Prentice A. Effect of pregnancy on recovery of lactational bone loss. Lancet. 1997;349:1518–9.CrossRefPubMedGoogle Scholar
  216. 216.
    America’s Bone Health. The State of Osteoporosis and Low Bone Mass in Our Nation. Washington DC: National Osteoporosis Foundation; 2002.Google Scholar
  217. 217.
    Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22:465–75.CrossRefPubMedGoogle Scholar
  218. 218.
    Weaver CM, Peacock M, Johnston CC. Adolescent nutrition in the prevention of postmenopausal osteoporosis. J Clin Endocrinol Metab. 1999;84:1839–43.CrossRefPubMedGoogle Scholar
  219. 219.
    Teegarden D, Proulx WR, Martin BR, Zhao J, McCabe GP, Lyle RM, et al. Peak bone mass in young women. J Bone Miner Res. 1995;10:711–5.CrossRefPubMedGoogle Scholar
  220. 220.
    Wiklund PK, Xu L, Wang Q, Mikkola T, Lyytikäinen A, Völgyi E, et al. Lactation is associated with greater maternal bone size and bone strength later in life. Osteoporos Int. 2012;23:1939–45.CrossRefPubMedGoogle Scholar
  221. 221.
    Chantry CJ, Auinger P, Byrd RS. Lactation among adolescent mothers and subsequent bone mineral density. Arch Pediatr Adolesc Med. 2004;158:650–6.CrossRefPubMedGoogle Scholar
  222. 222.
    Paton LM, Alexander JL, Nowson CA, Margerison C, Frame MG, Kaymakci B, et al. Pregnancy and lactation have no long-term deleterious effect on measures of bone mineral in healthy women: a twin study. Am J Clin Nutr. 2003;77:707–14.CrossRefPubMedGoogle Scholar
  223. 223.
    Hadji P, Ziller V, Kalder M, Gottschalk M, Hellmeyer L, Hars O, et al. Influence of pregnancy and breast-feeding on quantitative ultrasonometry of bone in postmenopausal women. Climacteric. 2002;5:277–85.CrossRefPubMedGoogle Scholar
  224. 224.
    Forsmo S, Schei B, Langhammer A, Forsén L. How Do Reproductive and Lifestyle Factors Influence Bone Density in Distal and Ultradistal Radius of Early Postmenopausal Women? The Nord-Trøndelag Health Survey, Norway. Osteoporos Int. 2001;12:222–9.CrossRefPubMedGoogle Scholar
  225. 225.
    Lenora J, Lekamwasam S, Karlsson MK. Effects of multiparity and prolonged breast-feeding on maternal bone mineral density: a community-based cross-sectional study. BMC Womens Health. 2009;9:19.CrossRefPubMedPubMedCentralGoogle Scholar
  226. 226.
    Yazici S, Korkmaz U, Erkan M, Korkmaz N, Erdem Baki A, Alçelik A, et al. The effect of breast-feeding duration on bone mineral density in postmenopausal Turkish women: a population-based study. Arch Med Sci. 2011;7:486–92.CrossRefPubMedPubMedCentralGoogle Scholar
  227. 227.
    Bauer DC, Browner WS, Cauley JA, Orwoll ES, Scott JC, Black DM, et al. Factors associated with appendicular bone mass in older women. The Study of Osteoporotic Fractures Research Group. Ann Intern Med. 1993;118:657–65.CrossRefPubMedGoogle Scholar
  228. 228.
    Schnatz PF, Barker KG, Marakovits KA, O’Sullivan DM. Effects of age at first pregnancy and breast-feeding on the development of postmenopausal osteoporosis. Menopause. 2010;17:1161–6.CrossRefPubMedGoogle Scholar
  229. 229.
    Crandall CJ, Liu J, Cauley J, Newcomb PA, Manson JE, Vitolins MZ, et al. Associations of parity, breastfeeding, and fractures in the Women’s Health Observational Study. Obstet Gynecol. 2017;130:171–80.CrossRefPubMedGoogle Scholar
  230. 230.
