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Calcium restriction during lactation has minimal effects on post-weaning mineral metabolism and bone recovery

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Abstract

Dietary calcium (Ca) restriction during lactation in the rat, which induces intra-cortical and endocortical remodeling, has been proposed as a model to study bone matrix maturation in the adult skeleton. The purpose of this study was to assess the effects of dietary Ca restriction during lactation on post-weaning mineral metabolism and bone formation. Mated female Sprague–Dawley rats were randomized into groups receiving either 0.6% Ca (lactation/normal Ca) or 0.01% Ca (lactation/low Ca) diets during lactation. Virgin animals fed normal Ca were used as controls (virgin/normal Ca). At the time of weaning, animals on the low Ca diet were returned to normal Ca and cohorts of all three groups were sacrificed at days 0, 1, 2, 7, and 14 post-weaning. Lactation caused bone loss, particularly at the endocortical surface, but the amount was not affected by dietary Ca. Rats in the lactation/low Ca group had increased cortical porosity compared to the other groups, particularly within the size range of secondary osteons. Dietary Ca restriction during lactation did not affect post-weaning bone formation kinetics or serum Ca and phosphate levels. In both lactation groups, there was a transient increase in phosphate and fibroblast growth factor 23 (FGF23) post-weaning, which trended toward virgin/normal Ca levels over time. Thus, the additional challenge of low dietary Ca during lactation to induce intra-cortical remodeling in the rat has minimal effects on bone formation kinetics and mineral metabolism during the post-weaning period, providing further justification for this model to study matrix maturation in the adult skeleton.

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References

  1. Kovacs CS (2016) Maternal mineral and bone metabolism during pregnancy, lactation, and post-weaning recovery. Physiol Rev 96:449–547. https://doi.org/10.1152/physrev.00027.2015

    Article  CAS  PubMed  Google Scholar 

  2. Kovacs CS (2005) Calcium and bone metabolism during pregnancy and lactation. J Mammary Gland Biol Neoplasia 10:105–118

    Article  PubMed  Google Scholar 

  3. Brommage R, DeLuca HF (1985) Regulation of bone mineral loss during lactation. Am J Physiol 248:E182–E187

    CAS  PubMed  Google Scholar 

  4. Ellinger GM, Duckworth J, Dalgarno AC, Quenouille MH (1952) Skeletal changes during pregnancy and lactation in the rat: effect of different levels of dietary calcium. Br J Nutr 6:235–253

    Article  CAS  PubMed  Google Scholar 

  5. Bowman BM, Siska CC, Miller SC (2002) Greatly increased cancellous bone formation with rapid improvements in bone structure in the rat maternal skeleton after lactation. J Bone Miner Res 17:1954–1960

    Article  CAS  PubMed  Google Scholar 

  6. Miller SC, Bowman BM (2004) Rapid improvements in cortical bone dynamics and structure after lactation in established breeder rats. Anat Rec A Discov Mol Cell Evol Biol 276:143–149

    Article  PubMed  Google Scholar 

  7. Ross RD, Sumner DR (2017) Bone matrix maturation in a rat model of intra-cortical bone remodeling. Calcif Tissue Int 101:193–203. https://doi.org/10.1007/s00223-017-0270-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kovacs CS (2011) Calcium and bone metabolism disorders during pregnancy and lactation. Endocrinol Metab Clin N Am 40:795–826

    Article  CAS  Google Scholar 

  9. Kovacs CS, Kronenberg HM (1997) Maternal-fetal calcium and bone metabolism during pregnancy, puerperium, and lactation. Endocr Rev 18:832–872

    CAS  PubMed  Google Scholar 

  10. Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Muller R (2010) Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res 25:1468–1486

    Article  PubMed  Google Scholar 

  11. Duranova H, Martiniakova M, Omelka R, Grosskopf B, Bobonova I, Toman R (2014) Changes in compact bone microstructure of rats subchronically exposed to cadmium. Acta Vet Scand 56:64. https://doi.org/10.1186/s13028-014-0064-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Martiniakova M, Chovancova H, Omelka R, Grosskopf B, Toman R (2011) Effects of a single intraperitoneal administration of cadmium on femoral bone structure in male rats. Acta Vet Scand 53:49. https://doi.org/10.1186/1751-0147-53-49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Burr DB, Akkus O (2014) Chapter 1—Bone morphology and organization. In: Burr DB, Allen MR (eds) Basic and applied bone biology. Academic Press, San Diego, pp 3–25. https://doi.org/10.1016/B978-0-12-416015-6.00001-0

  14. Donnelly E, Baker SP, Boskey AL, van der Meulen MC (2006) Effects of surface roughness and maximum load on the mechanical properties of cancellous bone measured by nanoindentation. J Biomed Mater Res A 77:426–435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. J Bone Miner Res 2:595–610

    Article  CAS  PubMed  Google Scholar 

  16. Miller SC, Shupe JG, Redd EH, Miller MA, Omura TH (1986) Changes in bone mineral and bone formation rates during pregnancy and lactation in rats. Bone 7:283–287

