Teriparatide Increases BMD More Than Alendronate in Glucocorticoid-Induced Osteoporosis

November 19, 2007 — In patients with glucocorticoid-induced osteoporosis at high risk for fracture, bone mineral density (BMD) increased more in patients receiving teriparatide vs those receiving alendronate, according to the 18-month results of an ongoing, 36-month, randomized controlled trial reported in the November 15 issue of the New England Journal of Medicine.
"Bisphosphonate therapy is the current standard of care for the prevention and treatment of glucocorticoid-induced osteoporosis," write Kenneth G. Saag, MD, from the University of Alabama at Birmingham, and colleagues. "Studies of anabolic therapy in patients who are receiving long-term glucocorticoids and are at high risk for fracture are lacking. . . . Teriparatide may be a rational treatment for glucocorticoid-induced osteoporosis because it directly stimulates osteoblastogenesis and inhibits osteoblast apoptosis, thereby counteracting two key mechanisms through which glucocorticoid therapy promotes bone loss."
In this 18-month, double-blind trial, 428 women and men with osteoporosis who had received glucocorticoids for at least 3 months (prednisone equivalent, 5 mg daily or more) were randomized to treatment with 20 μg of teriparatide once daily or 10 mg of alendronate once daily. Age range was 22 to 89 years. The main endpoint was change in BMD at the lumbar spine, and secondary endpoints included changes in BMD at the total hip, markers of bone turnover, time to changes in BMD, fracture incidence, and safety.
At the last measurement, mean BMD at the lumbar spine had increased more in the teriparatide vs the alendronate group (7.2% ± 0.7% vs 3.4% ± 0.7%; P < .001). By 6 months, the between-group difference was significant (P < .001). At 12 months, BMD at the total hip had increased more in the teriparatide vs the alendronate group.
There were fewer new vertebral fractures in the teriparatide vs the alendronate group (0.6% vs 6.1%; P = .004), but the incidence of nonvertebral fractures was similar in both groups (5.6% vs 3.7%; P = .36). At least 1 measure of serum calcium was elevated in significantly more patients in the teriparatide vs the alendronate group.
"Among patients with osteoporosis who were at high risk for fracture, bone mineral density increased more in patients receiving teriparatide than in those receiving alendronate," the study authors write. "At 18 months, teriparatide treatment was significantly less likely to be associated with radiographic evidence of new vertebral fractures."
Limitations of the study include insufficient power to determine a reduction in the risk for vertebral fracture, paired radiographs (baseline and post baseline) for the assessment of new vertebral fractures missing for 92 patients, and inability to detect transient hypercalcemia after the administration of a study drug.
"The standard of care for patients at risk for glucocorticoid-associated bone loss and osteoporosis includes a choice of antiresorptive agents," the study authors conclude. "On the basis of the known pathophysiology of glucocorticoid-induced osteoporosis, teriparatide might be considered as a therapeutic strategy for patients at high risk for fracture."
Eli Lilly, the maker of teriparatide supported, this study and employs 5 of its authors. Some of the other authors have disclosed various financial relationships with Eli Lilly; Merck; the maker of alendronate, Aventis; Amgen; Novartis; Roche; GlaxoSmithKline; Procter & Gamble; Pfizer; Sanofi-Aventis; and Servier.
In an accompanying editorial, Philip N. Sambrook, MD, from the Kolling Institute, University of Sydney in Australia, notes that more adverse events occurred in patients receiving teriparatide.
"Although primary prevention of bone loss in patients starting glucocorticoid therapy should optimally be the first aim for physicians, glucocorticoid-induced bone loss develops in many such patients with long-term use," Dr. Sambrook writes. "Given the available evidence, the first choice for prevention would be a potent oral bisphosphonate such as alendronate or risedronate or, for patients who cannot tolerate oral bisphosphonates, an intravenous bisphosphonate, with calcium and vitamin D as adjunctive therapy. However, for patients with low bone mineral density who are receiving long-term low-dose glucocorticoid therapy, the study by Saag et al. suggests that teriparatide should be considered as a potential first-line therapy."
Dr. Sambrook has disclosed no relevant financial relationships.
N Engl J Med. 2007;357:2028-2039, 2084-2086.