Raloxifene and PTH May Have Synergistic Effect on BMD


SAN ANTONIO — Women who are taking raloxifene for osteoporosis do not need to stop taking the bisphosphonate to begin parathyroid hormone therapy.

In fact, the two drugs may have some synergy, Chad Deal, M.D., said at the annual meeting of the American College of Rheumatology.

In a 6-month study comparing parathyroid hormone (1-34) plus raloxifene with parathyroid hormone monotherapy, the combination increased total hip bone density to a greater degree, observed Dr. Deal, who is the head of the center for osteoporosis and metabolic bone disease at the Cleveland Clinic Foundation.

The combination “could potentially enlarge the anabolic window, maximizing the formation of bone and minimizing the resorption of bone,” said Dr. Deal, whose study included measurements of bone turnover markers.

Dr. Deal's double-blind study enrolled 137 subjects who were randomized to daily therapy with either the combination of teriparatide (Forteo), 20 mcg, plus raloxifene (Evista), 60 mg, or to monotherapy with teriparatide, 20 mcg.

All of the study participants also received calcium and vitamin D supplementation.

At 6 months' follow-up, the combination increased bone mineral density over baseline by a mean 6.19% at the lumbar spine, a mean 2.23% at the femoral neck, and a mean 2.31% for the total hip, as measured by dual x-ray absorptiometry. By comparison, teriparatide increased lumbar spine density by a mean 5.19%, femoral neck density by a mean 1.03%, and total hip density by 0.68%.

The differences at the lumbar spine and the femoral neck were not statistically significant, but the difference at the total hip was, Dr. Deal said.

Investigators have been intrigued by the possibility of combination treatment for osteoporosis for some time, he said.

But the only other previous major study of combination treatment looked at the use of parathyroid hormone with alendronate; it suggested that the addition of alendronate appeared to inhibit the ability of parathyroid hormone to stimulate new bone formation.

The two studies differ in several ways that make them difficult to compare.

In the alendronate trial, the addition of alendronate decreased the level of serum procollagen type I N-terminal propeptide (PINP)—a marker of bone formation—by 15% from baseline at 6 months. In the raloxifene trial, PINP in the combination group was increased from baseline to a mean level similar to that seen among patients receiving teriparatide alone.

Moreover, bone resorption was suppressed by both the teriparatide alone and the raloxifene-teriparatide combination, as measured by serum type I collagen C-telopeptide level.

“The limitation of this trial, of course, is that it is too small to assess the important outcome, which is fracture,” Dr. Deal said.

The combination was well tolerated. Subjects in both groups had similar increases in serum uric acid levels, but there were no cases of gout, he added.

The trial was sponsored by Eli Lilly & Co., maker of both Evista and Forteo.