Bone loss in young women
Whether it is depleted by GnRH agonists, athleticism, or glucocorticoids, swift intervention can often restore BMD
CASE 2 HISTORY
The female athlete triad
A college-age dancer with an eating disorder
A 21-year-old elite ballet dancer, height 5’4” and weight 104 lb (BMI 17.8 kg/m2), presents with a history of a stress fracture of her foot. Besides being amenorrheic, she is on a high-fiber macrobiotic diet. DXA measurement demonstrates a Z score consistent with osteoporosis. She refuses to take estrogen-progestin contraceptives because she claims they impair her ability to train for her dance performances. She wonders if she should start alendronate therapy.
The female athlete triad is the combination of amenorrhea, disordered eating, and osteoporosis.8 In young female athletes, exercise and disordered eating may cause menstrual irregularity, and either disordered eating or menstrual irregularity, or both, may cause decreased BMD.9
Strenuous exercise has divergent effects on trabecular and cortical bone. By causing hypoestrogenism, strenuous exercise decreases bone density at cortical sites (vertebral spine). However, the weight-bearing exercise itself can lead to an increase in bone density at weight-bearing sites.10
Many elite athletes with the female athlete triad do not want to alter the intensity of their training or their diet, which might result in weight gain and resolution of the osteoporosis. Some elite athletes report that they do not want to take standard birth control pills because they believe the pill may impair their training and peak competitive performance. The clinician is often challenged by these strongly held beliefs to identify a treatment plan that will reverse the bone loss.
Is systemic disease involved? Occasionally, systemic disease causes or contributes to low bone mass in a young woman. Laboratory tests may help in screening some women for these diseases (TABLE 2).
FIGURE 2 Aim for the “sweet spot” in estradiol concentrations
According to the estrogen-threshold hypothesis, there is a range, or “sweet spot,” of estradiol concentrations where endometriosis lesion activity is suppressed and vasomotor symptoms and bone loss are not excessive. In humans, estrogen concentrations in the range of 30 pg/mL appear to be associated with decreased endometriosis pain and minimal degrees of bone loss. At estradiol levels of less than 10 pg/mL, bone loss is markedly accelerated.6 Reprinted from Barbieri RL. Hormone treatment of endometriosis: the estrogen threshold hypothesis. Am J Obstet Gynecol. 1992;166:740–745. ©1992 with permission from Elsevier.TABLE 1
Effective steroid hormone add-back regimens
Regimens that suppressed vasomotor symptoms and bone loss associated with long-term GnRH analogue use
| INVESTIGATOR | RANDOMIZATION SCHEME | STEROID HORMONE ADD-BACK REGIMEN |
|---|---|---|
| Howell et al5 | 50 women with endometriosis and pelvic pain randomized to GnRH agonist alone or GnRH agonist plus add-back regimen | Transdermal estradiol, 25 μg/d, plus oral medroxyprogesterone acetate, 2.5 mg/d |
| Lupron Add-Back Study Group4 | 201 women with endometriosis and pelvic pain randomized to GnRH agonist plus placebo or GnRH agonist plus 1 of 3 add-back regimens | Oral norethindrone acetate, 5 mg/d or Oral conjugated equine estrogen, 0.625 mg/d plus norethindrone acetate, 5 mg/d or Oral conjugated equine estrogen, 1.25 mg/d plus norethindrone, 5 mg/d |
TABLE 2
Screening for secondary causes of bone loss
| The following serum tests may be useful in screening women with osteoporosis for secondary causes of disordered bone metabolism |
| Calcium and albumin |
| Phosphorus |
| 25-Hydroxy vitamin D |
| Thyroid-stimulating hormone |
| Alkaline phosphatase |
| Creatinine |
Treatment of elite athletes
Peak bone mass depends on many factors, including genetics11; ovarian estrogen production12; adequate intake of calories, protein, vitamin D, and calcium9; exercise13; and achievement of target height and weight.14 When combinations of risk factors for osteoporosis are present, such as an eating disorder plus amenorrhea, correction of only one factor may not result in improved BMD.15
There are few clinical trials of the treatment of osteoporosis in women with the female athlete triad or an eating disorder. Treatment recommendations are largely based on clinical experience. If the woman resists lifestyle and dietary changes that will result in weight gain, other treatment recommendations to pursue include:
- vitamin D and calcium supplements,
- increased dietary protein,
- weight training,16 and
- smoking cessation.
Psychological counseling may help many young women with disordered eating.
Hormonal therapy has not been documented to reliably increase bone density in young amenorrheic women with an eating disorder. In 3 clinical trials, the effect of estrogen replacement on bone density in such patients was negligible or minimal.17-19 Given our understanding of the positive effect of estrogen on spinal BMD, it is difficult to understand these findings. Two possibilities are that compliance with estrogen replacement was modest because the women did not want a return of menses, or an insufficient dose of estrogen was prescribed. Another is that being underweight blocks the positive effect of estrogen on bone density. One small clinical trial did report that treatment of hypoestrogenic women with an estrogen-progestin contraceptive containing 35 μg of ethinyl estradiol resulted in a significant increase in lumbar spine BMD (5.4%) and a nonsignificant increase in femur BMD (3.6%).20 A logical recommendation, based on clinical experience, would be to prescribe an estrogen-progestin contraceptive to this woman to help preserve or improve her bone density.
