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RESEARCH ARTICLE

Physiological skeletal gains and losses in rat mothers during pregnancy and lactation are not observed following uteroplacental insufficiency

Tania Romano A B C D E , John D. Wark B C and Mary E. Wlodek A
+ Author Affiliations
- Author Affiliations

A Department of Physiology, The University of Melbourne, Vic. 3010, Australia.

B Department of Medicine, The University of Melbourne, Vic. 3010, Australia.

C Bone and Mineral Medicine, Royal Melbourne Hospital, Parkville, Vic. 3050, Australia.

D Department of Human Biosciences, La Trobe University, Bundoora, Vic. 3086, Australia.

E Corresponding author. Email: t.romano@latrobe.edu.au

Reproduction, Fertility and Development 26(3) 385-394 https://doi.org/10.1071/RD12378
Submitted: 26 November 2012  Accepted: 10 February 2013   Published: 12 March 2013

Abstract

Fluctuations in maternal bone mass during pregnancy and lactation facilitate calcium transfer to offspring. Uteroplacental insufficiency causes fetal growth restriction and programs poor adult bone health. We aimed to characterise maternal skeletal phenotype during normal pregnancy and pregnancy complicated by uteroplacental insufficiency. Uteroplacental restriction (Restricted) or sham surgery (Control) was performed on gestational Day 18 (term = 22 days) in pregnant Wistar-Kyoto rats. Maternal right femurs were collected on embryonic Day 20, postnatal Day 1 and Weeks 5, 7 and 9 postnatal. Dual-energy X-ray absorptiometry was used to quantify global bone mineral content, density and body composition. Peripheral quantitative computed tomography was utilised to determine trabecular and cortical content, density, circumferences and strength. Control rats exhibited expected reductions in trabecular and cortical content, density and bone strength from embryonic Day 20 to postnatal Day 1 (P < 0.05). These skeletal alterations were absent in Restricted rats. By postnatal Day 7, bone parameters in Control and Restricted rats were not different from non-pregnant rats, indicating restoration of maternal bone. The lack of bone loss in mothers suffering uteroplacental insufficiency suggests that calcium transfer to pups would be impaired. This reduction in calcium availability is a likely contributor to the programming of poor adult bone health in growth-restricted offspring.

Additional keywords: bone, growth restriction, perinatal, pQCT.


References

Affinito, P., Antonio, G., Tommaselli, A., Di Carlo, C., Guida, F., and Nappi, C. (1996). Changes in bone mineral density and calcium metabolism in breastfeeding women: a one-year follow-up study. J. Clin. Endocrinol. Metab. 81, 2314–2318.
Changes in bone mineral density and calcium metabolism in breastfeeding women: a one-year follow-up study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XjsFyktro%3D&md5=3b3a56fc96f58dde273fc599d76b87deCAS | 8964870PubMed |

Bawden, J. W., and McIver, F. T. (1964). Distribution of Ca45 during pregnancy under conditions of calcium deficiency in rats. J. Dent. Res. 43, 563–567.
Distribution of Ca45 during pregnancy under conditions of calcium deficiency in rats.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaF2c7ktFeltg%3D%3D&md5=e535cc763feec1d221111e5ced5df83bCAS | 14183345PubMed |

Black, A. J., Topping, J., Durham, B., Farquharson, R. G., and Fraser, W. D. (2000). A detailed assesment of alterations in bone turnover, calcium homeostasis and bone density in normal pregnancy. J. Bone Miner. Res. 15, 557–563.
A detailed assesment of alterations in bone turnover, calcium homeostasis and bone density in normal pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXitFakt70%3D&md5=afe237587fa634c6f8b0c449071362c5CAS | 10750571PubMed |

Boass, A., Lovdal, J. A., and Toverud, S. U. (1992). Pregnancy- and lactation-induced changes in active intestinal calcium transport in rats. Am. J. Physiol. 263, G127–G134.
| 1:CAS:528:DyaK38Xlt1yqsrY%3D&md5=3890dd3999f4463a2cdf1780c293a577CAS | 1636709PubMed |

Bowman, B. M., and Miller, S. C. (1999). Skeletal mass, chemistry and growth during and after multiple reproductive cycles in the rat. Bone 25, 553–559.
Skeletal mass, chemistry and growth during and after multiple reproductive cycles in the rat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXmvVKju74%3D&md5=940593842e3dc79656b53fdc37f8f2e3CAS | 10574575PubMed |