    Pregnancy SM. lactation as risk factors for subsequent bone loss and osteoporosis. J Bone Miner Res. 1996;11:1052–60.Google Scholar
  231. 231.
    Wysolmerski JJ. Interactions between breast, bone, and brain regulate mineral and skeletal metabolism during lactation. Ann N Y Acad Sci. 2010;1192:161–9.CrossRefPubMedPubMedCentralGoogle Scholar
  232. 232.
    Yeo UH, Choi CJ, Choi WS, Kim KS. Relationship between breast-feeding and bone mineral density among Korean women in the 2010 Korea National Health and Nutrition Examination Survey. J Bone Miner Metab. 2016;34:109–17.CrossRefPubMedGoogle Scholar
  233. 233.
    Hwang IR, Choi YK, Lee WK, Kim JG, Lee IK, Kim SW, et al. Association between prolonged breastfeeding and bone mineral density and osteoporosis in postmenopausal women: KNHANES 2010-2011. Osteoporos Int. 2016;27:257–65.CrossRefPubMedGoogle Scholar
  234. 234.
    Kim JH, Kwon H, Oh SW, Lee CM, Joh HK, Kim Y, et al. Breast Feeding is associated with postmenopausal bone loss: findings from the Korea National Health and Nutrition Examination Survey. Korean J Fam Med. 2015;36:216–20.CrossRefPubMedPubMedCentralGoogle Scholar
  235. 235.
    Rojano-Mejía D, Aguilar-Madrid G, López-Medina G, Cortes-Espinosa L, Hernández-Chiu MC, Canto-Cetina T, et al. Risk factors and impact on bone mineral density in postmenopausal Mexican mestizo women. Menopause. 2011;18:302–6.CrossRefPubMedGoogle Scholar
  236. 236.
    Okyay DO, Okyay E, Dogan E, Kurtulmus S, Acet F, Taner CE. Prolonged breast-feeding is an independent risk factor for postmenopausal osteoporosis. Maturitas. 2013;74:270–5.CrossRefPubMedGoogle Scholar
  237. 237.
    Bolzetta F, Veronese N, De Rui M, Berton L, Carraro S, Pizzato S, et al. Duration of breastfeeding as a risk factor for vertebral fractures. Bone. 2014;68:41–5.CrossRefPubMedGoogle Scholar
  238. 238.
    Tsvetov G, Levy S, Benbassat C, Shraga-Slutzky I, Hirsch D. Influence of number of deliveries and total breast-feeding time on bone mineral density in premenopausal and young postmenopausal women. Maturitas. 2014;77:249–54.CrossRefPubMedGoogle Scholar
  239. 239.
    Mgodi NM, Kelly C, Gati B, Greenspan S, Dai JY, Bragg V, et al. Factors associated with bone mineral density in healthy African women. Arch Osteoporos. 2014;10:206.Google Scholar
  240. 240.
    Petitti DB, Piaggio G, Mehta S, Cravioto MC, Meirik O. Steroid hormone contraception and bone mineral density: a cross-sectional study in an international population. Obstet Gynecol. 2000;95:736–44.PubMedGoogle Scholar
  241. 241.
    Dursun N, Akin S, Dursun E, Sade I, Korkusuz F. Influence of duration of total breast-feeding on bone mineral density in a Turkish population: does the priority of risk factors differ society to society? Osteoporos Int. 2006;17:651–5.CrossRefPubMedGoogle Scholar
  242. 242.
    Singh R, Gupta S, Awasthi A. Differential effect of predictors of bone mineral density and hip geometry in postmenopausal women: a cross-sectional study. Arch Osteoporos. 2015;10:39.CrossRefPubMedGoogle Scholar
  243. 243.
    Bjørnerem Å, Ghasem-Zadeh A, Wang X, Bui M, Walker SP, Zebaze R, et al. Irreversible deterioration of cortical and trabecular microstructure associated with breastfeeding. J Bone Miner Res. 2017;32:681–7.CrossRefPubMedGoogle Scholar
  244. 244.
    Shim RS, Baltrus P, Ye J, Rust G. Prevalence, Treatment, and Control of Depressive Symptoms in the United States: Results from the National Health and Nutrition Examination Survey (NHANES), 2005–2008. J Am Board Fam Med. 2011;24:33–8.CrossRefPubMedPubMedCentralGoogle Scholar
  245. 245.
    Gaynes BN, Gavin N, Meltzer-Brody S, Lohr KN, Swinson T, Gartlehner G, et al. Perinatal depression: prevalence, screening accuracy, and screening outcomes. Evid Rep Technol Assess (Summ). 2005;119:1–8.Google Scholar
  246. 246.
    Dietz PM, Williams SB, Callaghan WM, Bachman DJ, Whitlock EP, Hornbrook MC. Clinically identified maternal depression before, during, and after pregnancies ending in live births. Am J Psychiatry. 2007;164:1515–20.CrossRefPubMedGoogle Scholar
  247. 247.
    Ko JY, Rockhill KM, Tong VT, Morrow B, Farr SL. Trends in postpartum depressive symptoms – 27 states, 2004, 2008, and 2012. MMWR Morb Mortal Weekly Rep. 2017;66:153–8.CrossRefGoogle Scholar
  248. 248.
    Meltzer-Brody S. New insights into perinatal depression: pathogenesis and treatment during pregnancy and postpartum. Dialogues Clin Neurosci. 2011;13:89–100.PubMedPubMedCentralGoogle Scholar
  249. 249.
    Guille C, Newman R, Fryml LD, Lifton CK, Epperson CN. Management of postpartum depression. J Midwifery Womens Health. 2013;58:643–53.CrossRefPubMedPubMedCentralGoogle Scholar
  250. 250.
    Henderson JJ, Evans SF, Straton JA, Priest SR, Hagan R. Impact of postnatal depression on breastfeeding duration. Birth. 2003;30:175–80.CrossRefPubMedGoogle Scholar
  251. 251.
    Pippins JR, Brawarsky P, Jackson RA, Fuentes-Afflick E, Haas JS. Association of breastfeeding with maternal depressive symptoms. J Womens Health (Larchmt). 2006;15:754–62.CrossRefGoogle Scholar
  252. 252.
    Woolhouse H, James J, Gartland D, McDonald E, Brown SJ. Maternal depressive symptoms at three months postpartum and breastfeeding rates at six months postpartum: Implications for primary care in a prospective cohort study of primiparous women in Australia. Women Birth. 2016;29:381–7.CrossRefPubMedGoogle Scholar
  253. 253.
    McKinney CO, Hahn-Holbrook J, Chase-Lansdale PL, Ramey SL, Krohn J, Reed-Vance M, et al. Racial and ethnic differences in breastfeeding. Pediatrics. 2016;138:e20152388.CrossRefPubMedPubMedCentralGoogle Scholar
  254. 254.
    Ogbuanu CA, Probst J, Laditka SB, Liu J, Baek JD, Glover S. Reasons why women do not initiate breastfeeding: A southeastern state study. Womens Health Issues. 2010;19:268–78.CrossRefGoogle Scholar
  255. 255.
    Stuebe A. The risks of not breastfeeding for mothers and infants. Rev Obstet Gynecol. 2009;2:222–31.PubMedPubMedCentralGoogle Scholar
  256. 256.
    Shema L, Ore L, Ben-Shachar M, Haj M, Linn S. The association between breastfeeding and breast cancer occurrence among Israeli Jewish women: a case control study. J Cancer Res Clin Oncol. 2007;133:539–46.CrossRefPubMedGoogle Scholar
  257. 257.
