Changes in bone turnover and calcium homeostasis during pregnancy and lactation in mammals: a meta-analysis
Diego A. Torres A B , Mariella B. Freitas A and Reggiani V. Gonçalves A
+ Author Affiliations
- Author Affiliations
A Animal Biology Department, Federal University of Viçosa, Av. P.H. Rolfs, 36570-000, Viçosa, MG, Brazil.
B Corresponding author. Email: dtorresarboleda@gmail.com
Reproduction, Fertility and Development 30(5) 681-688 https://doi.org/10.1071/RD17163
Submitted: 26 April 2017 Accepted: 5 October 2017 Published: 15 November 2017
Abstract
Large amounts of calcium are required during pregnancy and lactation to support fetal and neonatal bone growth and calcification. An inadequate supply of calcium during these stages can lead to unsuccessful reproduction or impaired offspring fitness. During reproduction, female mammals undergo numerous physiological changes, including adaptations to allow an adequate supply of calcium. The lack of quantitative studies analysing these physiological changes from a comparative perspective limits our ability to explain and understand these adaptations. Herein, we present our meta-analysis of studies reporting changes in bone turnover and calcium homeostasis during pregnancy and lactation in 14 species of mammals. Our meta-analysis of 60 studies showed that all species have a similar pattern of physiological changes during pregnancy and lactation, which include: (1) decreased serum calcium concentrations; (2) bone tissue loss; (3) decreased serum calcitonin and parathyroid hormone concentrations; and (4) increased serum calcitriol concentration, regardless of changes in parathyroid hormone concentrations. In addition, we found a negative relationship between: (1) serum calcium concentrations and the number of teats; and (2) serum parathyroid hormone concentrations and litter mass.
Additional keywords: bone loss, bone physiology, calcium metabolism, calcium physiology, reproduction.
References
Bernard, R. T. F., and Davison, A. (1996). Does calcium constrain reproductive activity in insectivorous bats? Some empirical evidence for Schreibers’ long-fingered bat (Miniopterus schreibersii). S. Afr. J. Zool. 31, 218–220.| Does calcium constrain reproductive activity in insectivorous bats? Some empirical evidence for Schreibers’ long-fingered bat (Miniopterus schreibersii).Crossref | GoogleScholarGoogle Scholar |
Black, A. J., Topping, J., Durham, B., Farquharson, R. J., and Fraser, W. D. (2000). A detailed assessment of alterations in bone turnover, calcium homeostasis, and bone density in normal pregnancy. J. Bone Miner. Res. 15, 557–563.
| A detailed assessment of alterations in bone turnover, calcium homeostasis, and bone density in normal pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXitFakt70%3D&md5=536b4b5473abc716527c37df51062a37CAS |
Bowman, B. M., and Miller, S. C. (2001). Skeletal adaptations during mammalian reproduction. J. Musculoskelet. Neuronal Interact. 1, 347–355.
| 1:STN:280:DC%2BD2M7islGmsw%3D%3D&md5=42e7eb74260c94d8687461b859ea02e5CAS |
Brommage, R., and DeLuca, H. F. (1985). Regulation of bone mineral loss during lactation. Am. J. Physiol. 248, E182–E187.
| 1:CAS:528:DyaL2MXhs1GltL8%3D&md5=658f45228f03d57029e3a8fba12373b5CAS |
Charoenphandhu, N., Wongdee, K., and Krishnamra, N. (2010). Is prolactin the cardinal calciotropic maternal hormone? Trends Endocrinol. Metab. 21, 395–401.
| Is prolactin the cardinal calciotropic maternal hormone?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXosV2isbo%3D&md5=d7d023462d3ef6b29de130fc0c022411CAS |
Christakos, S., Dhawan, P., Porta, A., Mady, L. J., and Seth, T. (2011). Vitamin D and intestinal calcium absorption. Mol. Cell. Endocrinol. 347, 25–29.
| Vitamin D and intestinal calcium absorption.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtlKiur3M&md5=57624405f8b392f773e483d340821f4dCAS |
Clarke, M. V., Russell, P. K., Findlay, D. M., Sastra, S., Anderson, P. H., Skinner, J. P., Atkins, G. J., Zajac, J. D., and Davey, R. A. (2015). A role for the calcitonin receptor to limit bone loss during lactation in female mice by inhibiting osteocytic osteolysis. Endocrinology 156, 3203–3214.
