Sequential Tx Sustains Benefits Of Teriparatide in Osteoporosis

TORONTO — Patients with osteoporosis who took daily raloxifene following a yearlong course of treatment with teriparatide maintained bone mineral density gains, whereas those who had no further therapy rapidly lost bone, Dr. Silvano Adami reported at a world congress on osteoporosis.

Recombinant teriparatide (human parathyroid hormone 1–34) treatment increases bone mass and reduces fracture risk by stimulating bone formation and remodeling, but there are concerns about its long-term safety. The Fracture Prevention Trial was terminated early in 1998 because of the occurrence of osteosarcomas in rats, and although no sarcomas developed in patients in the study, the drug subsequently was not recommended for use for any longer than 2 years.

Clinical experience has shown, however, that once therapy with teriparatide ceases, the bone mineral density (BMD) gains achieved during treatment quickly diminish. Therefore, subsequent antiresorptive therapy has been suggested as a means of maintaining the improvements.

Results of a new study support this concept of sequential therapy, said Dr. Adami of the University of Verona, Italy.

The study included 380 postmenopausal women who had completed 1 year of open-label treatment with 20 mcg/day of teriparatide. They were randomized to an additional year of raloxifene (60 mg/day) or placebo and were followed with dual-energy X-ray absorptiometry.

One year of teriparatide significantly increased BMD at the lumbar spine and femoral neck, by 8.2% and 1.3%, respectively, Dr. Adami said at the meeting, which was sponsored by the International Osteoporosis Foundation. At the end of the second year, patients who had received raloxifene showed a further significant increase in femoral neck BMD of 2.3%. (See chart.)

Correlations also were seen between the changes in bone markers and BMD during the first 3 months after raloxifene therapy, he said.

The sequential approach to therapy is not the first combination strategy to be evaluated for teriparatide. An earlier hypothesis had been that concurrent administration of an antiresorptive drug with parathyroid hormone (PTH) might enhance teriparatide's anabolic effects.

This hypothesis was tested in two studies in which parathyroid hormones were given in combination with alendronate. In one of the studies, 238 postmenopausal women with low BMD were randomized to receive daily parathyroid hormone (100 mcg), alendronate (10 mg), or both for 12 months. The investigators found no evidence of synergy for the combination therapy, reporting that the increase in volumetric density of spinal trabecular bone in the parathyroid hormone group was about double that seen in the other groups. They suggested the concurrent use of alendronate might be attenuating the anabolic effects of teriparatide (N. Engl. J. Med. 2003;349:1207–15).

In the second study, 83 men who had low BMD were randomized to receive parathyroid hormone (40 mcg daily), alendronate (10 mg daily), or both. This study also showed no benefit, with BMD at the femoral neck increasing significantly more in those men who received the parathyroid hormone alone than it did in those who were in the alendronate or combination groups (N. Engl. J. Med. 2003;349:1216–26).

ELSEVIER GLOBAL MEDICAL NEWS

TORONTO — Patients with osteoporosis who took daily raloxifene following a yearlong course of treatment with teriparatide maintained bone mineral density gains, whereas those who had no further therapy rapidly lost bone, Dr. Silvano Adami reported at a world congress on osteoporosis.

Recombinant teriparatide (human parathyroid hormone 1–34) treatment increases bone mass and reduces fracture risk by stimulating bone formation and remodeling, but there are concerns about its long-term safety. The Fracture Prevention Trial was terminated early in 1998 because of the occurrence of osteosarcomas in rats, and although no sarcomas developed in patients in the study, the drug subsequently was not recommended for use for any longer than 2 years.

Clinical experience has shown, however, that once therapy with teriparatide ceases, the bone mineral density (BMD) gains achieved during treatment quickly diminish. Therefore, subsequent antiresorptive therapy has been suggested as a means of maintaining the improvements.

Results of a new study support this concept of sequential therapy, said Dr. Adami of the University of Verona, Italy.

The study included 380 postmenopausal women who had completed 1 year of open-label treatment with 20 mcg/day of teriparatide. They were randomized to an additional year of raloxifene (60 mg/day) or placebo and were followed with dual-energy X-ray absorptiometry.

One year of teriparatide significantly increased BMD at the lumbar spine and femoral neck, by 8.2% and 1.3%, respectively, Dr. Adami said at the meeting, which was sponsored by the International Osteoporosis Foundation. At the end of the second year, patients who had received raloxifene showed a further significant increase in femoral neck BMD of 2.3%. (See chart.)

