Bisphosphonate therapy has been studied in small groups of women with disordered eating and osteoporosis. In one small clinical trial, 32 women with anorexia nervosa were given 10 mg alendronate daily or placebo for 1 year. Alendronate treatment was associated with a nonsignificant increase in femoral neck and spine bone density of 4.4% and 3.5%, respectively. Weight gain was an important predictor of improved BMD.21
The young woman in this case probably should not be prescribed alendronate. The FDA drug information for alendronate warns: “Safety and efficacy have not been established in pregnant women. Animal studies have shown delays in delivery and fetal/neonatal death (secondary to hypocalcemia). Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. Based on limited case reports with pamidronate, serum calcium levels in the newborn may be altered if administered during pregnancy.”
Although there are minimal data in humans that alendronate will have adverse effects on fetal bone development and function, findings in rats treated with very high doses of alendronate leave some concern about the potential risk for human fetuses.
The young woman in this case may want to have children in the near future. Bisphosphonates may be incorporated into the bone and have a long residual half-life, resulting in potential exposure of the fetus to low doses of the compound. Very few malformations in human pregnancy have been reported after treatment with bisphosphonates.22 Based on a cautious approach to this situation, however, I would recommend that this woman of reproductive age who plans future child-bearing probably should not be treated with alendronate.
CASE 2 MANAGEMENT
The female athlete triad
Estrogen-progestin ring and mental health evaluation
Many women with the female athlete triad do not meet formal criteria for anorexia nervosa, but have disordered eating patterns. Questions in the medical history such as “Do you think you should be dieting?”23 may help initiate a conversation about eating practices and attitudes. The woman in Case 2 was screened for clinical depression. She reported that she was not blue over the past 2 weeks, but noted that she worried that she measured too much of her self-worth by her body image—a diagnostic criterion for anorexia nervosa. After extensive counseling, she was willing to start an estrogen-progestin contraceptive ring. She was also referred to a mental health provider for further evaluation.
CASE 3 HISTORY
Glucocorticoid-related bone loss
A 35-year-old woman with rheumatoid arthritis
This woman (G1P1) has been treated with various doses of prednisone over the past 10 years. Currently she is taking prednisone, 20 mg daily. She is oligomenorrheic with menstrual cycles every 45 days. She has undergone both bilateral hip replacement and bilateral tubal ligation. Her BMI is 20.5 kg/m2. DXA shows osteoporosis at her lumbar spine.
Glucocorticoids are a common cause of osteoporosis in young women. These drugs inhibit osteoblast activity and increase osteoclast activity. They also increase renal calcium excretion and decrease intestinal calcium absorption and adrenal androgen production. A meta-analysis of 89 publications reported that chronic glucocorticoid use increased both the risk of osteoporosis and clinically significant fractures.24 Chronic glucocorticoid treatment was associated with an increased relative risk of vertebral and hip fracture of 2.60 (95% confidence interval [CI], 2.31–2.92) and 1.61 (95% CI, 1.47–1.76), respectively. Daily doses of prednisone 10 mg or greater were clearly associated with an increased risk of fracture. The onset of the increased fracture risk occurred within 3 months of initiating therapy.
Treatment
Treatment for this woman should include:
- vitamin D and calcium supplementation,25 and
- consideration of estrogen-progestin therapy26 and/or bisphosphonates.
PTH analogue treatment could also be utilized if neither estrogen replacement nor bisphosphonate treatment were possible.27 If the patient could discontinue the glucocorticoid therapy and begin another treatment for rheumatoid arthritis, such as etanercept (Enbrel), her BMD might improve.
Bisphosphonates are a first-line option, since she has had a bilateral tubal ligation and is at very low risk for a future pregnancy. Many clinical trials demonstrate the efficacy of bisphosphonates in this clinical situation. Bisphosphonates are approved by the FDA for the prevention and treatment of osteoporosis in women receiving glucocorticoids.
In a study of alendronate, the rate of new vertebral fractures was 0.7% in the alendronate group and 6.8% in the placebo group.28 Subjects who were taking at least 7.5 mg prednisone daily were randomized to receive alendronate, 5 or 10 mg daily, or a placebo. After 2 years of treatment, there was a 3.7% increase in lumbar spine BMD in the group treated with alendronate, 10 mg daily, and a 0.8% loss in bone denisty in the placebo group (FIGURE 3).