PHILADELPHIA — Balicatib, an investigational agent that belongs to a new class of osteoporosis drugs, appears comparable to bisphosphonate therapy in increasing bone mineral density in postmenopausal women, according to trial results presented at the annual meeting of the American Society for Bone and Mineral Research.
“Balicatib was able to increase [bone mineral density] at both the spine and hip, with changes very similar to those seen with bisphosphonates,” said Dr. Silvano Adami.
Balicatib inhibits cathepsin K, a cysteine protease that plays an important role in the pathologic process of bone resorption. Cathepsin K is highly and selectively expressed by osteoclasts. Selective cathepsin K inhibitors provide a new method of action for reducing bone resorption and improving BMD.
In this randomized, placebo-controlled trial, 675 postmenopausal women with lumbar spine BMD T scores of less than −2 were randomized to receive 5 mg, 10 mg, 25mg, or 50 mg of daily oral balicatib or placebo, said Dr. Adami, head of gastroenterologic, rheumatologic, and vascular rehabilitation at the University of Verona (Italy). All patients received calcium and vitamin D supplements.
The women were assessed with dual-energy x-ray absorptiometry (DXA) measurements of spine and hip BMD, and levels of bone formation and resorption biomarkers were measured.
At baseline, the average patient age was 62 years. The average lumbar spine and total hip T scores were −2.6 and −1.4, respectively; 87% of the women had no morphometric vertebral fractures.
Following 1 year of treatment with balicatib, “the changes in BMD were quite remarkable,” said Dr. Adami. “With the highest dose [50 mg/day], the change in spine BMD was similar to that which [can be] achieved with bisphosphonate therapy.” Overall there was a dose-related increase in both spine and hip BMD (see table).
In terms of bone resorption, the researchers looked at levels of urinary N-terminal cross-linked telopeptides of type I collagen (normalized with respect to urine creatinine) and serum C-terminal collagen I telopeptide (CTX).
In the first month of treatment, a decrease was observed in serum CTX levels. However, over the next 11 months, there was a trend of rising CTX levels in all patients—even those in the placebo group. “We do not have an explanation,” said Dr. Adami. Overall, there was also a dose-related decrease in serum CTX and urinary NTX levels.
In terms of biomarkers of bone formation, the researchers measured serum osteocalcin and NTX. Serum osteocalcin and NTX decreased somewhat during the early stages but at 12 months, no differences were observed between the treated and placebo patients. Overall, bone resorption markers were decreased, while bone formation markers remained the same.
The numbers of adverse events were very similar between all of the groups. Two patients developed sclerodermic/morphea-like lesions, which improved when the treatment was stopped, Dr. Adami reported.
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