| A role for the calcitonin receptor to limit bone loss during lactation in female mice by inhibiting osteocytic osteolysis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhsVylsrjL&md5=0117ff7f0cf432a746802ca7af3ac2bbCAS |
Davey, R. A., and Findlay, D. M. (2013). Calcitonin: physiology or fantasy? J. Bone Miner. Res. 28, 973–979.
| Calcitonin: physiology or fantasy?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXmt1Kls7o%3D&md5=164f1fbcf2d59ef249f68a5350da5ad2CAS |
de Paula, F. J., and Rosen, C. J. (2010). Back to the future: revisiting parathyroid hormone and calcitonin control of bone remodeling. Horm. Metab. Res. 42, 299–306.
| Back to the future: revisiting parathyroid hormone and calcitonin control of bone remodeling.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXnt1OisL4%3D&md5=c275f6ef2936e82ce84bc273a6e1ea8bCAS |
DeLuca, H. F. (2004). Overview of general physiologic features and functions of vitamin D. Am. J. Clin. Nutr. 80, 1689S–1696S.
| 1:CAS:528:DC%2BD2cXhtFaisrvI&md5=2858675a1811286f4eb3620f249222b9CAS |
Dengler-Crish, C. M., and Catania, K. C. (2009). Cessation of reproduction-related spine elongation after multiple breeding cycles in female naked mole-rats. Anat. Rec. (Hoboken) 292, 131–137.
| Cessation of reproduction-related spine elongation after multiple breeding cycles in female naked mole-rats.Crossref | GoogleScholarGoogle Scholar |
DerSimonian, R., and Laird, N. (1986). Meta-analysis in clinical trials. Control. Clin. Trials 7, 177–188.
| 1:STN:280:DyaL2s7gsVamtA%3D%3D&md5=197cff299ed3374c7543aaefe67a98abCAS |
DerSimonian, R., and Laird, N. (2015). Meta-analysis in clinical trials revisited. Contemp. Clin. Trials 45, 139–145.
| Meta-analysis in clinical trials revisited.Crossref | GoogleScholarGoogle Scholar |
Dilworth, M. R., and Sibley, C. P. (2013). Review: transport across the placenta of mice and women. Placenta 34, S34–S39.
| Review: transport across the placenta of mice and women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXmtlejt78%3D&md5=3324ff43516e8b9a59f9cd46a5db42beCAS |
Doherty, A. H., Ghalambor, C. K., and Donahue, S. W. (2015). Evolutionary physiology of bone: bone metabolism in changing environments. Physiology (Bethesda) 30, 17–29.
| Evolutionary physiology of bone: bone metabolism in changing environments.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXislShsrc%3D&md5=9f62c742c1d34a4c089506c89905e78aCAS |
Farrugia, W., Fortune, C. L., Heath, J., Caple, I. W., and Wark, J. D. (1989). Osteocalcin as an index of osteoblast function during and after ovine pregnancy. Endocrinology 125, 1705–1710.
| Osteocalcin as an index of osteoblast function during and after ovine pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXlsFWit7s%3D&md5=04edaf4eeff1c725bcf9bd479c135b93CAS |
Golub, E. E., and Boesze-Battaglia, K. (2007). The role of alkaline phosphatase in mineralization. Curr. Opin. Orthop. 18, 444–448.
| The role of alkaline phosphatase in mineralization.Crossref | GoogleScholarGoogle Scholar |
Hautier, L., Bennett, N. C., Viljoen, H., Howard, L., Milinkovitch, M. C., Tzika, A. C., Goswami, A., and Asher, R. J. (2013). Patterns of ossification in southern versus northern placental mammals. Evolution 67, 1994–2010.
| Patterns of ossification in southern versus northern placental mammals.Crossref | GoogleScholarGoogle Scholar |
Hedges, L. V., and Olkin, I. (1985). ‘Statistical Methods for Meta-analysis.’ (Academic Press: New York.)
Hiyaoka, A., Yoshida, T., Cho, F., and Yoshikawa, Y. (1996). Changes in bone mineral density of lumbar vertebrae after parturition in African green monkeys (Cercopithecus aethiops). Exp. Anim. 45, 257–259.
| Changes in bone mineral density of lumbar vertebrae after parturition in African green monkeys (Cercopithecus aethiops).Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK28vjslChtA%3D%3D&md5=4320097f06979d160a268c8044827995CAS |
Hood, W. R. (2012). A test of bone mobilization relative to reproductive demand: skeletal quality is improved in cannibalistic females with large litters. Physiol. Biochem. Zool. 85, 385–396.
| A test of bone mobilization relative to reproductive demand: skeletal quality is improved in cannibalistic females with large litters.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xht1Ons7rP&md5=0dc0cd02690d76dd9fade91a248d52fcCAS |
Hood, W. R., Oftedal, O. T., and Kunz, T. H. (2006). Variation in body composition of female big brown bats (Eptesicus fuscus) during lactation. J. Comp. Physiol. B 176, 807–819.
| Variation in body composition of female big brown bats (Eptesicus fuscus) during lactation.Crossref | GoogleScholarGoogle Scholar |
Jones, K. E., Bielby, J., Cardillo, M., Fritz, S. A., O’Dell, J., Orme, C. D. L., Safi, K., Sechrest, W., Boakes, E. H., Carbone, C., Connolly, C., Cutts, M. J., Foster, J. K., Grenyer, R., Habib, M., Plaster, C. A., Price, S. A., Rigby, E. A., Rist, J., Teacher, A., Bininda-Emonds, O. R. P., Gittleman, J. L., Mace, J. M., and Purvis, A. (2009). PanTHERIA: a species-level database of life history, ecology, and geography of extant and recently extinct mammals. Ecology 90, 2648.
| PanTHERIA: a species-level database of life history, ecology, and geography of extant and recently extinct mammals.Crossref | GoogleScholarGoogle Scholar |
Kirby, B. J., Ma, Y., Martin, H. M., Buckle-Favaro, K. L., Karaplis, A. C., and Kovacks, C. S. (2013). Upregulation of calcitriol during pregnancy and skeletal recovery after lactation do not require parathyroid hormone. J. Bone Miner. Res. 28, 1987–2000.
| Upregulation of calcitriol during pregnancy and skeletal recovery after lactation do not require parathyroid hormone.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtlaisbnN&md5=4aeb471addec5a84929c2d2c32792e5aCAS |
Kovacs, C. S. (2005). Calcium and bone metabolism during pregnancy and lactation. J. Mammary Gland Biol. Neoplasia 10, 105–118.
| Calcium and bone metabolism during pregnancy and lactation.Crossref | GoogleScholarGoogle Scholar |
Kovacs, C. S. (2011). Calcium and bone metabolism disorders during pregnancy and lactation. Endocrinol. Metab. Clin. North Am. 40, 795–826.
| Calcium and bone metabolism disorders during pregnancy and lactation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhsFSjtLnL&md5=6e5bb7402cb906e4a5cabe7266af7b57CAS |
Kovacs, C. S. (2012). The role of vitamin D in pregnancy and lactation: insights from animal models and clinical studies. Annu. Rev. Nutr. 32, 97–123.
| The role of vitamin D in pregnancy and lactation: insights from animal models and clinical studies.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtlOjsrjJ&md5=72a0799a0dc2d5dc78005dfe9ee3cdd8CAS |
Kwiecinski, G. G., Krook, L., and Wimsatt, W. A. (1987). Annual skeletal changes in the little brown bat, Myotis lucifugus lucifugus, with particular reference to pregnancy and lactation. Am. J. Anat. 178, 410–420.
| Annual skeletal changes in the little brown bat, Myotis lucifugus lucifugus, with particular reference to pregnancy and lactation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2s3msleltg%3D%3D&md5=3087a462aa18cfbef352169ef8828ad3CAS |
Lakens, D. (2013). Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs. Front. Psychol. 4, 863.
| Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs.Crossref | GoogleScholarGoogle Scholar |
Lennox, A. R., and Goodship, A. E. (2008). Polar bears (Ursus maritimus), the most evolutionary advanced hibernators, avoid significant bone loss during hibernation. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 149, 203–208.
| Polar bears (Ursus maritimus), the most evolutionary advanced hibernators, avoid significant bone loss during hibernation.Crossref | GoogleScholarGoogle Scholar |
Li, X., Qin, L., Bergenstock, M., Bevelock, L. M., Novack, D. V., and Partridge, N. C. (2007). Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts. J. Biol. Chem. 282, 33098–33106.
| Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1Clur%2FK&md5=941a66276faa9d182872c1544af765f6CAS |
Macica, C. M., King, H. E., Wang, M., Mceachon, C. L., Skinner, C. W., and Tommasini, S. M. (2016). Novel anatomic adaptation of cortical bone to meet increased mineral demands of reproduction. Bone 85, 59–69.
| Novel anatomic adaptation of cortical bone to meet increased mineral demands of reproduction.Crossref | GoogleScholarGoogle Scholar |
McGee-Lawrence, M., Buckendah, P., Carpenter, C., Henriksen, K., Vaughan, M., and Donahue, S. (2015). Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation. J. Exp. Biol. 218, 2067–2074.
| Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation.Crossref | GoogleScholarGoogle Scholar |
More, C., Bettembuk, P., Bhattoa, H. P., and Balogh, A. (2001). The effects of pregnancy and lactation on bone mineral density. Osteoporos. Int. 12, 732–737.
| The effects of pregnancy and lactation on bone mineral density.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3MrlvFeksg%3D%3D&md5=8adc12aaa16223e3d921cc24678e78fdCAS |
Myhrvold, N. P., Baldridge, E., Chan, B., Sivam, D., Freeman, D. L., and Morgan-Ernest, S. K. (2015). An amniote life-history database to perform comparative analyses with birds, mammals, and reptiles. Ecology 96, 3109.
| An amniote life-history database to perform comparative analyses with birds, mammals, and reptiles.Crossref | GoogleScholarGoogle Scholar |
Naylor, K. E., Iqbal, P., Fledelius, C., Fraser, R. B., and Eastell, R. (2000). The effect of pregnancy on bone density and bone turnover. J. Bone Miner. Res. 15, 129–137.
| The effect of pregnancy on bone density and bone turnover.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXmsVynsA%3D%3D&md5=939c66b1f8b21db957409a982703ef02CAS |
Olausson, H., Goldberg, G. R., Laskey, M. A., Schoenmakers, I., Jarjou, L. M. A., and Prentice, A. (2012). Calcium economy in human pregnancy and lactation. Nutr. Res. Rev. 25, 40–67.
| Calcium economy in human pregnancy and lactation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XpvVOisb8%3D&md5=aa938370ad8c8048d83de8c735221259CAS |
Peacock, M. (2010). Calcium metabolism in health and disease. Clin. J. Am. Soc. Nephrol. 5, S23–S30.
| Calcium metabolism in health and disease.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXitVKksbg%3D&md5=6db5a5f18d72d03cca8b7cbee98c91c0CAS |
Qing, H., Ardeshirpour, L., Pajevic, P. D., Dusevich, V., Jahn, K., Kato, S., Wysolmerski, J., and Bonewald, L. (2012). Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation. J. Bone Miner. Res. 27, 1018–1029.
| Demonstration of osteocytic perilacunar/canalicular remodeling in mice during lactation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xls1ejsrw%3D&md5=fb54b9396376708f5a418cc7cbaf87efCAS |
Schmidt, C. M., and Hood, W. (2014). Bone loss is a physiological cost of reproduction in white-footed mice (Peromyscus leucopus). Mamm. Biol. 79, 96–100.
| Bone loss is a physiological cost of reproduction in white-footed mice (Peromyscus leucopus).Crossref | GoogleScholarGoogle Scholar |
Schmidt, C. M., and Hood, W. (2016). Female white-footed mice (Peromyscus leucopus) trade off offspring skeletal quality for self-maintenance when dietary calcium intake is low. J. Exp. Zool. A Ecol. Genet. Physiol 325, 581–587.
| Female white-footed mice (Peromyscus leucopus) trade off offspring skeletal quality for self-maintenance when dietary calcium intake is low.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2sXht1Cksr4%3D&md5=2c345c14c9ccde54c13da65941247cacCAS |
Seibel, M. J. (2005). Biochemical markers of bone turnover Part I: Biochemistry and variability. Clin. Biochem. Rev. 26, 97–122.
Speakman, J. R. (2008). The physiological costs of reproduction in small mammals. Philos. Trans. R. Soc. Lond. B Biol. Sci. 363, 375–398.
| The physiological costs of reproduction in small mammals.Crossref | GoogleScholarGoogle Scholar |
Symonds, H. W., Bubar, R. H., Crackel, W., and Twardock, A. R. (1978). The effect of litter size on placental blood flow and placental calcium transfer in multifoetate guinea-pig. Br. J. Nutr. 39, 347–356.
| The effect of litter size on placental blood flow and placental calcium transfer in multifoetate guinea-pig.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE1cXksFOjurY%3D&md5=77aa77b09df15e82893698f5e01cf0cbCAS |
Tabatabaei, N., Rodd, C. J., Kremer, R., Khavandgar, Z., Murshed, M., and Weiler, H. A. (2014). Dietary vitamin D during pregnancy has dose-dependent effects on long bone density and architecture in guinea pig offspring but not the sows. J. Nutr. 144, 1985–1993.
| Dietary vitamin D during pregnancy has dose-dependent effects on long bone density and architecture in guinea pig offspring but not the sows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXitVShurbP&md5=da1fe3e1df197514554fcee93819c6c8CAS |
Vajda, E. G., Kneissel, M., Muggenburg, B., and Miller, S. C. (1999). Increased intracortical bone remodeling during lactation in beagle dogs. Biol. Reprod. 61, 1439–1444.
| Increased intracortical bone remodeling during lactation in beagle dogs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXns1ynsLc%3D&md5=8169570d3473f81624204b896e90efdbCAS |
VanHouten, J. N., and Wysolmerski, J. J. (2003). Low estrogen and high parathyroid hormone-related peptide levels contribute to accelerated bone resorption and bone loss in lactating mice. Endocrinology 144, 5521–5529.
| Low estrogen and high parathyroid hormone-related peptide levels contribute to accelerated bone resorption and bone loss in lactating mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXpsV2nsr4%3D&md5=cf26839b597420d3e040a8f9c4258fefCAS |
Wallace, B. C., Dahabreh, I. J., Trikalinos, T. A., Lau, J., Trow, P., and Schmid, C. H. (2012). Closing the gap between methodologists and end-users: R as a computational back-end. J. Stat. Softw. 49, 1–15.
| Closing the gap between methodologists and end-users: R as a computational back-end.Crossref | GoogleScholarGoogle Scholar |
Woodrow, J. P., Sharpe, C. J., Fudge, N. J., Hoff, A. O., Gagel, R. F., and Kovacs, C. (2006). Calcitonin plays a critical role in regulating skeletal mineral metabolism during lactation. Endocrinology 147, 4010–4021.
| Calcitonin plays a critical role in regulating skeletal mineral metabolism during lactation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xpt1Sjt78%3D&md5=1867ce84c715b57005ace6f5ae6e70f3CAS |
Wysolmerski, J. J. (2002). The evolutionary origins of maternal calcium and bone metabolism during lactation. J. Mammary Gland Biol. Neoplasia 7, 267–276.
| The evolutionary origins of maternal calcium and bone metabolism during lactation.Crossref | GoogleScholarGoogle Scholar |
Wysolmerski, J. J. (2012). Parathyroid hormone-related protein: an update. J. Clin. Endocrinol. Metab. 97, 2947–2956.
| Parathyroid hormone-related protein: an update.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtlymurbJ&md5=c37b44d85fea79c9b5b5e6a76dd59722CAS |
Zoch, M. L., Clemens, T. L., and Riddle, R. C. (2016). New insights into the biology of osteocalcin. Bone 82, 42–49.
| New insights into the biology of osteocalcin.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhtVensr%2FL&md5=146e5782406da91f77ed1c0c58fd2294CAS |