    Article  CAS  PubMed  Google Scholar 

  17. Garner SC, Peng TC, Hirsch PF, Boass A, Toverud SU (1987) Increase in serum parathyroid hormone concentration in the lactating rat: effects of dietary calcium and lactational intensity. J Bone Miner Res 2:347–352. https://doi.org/10.1002/jbmr.5650020412

    Article  CAS  PubMed  Google Scholar 

  18. Gonen E, Sahin I, Ozbek M, Kovalak E, Yologlu S, Ates Y (2005) Effects of pregnancy and lactation on bone mineral density, and their relation to the serum calcium, phosphorus, calcitonin and parathyroid hormone levels in rats. J Endocrinol Invest 28:322–326

    Article  CAS  PubMed  Google Scholar 

  19. Hirsch PF, Hagaman JR (1986) Reduced bone mass in calcitonin-deficient rats whether lactating or not. J Bone Miner Res 1:199–206. https://doi.org/10.1002/jbmr.5650010206

    Article  CAS  PubMed  Google Scholar 

  20. Honda A, Kurabayashi T, Yahata T, Tomita M, Matsushita H, Takakuwa K, Tanaka K (2000) Effects of pregnancy and lactation on trabecular bone and marrow adipocytes in rats. Calcif Tissue Int 67:367–372

    Article  CAS  PubMed  Google Scholar 

  21. Miller SC, Halloran BP, DeLuca HF, Jee WS (1982) Role of vitamin D in maternal skeletal changes during pregnancy and lactation: a histomorphometric study. Calcif Tissue Int 34:245–252

    Article  CAS  PubMed  Google Scholar 

  22. Peng TC, Garner SC, Kusy RP, Hirsch PF (1988) Effect of number of suckling pups and dietary calcium on bone mineral content and mechanical properties of femurs of lactating rats. Bone Miner 3:293–304

    CAS  PubMed  Google Scholar 

  23. Rasmussen P (1977) Calcium deficiency, pregnancy, and lactation in rats. Microscopic and microradiographic observations on bones. Calcif Tissue Res 23:95–102

    Article  CAS  PubMed  Google Scholar 

  24. Tojo Y, Kurabayashi T, Honda A, Yamamoto Y, Yahata T, Takakuwa K, Tanaka K (1998) Bone structural and metabolic changes at the end of pregnancy and lactation in rats. Am J Obstet Gynecol 178:180–185

    Article  CAS  PubMed  Google Scholar 

  25. Warnock GM, Duckworth J (1944) Changes in the skeleton during gestation and lactation in the rat. Biochem J 38:220–224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wong KM, Singer L, Ophaug RH (1980) Metabolic aspects of bone resorption in calcium-deficient lactating rats. Calcif Tissue Int 32:213–219

    Article  CAS  PubMed  Google Scholar 

  27. Vajda EG, Bowman BM, Miller SC (2001) Cancellous and cortical bone mechanical properties and tissue dynamics during pregnancy, lactation, and postlactation in the rat. Biol Reprod 65:689–695

    Article  CAS  PubMed  Google Scholar 

  28. Bowman BM, Miller SC (1999) Skeletal mass, chemistry, and growth during and after multiple reproductive cycles in the rat. Bone 25:553–559

    Article  CAS  PubMed  Google Scholar 

  29. Chen H, Hayakawa D, Emura S, Ozawa Y, Okumura T, Shoumura S (2002) Effect of low or high dietary calcium on the morphology of the rat femur. Histol Histopathol 17:1129–1135

    PubMed  Google Scholar 

  30. de Winter FR, Steendijk R (1975) The effect of a low-calcium diet in lactating rats; observations on the rapid development and repair of osteoporosis. Calcif Tissue Res 17:303–316

    Article  PubMed  Google Scholar 

  31. Qing H, Ardeshirpour L, Pajevic PD, Dusevich V, Jahn K, Kato S, Wysolmerski J, Bonewald LF (2012) Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. J Bone Miner Res 27:1018–1029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wysolmerski JJ (2013) Osteocytes remove and replace perilacunar mineral during reproductive cycles. Bone 54:230–236. https://doi.org/10.1016/j.bone.2013.01.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Nango N, Kubota S, Hasegawa T, Yashiro W, Momose A, Matsuo K (2016) Osteocyte-directed bone demineralization along canaliculi. Bone 84:279–288. https://doi.org/10.1016/j.bone.2015.12.006

    Article  CAS  PubMed  Google Scholar 

  34. Kaya S, Basta-Pljakic J, Seref-Ferlengez Z, Majeska RJ, Cardoso L, Bromage TG, Zhang Q, Flach CR, Mendelsohn R, Yakar S, Fritton SP, Schaffler MB (2017) Lactation-induced changes in the volume of osteocyte lacunar-canalicular space alter mechanical properties in cortical bone tissue. J Bone Miner Res 32:688–697. https://doi.org/10.1002/jbmr.3044

