Teriparatide Found Superior to Alendronate in Steroid-Induced Osteoporosis


BIRMINGHAM, Ala., Nov. 15 -- For steroid-induced osteoporosis, injectable teriparatide (Forteo) increased bone-mineral density (BMD) twice as much as oral alendronate (Fosamax) did in a head-to-head comparison, investigators here found.
Action Points
Explain to interested patients that the use of teriparatide in this study is off-label. Currently the drug is FDA-approved for men and postmenopausal woman with osteoporosis who are at high risk for fractures.
Explain that certain side effects in this study were more common with teriparatide than with other osteoporosis drugs, and the dropout rate was higher for teriparatide than for alendronate.
Point out that this study was sponsored by the company that markets teriparatide.
Mean lumbar-spine BMD was up 7.2% after 18 months of off-label treatment with teriparatide, a parathyroid hormone-based agent, compared with 3.4% (P0.001) for patients taking alendronate, an oral bisphosphonate, reported Kenneth Saag, M.D., of the University of Alabama at Birmingham, and colleagues in the Nov. 15 issue of the New England Journal of Medicine.
The patients had developed osteoporosis after lengthy treatment with prednisone and related drugs for inflammatory and respiratory illnesses. About half had rheumatoid arthritis.
"In our study, teriparatide was associated with greater increases in [BMD] at the spine and hip and with significantly fewer new vertebral fractures," Dr. Saag's group wrote. But the dropout rate for adverse effects was twice as high for those taking teriparatide.
Only one out of 171 evaluable patients receiving teriparatide had radiographic evidence of a vertebral fracture, while 10 of 165 evaluable patients on alendronate had such fractures (P=0.004).
Nonvertebral fractures occurred at similar rates with the two treatments (5.6% versus 3.7%, P=0.36). BMD in the total hip increased with both drugs, though less dramatically than in the lumbar spine. Teriparatide increased hip BMD by 3.8% while it rose 2.4% in the alendronate group. The advantage for teriparatide was significant (P0.01). Significantly more patients in the teriparatide group had at least one elevated serum calcium measurement > 10.5 mg/dL (18% versus 5.7%, P0.001) and there was a tendency toward more patients with at least one measurement > 11 mg/dL (3.8% versus 1%, P=0.06).
Teriparatide is a recombinant peptide drug, based on a portion of the parathyroid hormone protein. Earlier studies had indicated that it leads to increased BMD.
In the randomized, double-blind trial, 428 patients were assigned to either 20 mcg of teriparatide or 10 mg of oral alendronate daily for 18 months. All patients received supplemental calcium carbonate (1,000 mg elemental calcium) and vitamin D (800 IU). BMD in the lumbar spine and total hip was measured at baseline and at three, six, 12, and 18 months. Fractures and other adverse events were monitored as well.
Nearly one-third of patients in both treatment groups failed to complete the study, a point highlighted by Philip N. Sambrook, M.D., of the University of Sydney, in an accompanying editorial.
The study's "moderately high discontinuation rate" may have been linked to adverse effects, he said. Twice as many patients on teriparatide as on alendronate did not complete the planned therapy because of adverse effects.
Nausea and insomnia were significantly more common with teriparatide and several other side effects showed trends toward higher frequency with teriparatide.
"Given the available evidence," Dr. Sambrook wrote, "the first choice for prevention would be a potent oral bisphosphonate such as alendronate or risedronate (Actonel) or, for patients who cannot tolerate oral bisphosphonates, an intravenous bisphosphonate, with calcium and vitamin D as adjunctive therapy."
The study's findings may not do much to assuage concerns about teriparatide's high cost.
Teriparatide has an estimated annual treatment cost of nearly $7,000, about eight times as much as for alendronate.
A 2006 study from Stanford University researchers found that teriparatide is less cost-effective than alendronate for postmenopausal women with severe osteoporosis. That finding assumed that teriparatide was 35% more effective than alendronate in reducing fractures -- about the same as in the new study.
But, said Dr. Sambrook, "for patients with low [BMD] 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."
A spokeswoman for Lilly said the company filed last February for U.S. approval to market teriparatide for steroid-induced osteoporosis. Currently the drug is approved for men and postmenopausal woman with osteoporosis who are at high risk for fractures.
She said a decision was expected within a few months. The approval, she added, would likely be for patients who develop osteoporosis despite prophylactic treatment with bisphosphonates.
The study was funded by Lilly, which markets teriparatide. Dr. Saag reported financial relationships with Lilly, Merck (maker of alendronate), Amgen, Aventis, Novartis, Roche and GlaxoSmithKline. Several co-authors on the paper are Lilly employees. Dr. Sambrook reported no relevant conflicts of interest.
Primary source: New England Journal of MedicineSource reference: Saag K, et al "Teriparatide or alendronate in glucocorticoid-induced osteoporosis"New England Journal of Medicine 2007; 357: 2028-39. Additional source: New England Journal of MedicineSource reference: Sambrook P, "Anabolic therapy in glucocorticoid-induced osteoporosis"New England Journal of Medicine 2007; 357: 2084-86.