Prevention of postmenopausal osteoporosis with oestrogen replacement therapy and associated compounds: update on clinical trials since 1995

Hormonal replacement therapy (HRT) is generally regarded as first choice fo r pharmacological prevention of osteoporosis in women. We reviewed recent s tudies of HRT regimens and selective oestrogen receptor modulators (SERMs), including controlled trials of at least one-year duration published since 1995 until February 2000 providing data on bone mineral density (BMD) or fr actures. Natural and synthetic oestrogens exert a continuum of positive eff ects on BMD in a dose-dependent, though non-proportional, fashion independe nt of age and mode of administration. Bone loss may be largely prevented by 25 mu g transdermal patch oestradiol, 0.3 mg conjugated equine or 0.3 mg e sterified oestrogens. Progestogens neither attenuate nor augment the effect of oestrogens; sole use of tibolone prevents bone loss. Both the SERMs, ta moxifen and raloxifene, slightly increase BMD. There are no adequately powe red fracture trials for any HRT regimen. Raloxifene 60 mg daily decreases t he relative risk of vertebral fractures by at least 30%, as demonstrated by one 3-year fracture study of osteoporotic women. In conclusion, the recomm endation to use oestrogen for postmenopausal osteoporosis, given both the l ack of fracture trials and the rare trials on long-term use of HRT in (late ) postmenopausal women, is not well supported. Fracture trials could overco me shortcomings of the current level of evidence.