    Chowdhury R, Sinha B, Jeeva Sankar M, Taneja S, Bhandari N, Rollins N, et al. Breastfeeding and maternal health outcomes: a systematic review and meta-analysis. Acta Pædiatrica. 2015;104:96–113.CrossRefPubMedPubMedCentralGoogle Scholar
  258. 258.
    Salone LR, Vann WF Jr, Dee DL. Breastfeeding: an overview of oral and general health benefits. J Am Dent Assoc. 2013;144:143–51.CrossRefPubMedGoogle Scholar
  259. 259.
    Jones G, Riley M, Dwyer T. Breastfeeding in early life and bone mass in prepubertal children: A longitudinal study. Osteoporos Int. 2000;11:146–52.CrossRefPubMedGoogle Scholar
  260. 260.
    Blanco E, Burrows R, Reyes M, Lozoff B, Gahagan S, Albala C. Breastfeeding as the sole source of milk for 6 months and adolescent bone mineral density. Osteoporos Int. 2017;28:2823–30.CrossRefPubMedGoogle Scholar
  261. 261.
    World Health Organization. Exclusive breastfeeding for six months best for babies everywhere. 2011. http://www.who.int/mediacentre/news/statements/2011/breastfeeding_20110115/en/. Accessed 6 Dec 2017.
  262. 262.
    American Academy of Pediatrics. Breastfeeding and the use of human milk, section on breastfeeding. Pediatrics. 2012;e827:129.Google Scholar
  263. 263.
    Office of Disease Prevention and Health Promotion. In: Healthy People 2020, Maternal, Infant, and Child Health. 2010. Retrieved from https://www.healthypeople.gov/2020/topics-objectives/topic/maternal-infant-and-child-health/objectives. Accessed 6 Dec 2017.
  264. 264.
    Ozcelik B, Ozcelik A, Debre M. Postpartum depression co-occurring with lactation-related osteoporosis. Psychosomatics. 2009;50(2)Google Scholar
  265. 265.
    Ressler KJ, Nemeroff CB. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety. 2000;12:2–19.CrossRefPubMedGoogle Scholar
  266. 266.
    Fabre V, Beaufour C, Evrarad A, Rioux A, Hanoun N, Lesch KP, et al. Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5-HT transporter. Eur J Neurosci. 2000;12:2299–310.CrossRefPubMedGoogle Scholar
  267. 267.
    Sghendo L, Mifsud J. Understanding the molecular pharmacology of the serotonergic system: using fluoxetine as a model. J Pharm Pharmacol. 2012;64:317–25.CrossRefPubMedGoogle Scholar
  268. 268.
    Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL. Trends in prescription drug use among adults in the United States from 1999-2012. JAMA. 2015;314:1818–31.CrossRefPubMedPubMedCentralGoogle Scholar
  269. 269.
    Anderson IM. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord. 2000;58:19–36.CrossRefPubMedGoogle Scholar
  270. 270.
    Hayes RM, Wu P, Shelton RC, Cooper WO, Dupont WD, Mitchel E, et al. Maternal antidepressant use and adverse outcomes: a cohort study of 228.876 pregnancies. Am J Obstet Gynecol. 2012;207:49.CrossRefPubMedPubMedCentralGoogle Scholar
  271. 271.
    Weissman AM, Levy BT, Hartz AJ, Bentler S, Donohue M, Ellingrod VL, et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161:1066–78.CrossRefPubMedGoogle Scholar
  272. 272.
    Alvarez JC, Gluck N, Fallet A, Grégoire A, Chevalier JF, Advenier C, et al. Plasma serotonin level after 1 day of fluoxetine treatment: a biological predictor for antidepressant response? Psychopharmacology (Berl). 1998;143:97–101.CrossRefGoogle Scholar
  273. 273.
