Correspondence
Teriparatide or Alendronate in Glucocorticoid-Induced Osteoporosis
N Engl J Med 2008; 358:1302-1304March 20, 2008
- Article
To the Editor:
The trial reported by Saag and colleagues (Nov. 15 issue)1 compared teriparatide (Forteo) with alendronate (Fosamax) in patients with glucocorticoid-induced osteoporosis. The study enrolled patients who had received long-term treatment with glucocorticoids, defined as a mean daily dose of 5 mg or more of prednisone or its equivalent for 3 or more consecutive months preceding the screening visit.
This exposure constitutes a reasonable risk.1 However, we believe that it is not sufficient to make a proper diagnosis of glucocorticoid-induced osteoporosis in the absence of an objective assessment of the bone mineral density before the initiation of treatment with glucocorticoids in patients with underlying chronic conditions that in themselves could cause osteoporosis — for example, rheumatoid arthritis and inflammatory bowel diseases.2,3 The osteoporosis in such patients might be related to the underlying disorder.
More important, the authors report the dose of prednisone before the initiation of the study, but no mention is made of the exposure during the 18-month period of the study. In the absence of data about the cumulative exposure of the two groups to glucocorticoids, a reliable comparison cannot be made.
3 ReferencesCarlo M. Rossi, B.S.
Gabriele Di Comite, M.D.
Università Vita-Salute San Raffaele, 20132 Milan, Italy
dicomite.gabriele@hsr. it 1
Saag KG ,Shane E ,Boonen S , et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med 2007;357:2028-2039
Full Text | Web of Science | Medline2
O'Dell JR . Therapeutic strategies for rheumatoid arthritis. N Engl J Med 2004;350:2591-2602
Full Text | Web of Science | Medline3
Podolsky DK . Inflammatory bowel disease. N Engl J Med 2002;347:417-429
Full Text | Web of Science | Medline
To the Editor:
In their 18-month, randomized, double-blind, controlled trial, Saag et al. note that teriparatide was significantly better than alendronate in the treatment of patients with glucocorticoid-induced osteoporosis. In the accompanying editorial, Sambrook1 advises, on the basis of this study, that teriparatide “be considered as a potential first-line therapy.”
However, both Saag et al. and Sambrook fail to mention the large difference in cost between these two drugs. In our local pharmacy, the cost of 1 month of alendronate (10 mg per day) is approximately $100 as compared with $900 for teriparatide (20 μg per day). Given this important disparity in cost, the need to administer teriparatide by injection, and the increased adverse events with the latter drug, albeit minor in nature, I wonder whether the case for teriparatide over alendronate in the secondary prevention of glucocorticoid-induced osteoporosis should be revisited.
1 ReferencesRichard R. Babb, M.D.
Palo Alto Clinic, Palo Alto, CA 94302
babbr@pamf.org 1
Sambrook PN . Anabolic therapy in glucocorticoid-induced osteoporosis. N Engl J Med 2007;357:2084-2086
Full Text | Web of Science | Medline
To the Editor:
Saag et al. discuss teriparatide, a parathyroid hormone analogue, for the treatment of glucocorticoid-induced osteoporosis. Although the authors excluded patients with “substantial renal impairment,” this was not defined. We would like to point out the potential hazards of treatment with parathyroid hormone in patients with impaired kidney function and kidney-transplant recipients with underlying, persistent secondary hyperparathyroidism.
Secondary hyperparathyroidism and renal osteodystrophy complicate chronic kidney disease. Osteoporosis may occur in such cases.1 Secondary hyperparathyroidism improves over a period of several months after kidney transplantation but may persist for much more than a year.2 Also, osteoporosis is a complication after kidney transplantation.3
No clinical studies have evaluated the safety and efficacy of teriparatide in patients with chronic kidney disease or kidney-transplant recipients who may already have elevated parathyroid hormone levels. Parathyroid hormone analogues can potentially worsen bone disease or cause hypercalcemia. In addition, skeletal resistance to parathyroid hormone in uremia raises doubts about the usefulness of teriparatide in chronic kidney disease.4
We suggest that before teriparatide is used for the treatment of osteoporosis from any cause, patients with chronic kidney disease and kidney-transplant recipients with secondary hyperparathyroidism be identified and excluded.
