title: Intrauterine programming of bone. Part 1: alteration of the osteogenic environment.
abstract: Osteoporosis is believed to partly be programmed in utero. Rat dams were given a low protein diet during pregnancy and 135 offspring studied at different ages. Bone biochemistry showed altered characteristics. Altered in utero diet has consequences for later life.
  
  
  BACKGROUND
  Epidemiological studies suggest skeletal growth is programmed during intrauterine and early postnatal life. We have investigated this in a rat model of maternal protein insufficiency.
  
  
  METHODS
  Dams received either 18% w/w (control) or 9% w/w (low protein) diet during pregnancy, and the offspring were studied at selected time points (4, 8, 12, 16, 20, 47 weeks).
  
  
  RESULTS
  Alkaline phosphatase activity in controls reached peak levels from 8 to 20 weeks of age. In contrast, restricted diet offspring were at peak levels from 4 weeks of age. Peak levels were similar in both groups. Serum IGF-1 levels were lower in female restricted diet offspring at 4 weeks of age, and serum osteocalcin was significantly higher at 4 weeks of age in male and female offspring from mothers fed the restricted diet, whereas serum 25-OH vitamin D was significantly lower in restricted diet males at 8, 12, and 20 weeks of age.
  
  
  CONCLUSIONS
  These data indicate that a low protein diet in utero affected the osteogenic environment in the offspring with effects that persist into late adulthood. These results indicate the key role of the nutritional environment in early development on programming of skeletal development with implicit consequences in later life.
authors: Bone and Joint Research Group, Developmental Origins of Health and Disease, University of Southampton, Southampton, SO16 6YD, UK. S.A.Lanham@soton.ac.uk.
authors: S A
authors: SA
authors: Lanham
authors: C
authors: C
authors: Roberts
authors: C
authors: C
authors: Cooper
authors: R O C
authors: RO
authors: Oreffo
mesh_terms: D000375:Aging / Q000502:physiology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001724:Birth Weight; D001854:Bone Marrow Cells / Q000201:enzymology; D001842:Bone and Bones / Q000196:embryology* / Q000503:physiopathology; D002112:Calcifediol / Q000097:blood; D002478:Cells, Cultured; D018753:Diet, Protein-Restricted; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008098:Litter Size; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D039401:Prenatal Nutritional Physiological Phenomena; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain
chemical_list: C519530:insulin-like growth factor-1, mouse; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase; D002112:Calcifediol
references: Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R85-90
references: 15374820
references: J Bone Miner Res. 2000 Aug;15(8):1555-63
references: 10934654
references: Rheumatology (Oxford). 2000 Dec;39(12):1312-5
references: 11136871
references: Life Sci. 1998;63(7):605-15
references: 9718086
references: J Bone Miner Res. 1995 Jun;10 (6):940-7
references: 7572318
references: J Clin Invest. 2002 Sep;110(6):771-81
references: 12235108
references: Hypertension. 2005 Dec;46(6):1374-80
references: 16230509
references: Am J Clin Nutr. 2000 May;71(5 Suppl):1344S-52S
references: 10799412
references: J Bone Miner Res. 2000 Apr;15(4):683-90
references: 10780860
references: Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7324-9
references: 10377413
references: J Physiol. 1989 Jul;414:55-71
references: 2607442
references: Horm Res. 2001;56 Suppl 1:7-12
references: 11786678
references: Stem Cell Rev. 2005;1(2):169-78
references: 17142852
references: Eur J Clin Nutr. 1992 Oct;46 Suppl 3:S3-9
references: 1425543
references: Life Sci. 1999;64(11):965-74
references: 10201645
references: J Physiol. 2001 Jan 1;530(Pt 1):141-52
references: 11136866
references: Mech Ageing Dev. 2005 Jun-Jul;126(6-7):804-12
references: 15888335
references: Calcif Tissue Int. 2002 Dec;71(6):493-8
references: 12202956
references: Osteoporos Int. 1998;8 Suppl 1:S37-42
references: 9682796
references: Calcif Tissue Int. 2002 May;70(5):391-4
references: 11960204
references: Am J Physiol. 1996 Apr;270(4 Pt 1):E559-64
references: 8928759
references: Endocrinology. 2000 Sep;141(9):3149-55
references: 10965885
references: Br J Nutr. 1999 Jan;81(1):5-6
references: 10341669
references: Lancet. 1984 May 19;1(8386):1091-3
references: 6144827
references: Science. 2004 Sep 17;305(5691):1733-6
references: 15375258
references: Gerontology. 2001 Jan-Feb;47(1):9-14
references: 11244286
references: Osteoporos Int. 1998;8 Suppl 2:S35-9
references: 10197181
references: Clin Orthop Relat Res. 1973 Sep;(95):288-94
references: 4754213
references: Am J Hypertens. 1995 Sep;8(9):894-901
references: 8541004
references: Bone. 2003 Jul;33(1):100-7
references: 12919704
references: JAMA. 2001 Feb 14;285(6):785-95
references: 11176917
references: Ann Rheum Dis. 1997 Jan;56(1):17-21
references: 9059135
references: Clin Sci (Lond). 1996 Nov;91(5):607-15
references: 8942400
references: J Clin Endocrinol Metab. 1998 Jan;83(1):135-9
references: 9435430
references: J Nutr. 2000 Sep;130(9):2326-32
references: 10958831
references: Pediatr Res. 1997 Sep;42(3):370-7
references: 9284279
references: Nature. 2004 Jul 22;430(6998):419-21
references: 15269759
references: J Nutr. 1999 Nov;129(11):2061-9
references: 10539785
references: J Cell Biochem. 1999 Dec 1;75(3):382-92
references: 10536362