Intrauterine programming of bone. Part 1: alteration of the osteogenic environment.
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.
Lanham
S A
SA
Bone and Joint Research Group, Developmental Origins of Health and Disease, University of Southampton, Southampton, SO16 6YD, UK. S.A.Lanham@soton.ac.uk.
Roberts
C
C
Cooper
C
C
Oreffo
R O C
RO
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
C519530:insulin-like growth factor-1, mouse; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase; D002112:Calcifediol
Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R85-90
15374820
J Bone Miner Res. 2000 Aug;15(8):1555-63
10934654
Rheumatology (Oxford). 2000 Dec;39(12):1312-5
11136871
Life Sci. 1998;63(7):605-15
9718086
J Bone Miner Res. 1995 Jun;10 (6):940-7
7572318
J Clin Invest. 2002 Sep;110(6):771-81
12235108
Hypertension. 2005 Dec;46(6):1374-80
16230509
Am J Clin Nutr. 2000 May;71(5 Suppl):1344S-52S
10799412
J Bone Miner Res. 2000 Apr;15(4):683-90
10780860
Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7324-9
10377413
J Physiol. 1989 Jul;414:55-71
2607442
Horm Res. 2001;56 Suppl 1:7-12
11786678
Stem Cell Rev. 2005;1(2):169-78
17142852
Eur J Clin Nutr. 1992 Oct;46 Suppl 3:S3-9
1425543
Life Sci. 1999;64(11):965-74
10201645
J Physiol. 2001 Jan 1;530(Pt 1):141-52
11136866
Mech Ageing Dev. 2005 Jun-Jul;126(6-7):804-12
15888335
Calcif Tissue Int. 2002 Dec;71(6):493-8
12202956
Osteoporos Int. 1998;8 Suppl 1:S37-42
9682796
Calcif Tissue Int. 2002 May;70(5):391-4
11960204
Am J Physiol. 1996 Apr;270(4 Pt 1):E559-64
8928759
Endocrinology. 2000 Sep;141(9):3149-55
10965885
Br J Nutr. 1999 Jan;81(1):5-6
10341669
Lancet. 1984 May 19;1(8386):1091-3
6144827
Science. 2004 Sep 17;305(5691):1733-6
15375258
Gerontology. 2001 Jan-Feb;47(1):9-14
11244286
Osteoporos Int. 1998;8 Suppl 2:S35-9
10197181
Clin Orthop Relat Res. 1973 Sep;(95):288-94
4754213
Am J Hypertens. 1995 Sep;8(9):894-901
8541004
Bone. 2003 Jul;33(1):100-7
12919704
JAMA. 2001 Feb 14;285(6):785-95
11176917
Ann Rheum Dis. 1997 Jan;56(1):17-21
9059135
Clin Sci (Lond). 1996 Nov;91(5):607-15
8942400
J Clin Endocrinol Metab. 1998 Jan;83(1):135-9
9435430
J Nutr. 2000 Sep;130(9):2326-32
10958831
Pediatr Res. 1997 Sep;42(3):370-7
9284279
Nature. 2004 Jul 22;430(6998):419-21
15269759
J Nutr. 1999 Nov;129(11):2061-9
10539785
J Cell Biochem. 1999 Dec 1;75(3):382-92
10536362