Osteoporosis International

, Volume 19, Issue 2, pp 147–156 | Cite as

Intrauterine programming of bone. Part 1: Alteration of the osteogenic environment

  • S. A. LanhamEmail author
  • C. Roberts
  • C. Cooper
  • R. O. C. Oreffo
Original Article



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.


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.


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).


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.


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.


Bone marrow In utero Maternal Osteogenic programming 



This work was supported by a programme grant from Research into Ageing. We acknowledge useful discussion with Professors Mark Hanson, Nicholas Clarke and Dr Trudy Roach and the support of the Biomedical Research Facility. We thank statistician Karen Jameson from the MRC Epidemiology Resource Centre for helpful assistance with statistical analysis.

Conflict of interest statement

All authors have no conflicts of interest.


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2007

Authors and Affiliations

  • S. A. Lanham
    • 1
    • 2
    Email author
  • C. Roberts
    • 1
  • C. Cooper
    • 1
  • R. O. C. Oreffo
    • 1
  1. 1.Bone and Joint Research Group, Developmental Origins of Health and DiseaseUniversity of SouthamptonSouthamptonUK
  2. 2.Bone and Joint Research Group, MP887, Institute of Developmental Sciences, Southampton General HospitalSouthamptonUK

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