BMD Assessment and Preventive Measures
Although the risk of CIO and increased fracture risk is well cited, only 62% of surveyed physicians in one study12 rated osteoporosis as one of the 3 most significant side effects discussed with patients taking high-dose steroids, and 2 cohort studies13,14 found only a 5.6% and a 14% prescription rate for preventative medications when patients were prescribed glucocorticoids. Perhaps this mediocre reaction from primary care providers results from a shortage of clinical evidence to support preventive measures. Ideally, clinical decisions should be made using data concerning fracture risk reduction. Unfortunately, studies have not been sufficiently powered to assess fracture risk reduction, making it difficult to base therapeutic decisions on patient-oriented outcomes. The primary outcome assessed is the difference in percentage change from baseline in the BMD of the lumbar spine, femoral neck, and femoral trochanter between the treatment and placebo groups. It is important to recognize that the percentage change in BMD is a surrogate marker and has not been shown to directly correlate with decreased fracture risk. Other factors, such as bone strength and rate of turnover, may also contribute to fragility.
A BMD taken at one site, such as vertebrae or hip, correlates with risk of fracture at other sites; the best predictor of fracture, however, seems to be a BMD at the site in question.15 Patients at risk for CIO may have a comparatively higher risk of fracture at a given bone density than patients at risk for osteoporosis from other causes.16 A decrease in BMD of 1 SD below the mean of that of healthy adults aged 35 years will lead to a 1.5-fold to 3-fold increase in fracture risk,15 but this same bone density measure in the same woman taking corticosteroids may underestimate her risk of fracture.17
Presently the gold standard for BMD measurement is dual energy X-ray absorptiometry (DEXA). At this time, anteroposterior DEXA is recommended of both the lumbar spine and femoral neck for patients at risk for CIO.17,18 If only one site can be obtained, the recommended site depends on the age of the patient. The lumbar spine is the site of choice for men and women younger than 60 years, while the femoral neck should be evaluated in men and women 60 years and older.18
Practice Guidelines
Two current sets of guidelines on the management of CIO are presently available: the recommendations of the 1998 United Kingdom (UK) Consensus Group17 and the 1996 American College of Rheumatology (ACR) Task Force on Osteoporosis Guidelines.18 Prevention and treatment options include risk factor modification (smoking cessation, fall prevention, and so forth) adequate calcium (1500 mg/day) and vitamin D3 intake (800 IU/day), hormone replacement when appropriate, bisphosphonates, and calcitonin (Figure). Other less-proven therapies such as thiazide diuretics, anabolic steroids, and fluoride are considered.
The ACR and UK guidelines differ considerably with respect to use of bisphosphonates in patients receiving long-term high-dose glucocorticoid therapy. The ACR task force recommends bisphosphonates only in patients with contraindications to hormone replacement therapy (HRT) or established osteoporosis.18 This class is not recommended in premenopausal women or men age younger than 50 years because of the lack of long-term safety data. The newer UK publication emphasizes that of all therapeutic options bisphosphonates have the most compelling BMD data and should be considered first-line treatment.17
Since the UK guidelines were published, 8 trials showing beneficial effects of bisphosphonates in the treatment of CIO have been published or presented at major medical meetings. Encouraging clinical data have resulted in alendronate and risedronate receiving United States Food and Drug Administration (FDA) approval for the indication of CIO. Our objective was to provide an evidence-based perspective of the use of bisphosphonates in corticosteroid-treated patients.
Methods
Literature searches were conducted independently by 2 authors using the MEDLINE, CURRENT CONTENTS, and HEALTHSTAR electronic databases to identify studies of bisphosphonates in the prevention or treatment of corticosteroid-induced osteoporosis. Medical subject headings and search terms included “bisphosphonates,” “diphosphonates,” “glucocorticoids,” “steroids,” and “osteoporosis.” We examined bibliographies of selected citations and review articles to obtain additional references. Unpublished information was obtained by hand-searching abstracts from recent meetings (1998) of the American Society for Bone and Mineral Research and the ACR. Studies were included if the design was randomized and controlled and if they evaluated the use of oral bisphosphonates in adults. Obtaining BMD results using the gold standard of measurement—central DEXA—was also necessary for study inclusion. Two authors assessed the methodologic quality of the trials using the 5-point criteria developed by Jadad and colleagues.19
Results
Bisphosphonates have been studied for use in CIO for more than a decade. Our search yielded a total of 34 citations of studies researching bisphosphonates for this indication. Twenty-one of these20-40 were excluded for not meeting the specified inclusion criteria. The 13 studies included in our analysis41-53 addressed the use of bisphosphonates in the prevention and treatment of corticosteroid-induced osteoporosis. Each bisphosphonate had the following number of citations and total number of patients in all studies combined: risedronate, 3 (n=638); etidronate, 8 (n=522); alendronate, 1 (n=477); and clodronate, 1 (n=74). The demographics pertaining to each study are summarized in [Table 1].