Bowman, B. M., Siska, C. C., and Miller, S. C. (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.
Greatly increased cancellous bone formation with rapid improvements in bone structure in the rat maternal skeleton after lactation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD38nltFGntg%3D%3D&md5=18b2d2a8b358ad63b3352f3b82438f52CAS | 12412802PubMed |

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=8bb4184d50ecca67c56091318b43f041CAS | 3970193PubMed |

Care, A. D., Abbas, S. K., Pickard, D. W., Barri, M., Drinkhill, M., Findlay, J. B. C., White, I. R., and Caple, I. W. (1990). Stimulation of ovine placental transport of calcium and magnesium by mid-molecule fragments of human parathyroid hormone-related protein. Exp. Physiol. 75, 605–608.
| 1:CAS:528:DyaK3MXksVagu7s%3D&md5=f1236bcb9fb75117a54db55501312206CAS | 2223059PubMed |

Christiansen, C., Rodbro, P., and Heinild, B. (1976). Unchanged total body calcium in normal human pregnancy. Acta Obstet. Gynecol. Scand. 55, 141–143.
Unchanged total body calcium in normal human pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE28XksVCgt7s%3D&md5=0f048798e6ff0f04929930bcc6de89b4CAS | 1258620PubMed |

Cooper, C., Westlake, S., Harvey, N., Javaid, K., Dennison, E., and Hanson, M. (2006). Review: developmental origins of osteoporotic fracture. Osteoporos. Int. 17, 337–347.
Review: developmental origins of osteoporotic fracture.Crossref | GoogleScholarGoogle Scholar | 16331359PubMed |

Cross, N. A., Hillman, L. S., Allen, S. H., and Krause, G. F. (1995). Changes in bone mineral density and markers of bone remodelling during lactation and postweaning in women consuming high amounts of calcium. J. Bone Miner. Res. 10, 1312–1320.
Changes in bone mineral density and markers of bone remodelling during lactation and postweaning in women consuming high amounts of calcium.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXotlyhsbc%3D&md5=ce5f62b3319bb169d99e9df83e00e380CAS | 7502702PubMed |

Curtis, N. E., Thomas, R. J., Ho, P. W. M., Gillespie, M. T., King, R. G., Rice, G. E., and Wlodek, M. E. (1998). Parathyroid hormone-related protein (PTHrP) mRNA splicing and parathyroid hormone/PTHrP receptor mRNA expression in human placenta and fetal membranes. J. Mol. Endocrinol. 21, 225–234.
Parathyroid hormone-related protein (PTHrP) mRNA splicing and parathyroid hormone/PTHrP receptor mRNA expression in human placenta and fetal membranes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXntVSnu7c%3D&md5=5feee625b14cd4a7c7851bf9fa2275e2CAS | 9801466PubMed |

Drinkwater, B. L., and Chesnut, C. H. (1991). Bone density changes during pregnancy and lactation in active women: a longitudinal study. Bone Miner. 14, 153–160.
Bone density changes during pregnancy and lactation in active women: a longitudinal study.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK38%2FgsVajsg%3D%3D&md5=80ebba4c25860c0e0f42fb1a2a09fd36CAS | 1912763PubMed |

Ellinger, G. M., Duckworth, J., and Dalgarno, A. C. (1952). Skeletal changes during pregnancy and lactation in the rat: effects of different levels of dietary calcium. Br. J. Nutr. 6, 235–253.
Skeletal changes during pregnancy and lactation in the rat: effects of different levels of dietary calcium.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaG3sXktV2j&md5=25f30e5f32efb7b9fedbb09477041af8CAS | 12978211PubMed |

Farrugia, W., Ho, P. W. M., Rice, G. E., Moseley, J. M., Permezel, M., and Wlodek, M. E. (2000). Parathyroid hormone-related protein (1–34) in gestational fluids and release from human gestational tissues. J. Endocrinol. 165, 657–662.
Parathyroid hormone-related protein (1–34) in gestational fluids and release from human gestational tissues.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXktl2qtrs%3D&md5=a6cfec5bc46997032c5bc2d3373feea7CAS | 10828849PubMed |