4 ReferencesUday S. Nori, M.D.
Anil K. Agarwal, M.D.
Brad H. Rovin, M.D.
Ohio State University Medical Center, Columbus, OH 43210
uday.nori@osumc. edu 1
Gal-Moscovici A ,Sprague SM . Osteoporosis and chronic kidney disease. Semin Dial 2007;20:423-430
CrossRef | Web of Science | Medline2
Julian BA ,Quarles LD ,Niemann KM . Musculoskeletal complications after renal transplantation: pathogenesis and treatment. Am J Kidney Dis 1992;19:99-120
Web of Science | Medline3
Cunningham J . Posttransplantation bone disease. Transplantation 2005;79:629-634
CrossRef | Web of Science | Medline4
Fukagawa M ,Kazama JJ ,Shigematsu T . Skeletal resistance to PTH as a basic abnormality underlying uremic bone diseases. Am J Kidney Dis 2001;38:Suppl 1:S152-S155
CrossRef | Web of Science | Medline
Author/Editor Response
Rossi and Di Comite question the contribution of underlying disease to the diagnosis of glucocorticoid-induced osteoporosis and ask whether exposure to glucocorticoids was similar between the treatment groups during our study. Although osteoporosis may occur with chronic inflammatory diseases, glucocorticoid exposure further increases this risk. Because patients using glucocorticoids have fractures at higher bone density than those not using glucocorticoids,1 international guidelines advocate pharmacologic therapy for patients receiving prolonged glucocorticoid treament, either without reference to bone density or at a bone-density threshold that is less stringent than the threshold used for other forms of osteoporosis.2,3 As compared with subjects in other studies of glucocorticoid-induced osteoporosis, subjects in our study had lower bone density and a higher prevalence of fracture. Although it is challenging to dissect the overlapping contributions of glucocorticoids and underlying disease to bone loss, bone density increased in patients receiving either alendronate or teriparatide, despite continued treatment with glucocorticoid doses that were similar to the initial mean dose of 10 mg per day of prednisone or its equivalent. At 18 months, the mean (±SD) glucocorticoid doses were 8.4±5.2 and 8.9±5.4 mg per day in the teriparatide and alendronate groups, respectively (P=0.63).
Babb questions the recommendation to use teriparatide, given the lower cost and greater convenience of alendronate. As is consistent with the approved indications in postmenopausal and male osteoporosis, we recommended that teriparatide be considered for patients at high risk for fracture who require sustained use of glucocorticoids and who have either osteoporosis or low bone mass with a prevalent fracture. In his editorial, Sambrook suggests the use of teriparatide as a first-line therapy. We believe that the gain in bone mineral density achieved with teriparatide may outweigh the potential drawbacks of higher cost and greater inconvenience in certain patients with or at risk for severe glucocorticoid-induced osteoporosis.
Nori and colleagues sound a cautionary note about the use of teriparatide in patients with chronic kidney disease and in kidney-transplant recipients with secondary hyperparathyroidism. Patients with kidney disease, defined as a serum creatinine level that, in the opinion of the investigator, indicated significant renal impairment or a creatinine clearance of 30 ml per minute or less were excluded from our trial. This is consistent with Food and Drug Administration labeling, which states that there is limited information available to evaluate the safety of teriparatide in patients with kidney disease. We concur that clinical evaluation and judgment are needed before prescribing any medication.
3 ReferencesKenneth G. Saag, M.D.
University of Alabama at Birmingham, Birmingham, AL 35294
ksaag@uab.edu Elizabeth Shane, M.D.
Columbia University College of Physicians and Surgeons, New York, NY 10032Robert Marcus, M.D.
Eli Lilly, Indianapolis, IN 462851
Van Staa TP ,Laan RF ,Barton IP ,Cohen S ,Reid DM ,Cooper C . Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 2003;48:3224-3229
CrossRef | Web of Science | Medline2
American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis
CrossRef | Web of Science | Medline3
Geusens PP ,de Nijs RN ,Lems WF , et al. Prevention of glucocorticoid osteoporosis: a consensus document of the Dutch Society for Rheumatology. Ann Rheum Dis 2004;63:324-325
CrossRef | Web of Science | Medline
