Experimental Osteoporosis Drug Proves Safe at Therapeutic Dosage

Researchers have established the therapeutic window and optimal safe dosage of parathyroid hormone-related protein (PTHrP), an experimental drug being tested for treatment of osteoporosis.

Investigators at the University of Pittsburgh School of Medicine (PA, USA) conducted a single-blinded, two-part, dose-escalating clinical trial that involved 41 healthy postmenopausal women between the ages of 45 and 75. Each subject received either PTHrP or a placebo in a dose-escalating regimen for a period of three weeks. During this period, safety measures (hypercalcemia, nausea, vomiting, hemodynamics, flushing, etc.) and bone turnover markers were measured.

Results of the study were published in the January 8, 2010, online edition of the Journal of Clinical Endocrinology and Metabolism. They revealed that daily doses of 500 and 625 micrograms could be tolerated without serious adverse events. Subjects receiving 750 micrograms per day developed mild hypercalcemia. Bone turnover markers suggested that even at the highest doses, daily treatment with PTHrP did not activate bone resorption (break down). When hypercalcemia occurred, it may have resulted not from bone resorption but from activation of intestinal calcium absorption by 1,25 dihydroxyvitamin D.

"When we studied PTHrP several years ago in small numbers of postmenopausal women with osteoporosis, we found that bone density increased by nearly 5% after only three months of treatment," said senior author Dr. Andrew F. Stewart, professor of endocrinology and metabolism at the University of Pittsburgh School of Medicine. "And even at the highest doses, the side effects were negligible."

A follow-up study will compare results of treatment with PTHrP to those obtained with teriparitide, a drug that already is FDA-approved for osteoporosis treatment. The study will involve 105 participants.

"We are very eager to find out how this new drug compares to a therapy that is currently available," said first author Dr. Mara Horwitz, assistant professor of medicine at the University of Pittsburgh School of Medicine. "Our previous studies suggest that it may increase bone density more dramatically with fewer side effects, but this is the first head-to-head comparison."

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