Ferretti, J. L., Capozza, R. F., and Zanchetta, J. R. (1996). Mechanical validation of a tomographic (pQCT) index for non-invasive estimation of rat femur bending strength. Bone 18, 97–102.
Mechanical validation of a tomographic (pQCT) index for non-invasive estimation of rat femur bending strength.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK28vjtVSmsA%3D%3D&md5=9f535673e76989539f2c086bfc7e1898CAS | 8833202PubMed |

Fowden, A. L., Giussani, D. A., and Forhead, A. J. (2006). Intrauterine programming of physiological systems: causes and consequences. Physiology (Bethesda) 21, 29–37.
Intrauterine programming of physiological systems: causes and consequences.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XitVWlsrs%3D&md5=da52bae140cc3660497a26da6ad77006CAS |

Fritz, H., and Hess, R. (1970). Ossification of the rat and mouse skeleton in the perinatal period. Teratology 3, 331–337.
Ossification of the rat and mouse skeleton in the perinatal period.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE2M7nvVGqsQ%3D%3D&md5=ba1650457519fa49849db94c58ff1177CAS | 5538530PubMed |

Garner, S. C., Peng, T. C., Hirsch, P. F., Boass, A., and Toverud, S. U. (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.
Increase in serum parathyroid hormone concentration in the lactating rat: effects of dietary calcium and lactational intensity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1cXhs1KhtQ%3D%3D&md5=bc8d150849d270814a05490447993274CAS | 3455618PubMed |

Giesemann, M. A., Lewis, A. J., Miller, P. S., and Akhter, M. P. (1998). Effects of the reproductive cycle and age on calcium and phosphorus metabolism and bone integrity of sows. J. Anim. Sci. 76, 796–807.
| 1:CAS:528:DyaK1cXhslOkuro%3D&md5=1d443e3fbe165c72436bb79477d4a4fbCAS | 9535340PubMed |

Halloran, B. P., and DeLuca, H. F. (1980). Skeletal changes during pregnancy and lactation: the role of vitamin D. Endocrinology 107, 1923–1929.
Skeletal changes during pregnancy and lactation: the role of vitamin D.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3MXivFWgtA%3D%3D&md5=c10dfbf4122b2e224a91cff4cc96a52dCAS | 7428698PubMed |

Henriksen, T., and Clausen, T. (2002). The fetal origins hypothesis: placental insufficiency and inheritance versus maternal malnutrition in well-nourished populations. Acta Obstet. Gynecol. Scand. 81, 112–114.
The fetal origins hypothesis: placental insufficiency and inheritance versus maternal malnutrition in well-nourished populations.Crossref | GoogleScholarGoogle Scholar | 11942899PubMed |

Holmberg-Marttila, D., Sievanen, H., and Tuimala, R. (1999). Changes in bone mineral density during pregnancy and postpartum: prospective data on five women. Osteoporos. Int. 10, 41–46.
Changes in bone mineral density during pregnancy and postpartum: prospective data on five women.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1MvjtFKiuw%3D%3D&md5=bc035a15b5c9d30fa7cfcd6cd7747eb3CAS | 10501778PubMed |

Holmberg-Marttila, D., Leino, A., and Sievanen, H. (2003). Bone-turnover markers during lactation, postpartum amenorrhea and resumption of menses. Osteoporos. Int. 14, 103–109.
| 1:CAS:528:DC%2BD3sXjsVGkt7Y%3D&md5=e998e7c4dafd46865081dfc241d7e441CAS | 12730783PubMed |

Karlsson, R., Eden, A., Eriksson, L., and von Schoultz, B. (1992). Osteocalcin 24-hour profiles during normal pregnancy. Gynecol. Obstet. Invest. 34, 197–201.
Osteocalcin 24-hour profiles during normal pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXitFSjtLk%3D&md5=c52b42a5f26d824ab8c60d57906875deCAS | 1487175PubMed |

Kent, G. N., Price, R. I., Gutteridge, D. H., Smith, M., Allen, J. R., Bhagat, C. I., Barnes, M. P., Hickling, C. J., Retallack, R. W., and Wilson, S. G. (1990). Human lactation: forearm trabecular bone loss, increased bone turnover and renal conservation of calcium and inorganic phosphate with recovery of bone mass following weaning. J. Bone Miner. Res. 5, 361–369.
Human lactation: forearm trabecular bone loss, increased bone turnover and renal conservation of calcium and inorganic phosphate with recovery of bone mass following weaning.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3c3mtFGgtg%3D%3D&md5=5b29f7af307b70cab06aa2cc16df92a3CAS | 2343775PubMed |

