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Intrauterine programming of bone. Part 2: Alteration of skeletal structure

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Abstract

Summary

Osteoporosis is believed to be partly programmed in utero. Rat dams were given a low protein diet during pregnancy, and offspring were studied at different ages. Old aged rats showed site-specific strength differences. In utero nutrition has consequences in later life.

Introduction

Epidemiological studies suggest skeletal growth is programmed during intrauterine and early postnatal life. We hypothesize that age-related decrease in bone mass has, in part, a fetal origin and investigated this using a rat model of maternal protein insufficiency.

Methods

Dams received either 18% w/w (control) or w/w 9% (low protein) diet during pregnancy, and the offspring were studied at selected time points (4, 8, 12, 16, 20, 47, 75 weeks).

Results

Using micro-CT, we found that at 75 weeks of age female offspring from mothers fed a restricted protein diet during pregnancy had femoral heads with thinner, less dense trabeculae, femoral necks with closer packed trabeculae, vertebrae with thicker, denser trabeculae and midshaft tibiae with denser cortical bone. Mechanical testing showed the femoral heads and midshaft tibiae to be structurally weaker, whereas the femoral necks and vertebrae were structurally stronger.

Conclusions

Offspring from mothers fed a restricted protein diet during pregnancy displayed significant differences in bone structure and density at various sites. These differences result in altered bone characteristics indicative of significantly altered bone turnover. These results further support the need to understand the key role of the nutritional environment in early development on programming of skeletal development and consequences in later life.

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Acknowledgements

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.

Author information

Authors and Affiliations

  1. Bone and Joint Research Group, Developmental Origins of Health and Disease, University of Southampton, Southampton, SO16 6YD, UK

    S. A. Lanham, C. Roberts, C. Cooper & R. O. C. Oreffo

  2. Department of Anatomy, University of Bristol, Bristol, UK

    M. J. Perry

  3. Bone and Joint Research Group, MP887, Institute of Developmental Sciences, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK

    S. A. Lanham

Authors
  1. S. A. Lanham
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  2. C. Roberts
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  3. M. J. Perry
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  4. C. Cooper
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  5. R. O. C. Oreffo
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Corresponding author

Correspondence to S. A. Lanham.

Additional information

This work was supported by Research into Ageing.

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Lanham, S.A., Roberts, C., Perry, M.J. et al. Intrauterine programming of bone. Part 2: Alteration of skeletal structure. Osteoporos Int 19, 157–167 (2008). https://doi.org/10.1007/s00198-007-0448-3

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  • DOI: https://doi.org/10.1007/s00198-007-0448-3

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