ABSTRACT
Knowledge of oestrogen signalling pathways
has advanced rapidly in recent years and has
facilitated the development of selective
oestrogen receptor modulators, discussed
elsewhere in this book. The precise
mechanisms by which oestrogen exerts its
beneficial effects on bone remain, however, to
be clearly defined; these effects extend
throughout most of the lifespan of women
and probably also of men. Oestrogen-induced
effects on the skeleton may be exerted via
either genomic or non-genomic actions; the
importance of the latter is increasingly
recognized in the mediation of rapid responses
to the hormone by both osteoblasts and
Oestrogen receptors belong to a family of
steroid hormone receptors which includes
glucocorticoid, androgen, progesterone, and
mineralocorticoid receptors. At least two
main subtypes of the oestrogen receptor (ER)
exist, namely, ER and .3 Several isoforms
of ER and at least two of ER, created by
alternative splicing or alternative initiation of
translation, have also been demonstrated,
mainly at mRNA level. Both receptor
subtypes have been reported in human bone;
their distribution appears to be overlapping
but not identical and recent evidence suggests
that ER is predominant in cortical bone
whereas ER is the main form in cancellous
bone. Oestrogen receptors have been
described on all the main cell types of bone,
namely, osteoclasts,4,5 osteoblasts,6,7 and
Oestrogen has effects on the production of
a number of cytokines and growth factors
involved in the regulation of bone
remodelling (Table 4.1). The bone-preserving
effect of oestrogen is mediated predominantly
through effects on osteoclast number and
activity, the latter encompassing both
resorptive activity and lifespan of the cell.