Kent, G. N., Price, R. I., Gutteridge, D. H., Allen, J. R., Rosman, K. J., Smith, M., Bhagat, C. I., Wilson, S. G., and Retallack, R. W. (1993). Effect of pregnancy and lactation on maternal bone mass and calcium metabolism. Osteoporos. Int. 3, 44–47.
Effect of pregnancy and lactation on maternal bone mass and calcium metabolism.Crossref | GoogleScholarGoogle Scholar | 8461575PubMed |

Kilborn, S. H., Trudel, G., and Uhthoff, H. (2002). Review of growth-plate closure compared with age at sexual maturity and lifespan in laboratory animals. Contemp. Top. Lab. Anim. Sci. 41, 21–26.
| 1:CAS:528:DC%2BD38XnsVGgsbs%3D&md5=0764f7b92bc946c3ccaa3477d798fc79CAS | 12213043PubMed |

Kovacs, C. S., Lanske, B., Hunzelman, J. L., Guo, J., Karaplis, A. C., and Kronenberg, H. M. (1996). Parathyroid hormone-related peptide (PTHrP) regulates fetal–placental calcium transport through a receptor distinct from the PTH/PTHrP receptor. Proc. Natl. Acad. Sci. USA 93, 15233–15238.
Parathyroid hormone-related peptide (PTHrP) regulates fetal–placental calcium transport through a receptor distinct from the PTH/PTHrP receptor.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXntFGn&md5=7589d343a5484093859b665c25dd7095CAS | 8986793PubMed |

Kovacs, C. S., Chafe, L. L., Fudge, N. J., Friel, J. K., and Manley, N. R. (2001). PTH regulates fetal blood calcium and skeletal mineralization independently of PTHrP. Endocrinology 142, 4983–4993.
PTH regulates fetal blood calcium and skeletal mineralization independently of PTHrP.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXnslKjsr8%3D&md5=e55ee9c85fca6821e553f6d781a74a9dCAS | 11606467PubMed |

Krebs, N. F., Reidinger, C. J., Robertson, A. D., and Brenner, M. (1997). Bone mineral density changes during lactation: maternal, dietary and biochemical correlates. Am. J. Clin. Nutr. 65, 1738–1746.
| 1:CAS:528:DyaK2sXjs1WktLc%3D&md5=35a81eb6ab6b101adead378a38196206CAS | 9174469PubMed |

Lees, C. J., Jerome, C. P., Register, T. C., and Carlson, C. S. (1998). Changes in bone mass and bone biomarkers of cynomolgus monkeys during pregnancy and lactation. J. Clin. Endocrinol. Metab. 83, 4298–4302.
Changes in bone mass and bone biomarkers of cynomolgus monkeys during pregnancy and lactation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXnvFOrt7g%3D&md5=d7f0ada862ae7f50b06f4b918bdcac4eCAS | 9851767PubMed |

Liesegang, A., Risteli, J., and Wanner, M. (2006). The effects of first gestation and lactation on bone metabolism in dairy goats and milk sheep. Bone 38, 794–802.
The effects of first gestation and lactation on bone metabolism in dairy goats and milk sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XlsVenu7g%3D&md5=a1bcbf97c8432e15b3d6a22d7072b934CAS | 16364707PubMed |

Macgill, K., Wlodek, M. E., Moseley, J. M., Martin, T. J., Brennecke, S. P., and Rice, G. E. (1997). Vascular effects of PTHrP(1–34) in the human fetal–placental circulation. Placenta 18, 587–592.
Vascular effects of PTHrP(1–34) in the human fetal–placental circulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXmt1ajsrw%3D&md5=9b8c8d2dee3b64a1236176cf882e7b3cCAS | 9290155PubMed |

Miller, S. C., and Bowman, B. M. (2004). Rapid improvements in cortical bone dynamics and structure after lactation in established breeder rats. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 276A, 143–149.
Rapid improvements in cortical bone dynamics and structure after lactation in established breeder rats.Crossref | GoogleScholarGoogle Scholar |

