NEW YORK (Reuters Health) Dec 31 - Findings from a study of bone biopsies from women who took alendronate to prevent postmenopausal osteoporosis indicate that long-term treatment with the bisphosphonate actually increases rather than decreases the number of osteoclasts, as had been theorized.
Furthermore, the report in the January 1 issue of The New England Journal of Medicine shows that alendronate treatment gives rise to previously unrecognized giant multinucleated osteoclasts.
The 51 women who provided the bone samples were participants in a randomized placebo-controlled dose-ranging trial. Subjects in the alendronate arms had taken either 1, 5, or 10 mg/day for 3 years or 20 mg/day for 2 years followed by placebo for a year.
"The number of osteoclasts was increased by a factor of 2.6 in patients receiving 10 mg of alendronate per day for 3 years as compared with the placebo group," according to the paper. "Moreover, the number of osteoclasts increased as the cumulative dose of the drug increased."
The bisphosphonate was associated with the presence of what lead author Dr. Robert S. Weinstein from the University of Arkansas for Medical Sciences in Little Rock described to Reuters Health as "a drug-induced abnormality -- giant osteoclasts much larger and containing far more nuclei than normal."
The giant cells were detached from the bone surface, "with a seemingly protracted duration of apoptosis," the researchers found.
"Alendronate decreases the ability of the osteoclasts to erode bone but significantly increases the number of these cells," Dr. Weinstein said, adding that the observed effect is "akin to disarming the soldiers...but increasing the size of the army."
The giant osteoclasts were still present a year after therapy was stopped, the team reports.
Dr. Weinstein called the discoveries "a dramatic departure from current thinking." He commented that drugs are often used on the basis of practical experience and added, "We often don't know as much about drugs as we would like... We can know that they work, but not how they work."
Although the giant osteoclasts may be dysfunctional and of no pathophysiologic significance, "awareness of a drug's side effects is crucial," Dr. Weinstein said.
He and his colleagues caution that the giant osteoclasts "could lead to mistaken diagnosis of Paget's disease or hyperparathyroidism," but they point out that in these conditions, "osteoid and osteoblasts are abundant, whereas after long-term oral therapy with nitrogen-containing bisphosphonates, reductions in osteoid, osteoblasts, and bone formation are expected."
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου