Dr Jonathan Reeve

The principal health problem affecting bone is osteoporosis. This leads to increased fracture risk, usually after age 50. Physical activity and associated mechanical loading are implicated in determining risk of those fractures commonly seen in the community. Wrist fractures are increased by physical activity, hip fractures (which have a much more severe impact) are reduced by physical activity, whereas vertebral fractures have a weak and probably J-shaped relationship with physical activity. Marked physical inactivity (as following paraplegia or hemiplegia) leads to bone loss, with fenestration of trabecular bone and the development of 'giant' cavities in cortical bone. Classical (Euler) approaches to analysing the consequences of this type of bone loss suggest that both processes have adverse implications for the mechanical properties of bone.

Recent epidemiological research suggests that women have increased fracture risk compared to men largely because they lose bone rapidly for a period after the menopause; when this bone loss is adjusted for, the sexes have similar fracture risk. But fracture risk increases approximately two-fold for every decade of age after the 50th birthday even after adjusting for the effects of bone loss. This effect of age is so far unexplained. In many (but not all) of those who suffer hip fracture we have shown effects on microscopic structure of cortical bone in the proximal femur, which resemble closely the expected effects of mechanical unloading. In contrast, the healthy elderly participating in the EPIC-Norfolk study show changes in the proximal femur which can best be explained as an appropriate and commensurate response to gradual enlargement of the marrow cavity, with a proportionate expansion of the bony envelope so as to maintain resistance to bending of the femoral cantilever. Thus the effect of ageing to reduce fracture resistance in the healthy elderly remains unexplained and directs our attention to the biology of the regulation of the material properties of bone at higher levels of magnification.

Osteocytes are the most numerous cell type, specific to bone and form a dendritic network throughout the bone substance. They may be induced to die, by apoptosis, by sudden oestrogen withdrawal in women or by corticosteroid therapy, events, which are succeeded by bone loss. Conversely, parathyroid hormone injection treatment, recently licensed in the USA for the treatment of osteoporosis, can prevent the death of osteoblasts and osteocytes. Recent experimental studies have shown that mechanical loading up to the normally experienced limit of 3-4000 microstrain enhances survival of osteocytes, whereas damage-inducing levels of overloading promotes widespread apoptosis, followed by cavity formation and replacement of old damaged bone by new. Paradoxically, underloading may also be associated with osteocyte apoptosis; but this is usually followed by the replacement of bone by marrow, the most healthy example of which is to be found in the normal growth of bones such as the skull and (in width) of long bones. During normal growth and repair, the bone remodelling units (comprising osteoclasts and osteoblasts) exhibit sophisticated forms of control so as to ensure that at most, if not all, levels of organisation the orientation (anisotropy) of structural elements is optimised for resistance to bending. The promotion of 'toughness' (the opposite of brittleness) is much less well understood, but toughness may be lost with ageing and so should be the focus of our future attention.

View presentation

Last updated: