Abstract 665: Active-Comparator Trial of Teriparatide Versus Alendronate in the Treatment of Glucocorticoid-Induced Osteoporosis
Assil Saleh, M.D.
Authors:
Kenneth G. Saag, Elizabeth Shane, Steven Boonen, David W. Donley, Fernando Marin, Margaret R. Warner, Kathleen A. Taylor, Gail P. Dalsky, Robert Marcus.
Background:
Antiresorptive bone agents, particularly bisphosphonates, have been shown to be effective in the prevention and treatment of steroid-induced osteoporosis. As a result, they have been standard therapy since the 1990s. The anabolic bone agent teriparatide, a recombinant parathyroid hormone, has been recently approved by the FDA for the treatment of osteoporosis in men and post-menopausal women. This agent has been shown to increase spinal bone mass in post-menopausal women with glucocorticoid-induced osteoporosis who were already taking estrogen therapy. The objective of this study was to compare the efficacy of daily teriparatide to daily alendronate therapy in the treatment of steroid-induced osteoporosis.
Methods:
428 patients with documented glucocorticoid-induced osteoporosis (demonstrated by low BMD or low BMD with a history of prior fracture) were evaluated for 18-months in a randomized, double-blind trial. Each subject had to be taking at least 5mg of daily prednisone for at least three consecutive months prior to randomization. Subjects were randomized to either daily teriparatide (20mg) or alendronate (10mg). There were 214 subjects in each arm. The primary end point was change in BMD at the lumbar spine.
Results:
The results of the primary phase (first 18 months) have been published (N Engl J Med 2007; 357:2028-39). On the final measurement, mean bone mineral density at the lumbar spine increased to a greater degree in subjects randomized to teriparatide than alendronate (7.2+/-0.7% vs. 3.4+/-0.7%, P<0.001). Similarly, at the total hip, teriparatide patients showed a greater increase in bone mineral density. They also exhibited fewer new vertebral fractures than alendronate patients (0.6% vs. 6.1%, p=0.004). Non-vertebral fracture incidence was similar in the two groups.
Percent changes from baseline in bone mineral density (g/cm2) |
||||
Time point |
N |
Alendronate |
N |
Teriparatide |
|
||||
Lumbar spine |
184 |
1.7 [0.5]* |
183 |
2.5 [0.5]* |
Month 6 |
173 |
2.2 [0.5]* |
178 |
4.3 [0.5]*‡ |
Month 12 |
159 |
3.5 [0.6]* |
170 |
6.7 [0.5]*‡ |
Month 18 |
148 |
3.9 [0.6]* |
156 |
8.2 [0.6]*‡ |
Endpoint |
195 |
3.4 [0.7]* |
198 |
7.2 [0.7]*‡ |
Total Hip |
157 |
1.9 [0.5]* |
167 |
3.1 [0.5]*† |
Month 18 |
144 |
2.4 [0.6]* |
156 |
3.8 [0.6]*‡ |
Endpoint |
176 |
2.2 [0.5]* |
185 |
3.6 [0.5]*‡ |
Femoral Neck |
157 |
2.1 [0.8]* |
167 |
4.1 [0.8]*‡ |
Month 18 |
144 |
2.8 [0.8]* |
156 |
4.4 [0.8]*† |
Endpoint |
176 |
2.1 [0.7]* |
185 |
3.7[0.8]*† |
|
||||
*P<0.01 Within treatment; ‡P<0.01, †P<0.05 Between treatment |
||||
Conclusions:
Teriparatide was shown in this study to be more effective than alendronate in treating glucocorticoid-induced osteoporosis. It triggered a greater increase in BMD and lowered the incidence of vertebral fractures.
Editorial Comment:
Glucocorticoids appear to directly affect osteoblastic cells to inhibit bone formation. Teriparatide directly stimulates osteoblastogenesis and inhibits osteoblast apoptosis, negating two principal inhibitory effects of glucocorticoids on bone formation. In this study, teriparatide was shown to more potently halt glucocorticoid-induced osteoporosis than alendronate.
Daily dosing of alendronate was employed in this study, but the current standard of care is weekly, which somewhat complicates extrapolation of these results. Although the secondary outcome in the study was a decrease in the incidence of spinal fractures, the study was not statistically powered to detect a decrease in fracture risk. Nonetheless, this work represents a major step forward in our understanding of therapy of steroid-induced osteoporosis. Teriparatide should now be considered first-line therapy, particularly for secondary prevention of glucocoricoid-induced osteoporosis.
