Bisphosphonates INCREASE osteoclast number?

A new study published in NEJM questions the long-held belief that bisphosphonate use promotes osteoclast apoptosis.
This study examined 51 bone-biopsy specimens obtained after a 3-year, double-blind, randomized, placebo-controlled, dose-ranging trial of oral alendronate to prevent bone resorption among healthy postmenopausal women 40 through 59 years of age. The patients were assigned to one of five groups: those receiving placebo for 3 years; alendronate at a dose of 1, 5, or 10 mg per day for 3 years; or alendronate at a dose of 20 mg per day for 2 years, followed by placebo for 1 year. Formalin-fixed, undecalcified planar sections were assessed by bone histomorphometric methods.

The Results were startling:
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 (P<0.01).> the number of osteoclasts increased as the cumulative dose of the drug increased (r=0.50, P<0.001).> of these osteoclasts were giant cells with pyknotic nuclei that were adjacent to superficial resorption cavities. Furthermore, giant, hypernucleated, detached osteoclasts with 20 to 40 nuclei were found after alendronate treatment had been discontinued for 1 year. Of these large cells, 20 to 37% were apoptotic, according to both their morphologic features and positive findings from in situ end labeling.

The discussion also has a great explanation as to why this may be occurring. It is too long to add here but to paraphrase, it appears the signal for the osteoclasts to undergo apoptosis is from the calcium they have just absorbed. Since the bisphosphonates inhibit this bone resoption, they stop the signal to enter into apoptosis.

Can read further here...