    Article  CAS  PubMed  Google Scholar 

  35. Anderson JJ, Garner SC, Mar MH, Boass A, Toverud SU, Parikh I (1990) The ovariectomized, lactating rat as an experimental model for osteopenia: calcium metabolism and bone changes. Bone Miner 11:43–53

    Article  CAS  PubMed  Google Scholar 

  36. Boass A, Garner SC, Schultz VL, Toverud SU (1997) Regulation of serum calcitriol by serum ionized calcium in rats during pregnancy and lactation. J Bone Miner Res 12:909–914

    Article  CAS  PubMed  Google Scholar 

  37. Garner SC, Boass A, Toverud SU (1989) Hypercalcemia fails to suppress elevated serum parathyroid hormone concentrations during lactation in rats. J Bone Miner Res 4:577–583

    Article  CAS  PubMed  Google Scholar 

  38. Miller SC, Bowman BM (2007) Rapid inactivation and apoptosis of osteoclasts in the maternal skeleton during the bone remodeling reversal at the end of lactation. Anat Rec (Hoboken) 290:65–73

    Article  CAS  Google Scholar 

  39. Pike JW, Parker JB, Haussler MR, Boass A, Toverud SV (1979) Dynamic changes in circulating 1,25-dihydroxyvitamin D during reproduction in rats. Science 204:1427–1429

    Article  CAS  PubMed  Google Scholar 

  40. Garner SC, Peng TC, Toverud SU (1988) Modulation of serum parathyroid hormone and ionized calcium concentrations during reproduction in rats fed a low calcium diet. J Bone Miner Res 3:319–323

    Article  CAS  PubMed  Google Scholar 

  41. Sowers MF, Hollis BW, Shapiro B, Randolph J, Janney CA, Zhang D, Schork A, Crutchfield M, Stanczyk F, Russell-Aulet M (1996) Elevated parathyroid hormone-related peptide associated with lactation and bone density loss. JAMA 276:549–554

    Article  CAS  PubMed  Google Scholar 

  42. Lippuner K, Zehnder HJ, Casez JP, Takkinen R, Jaeger P (1996) 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 11:1394–1399. https://doi.org/10.1002/jbmr.5650111004

    Article  CAS  PubMed  Google Scholar 

  43. Datta NS, Abou-Samra AB (2009) PTH and PTHrP signaling in osteoblasts. Cell Signal 21:1245–1254. https://doi.org/10.1016/j.cellsig.2009.02.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kovacs CS (2014) The role of PTHrP in regulating mineral metabolism during pregnancy, lactation, and fetal/neonatal development. Clin Rev Bone Miner Metab 12:142–164

    Article  CAS  Google Scholar 

  45. Blahosova A, Neradilova M, Velicky J, Titlbach M, Marsikova L, Reisenauer R (1974) Dynamics of changes of calcium and phosphorus metabolism in relation to the morphology of parafollicular thyroid cells in rats during lactation and forced weaning. Endokrinologie 63:122–136

    CAS  PubMed  Google Scholar 

  46. Garner SC, Boass A, Toverud SU (1990) Parathyroid hormone is not required for normal milk composition or secretion or lactation-associated bone loss in normocalcemic rats. J Bone Miner Res 5:69–75

    Article  CAS  PubMed  Google Scholar 

  47. Martin A, David V, Quarles LD (2012) Regulation and function of the FGF23/klotho endocrine pathways. Physiol Rev 92:131–155. https://doi.org/10.1152/physrev.00002.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Razzaque MS (2009) The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis. Nat Rev Endocrinol 5:611–619. https://doi.org/10.1038/nrendo.2009.196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kumar N, Manimaran A, Kumaresan A, Jeyakumar S, Sreela L, Mooventhan P, Sivaram M (2017) Mastitis effects on reproductive performance in dairy cattle: a review. Trop Anim Health Prod 49:663–673. https://doi.org/10.1007/s11250-017-1253-4

    Article  PubMed  Google Scholar 

  50. Hodnett DW, DeLuca HF, Jorgensen NA (1992) Intestine, bone, and mammary gland contributions to maternal plasma calcium increase after abrupt weaning. Proc Soc Exp Biol Med 199:332–336

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Meghan Moran, Brittany Wilson, and Maleeha Mashiatulla for their help with the animal husbandry and tissue collections. Micro-Computed Tomography was performed at the Rush University microCT/Histology Core. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R21AR065604. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Correspondence to D. Rick Sumner.

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All applicable institutional and/or national guidelines for the care and use of animals were followed. The articles does not contain any studies with human participants performed by any of the authors.

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Ross, R.D., Meagher, M.J. & Sumner, D.R. Calcium restriction during lactation has minimal effects on post-weaning mineral metabolism and bone recovery. J Bone Miner Metab 37, 648–657 (2019). https://doi.org/10.1007/s00774-018-0969-1

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