Any Amount of Estrogen Has an Effect on Bone
Source: Ettinger B, et al. J Clin Endocrinol Metab 1998;83: 2239-2243.
Ettinger and colleagues from the study of Osteoporotic Fractures Research Group measured serum estradiols with extremely sensitive assays and compared the results with bone density measurements and the incidence of vertebral deformities in 247 elderly women. Low levels of estradiol were found to exert a protective effect. Women with estradiol levels as low as 10-25 pg/mL had greater bone densities and fewer vertebral changes than women with levels below 5 pg/mL. This protective effect was exerted at all sites measured: hip, calcaneus, radius, and spine. Thus, Ettinger et al conclude that even very low physiologic levels of estradiol can provide some protection for bone.
Comment by Leon Speroff, MD
This report and several others still in press from the Study of Osteoporotic Fractures challenges the conventional wisdom that an estradiol level of about 50 pg/mL is required to protect bone. These new data indicate that there is a linear relationship with the estradiol level in a woman and the degree of protection against fracture due to osteoporosis. This relationship exists even when adjusted for body weight. It is possible that some estrogen actions are more affected at lower estrogen concentrations, or all may be slightly affected. These actions include direct suppression of bone remodeling, increased renal calcium conservation, increased production of 1.25dihydroxyvitamin D, and increased intestinal calcium absorption.
Even though we can now reassure patients that any amount of estrogen exerts a beneficial effect on bone, important questions remain. Below the standard doses of estrogen (that produces an estradiol blood level that is at least 50 pg/mL), are there more non-responders? Does it require standard doses to achieve maximal responses (at this point, we believe it does)? Does this linear relationship (in essence a dose-response curve) continue at higher dose (we do not believe this is true)?
About one year ago, I was puzzled by the report indicating that a positive effect on bone was observed even with the use of the vaginal ring that delivers a very small amount of estradiol with minimal systemic absorption (J Am Obstet Gynecol 1997;177:115-119). These studies now make that report believable-any amount of estrogen has an effect. However, this doesn't change the clinical recommendation that the best protection requires the standard doses of estrogen we use for postmenopausal hormone therapy. Patients who insist on using lower doses should be assessed for bone response by either urinary markers or bone density measurements.
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