BIRMINGHAM, Alabama—Teriparatide (Forteo®, Eli Lilly and Co) increased lumbar spine bone-mineral density (BMD) twice as much as alendronate (Fosamax®, Merck & Co, Inc) in the first head-to-head trial of the two drugs in patients with glucocorticoid (GC)-induced osteoporosis. Teriparatide also increased total hip BMD significantly more and reduced the incidence of new vertebral fractures to about one-tenth the level seen in the alendronate patients. Kenneth G. Saag, MD, and colleagues report the randomized, double-blind, controlled trial in The New England Journal of Medicine.¹

"In this active-comparator trial, the anabolic agent teriparatide appeared to show significant skeletal benefits in patients with glucocorticoid-induced osteoporosis, as compared with the bisphosphonate alendronate. At 18 months, teriparatide treatment was significantly less likely to be associated with radiographic evidence of new vertebral fractures," wrote Dr. Saag, with the University of Alabama at Birmingham.

The Lilly-funded study enrolled patients who had received the equivalent of at least 5 mg/day of prednisone for at least 3 months and who had either a T-score for BMD at the lumbar spine or total hip score of <e;-20 or a T-score of <e;-1 plus at least one fragility fracture during GC treatment.

Patients were randomized either to injectable teriparatide (20 μg/day as sc injection using a prefilled pen) plus oral placebo or to oral alendronate (10 mg/day) plus injectable placebo. Patients also received supplemental calcium carbonate and vitamin D. The study was powered to detect a between-treatment difference of 0.015 per square centimeter (~2%) in the absolute change in lumbar spine BMD from baseline to the last measurement during the first 18 months of therapy.

The researchers reported

• significantly greater increase in lumbar spine BMD at 18 months with teriparatide versus alendronate (7.2% vs 3.4%, P <.001)
• significant difference between the teriparatide and alendronate groups in BMD by month 6 of treatment (P <.001)
• significantly greater increase in total hip BMD by 18 months with teriparatide versus alendronate (38% vs 2.4%, P = .005; 1.4% between-group difference, 95% CI 0.4 to 2.4).
• significantly fewer vertebral fractures with teriparatide (0.6% vs 6.1%, P = .004)
• no significant difference in nonvertebral fractures

Teriparatide, a recombinant human parathyroid hormone, stimulates bone formation by directly affecting osteoblasts. "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," the authors write.

About 30% of patients in each group discontinued treatment. More patients in the alendronate group dropped out at their own request (14% vs 7.5%, P = .03). More patients in the teriparatide group discontinued because of an adverse event (11.7% vs 6.2%, P = .04). However, safety profiles were similar, and there were no significant differences in overall adverse event rates or serious adverse event rates. Three patients in the teriparatide group had hyperuricemia, and one reported gout. More patients in the teriparatide group had at least one serum urate level >9 mg/dL (8% vs 4.8%, P = .18). More patients in the teriparatide group also had at least one serum calcium level >10.5 mg/dL (18% vs 5.7%, P <.001).

Dr. Saag concluded, "In our study, teriparatide was associated with greater increases in bone mineral density at the spine and hip and with significantly fewer new vertebral fractures, with no significant differences between groups in the incidence of nonvertebral fractures or serious adverse events."

In an editorial commenting on this study, Philip N. Sambrook, MD, from the Kolling Institute at the University of Sydney in Australia, notes that the first choice for preventing GC-induced bone loss "would be a potent oral bisphosphonate such as alendronate or risedronate or, for patients who cannot tolerate oral bisphosphonates, an intravenous bisphosphonate..." but that Dr. Saag's study "suggests that teriparatide should be considered as a potential first-line therapy" for patients with low BMD on chronic low-dose GC therapy.

MSK Report editorial board member Nancy E. Lane, MD, largely agrees with Dr. Sambrook. Dr. Lane, director of the Aging Center at the University of California at Davis, said that for patients with mild-to-moderate GC-induced bone loss, "a bisphosphonate is fine," but that teriparatide might be a reasonable choice for patients with low BMD despite bisphosphonate treatment, for patients with a higher risk of fracture, or for those who have already had a low-impact fracture.  

Teriparatide is currently approved for men and postmenopausal women with osteoporosis who are at high risk for fracture, and Lilly has filed for US approval to market the drug for steroid-induced osteoporosis.

Effect of Teriparatide on Bone

• Stimulates osteoblastogenesis
• Inhibits osteoblast apoptosis
• Stimulates bone formation
• Increases bone mass

18-Month Results of RCT Comparing Teriparatide With Alendronate in Steroid-Induced Osteoporosis

Outcome	Teriparatide (%)	Alendronate (%)	P
Increase in lumbar BMD	±7.2	±3.4	<.001
Increase in total hip BMD	±3.8	±2.4	.005
New vertebral fractures	0.6	6.1	.004

Source: Saag et al. American College of Rheumatology Meeting, 2007.¹

References