Miller, S. C., Halloran, B. P., DeLuca, H. F., and Jee, W. S. (1982). Role of vitamin D in maternal skeletal changes during pregnancy and lactation: a histomorphometric study. Calcif. Tissue Int. 34, 245–252.
Role of vitamin D in maternal skeletal changes during pregnancy and lactation: a histomorphometric study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL38XksFCnsLo%3D&md5=a9fa621783fb6634085a684ebe8a90d7CAS | 6809285PubMed |

Miller, S. C., Shupe, J. G., Redd, E. H., Miller, M. A., and Omura, T. H. (1986). Changes in bone mineral and bone formation rates during pregnancy and lactation in rats. Bone 7, 283–287.
Changes in bone mineral and bone formation rates during pregnancy and lactation in rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28XlvVygtLY%3D&md5=0bd6bd36b5598533f3ecd079bf8a502fCAS | 3768208PubMed |

Miller, M. A., Omura, T. H., and Miller, S. C. (1989). Increased cancellous bone remodelling during lactation in beagles. Bone 10, 279–285.
Increased cancellous bone remodelling during lactation in beagles.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3c%2Fisl2jsA%3D%3D&md5=e9595eb4761d129a02b3c5946d12301dCAS | 2803864PubMed |

Mughal, M. Z., Ross, R., and Tsang, R. C. (1989). Clearance of calcium across in situ-perfused placentas of intrauterine growth-retarded rat fetuses. Pediatr. Res. 25, 420–422.
Clearance of calcium across in situ-perfused placentas of intrauterine growth-retarded rat fetuses.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXhvFSgu7s%3D&md5=cca4d7dfe34144758ba4a936b3e65aa0CAS | 2498832PubMed |

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=1c758edfb46330b53711850c9bade9b6CAS | 10646122PubMed |

Nishiwaki, M., Yasumizu, T., Hoshi, K., and Ushijima, H. (1999a). Effect of pregnancy, lactation and weaning on bone mineral density in rats as determined by dual-energy X-ray absorptiometry. Endocr. J. 46, 711–716.
Effect of pregnancy, lactation and weaning on bone mineral density in rats as determined by dual-energy X-ray absorptiometry.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3c7jsVaiug%3D%3D&md5=012e549d03eb0eb634519b112c6d753bCAS | 10670758PubMed |

O’Dowd, R., Kent, J. C., Moseley, J. M., and Wlodek, M. E. (2008). Effects of uteroplacental insufficiency and reducing litter size on maternal mammary function and postnatal offspring growth. Am. J. Physiol. 294, R539–R548.
| 1:CAS:528:DC%2BD1cXit1ylu78%3D&md5=1a523bcd7714d8c65bb8e56dc8cec71dCAS |

Paton, L. M., Alexander, J. L., Nowson, C. A., Margerison, C., Frame, M. G., Kaymakci, B., and Wark, J. D. (2003). Pregnancy and lactation have no long-term deleterious effect on measures of bone mineral in healthy women: a twin study. Am. J. Clin. Nutr. 77, 707–714.
| 1:CAS:528:DC%2BD3sXnsVSru7w%3D&md5=b96676997c70c9cf2bb55684e00483beCAS | 12600865PubMed |

Quan-Sheng, D., and Miller, S. C. (1989). Calcitrophic hormone levels and calcium absorption during pregnancy in rats. Am. J. Physiol. 257, E118–E123.
| 1:STN:280:DyaL1MzitVKrsw%3D%3D&md5=d607394a2e46fe1bf23f6a0e333ccc5eCAS | 2750894PubMed |

Rasmussen, P. (1977). Calcium deficiency, pregnancy and lactation in rats. Some effects on blood chemistry and the skeleton. Calcif. Tissue Int. 23, 87–94.
Calcium deficiency, pregnancy and lactation in rats. Some effects on blood chemistry and the skeleton.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE2sXksFWitL0%3D&md5=7109d8d87fbcb92e97ece8744531de7cCAS |

Rodin, A., Duncan, A., Quartero, H. W., Pistofidis, G., Mashiter, G., Whitaker, K., Crook, D., Stevenson, J. C., Chapman, M. G., and Fogelman, I. (1989). Serum concentrations of alkaline phosphatase isoenzymes and osteocalcin in normal pregnancy. J. Clin. Endocrinol. Metab. 68, 1123–1127.
Serum concentrations of alkaline phosphatase isoenzymes and osteocalcin in normal pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXkt1Wnt78%3D&md5=d2554df1c226175c182640752e80c6deCAS | 2786001PubMed |