    Epperson CN, Jatlow PI, Czarkowski K, Anderson GM. Maternal fluoxetine treatment in the postpartum period: Effects on platelet serotonin and plasma drug levels in breastfeeding mother-infant pairs. Pediatrics. 2003;112:e425-e429.CrossRefGoogle Scholar
  274. 274.
    Epperson CN, Czarkowski KA, Ward-O’Brien D, Weiss E, Gueorguieva R, Jatlow P, et al. Maternal sertraline treatment and serotonin transport in breast-feeding mother-infant pairs. Am J Psychiatry. 2001;158:1631–7.CrossRefPubMedGoogle Scholar
  275. 275.
    Jury NJ. Interaction of lactation and response to SSRI. In: Alterations in peripheral and central serotonin physiologies during lactation: Relevance to mood during the postpartum (Ph.D. Thesis). Cincinnati: University of Cincinnati Neuroscience / Medical Science Scholars Interdisciplinary; 2012. p. 116.Google Scholar
  276. 276.
    Dias CC, Figueiredo B. Breastfeeding and depression: a systematic review of the literature. J Affect Disord. 2015;171:142–54.CrossRefPubMedGoogle Scholar
  277. 277.
    Marshall AM, Nommsen-Rivers LA, Hernandez LL, Dewey KG, Chantry CJ, Gregerson KA, et al. Serotonin transport and metabolism in the mammary gland modulates secretory activation and involution. J Clin Endocrinol Metab. 2010;95:837–46.CrossRefPubMedGoogle Scholar
  278. 278.
    Gorman JR, Kao K, Chambers CD. Breastfeeding among women exposed to antidepressants during pregnancy. J Hum Lact. 2012;28:181–8.CrossRefPubMedGoogle Scholar
  279. 279.
    Hillhouse TM, Porter JHA. brief history of the development of antidepressant drugs: From monoamines to glutamate. Exp Clin Psychopharmacol. 2015;23:1–21.CrossRefPubMedPubMedCentralGoogle Scholar
  280. 280.
    Lattimore KA, Donn SM, Kaciroti N, Kemper AR, Neal CR Jr, Vazquez DM. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: a meta-analysis. J Perinatol. 2005;25:595–604.CrossRefPubMedGoogle Scholar
  281. 281.
    Kiryanova V, McAllister BB, Dyck RH. Long-term outcomes of developmental exposure to fluoxetine: A review of the animal literature. Dev Neurosci. 2013;35:437–49.CrossRefPubMedGoogle Scholar
  282. 282.
    Glover ME, Clinton SM. Of rodents and humans: A comparative review of the neurobehavioral effects of early life SSRI exposure in preclinical and clinical research. Int J Dev Neurosci. 2016;51:50–72.CrossRefPubMedPubMedCentralGoogle Scholar
  283. 283.
    Warden SJ, Robling AG, Sanders MS, Bliziotes MM, Turner CH. Inhibition of the serotonin (5-hydroxytryptamine) transporter reduces bone accrual during growth. Endocrinology. 2005;146:685–93.CrossRefPubMedGoogle Scholar
  284. 284.
    Ortuño MJ, Robinson ST, Subramanyam P, Paone R, Huang Y, Guo XE, et al. Serotonin reuptake inhibitors act centrally to cause bone loss in mice by counteracting a local antiresorptive effect. Nat Med. 2016;22:1170–9.CrossRefPubMedPubMedCentralGoogle Scholar
  285. 285.
    Hodge JM, Wang Y, Berk M, Collier FM, Fernandes TJ, Constable MJ, et al. Selective serotonin reuptake inhibitors inhibit human osteoclast and osteoblast formation and function. Biol Psychiatry. 2013;74:32–9.CrossRefPubMedGoogle Scholar
  286. 286.
    Bradaschia-Correa V, Josephson AM, Mehta D, Mizrahi M, Neibart SS, Liu C, et al. The Selective Serotonin Reuptake Inhibitor Fluoxetine directly inhibits osteoblast differentiation and mineralization during fracture healing in mice. J Bone Miner Res. 2017;32:821–33.CrossRefPubMedGoogle Scholar
  287. 287.
