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Alendronate treatment increased number of osteoclasts
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Long-term alendronate was associated with an increase in the number of osteoclasts, including distinctive giant, hypernucleated, detached osteoclasts undergoing protracted apoptosis, according to study findings.
Researchers randomly assigned postmenopausal women to placebo for three years; 1 mg, 5 mg or 10 mg per day of alendronate (Fosamax, Merck) for three years; or 20 mg per day of alendronate for two years followed by placebo for one year. They examined 51 bone biopsy specimens.
Compared with the placebo group, the number of osteoclasts increased by a factor of 2.6 in patients assigned to 10 mg of alendronate per day for three years (P<.01), according to the researchers.
The number of osteoclasts increased as the cumulative dose of alendronate increased (P<.001), according to the researchers. Twenty-seven percent of the osteoclasts were giant cells with pyknotic nuclei and were adjacent to superficial resorption cavities.
After treatment had been discontinued for one year, researchers found giant, hypernucleated, detached osteoclasts with 20 to 40 nuclei, and 20% to 37% of these osteoclasts were apoptotic. – by Christen Haigh
N Engl J Med. 2009;360:53-62.
This article provides some explanation and some concern. This study provides the anatomic explanation of what bisphosphonates do and provides an explanation of why there is long-term effect of fracture risk reduction, even if the bisphosphonate is discontinued. The drug, by inhibiting a key step in the metabolism of the osteoclast, prevents the cell from attaching to bone and in so doing, prevents bone from being resorbed. But the drug also prolongs the life of the oseoclast, by interfering with programmed cell death, possibly by decreasing the cell's access to calcium. The practical question is whether the prolonged survival of these altered osteoclasts will have long-term consequences in bone remodeling, bone microstructure and bone strength. That is not yet clear.
– Donald A. Bergman, MD
Endocrine Today Editorial Board member