Romano, T., Wark, J. D., Owens, J. A., and Wlodek, M. E. (2009). Prenatal growth restriction and postnatal growth restriction followed by accelerated growth independently program reduced bone growth and strength. Bone 45, 132–141.
Prenatal growth restriction and postnatal growth restriction followed by accelerated growth independently program reduced bone growth and strength.Crossref | GoogleScholarGoogle Scholar | 19332163PubMed |

Romano, T., Wark, J. D., and Wlodek, M. E. (2010). Calcium supplementation does not rescue the programmed adult bone deficits associated with perinatal growth restriction. Bone 47, 1054–1063.
Calcium supplementation does not rescue the programmed adult bone deficits associated with perinatal growth restriction.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlKlsrvL&md5=349f8cf6b5f5649af45d0c2beaa1734eCAS | 20817129PubMed |

Rowland, G. N., Capen, C. C., Young, D. M., and Black, H. E. (1972). Microradiographic evaluation of bone from cows with experimental hypervitaminosis D, diet-induced hypocalcemia and naturally-occurring parturient paresis. Calcif. Tissue Res. 9, 179–193.
Microradiographic evaluation of bone from cows with experimental hypervitaminosis D, diet-induced hypocalcemia and naturally-occurring parturient paresis.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE383ltlaktQ%3D%3D&md5=bb6d5bae05f048911a148090c449b104CAS | 5050206PubMed |

Schultz, V. L., Boass, A., Garner, S. C., and Toverud, S. U. (1997). Altered regulation of parathyroid hormone secretion by calcium in pregnant and lactating rats. J. Bone Miner. Res. 12, 903–908.
Altered regulation of parathyroid hormone secretion by calcium in pregnant and lactating rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXjs1yltrg%3D&md5=3a3f0db0a9127fa9a979ce0fb1eda8e5CAS | 9169348PubMed |

Seki, K., Makimura, N., Mitsui, C., Hirata, J., and Nagata, I. (1991). Calcium-regulating hormones and osteocalcin levels during pregnancy: a longitudinal study. Am. J. Obstet. Gynecol. 164, 1248–1252.
| 1:STN:280:DyaK3M3ktFWkuw%3D%3D&md5=2888d618ac452cf0f61a2c1f5f6acefcCAS | 2035567PubMed |

Sowers, M., Crutchfield, M., Jannausch, M., Updike, S., and Corton, G. (1991). A prospective evaluation of bone mineral change in pregnancy. Obstet. Gynecol. 77, 841–845.
| 1:STN:280:DyaK3M3jt1Olug%3D%3D&md5=76492a3f3ac65a71bb0bca2deb93385fCAS | 2030854PubMed |

Tojo, Y., Kurabayashi, T., Honda, A., Yamamoto, Y., Yahata, T., Takakuwa, K., and Tanaka, K. (1998). Bone structural and metabolic changes at the end of pregnancy and lactation in rats. Am. J. Obstet. Gynecol. 178, 180–185.
Bone structural and metabolic changes at the end of pregnancy and lactation in rats.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1c7is12ktg%3D%3D&md5=4b5ec3260a80161d65011ac582b27195CAS | 9465826PubMed |

Trudel, G., Kilborn, S. H., and Uhthoff, H. K. (2001). Bone growth increases the knee flexion contracture angle: a study using rats. Arch. Phys. Med. Rehabil. 82, 583–588.
Bone growth increases the knee flexion contracture angle: a study using rats.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3M3ltVKhug%3D%3D&md5=4cf598948464cc3371ef2fc128168d82CAS | 11346832PubMed |

Tsang, R., and Oh, W. (1970). Neonatal hypocalcemia in low-birthweight infants. Pediatrics 45, 773–781.
| 1:STN:280:DyaE3c7osVClsQ%3D%3D&md5=a6fedf256e71fa6b6ded435e5c48e1c4CAS | 5462810PubMed |

