Teriparatide

HONOLULU -- New research unveiled at an international symposium sponsored by the National Osteoporosis Foundation emphasized the mechanistic differences between anabolic therapy and currently approved osteoporosis drugs, including bisphosphonates, all of which slow bone turnover and inhibit resorption.

The parathyroid hormone (PTH) teriparatide, which is awaiting Food and Drug Administration approval for the treatment of osteoporosis, actually increases bone turnover, but it does so in a manner that "uncouples" the normal relationship between resorption and bone formation, focusing its power on formation of stronger bone.

Subsequent changes in the microarchitecture of bone are so distinct with teriparatide that some researchers now "dare to dream" that osteoporotic bone may be capable of returning to normal levels of bone mineral density (BMD) and strength. The best hope with most previously available therapies is to stem rapid loss of bone, said Dr. John P. Bilezikian, chief of endocrinology and director of the metabolic bone diseases program at Columbia-Presbyterian Medical Center in New York City.

Specifically, teriparatide acts on cancellous bone, which is why bone density of the lumbar spine is dramatically increased in subjects taking the injected drug, while density in the cortical bone of the radius remains stable or even declines among treated subjects, he said.

The strengthening ability of PTH was highlighted in a separate presentation by David W. Dempster, Ph.D., professor of clinical pathology at Columbia University, New York, and director of the regional bone center at Helen Hayes Hospital in West Haverstraw, N.Y.

Microarchitecture of bone in patients receiving PTH exhibits a sevenfold thickening of trabeculae, which are horizontal struts that Dr. Dempster likened to the flying buttresses providing stability to structures such as Notre Dame Cathedral. Trabecular connectivity also increases with PTH, especially in conjunction with hormone replacement therapy he has shown.

Intriguingly, it now appears that parathyroid hormone's strengthening abilities extend to cortical bone as well as cancellous bone, even when bone mineral density remains unchanged or diminished, he said.

This finding, hinted at by the fact that fracture risk does not appear to increase in the forearm among patients taking teriparatide, was brought home by a study reported at the meeting by Dr. Lars Hyldstrup, professor of endocrinology at Hvidovre Hospital of the University of Copenhagen.

He and associates used digital x-ray radiogrammetry to evaluate the changes in cortical bone thickness among 40 postmenopausal women with osteoporosis, 28 of whom received 20 [mu]g or 40 [mu]g of teriparatide daily for 1 year.

Teriparatide increased the outer diameter (p = 0.016) and tended to decrease the inner diameter (p = 0.08) of bone on DXR studies of the radius, ulna, and metacarpals 2, 3, and 4. Consistent trends suggested an increase in cortical thickness at individual sites, although it was statistically significant only at metacarpal 4 and the combined metacarpal sites, concluded the study, which was sponsored by Eli Lilly & Co.

Other studies reported at the meeting focused on benefits of teriparatide for specific types of patients, and on the persistence of bone mineral density once the drug is stopped.

Dr. Alexandra Papaioannou of McMaster University in Hamilton, Ont., led a study demon strating that total body bone mineral content was maintained 18 months after discontinuation of teriparatide treatment that lasted an average 14 months in 52 women. In contrast, 53 women who received 10 mg of daily alendronate during the active treatment phase of the trial returned to their baseline total bone mineral content levels during the observation phase.

Gains in bone mineral density were larger during treatment and better preserved following treatment in the lumbar spine, total hip, and femoral neck of teriparatide patients. However, those patients lost BMD during treatment at the distal radius. Even though some bone mineral density was regained, they still had significantly lower BMD at that site 34 months after baseline than did the patients on alendronate.

Lilly-sponsored secondary analyses of previously reported trials drew several conclusions about subgroups of patients. One determined that the absolute change in baseline BMD of the lumbar spine was equally significant in women with or without vertebral osteoporosis as defined by previous vertebral fractures or lumbar spine BMD. By 18 months of therapy, 82 of 99 of all women treated with teriparatide in the trial were responders.

A secondary analysis of a study of 437 men found that teriparatide increased BMD at the lumbar spine and femoral neck (and at the total hip and total body at higher doses) in men with idiopathic or hypogonadal osteoporosis independent of their baseline free testosterone or estradiol.

Finally, it was reported that men and postmenopausal women with osteoporosis have equally significant increases in absolute bone mineral density in spite of gender differences in pharmacokinetic and bone turnover marker responses.

COPYRIGHT 2002 International Medical News Group
COPYRIGHT 2002 Gale Group