Bisphosphonates impair the onset of bone formation at remodeling sites

Bisphosphonates are widely used anti-osteoporotic drugs targeting osteoclasts. They strongly inhibit bone resorption, but also reduce formation. This reduced formation is commonly ascribed to the mechanism maintaining resorption/formation balance during remodeling. The present study provides evidence for an additional where bisphosphonates actually impair onset of after resorption. based on morphometric parameters recently developed assess activities reversing resorption Herein, we compare these in cancellous alendronate- and placebo-treated postmenopausal osteoporotic patients. Alendronate increases prevalence eroded surfaces characterized by reversal cells/osteoprogenitors at low cell density remote from active surfaces. indicates deficient expansion – event that indispensable start Furthermore, alendronate decreases coverage remodeling compartment canopies, a putative source cells/osteoprogenitors. Finally, activation frequency formation, more formative compared All correlate with each other. These observations lead model hamper osteoprogenitor recruitment required initiate effect results larger surface, thereby explaining well-known paradox without decreasing possible hampered discussed: may decrease release osteogenic factors osteoclasts, and/or released osteoclasts act directly neighboring cells as reported preclinical studies.