Dennis Black, PhD

Disclosures

November 25, 2003

Question

When should I use the new parathyroid hormone medication teriparatide (Forteo) in the scheme of osteoporosis treatment?

Douglas Krell, MD

Response from Dennis Black, PhD

Dennis Black, PhD
Professor of Epidemiology & Biostatistics, University of California, San Francisco

Teriparatide (human recombinant PTH[1-34]), sold under the trade name Forteo, consists of the first 34 amino acids of the 84-amino acid protein parathyroid hormone (PTH). A 20-mcg formulation for daily self-injection was approved in December 2002 by the US Food and Drug Administration. A randomized trial of teriparatide (average follow-up 21 months) showed that it increased bone mineral density (BMD) by 10% to 12% over that period and decreased the risk of vertebral fractures and nonvertebral fractures by approximately 65%.[1] As an anabolic agent, teriparatide works by increasing bone formation. This is different from the other approved antifracture agents, the antiresorptive drugs, which work by decreasing bone resorption.

Teriparatide is indicated for treatment of postmenopausal women with osteoporosis who are at high risk of fracture, including women with a history of postmenopausal fracture and those with multiple risk factors for fracture. In clinical terms, this means that teriparatide is best reserved for the treatment of patients with severe osteoporosis. Most physicians interpret this to mean patients with both low bone mass and either an existing vertebral fracture or a history of multiple nonvertebral (nontraumatic) fractures. Although there are no fracture data in men, teriparatide has been shown over an average of 10 months to increase BMD to a similar extent as in women.[2]

The osteoporosis research community has been excited about the availability of teriparatide, as it is the first anabolic agent for osteoporosis (other formulations of PTH and other anabolic agents are in development). Various studies in animals and some in humans have suggested that PTH increases trabecular thickness and connectivity (but not trabecular number) and may increase cortical thickness.

In light of these positive results as well as the large fracture reductions in the large phase 3 trial, why is it that PTH is reserved only for those with the most severe disease? There are several reasons. Most prominently, teriparatide was shown to increase the risk of osteosarcoma in rodents.[3,4] Although no cases of osteosarcoma have ever occurred in humans taking this medication, the drug carries a black-box warning about risk of osteosarcoma, and the treatment period is limited to 2 years. Other potential reasons that teriparatide is best reserved for patients with more severe disease include the fact that it is costly and requires daily self-injection.

An important clinical question about teriparatide is whether it can be used in patients who have been on antiresorptive medication who continue to have low bone mass and/or continue to fracture. This question is far from answered, but several recent studies have begun to shed some light. One study presented at the recent American Society of Bone and Mineral Research meeting in September tested open-label teriparatide in 2 groups of patients who had been on antiresorptive therapy for about 3 years.[5,6] One group had been taking raloxifene and the other had been taking alendronate. Both groups had their antiresorptive agents stopped during the 18 months they were taking teriparatide. The study found that bone formation increased in both groups, and spine BMD increased as well. The increases in BMD were substantial in both groups, although somewhat lower in those who had been on alendronate compared with those on raloxifene. This suggests that teriparatide can be used in patients who had been on antiresorptive therapy but remain at high risk.

Two recently published papers have examined concurrent use of teriparatide with alendronate and concluded that concurrent use of alendronate with teriparatide was not more effective than either agent alone.[7,8] This suggests that if teriparatide is going to be used, it is best used alone and not combined with antiresorptives (or at least bisphosphonates).

The last clinical quandary concerns what to do following teriparatide therapy. Some small preliminary studies suggest that initiating alendronate therapy will allow continued BMD increase; otherwise, BMD will start to decrease.[5,9] There are no data concerning the effects on BMD of beginning other antiresorptive agents following teriparatide treatment.

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