Correspondence
Intermittent Etidronate and Corticosteroid-Induced Osteoporosis
N Engl J Med 1997; 337:1921December 25, 1997
- Article
To the Editor:
The study by Adachi et al. (Aug. 7 issue)1 of intermittent etidronate therapy for the prevention of corticosteroid-induced osteoporosis addresses one of the greatest challenges in rheumatology: how to harness the benefit of the most potent antiinflammatory drug available while lessening its side effects. Unfortunately, the study has several problems.
There was a disproportionate number of patients with rheumatoid arthritis in the placebo group (21, vs. 13 in the etidronate group). Patients with this disorder are known to have an increased risk of fractures that is independent of corticosteroid therapy.2 A major finding of the study was the 85 percent reduction in the proportion of postmenopausal women with new vertebral fractures in the etidronate group (1 of 31 women, vs. 7 of 32 women in the placebo group). It is likely that most of the patients with rheumatoid arthritis were postmenopausal women, and therefore, the beneficial effect of etidronate on vertebral fractures simply reflects the excess of patients with rheumatoid arthritis in the placebo group. Furthermore, the base-line lumbar-spine bone density in the postmenopausal women in the placebo group was nearly 1 SD below the mean of the etidronate group, providing further evidence of their greater vulnerability to fracture.
The choice of a calcium supplement of only 500 mg daily (and no supplement of vitamin D) was questionable; it was, interestingly, only one third of the dose mentioned in the accompanying editorial.3 Also disturbing was the greater frequency of vertebral fractures among the men in the etidronate group (4 of 19 men, vs. 3 of 25 men in the placebo group). Etidronate has been reported to increase the risk of fractures by interfering with bone mineralization, although at higher doses.4
It seems premature to conclude from these results that etidronate is effective and safe in preventing osteoporotic fractures in patients treated with corticosteroids.
4 ReferencesEddys Disla, M.D.
Beatriz Tamayo, M.D.
Ahmed Fahmy, M.D.
Cabrini Medical Center, New York, NY 100031
Adachi JD ,Bensen WG ,Brown J , et al. Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N Engl J Med 1997;337:382-387
Full Text | Web of Science | Medline2
Michel BA ,Bloch DA ,Wolfe F ,Fries JF . Fractures in rheumatoid arthritis: an evaluation of associated risk factors. J Rheumatol 1993;20:1666-1669
Web of Science | Medline3
Reid IR . Preventing glucocorticoid-induced osteoporosis. N Engl J Med 1997;337:420-421
Full Text | Web of Science | Medline4
Adami S ,Zamberlan N . Adverse effects of bisphosphonates: a comparative review. Drug Saf 1996;14:158-170
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: We agree that patients with rheumatoid arthritis are predisposed to osteoporosis. Our control population, however, was one that required corticosteroid therapy. To our knowledge there is no evidence that patients with other disorders requiring corticosteroids are any less prone to fractures than those with rheumatoid arthritis. In our study, only one patient with rheumatoid arthritis in the placebo group had a new vertebral fracture, whereas there were two in the etidronate group.
In spite of randomization, bone mineral density at base line in the postmenopausal women was lower in the placebo group than in the etidronate group. In a post hoc logistic-regression analysis of the incidence of fracture in postmenopausal women, in which bone mineral density of the lumbar spine (T-score) was fitted as a covariate in addition to treatment group, the statistical significance of the treatment effect was reduced (P = 0.19). The study was not designed to demonstrate the effect of etidronate on the incidence of fracture.
As is discussed in Dr. Reid's editorial, the evidence that vitamin D is beneficial in the prevention of bone loss in corticosteroid-treated patients is controversial. In our study all patients had normal serum 25-hydroxyvitamin D concentrations at base line. We agree that calcium may be important in the prevention of corticosteroid-induced bone loss. Dr. Reid recommended a total daily calcium intake of 1500 mg. We expected that the combination of dietary calcium intake and supplementation would result in an average daily intake of more than 1000 mg per day in our study subjects.
The greater frequency of fractures in etidronate-treated men represents only one more fracture in the etidronate group than in the placebo group. The small numbers preclude any meaningful interpretation. The statement about defective mineralization is misleading because it relates to patients with Paget's disease of bone.1 Generalized osteomalacia does not occur in patients with osteoporosis who are receiving cyclical etidronate therapy, and a number of studies have confirmed the finding of a reduction in the vertebral-fracture rate.2,3
3 ReferencesJonathan D. Adachi, M.D.
St. Joseph's Hospital, Hamilton, ON L8N 4A6, CanadaSimon Pack, Ph.D.
Arkadi A. Chines, M.D.
Procter & Gamble Pharmaceuticals, Cincinnati, OH 452411
Adami S ,Zamberlan N . Adverse effects of bisphosphonates: a comparative review. Drug Saf 1996;14:158-170
CrossRef | Web of Science | Medline2
Harris ST ,Watts NB ,Jackson RD , et al. Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three years of blinded therapy followed by one year of open therapy. Am J Med 1993;95:557-567
CrossRef | Web of Science | Medline3
Storm T ,Thamsborg G ,Steiniche T ,Genant HK ,Sorensen OH . Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 1990;322:1265-1271
Full Text | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Pauline Boulos, George Ioannidis, Jonathan D. Adachi. (2000) Glucocorticoid-induced osteoporosis. Current Rheumatology Reports 2:1, 53-61
CrossRef
