HONOLULU, Hawaii—The common practice of switching from an antiresorptive drug to the anabolic agent teriparatide (TPTD) (Forteo®, Eli Lilly and Co), is likely to change as a result of compelling new data showing that adding TPTD to background antiresorptive therapy is much more effective than switching. The randomized trial reported by Felicia Cosman, MD, and colleagues at the American Society for Bone and Mineral Research 2007 meeting found that although biochemical markers of bone formation and resorption look better with sequential treatment, bone mineral density (BMD) increases significantly more with combination therapy^.1

"We were very surprised that those patients who had the bigger biochemistry response did not have the bigger bone density response. We were also surprised that even after almost 4 years of alendronate (ALN), stopping the drug made such a big difference. The bisphosphonate is buried in the skeleton, so we thought it would continue to act. But our data show that what matters is the ongoing administration of the bisphosphonate and the ongoing administration of teriparatide," Dr. Cosman told CIAOMed. Dr. Cosman is medical director of the clinical research center at Helen Hayes Hospital, in West Haverstraw, New York. The study was supported by Eli Lilly and Co.

Surprising results after long-term ALN or raloxifene

The researchers studied postmenopausal women with osteoporosis previously treated for at least 18 months with ALN (Fosamax®, Merck & Co, Inc) at 70 total mg/week, median treatment duration 37.3 months, or with the selective estrogen receptor modulator raloxifene (RLX) (Evista®, Eli Lilly and Co)  at 60 mg/d, median treatment duration 36.9 months. Patients were randomized either to add TPTD to ongoing ALN or RLX or to switch to TPTD for 6 months.

"We were trying to figure out, if you want to start teriparatide in a patient who is already on an antiresorptive drug such as alendronate because her bone density is falling or because she has had a fracture or her BMD is still really low, should you add teriparatide and continue the antiresorptive drug or stop the antiresorptive drug," Dr Cosman explained.

Outcome endpoints included markers of bone turnover and BMD determined by DXA scan. The patients were similar at baseline except that those previously treated with ALN had lower baseline bone turnover than previous RLX patients.

Dr. Cosman reported, "All treatment groups had significant increases in lumbar spine BMD. In the prior alendronate stratum, adding teriparatide increased DXA lumbar spine BMD significantly more than switching to teriparatide. In the prior raloxifene stratum, switching to or adding teriparatide resulted in similar increases in lumbar spine BMD. In the prior alendronate stratum, femoral neck DXA BMD did not significantly increase in either group. In the prior raloxifene stratum, patients who added teriparatide had a significant increase from baseline in femoral neck DXA BMD; this increase was not observed in those who switched to teriparatide. However, there were no significant differences in femoral neck DXA BMD between treatment groups in the prior raloxifene stratum."

Hip BMD increased significantly more with added TPTD in both the ALN and the RLX group, compared with patients who switched to teriparatide.

Time for a change

"Even though the biochemistry was more exuberant in patients who switched to teriparatide, the bone density changes were better in those who had teriparatide added to their ongoing antiresorptive drug," Dr. Cosman said. "In the past, most of us have been stopping the ongoing antiresorptive drug when we start teriparatide. These data suggest that we should keep it going, so this study has some serious clinical implications."

Reference

1. Cosman F, Wermers RA, Recknor C, et al. Efficacy of adding teriparatide versus switching to teriparatide in postmenopausal women with osteoporosis previously treated with raloxifene or alendronate. Presented at: ASBMR 2007 meeting; September 16, 2007; Honolulu, HI .Abstract 423.