Correlations also were seen between the changes in bone markers and BMD during the first 3 months after raloxifene therapy, he said.

The sequential approach to therapy is not the first combination strategy to be evaluated for teriparatide. An earlier hypothesis had been that concurrent administration of an antiresorptive drug with parathyroid hormone (PTH) might enhance teriparatide's anabolic effects.

This hypothesis was tested in two studies in which parathyroid hormones were given in combination with alendronate. In one of the studies, 238 postmenopausal women with low BMD were randomized to receive daily parathyroid hormone (100 mcg), alendronate (10 mg), or both for 12 months. The investigators found no evidence of synergy for the combination therapy, reporting that the increase in volumetric density of spinal trabecular bone in the parathyroid hormone group was about double that seen in the other groups. They suggested the concurrent use of alendronate might be attenuating the anabolic effects of teriparatide (N. Engl. J. Med. 2003;349:1207–15).

In the second study, 83 men who had low BMD were randomized to receive parathyroid hormone (40 mcg daily), alendronate (10 mg daily), or both. This study also showed no benefit, with BMD at the femoral neck increasing significantly more in those men who received the parathyroid hormone alone than it did in those who were in the alendronate or combination groups (N. Engl. J. Med. 2003;349:1216–26).

ELSEVIER GLOBAL MEDICAL NEWS

TORONTO — Patients with osteoporosis who took daily raloxifene following a yearlong course of treatment with teriparatide maintained bone mineral density gains, whereas those who had no further therapy rapidly lost bone, Dr. Silvano Adami reported at a world congress on osteoporosis.

Recombinant teriparatide (human parathyroid hormone 1–34) treatment increases bone mass and reduces fracture risk by stimulating bone formation and remodeling, but there are concerns about its long-term safety. The Fracture Prevention Trial was terminated early in 1998 because of the occurrence of osteosarcomas in rats, and although no sarcomas developed in patients in the study, the drug subsequently was not recommended for use for any longer than 2 years.

Clinical experience has shown, however, that once therapy with teriparatide ceases, the bone mineral density (BMD) gains achieved during treatment quickly diminish. Therefore, subsequent antiresorptive therapy has been suggested as a means of maintaining the improvements.

Results of a new study support this concept of sequential therapy, said Dr. Adami of the University of Verona, Italy.

The study included 380 postmenopausal women who had completed 1 year of open-label treatment with 20 mcg/day of teriparatide. They were randomized to an additional year of raloxifene (60 mg/day) or placebo and were followed with dual-energy X-ray absorptiometry.

One year of teriparatide significantly increased BMD at the lumbar spine and femoral neck, by 8.2% and 1.3%, respectively, Dr. Adami said at the meeting, which was sponsored by the International Osteoporosis Foundation. At the end of the second year, patients who had received raloxifene showed a further significant increase in femoral neck BMD of 2.3%. (See chart.)

Correlations also were seen between the changes in bone markers and BMD during the first 3 months after raloxifene therapy, he said.

The sequential approach to therapy is not the first combination strategy to be evaluated for teriparatide. An earlier hypothesis had been that concurrent administration of an antiresorptive drug with parathyroid hormone (PTH) might enhance teriparatide's anabolic effects.

This hypothesis was tested in two studies in which parathyroid hormones were given in combination with alendronate. In one of the studies, 238 postmenopausal women with low BMD were randomized to receive daily parathyroid hormone (100 mcg), alendronate (10 mg), or both for 12 months. The investigators found no evidence of synergy for the combination therapy, reporting that the increase in volumetric density of spinal trabecular bone in the parathyroid hormone group was about double that seen in the other groups. They suggested the concurrent use of alendronate might be attenuating the anabolic effects of teriparatide (N. Engl. J. Med. 2003;349:1207–15).

In the second study, 83 men who had low BMD were randomized to receive parathyroid hormone (40 mcg daily), alendronate (10 mg daily), or both. This study also showed no benefit, with BMD at the femoral neck increasing significantly more in those men who received the parathyroid hormone alone than it did in those who were in the alendronate or combination groups (N. Engl. J. Med. 2003;349:1216–26).

ELSEVIER GLOBAL MEDICAL NEWS