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Authors’ Response: Alendronate in Anorexia Nervosa

Division of Adolescent Medicine, Schneider Children’s Hospital, New Hyde Park, New York 11040

Address correspondence to: Neville H. Golden, Division of Adolescent Medicine, Schneider Children’s Hospital, 410 Lakeville Road, Suite 108, New Hyde Park, New York 11040.

To the editor:

We thank Dr. Ott for her thoughtful comments (1). We had stated that "to our knowledge there were no reports of adverse effects of bisphosphonates on the fetuses of humans or animals." We acknowledge that animals administered bisphosphonates during pregnancy at daily doses approximately 10 times the recommended human therapeutic dose developed maternal toxicity, death of embryos, and growth retardation of the fetuses (2, 3, 4). The use of bisphosphonates during pregnancy is clearly contraindicated.

There is very little information on infants born to mothers who took bisphosphonates before pregnancy. In the few published case reports, there have been no documented cases of teratogenicity or major skeletal defects found. As Dr. Ott stated, a recent case report described two women with osteogenesis imperfecta (OI) who were treated with pamidronate before conception (5). One infant developed transient hypocalcemia, probably attributed to the bisphosphonates, and the other was born with bilateral talipes equinovarus. Both infants had OI. Although the incidence of talipes equinovarus in OI is not known, the authors had treated another patient with both conditions in whom there had been no previous exposure to bisphosphonates. However, the association between talipes equinovarus and previous bisphosphonate treatment could not be excluded.

In our study of young women with anorexia nervosa, body weight was the most important determinant of bone density (6). We also found that despite weight restoration, at the end of the study period, only 17% of subjects had a BMD of the spine in the normal range for age. Weight restoration alone is not sufficient to restore BMD to normal levels, and because of the increased fracture risk, there is a compelling need to find a safe and effective treatment to increase BMD in this condition.

We do not recommend the widespread use of alendronate for the treatment of osteopenia in anorexia nervosa. What we do advocate is careful research on the long-term safety and efficacy of the bisphosphonates for this condition. Newer preparations are being developed with shorter terminal half-lives that may reduce the potential for future adverse events in the offspring of treated women. If it is ultimately found to be safe and effective, the decision to use such a medication will still depend on a very careful risk-benefit assessment by the physician and the patient.

Received June 28, 2005.

References

1. Ott SM 2005 Letter re: Alendronate in anorexia nervosa. J Clin Endocrinol Metab 90:5508 (Letter)[Free Full Text]
2. Graepel P, Bentley P, Fritz H, Miyamoto M, Slater SR 1992 Reproduction toxicity studies with pamidronate. Arzneimittelforschung 42:654–667[Medline]
3. Minsker DH, Manson JP, Peter CP 1993 Effects of the bisphosphonate, alendronate, on parturition in the rat. Toxicol Appl Pharmacol 121:217–223[CrossRef][Medline]
4. Patlas N, Golomb G, Yaffe P, Pinto T, Breuer E, Ornoy A 1999 Transplacental effects of bisphosphonates on fetal skeletal ossification and mineralization in rats. Teratology 60:68–73[CrossRef][Medline]
5. Munns CF, Rauch F, Ward L, Glorieux FH 2004 Maternal and fetal outcome after long-term pamidronate treatment before conception: a report of two cases. J Bone Miner Res 19:1742–1745[CrossRef][Medline]
6. Golden NH, Iglesias EA, Jacobson MS, Carey D, Meyer W, Schebendach J, Hertz, Shenker IR 2005 Alendronate for the treatment of osteopenia in anorexia nervosa: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab 90:3179–3185[Abstract/Free Full Text]

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				N. H. Golden Authors' Response: Alendronate in Anorexia Nervosa J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5508 - 5508. [Full Text] [PDF]

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