Vajda, E. G., Bowman, B. M., and Miller, S. C. (2001). Cancellous and cortical bone mechanical properties and tissue dynamics during pregnancy, lactation and postlactation in the rat. Biol. Reprod. 65, 689–695.
Cancellous and cortical bone mechanical properties and tissue dynamics during pregnancy, lactation and postlactation in the rat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXmtFenu7c%3D&md5=c214f5e1761d5400e9a2c33ea8434ed7CAS | 11514329PubMed |

VanHouten, J., and Wysolmerski, J. J. (2003). Low oestrogen and high parathyroid hormone-related peptide levels contribute to accelerated bone resorption and bone loss in lactating mice. Endocrinology 144, 5521–5529.
Low oestrogen 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=de940a84177d31b87c2f86834f1a9e30CAS | 14500568PubMed |

Warnock, G. M., and Duckworth, J. (1944). Changes in the skeleton during gestation and lactation in the rat. Biochem. J. 38, 220–224.
| 1:CAS:528:DyaH2MXjtl2l&md5=77a1dd4a176573d6fd05cbb6a49d0195CAS | 16747783PubMed |

Wlodek, M. E., Ho, P. W. M., Rice, G. E., Moseley, J. M., Martin, T. J., and Brennecke, S. P. (1995). Parathyroid hormone-related protein (PTHrP) concentrations in human amniotic fluid during gestation and at the time of labour. Reprod. Fertil. Dev. 7, 1509–1513.
Parathyroid hormone-related protein (PTHrP) concentrations in human amniotic fluid during gestation and at the time of labour.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XisFOqtL0%3D&md5=f0b718a195255872005bc80dee38835dCAS | 8743156PubMed |

Wlodek, M. E., Westcott, K. T., Ho, P. W. M., Serruto, A., Di Nicolantonio, R., Farrugia, W., and Moseley, J. M. (2000). Reduced fetal, placental and amniotic fluid PTHrP in the growth-restricted spontaneously hypertensive rat. Am. J. Physiol. 279, R31–R38.
| 1:CAS:528:DC%2BD3cXltlyqsrg%3D&md5=bb95eabc22ae2e2cda2aa50d37a710adCAS |

Wlodek, M. E., Westcott, K. T., O’Dowd, R., Serruto, A., Wassef, L., Moritz, K. M., and Moseley, J. M. (2005). Uteroplacental restriction in the rat impairs fetal growth in association with alterations in placental growth factors including PTHrP. Am. J. Physiol. 288, R1620–R1627.
| 1:CAS:528:DC%2BD2MXlsVyms7s%3D&md5=4a4f84dd9f6972bee6655a3295c2cbb2CAS |

Wlodek, M. E., Mibus, A., Tan, A., Siebel, A. L., Owens, J. A., and Moritz, K. M. (2007). Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat. J. Am. Soc. Nephrol. 18, 1688–1696.
Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXnt1Squrg%3D&md5=d4177528ebb14898f0a3fa6642f533abCAS | 17442788PubMed |

Wong, K. M., Singer, L., and Ophaug, R. H. (1980). Metabolic aspects of bone resorption in calcium-deficient lactating rats. Calcif. Tissue Int. 32, 213–219.
Metabolic aspects of bone resorption in calcium-deficient lactating rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3cXmtF2mt70%3D&md5=cf45104b2a51570a53e58303bbb58363CAS | 6253031PubMed |

Wróbel, J., and Nagel, G. (1980). Diurnal variations of active calcium transport in the intestine of the pregnant and lactating rat. Biomedicine 33, 143–145.
| 7192163PubMed |

Yamaga, A., Taga, M., Minaguchi, H., and Sato, K. (1996). Changes in bone mass as determined by ultrasound and biochemical markers of bone turnover during pregnancy and puerperium: a longitudinal study. J. Clin. Endocrinol. Metab. 81, 752–756.
Changes in bone mass as determined by ultrasound and biochemical markers of bone turnover during pregnancy and puerperium: a longitudinal study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XhtVyktL8%3D&md5=f2d64b1e27e5a68ff1d9d5a57f062ab5CAS | 8636299PubMed |

Zeni, S. N., Di Gregorio, S., and Mautalen, C. (1999). Bone mass changes during pregnancy and lactation in the rat. Bone 25, 681–685.
Bone mass changes during pregnancy and lactation in the rat.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3c%2FlvV2rtA%3D%3D&md5=9eda27c816bdc210fec2b343d1363037CAS | 10593413PubMed |