Hormones and Hip Fractures: Who's At Risk?

Frederick R. Jelovsek MD

Although postmenopausal hormone replacement therapy is recommended for women in order to prevent osteoporosis and bone fractures, the truth is that many women cannot take or choose not to take hormone replacement. Do we just declare those women at high risk and do nothing further or can we further classify risk within that group of women, say over 65 years of age who are not taking any estrogens?

A recent article, Cummings SR et al.: Endogenous hormones and the risk of hip and vertebral fractures among older women. N Engl J Med 1998;339:733-8., looked at exactly this question. They recruited women 65 years of age and older who were not using any hormonal therapy. They didn't accept anyone with known hip problems or any fractures. They recorded whether they were taking any calcium or vitamin D supplements and what their dietary and smoking habits were. Baseline blood measurements were obtained for estradiol, estrone, sex hormone binding globulin (SHBG), free testosterone, Vitamin D (25OH and 1,25OH vitamin D) and parathyroid hormone.

The women were followed for approximately 10 years. As compared with controls, women who had hip or vertebral fractures were lighter and had lower bone density at the start of the project. The fractures occurred at 3.9 years, on the average, after the start of the project. Even when corrections were made for different weights, smoking, taking supplements and bone density at the start, the authors found some interesting hormonal relationships.

• One third of the women had undetectable estradiol levels (less than 5 pg/ml) and had a risk ratio of 2.5 for hip and vertebral fractures compared to women who had more than 5 pg/ml estradiol levels
• Three-fourths of the women had high SHBG levels (greater than 1.0ug/dl ) which binds estrogens and makes even less hormone available and had risk ratios of 2.3-2.7 for hip and vertebral fractures
• Women who had both undetectable estradiol levels and elevated SHBG levels had risk ratios of 6.9-7.9 for fractures even when corrected for weight
• Women who had low vitamin D levels (less than 24 pg/ml) also had an increased risk for hip fractures of 2.1
• There was no association between low parathyroid hormone levels and fractures
• There was no association with testosterone levels with fractures independent of the associated estradiol level

The significance of these findings is twofold:

1. Very low levels of estrogen supplement can elevate serum levels above 5 pg/ml. Standard estrogen doses of 0.625 mg conjugated estrogen (CE) equivalent raises serum estrogen to 40 pg/ml on the average. Therefore even supplements below 0.3mg of CE equivalent might be enough to prevent bone fractures in older women.
2. Sex hormone binding globulin (SHBG) is not often measured, but this would be an instance where it's measurement could be useful in risk prediction. There are medicines that can raise SHBG such as spironolactone.