December 2007 Safety labeling updates & new warnings: rosiglitazone, erythropoiesis-stimulating agents, aprotinin

Key Points

Patients with glucocorticoid-induced osteoporosis who are at high risk for fracture may experience greater increases in bone mineral density (BMD) with teriparatide than with alendronate, according to an international, randomized, double-blind, controlled trial published in the New England Journal of Medicine (NEJM).

The 18-month trial included 428 patients aged 22 to 89 years with osteoporosis who had been treated with glucocorticoids for ≥3 months. Patients were randomized to receive teriparatide 20 mcg via subcutaneous (SC) injection once daily plus an oral placebo (n=214) or oral alendronate 10 mg once daily plus a placebo via SC injection (n=214). All patients also received calcium carbonate and vitamin D once daily.

Patients who had been treated with a bisphosphonate for >2 weeks in the 6 months before enrollment, had been treated with a bisphosphonate for >2 years within 3 years of enrollment, or had nontrivial exposure to other osteoporosis medications were excluded from the trial.

At the time of last measurement, treatment with teriparatide was associated with a significantly greater mean increase in BMD at the lumbar spine compared with alendronate (7.2% vs 3.4%; P<.001). A significant difference was observed between the treatment groups by 6 months (P<.001).

At 12 months, a significantly greater mean increase in BMD at the total hip was observed in patients treated with teriparatide compared with those treated with alendronate (P=.01). At 18 months, patients treated with teriparatide had a mean increase in BMD at the total hip of 3.8% versus 2.4% among patients who received alendronate (P=.005).

Bone turnover was assessed by measuring levels of N-terminal propeptide of type I collagen and C-telopeptide of type I collagen, markers of bone formation and resorption, respectively. Levels of these markers were increased at Month 1 and peaked at Month 6 in patients who received teriparatide. Treatment with alendronate was associated with decreases in the levels of these markers at Month 1; the levels remained suppressed at Month 18.

The incidence of new vertebral fractures was lower among patients who received teriparatide compared with those who received alendronate (0.6% vs 6.1%; P=.004). There were no significant differences between treatment groups in the incidence of new nonvertebral fractures.

The rate of therapy adherence, assessed by interviewing patients at each follow-up visit and by quantifying the medications returned to the researchers, was similar in both treatment groups.

There were no significant differences between treatment groups in the overall incidence of adverse events, the number of serious adverse events, or the number of events that led to withdrawal from the study or were potentially related to the study drugs. The types of adverse events differed significantly between treatment groups. Teriparatide was associated with nausea, insomnia, pharyngitis, and viral infection. Alendronate was associated with rash, decreases in weight, sciatica, and asthma. A greater number of patients in the teriparatide group experienced ≥1 elevated measure (>10.5 mg/dL) of serum calcium before receiving treatment, but there were no significant differences for sustained elevations between treatment groups.

A total of 70 patients (32.7%) randomized to alendronate withdrew from the study early; 13 of these withdrawals (6.1%) were because of an adverse event. A total of 64 patients (29.9%) randomized to teriparatide withdrew from the study early; 25 of these withdrawals (11.7%) were because of an adverse event. A total of 19 patients died during the trial (12 patients assigned to alendronate and 7 patients assigned to teriparatide), including 1 teriparatide-treated patient who died the day after withdrawing from the study because of an adverse event.

In a related editorial, Philip N. Sambrook, MD, stated that for the prevention of osteoporosis in patients who are receiving long-term glucocorticoids, oral bisphosphonates such as alendronate and risedronate plus calcium and vitamin D should be considered for first-line therapy; intravenous (IV) bisphosphonates should be considered for patients who cannot tolerate oral therapy. Dr Sambrook added, however, that based on the results of this trial, "teriparatide should be considered as a potential first-line therapy" for patients with low BMD who are receiving long-term treatment with low-dose glucocorticoids.

SOURCES

Saag KG, Shane E, Boonen S, et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med. 2007;357:2028–2039.

Sambrook PN. Anabolic therapy in glucocorticoid-induced osteoporosis [editorial]. N Engl J Med. 2007;357:2084–2086.