Authors' objectives:

The aim of this report is to assess the clinical and cost effectiveness of teriparatide relative to the bisphosphonates for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. The clinical analysis will compare teriparatide to bisphosphonates or placebo, and the economic analysis will compare teriparatide to bisphosphonates or no drug therapy. The report will also assess the budget impact of funding teriparatide and the bisphosphonates by publicly funded drug plans.

Authors' results and conclusions: Two teriparatide trials met the selection criteria. In these studies, teriparatide was evaluated for the secondary prevention of osteoporosis. It was not feasible to pool study data for analysis, because the trials used different comparison groups. One trial indicated that teriparatide, at 20 micrograms or 40 micrograms per day administered subcutaneously, reduces the risk of vertebral and non-vertebral fractures, compared with placebo. Non-vertebral fractures included a pooled analysis of all fracture sites other than the vertebrae. Patients treated with teriparatide 40 micrograms per day had a higher rate of withdrawal due to adverse events than patients in the placebo group. The other trial compared teriparatide 40 micrograms per day with oral alendronate 10 mg per day, and reported no difference in the rate of non-vertebral fractures. There were no differences between the two agents in withdrawals due to adverse events or any cause. The previous CADTH review of bisphophonates identified 28 trials that met the selection criteria. RCTs were categorized as primary or secondary prevention, based on the absence or presence of pre-existing fractures, or on BMD. Meta-analyzed data from 11 etidronate RCTs (1,248 women), 11 alendronate RCTs (12,099 women) and six risedronate RCTs (13,795 women) were used to estimate the impact on fractures and adverse events. Seven RCTs (three etidronate, three alendronate, one risedronate) were primary prevention trials. Evidence from the CADTH review indicates that the main benefits of bisphosphonate therapy, relative to placebo, lie in the secondary prevention of osteoporotic fractures (i.e., the prevention of fractures in patients with a BMD=2 standard deviations below the peak bone mass or with preexisting osteoporotic fractures). The magnitude of this effect varies among bisphosphonates. Etidronate is associated with a reduction in vertebral fractures. Risedronate reduces vertebral, hip, and non-vertebral fractures. Alendronate was associated with reductions in vertebral, nonvertebral, hip, and wrist fractures, although statistical significance was only reached for wrist fractures when a yearly fixed-effect analysis was applied. Available data suggested no statistically significant differences in the rates of drop-out or discontinuation due to adverse events between bisphosphonate and placebo recipients in clinical trials. Indirect comparisons with the bisphosphonates suggest that teriparatide is more effective in the secondary prevention of vertebral fractures, whereas alendronate is more effective in reducing hip and wrist fractures.

Authors' recommendations: Clinical Compared with placebo, teriparatide 20 micrograms administered daily by subcutaneous injection confers a significant reduction in the risk of vertebral and non-vertebral fractures as secondary prevention. Teriparatide 40 micrograms daily and alendronate 10 mg daily are not significantly different in the secondary prevention of non-vertebral fractures. . Teriparatide 20 micrograms per day, the recommended dose, has not been compared in head-to-head fracture trials with any bisphosphonate. No trials with teriparatide studied the primary prevention of osteoporotic fractures in women. Limited evidence support the use of bisphosphonates in the primary prevention of osteoporotic fractures. Only alendronate has been shown to be effective in primary prevention, and this effect is limited to vertebral fractures. Compared with placebo, etidronate is effective in the secondary prevention of vertebral fractures. Compared with placebo, alendronate is effective in the secondary prevention of vertebral, non-vertebral, hip, and wrist fractures. Compared with placebo, risedronate is effective in the secondary prevention of vertebral, nonvertebral, and hip fractures. Economic Alendronate or no drug therapy is the optimal treatment option. The choice between the two depends on the woman1s age (i.e., alendronate is more cost-effective for women > or = 80 years because of an increase in the baseline risk of fracture), and the maximum willingness of decision makers to pay for a QALY gained (e.g., ICER of C$169,600 for alendronate versus no drug therapy among women 65 years of age). Teriparatide is not cost-effective compared to bisphosphonates under any scenario. If no drug therapy is the only available alternative, then teriparatide in an 80-year-old woman with a previous fracture is cost-effective if the health care system is prepared to pay C$851,000 for a QALY. Etidronate was dominated by alendronate in all age groups. It is estimated that by 2006, if teriparatide were listed as a limited use benefit on publicly funded drug plans, governments could incur C$115 million to C$230 million in additional drug costs, depending on the utilization, and the number of patients treated.

Authors' methods: Systematic review

Project Status: Completed

URL for project: http://www.cadth.ca/publication/658

Year Published: 2006

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Organisation Name: Canadian Agency for Drugs and Technologies in Health

Contact Address: 600-865 Carling Avenue, Ottawa, ON K1S 5S8 Canada. Tel: +1 613 226 2553; Fax: +1 613 226 5392;

Contact Name: requests@cadth.ca

Contact Email: requests@cadth.ca

Copyright: Canadian Agency for Drugs and Technologies in Health (CADTH)