Observational studies and clinical ...

Observational studies and clinical trials have shown that estrogen use can attenuate bone los and contract fracture risk in postmenopausal women The Women's Health Initiative (WHI) supports findings from previous studies of estrogen and osteoporosis. (1) In this large, population-based primary prevention trial, the rate of total osteoporotic fractures among women with unknown baseline bone density who were randomized to treatment with estrogen and progestin was significantly reduc compared with women randomized to receive placebo (adjusted hazard ratio: 077; 95 percent confidence interval: 063 to 094) Hip and vertebral fracture rates also were reduc although these decreases were not statistically significant.

The WHI also demonstrated higher rates of cardiovascular issues and breast cancer among estrogen users in the trial. These breast cancer findings were consistent with findings from about previous studies. The cardiovascular findings were inconsistent with conclusions of several observational studies (2) that showed benefit yet more consistent with the findings of the Heart and Estrogen/progestin Replacement investigation follow-up randomized controlled trial, (3) which showed that hormone replacement did not abridge the risk of cardiovascular results in women with coronary heart disease.

The WHI report at hands a dilemma for clinicians and patients on offering stronger evidence that estrogen use is associated with the two benefit and harm in postmenopausal women in the general population. In light of this novel evidence, we must ask, "Does estrogen have a character in osteoporosis prevention and treatment?"

part in Prevention

A meta-analysis of 57 randomized controll trials of hormone therapy indicate a consistent bone-sparing effect at the lumbar spine, femoral neck and forearm, and a nonsignificant inclination toward reduced incidence of vertebral and nonvertebral fractures. (4) This evidence is not definitive. Prevention trials would ne to be true large and extend over 20 to 30 years to clarify who might benefit from therapy, when preventive therapy should be initiated, and for what cause long it should continue.

Observational data from the cogitation of Osteoporotic Fractures, (5) a large, prospective cohort of U women 65 years of age and older move that women should begin taking estrogen at menopause and continue indefinitely to be shielded against fractures. Once estrogen use is discontinued, the beneficial force diminishes to the level of the never-user. plane among women who take estrogen continuously beginning at menopause, older women still commonly sustain fractures, although at lower rates than non-estrogen-users. (6) Prevention trials of bisphosphonates and selective estrogen receptor modulators report improved bone density moreover not reduced fracture rates. (7-9)

to what extent does this evidence apply to patient care? The character of estrogen in fracture prevention has been diminished because of potential harms. The U Preventive Services Task Force (USPSTF) freshly recommended against the routine use of estrogen and progestin for the prevention of chronic conditions in postmenopausal women (grade D recommendation) and conclud that the evidence was insufficient to make acceptable for or against the use of unopposed estrogen for chronic disease prevention (grade I recommendation). (10) The Task Force encourages clinicians to admonition patients about other strategies for preventing osteoporosis and fractures.

To date, no studies have been waysed that compare the effects of different prevention strategies. Randomized, head-to-head comparisons of medical and nonmedical interventions would improve our present approach to osteoporosis prevention. A limited number of studies of nonmedical interventions, as it is as exercise, adequate intake of calcium and vitamin D (11) and the use of hip protectors in frail patients, refer to benefit. (12) A recent analysis of data from the Nurses' Health application of mind indicated that walking for at least four hours by means of week was associated with a 41 percent lower risk of hip fracture. (13) on a levels of fracture risk in women who were not using estrogen approximated that of estrogen users as exercise flushs increased.

Role in Treatment

The U victuals and Drug Administration has approved the use of estrogen for prevention, still not treatment, of postmenopausal osteoporosis. No large treatment trials have examined the purport of estrogen in reducing fractures in women with existing osteoporosis.

Trials of bisphosphonates enlisted predominantly older women and showed that women with the lowest bone density were the most numerous likely to benefit. (14) In these women risks for vertebral and nonvertebral fractures were reduc by way of 40 to 50 percent compared with risks in placebo clumps (7,8) Mean T scores in women in bisphosphonate treatment trials ranged from -22 to -33 (the diagnostic gate for osteoporosis is a T score of -25) Because no fracture benefit was reported in women with mildly reduc bone density in these trials, identification of treatment candidates with bone density testing is important before initiating therapy.