    Bonnet N, Bernard P, Beapied H, Bizot JC, Trovero F, Courteix D, et al. Various effects of antidepressant drugs on bone microarchitecture, mechanical properties and bone remodeling. Toxicol Appl Pharmacol. 2007;221:111–8.CrossRefPubMedGoogle Scholar
  288. 288.
    Warden SJ, Nelson IR, Fuchs RK, Bliziotes MM, Turner CH. Serotonin (5-hydroxytryptamine) transporter inhibition causes bone loss in adult mice independently of estrogen deficiency. Menopause. 2008;15:1176–83.CrossRefPubMedGoogle Scholar
  289. 289.
    Schwan S, Hallberg P. SSRIs, bone mineral density, and risk of fractures - a review. Eur Neuropsychopharmacol. 2009;19:683–92.CrossRefPubMedGoogle Scholar
  290. 290.
    Michelson D, Stratakis C, Hill L, Reynolds J, Galliven E, Chrousos G, et al. Bone mineral density in women with depression. N Engl J Med. 1996;335:1176–81.CrossRefPubMedGoogle Scholar
  291. 291.
    Yirmiya R, Bab I. Major depression is a risk factor for low bone mineral density: a meta-analysis. Biol Psychiatry. 2009;66:423–32.CrossRefPubMedGoogle Scholar
  292. 292.
    Atteritano M, Lasco A, Mazzaferro S, Macrì I, Catalano A, Santangelo A, et al. Bone mineral density, quantitative ultrasound parameters and bone metabolism in postmenopausal women with depression. Intern Emerg Med. 2013;8:485–91.CrossRefPubMedGoogle Scholar
  293. 293.
    Bab I, Yirmiya R. Depression, selective serotonin reuptake inhibitors, and osteoporosis. Curr Osteoporos Rep. 2010;8:185–91.CrossRefPubMedGoogle Scholar
  294. 294.
    Rauma PH, Honkanen RJ, Williams LJ, Tuppurainen MT, Kröger HP, Koivumaa-Honkanen H. Effects of antidepressants on postmenopausal bone loss - A 5-year longitudinal study from the OSTPRE cohort. Bone. 2016;89:25–31.CrossRefPubMedGoogle Scholar
  295. 295.
    Rabenda V, Nicolet D, Beaudart C, Bruyére O, Reginster JY. Relationship between use of antidepressants and risk of fractures: a meta-analysis. Osteoporos Int. 2013;24:121–37.CrossRefPubMedGoogle Scholar
  296. 296.
    Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM, Bliziotes MM, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007;167:1240–5.CrossRefPubMedGoogle Scholar
  297. 297.
    Ziere G, Dieleman JP, van der Cammen TJ, Hofman A, Pols HA, Stricker BH. Selective serotonin reuptake inhibiting antidepressants are associated with an increased risk of nonvertebral fractures. J Clin Psychopharmacol. 2008;28:411–7.CrossRefPubMedGoogle Scholar
  298. 298.
    Feuer AJ, Demmer RT, Thai A, Vogiatzi MG. Use of selective serotonin reuptake inhibitors and bone mass in adolescents: An NHANES study. Bone. 2015;78:28–33.CrossRefPubMedGoogle Scholar
  299. 299.
    Seifert CF, Wiltrout TR. Calcaneal bone mineral density in young adults prescribed selective serotonin reuptake inhibitors. Clin Ther. 2013;35:1412–7.CrossRefPubMedGoogle Scholar
  300. 300.
    Cauley JA, Fullman RL, Stone KS, Zmuda JM, Bauer DC, Barrett-Connor E, et al. Factors associated with the lumbar spine and proximal femur bone mineral density in older men. Osteoporos Int. 2005;16:1525–37.CrossRefPubMedGoogle Scholar
  301. 301.
    Ak E, Bulut SD, Bulut S, Akdag HA, Öter GB, Kaya H, et al. Evaluation of the effect of selective serotonin reuptake inhibitors on bone mineral density: an observational cross-sectional study. Osteoporos Int. 2015;26:273–9.CrossRefPubMedGoogle Scholar
  302. 302.
    Dubnov-Raz G, Hemilä H, Vurembrand Y, Kuint J, Maayan-Metzger A. Maternal use of selective serotonin reuptake inhibitors during pregnancy and neonatal bone density. Early Hum Dev. 2012;88:191–4.CrossRefPubMedGoogle Scholar
  303. 303.
    Diem SJ, Joffe H, Larson JC, Tsai JN, Guthrie KA, LaCroix AZ, et al. Effects of escitalopram on markers of bone turnover: A randomized clinical trial. J Clin Endocrinol Metab. 2014;99:E1732–7.CrossRefPubMedPubMedCentralGoogle Scholar
  304. 304.
    Calarge CA, Mills JA, Janz KF, Burns TL, Schlechte JA, Coryell WH, et al. The effect of depression, generalized anxiety, and selective serotonin reuptake inhibitors on change in bone metabolism in adolescents and emerging adults. J Bone Miner Res. 2017;32:2367–74.CrossRefPubMedGoogle Scholar
  305. 305.
    Ham AC, Aarts N, Noordam R, Rivadendeira F, Ziere G, Zillikens MC, et al. Use of selective serotonin reuptake inhibitors and bone mineral density change: a population-based longitudinal study in middle-aged and elderly individuals. J Clin Psychopharmacol. 2017;37:524–30.CrossRefPubMedGoogle Scholar
  306. 306.
    Saraykar S, John V, Cao B, Hnatow M, Ambrose CG, Rianon N. Association of selective serotonin reuptake inhibitors and bone mineral density in elderly women. J Clin Densitom. 2017;  https://doi.org/10.1016/j.jocd.2017.05.016.
  307. 307.
    Bolo NR, Hodé Y, Macher JP. Long-term sequestration of fluorinated compounds in tissues after fluvoxamine or fluoxetine treatmetn: a fluorine magnetic resonance spectroscopy study in vivo. MAGMA. 2004;16:268–76.CrossRefPubMedGoogle Scholar
  308. 308.
    Tolstykh EI, Shagina NB, Peremyslova LM, Degteva MO, Phipps AW, Harrison JD, et al. Reconstruction of 90Sr intake for breast-fed infants in the Techa riverside settlements. Radiat Environ Biophys. 2008;47:349–57.CrossRefPubMedGoogle Scholar
  309. 309.
    Bliziotes MM, Eshleman AJ, Zhang XW, Wiren KM. Neurotransmitter action in osteoblasts: expression of a functional system for serotonin receptor activation and reuptake. Bone. 2001;29:477–86.CrossRefPubMedGoogle Scholar
  310. 310.
    Gustafsson BI, Thommesen L, Stunes AK, Tommeras K, Westbroek I, Waldum HL, et al. Serotonin and fluoxetine modulate bone cell function in vitro. J Cell Biochem. 2006;98:139–51.CrossRefPubMedGoogle Scholar
  311. 311.
    Dai SQ, Yu LP, Shi X, Wu H, Shao P, Yin GY, et al. Serotonin regulates osteoblast proliferation and function in vitro. Braz J Med Biol Res. 2014;47:759–65.CrossRefPubMedPubMedCentralGoogle Scholar
  312. 312.
    Kode A, Mosialou I, Silva BC, Rached MT, Zhou B, Wang J, et al. FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin. J Clin Invest. 2012;122:3490–503.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Endocrine and Reproductive Physiology ProgramUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Department of Dairy ScienceUniversity of Wisconsin-MadisonMadisonUSA

Personalised recommendations