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

Lanham, S.A., Roberts, C., Perry, M.J., Cooper, C. and Oreffo, R.O. (2007) Intrauterine programming of bone. Part 2: alteration of skeletal structure Osteoporosis International, 19, (2), pp. 157-167. (doi:10.1007/s00198-007-0448-3).


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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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1007/s00198-007-0448-3
ISSNs: 0937-941X (print)
Keywords: growth, in-utero, bone, mass, origins, neck, later life, research, bone mass, development, disease, consequences, head, methods, developmental origins, pregnancy, time, health, environment, rat, maternal, female, aged, diet, mothers, protein, programming, fetal, nutrition, rats, osteoporosis
Organisations: Human Development & Health
ePrint ID: 61318
Date :
Date Event
2007e-pub ahead of print
February 2008Published
Date Deposited: 09 Sep 2008
Last Modified: 16 Apr 2017 17:31
Further Information:Google Scholar

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