Correspondence

Treatment of Postmenopausal Osteoporosis

N Engl J Med 1998; 339:202-203July 16, 1998

Article

To the Editor:

In his review of the treatment of osteoporosis in postmenopausal women (March 12 issue),1 Eastell says that the response to therapy should be evaluated by performing serial measurements of bone density. Serial measurements of bone density appear reasonable, because one would like to know that the therapy is causing the desired increase in bone density. But are there data from prospective trials demonstrating that adjustment of antiresorptive therapy based on bone-density measurements reduces fracture rates? Another argument in favor of serial measurement of bone density is that demonstrating the effectiveness of drug therapy on bone density improves compliance. However, in a study of 400 postmenopausal women surveyed eight months after initial measurement of bone density, the rate of noncompliance with estrogen-replacement therapy was high, even though the patients knew their bone density was low.2 Do serial measurements of bone density indeed improve compliance?

Eastell lists several nonskeletal benefits of estrogen-replacement therapy, but does not mention that it reduces mortality from all causes.3,4 Given this point and the lack of data on the efficacy of combining estrogen with other antiresorptive drugs, are serial measurements of bone density of any value in women already taking estrogen?

Arthur C. Liu, M.D.
Palo Alto Medical Foundation, Los Altos, CA 94022

4 References

1. 1

   Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med 1998;338:736-746
   Full Text | Web of Science | Medline

2. 2

   Ryan PJ, Harrison R, Blake GM, Fogelman I. Compliance with hormone replacement therapy (HRT) after screening for postmenopausal osteoporosis. Br J Obstet Gynaecol 1992;99:325-328
   CrossRef | Medline

3. 3

   Ettinger B, Friedman GD, Bush T, Quesenberry CP Jr. Reduced mortality associated with long-term postmenopausal estrogen therapy. Obstet Gynecol 1996;87:6-12
   CrossRef | Web of Science | Medline

4. 4

   Grodstein F, Stampfer MJ, Colditz GA, et al. Postmenopausal hormone therapy and mortality. N Engl J Med 1997;336:1769-1775
   Full Text | Web of Science | Medline

To the Editor:

Eastell discusses a study by Tilyard et al.1 of the effects of calcitriol as compared with calcium on the rate of new vertebral fractures in women with previous vertebral fractures. Calcitriol reduced the rate of vertebral fractures by a factor of three (in women who had had five or fewer fractures at base line) and reduced the rate of peripheral fractures by a factor of two, as compared with calcium. In Table 4 of the article, Eastell notes that calcitriol led to a decrease in fractures, but in the text he states that calcitriol had no effect on the rate of vertebral fractures and that calcium increased the rate of vertebral fractures. Given that Tilyard et al. did not report data on fracture rates before treatment and that calcium may have a weak beneficial effect on bone strength, the former interpretation may be the more appropriate.

Mark Lloyd, M.B., Ch.B.
St. Thomas' Hospital, London SE1 7EH, United Kingdom

1 References

1. 1

   Tilyard MW, Spears GFS, Thomson J, Dovey S. Treatment of postmenopausal osteoporosis with calcitriol or calcium. N Engl J Med 1992;326:357-362
   Full Text | Web of Science | Medline

Author/Editor Response

Dr. Eastell replies:

To the Editor: Liu raises three important questions about the use of bone densitometry to monitor treatment of osteoporosis. First, is the risk of fracture altered by a change in therapy (type or dose of medication) in a patient who does not have a response to the initial therapy? There are no data on this question; indeed, there are no data showing that the magnitude of the change in bone density during any treatment is related to the change in the risk of fracture. However, we have learned from practical experience that some patients take their medication incorrectly (e.g., they take a bisphosphonate with food) or have an underlying disease that results in bone loss despite therapy (e.g., thyrotoxicosis). Monitoring is valuable for identifying these patients.

Second, do serial measurements of bone density improve compliance with therapy? Again, there are no data that support this approach, even though it is likely to be true. A low bone mineral density measurement does encourage women to start estrogen therapy1 and to take other measures to prevent fracture,2 but we do not know the effect of subsequent measurements on compliance with therapy.

Third, why measure bone density if women receive many other benefits from estrogen therapy? I recommend measuring bone density only if the primary reason for the therapy is osteoporosis.

Lloyd suggests that the study of calcitriol as compared with calcium in women with postmenopausal osteoporosis3 showed a clear reduction in the risk of fracture. In that study, the reduction in the number of women with peripheral fractures in the calcitriol group was of borderline statistical significance. The numbers of women with new fractures in the calcium group during years 1, 2, and 3 were 17, 30, and 44, respectively, as compared with 14, 14, and 12, respectively, in the calcitriol group. The calcitriol group had fewer vertebral fractures, but the most striking finding in this study was the increase in the fracture rate in the calcium group, which makes it difficult to draw clear conclusions from the study.

Richard Eastell, M.D.
University of Sheffield, Sheffield S5 7AU, United Kingdom

3 References

1. 1

   Torgerson DJ, Thomas RE, Campbell MK, Reid DM. Randomized trial of osteoporosis screening: use of hormone replacement therapy and quality-of-life results. Arch Intern Med 1997;157:2121-2125
   CrossRef | Web of Science | Medline

2. 2

   Rubin SM, Cummings SR. Results of bone densitometry affect women's decisions about taking measures to prevent fractures. Ann Intern Med 1992;116:990-995
   Web of Science | Medline

3. 3

   Tilyard MW, Spears GFS, Thomson J, Dovey S. Treatment of postmenopausal osteoporosis with calcitriol or calcium. N Engl J Med 1992;326:357-362
   Full Text | Web of Science | Medline

Citing Articles (1)

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