UK scientists curious to discover why unlike the weight-bearing bone in our limbs, the skull bone does not get thin as it ages, even in post-menopausal women, have found some quite remarkable differences between the two bone types that could help develop new treatments and prevent osteoporosis.

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The skull bone is not weight-bearing, unlike the limb bones.

Researchers at Queen Mary, University of London, led the investigation, which was published last week as a study in the open access journal PLoS ONE.

Lead author, Dr Simon Rawlinson, Lecturer in Oral Biology at Queen Mary, University of London, told the press that the discovery was exciting because it tells us why our skulls remain tough while the bones in our arms and legs weaken as we age; thus helping us understand osteoporosis better:

“And this has opened up many new lines of research into how the disease could be treated or even prevented,” he added.

Osteoporosis causes bones to become fragile and easy to break: it is more common in older people, especially women past the menopause. Among people aged 50 and over, half of women and one fifth men suffer from the condition, and as our populations age, the numbers of cases and deaths increase accordingly.

Unlike the skeleton one might remember hanging lifeless in the corner of the biology lab at high school, bone is not a dead material but a living, dynamic, and finely balanced system of bone formation and breakdown: with cells called osteoblasts making new bone by producing a “matrix” that then becomes mineralized, while cells called osteoclasts break it down.

Rawlinson and colleagues suggested that one explanation for why skull bone does not get thinner with age like limb bones do is because it has different bone matrix characteristics due to differences in osteoblasts.

For the study, they compared cells taken from the skull and limb bones of adult rats and found differences in appearance and behaviour in the lab, more specifically at the “organ, cell and transcriptome levels”.

They found that:
    • Limb bones “contain greater amounts of polysulphated glycosaminoglycan stained with Alcian Blue and have significantly higher osteocyte densities than skull bone”.

    • Patterns for limb and skull bone were different when their cells were cultured and treated with oestrogen, which appeared to affect limb bone far more strongly.

    • Cultures of limb and skull bone cells also showed differences in gene expression.

    • There was an astonishing total of 1,236 differences; meaning that about 4 per cent of the genome showed different levels of activity in the two types of bone cell.

  • Some of the genes affected are known to be involved in making healthy bones.
Rawlinson and colleagues suggested that because the differences between limb and skull bone were so profound, they must arise early in life, probably at the stage when they are still forming in the womb.

“We assign these differences, not to mode of primary ossification, but to the embryological cell lineage,” they wrote.

“Adult Rat Bones Maintain Distinct Regionalized Expression of Markers Associated with Their Development.”
Simon C. F. Rawlinson, Ian J. McKay, Mandeep Ghuman, Claudia Wellmann, Paul Ryan, Saengsome Prajaneh, Gul Zaman, Francis J. Hughes, Virginia J. Kingsmill.
PLoS ONE 4(12): e8358, published online 18 December 2009.

Sources: Queen Mary, University of London.

Written by: Catharine Paddock, PhD