Alendronate reduces osteoclast precursors in osteoporosis.
This study evaluates the effect of alendronate on osteoclastogenesis, cytokine production, and bone resorption in postmenopausal women. We suggest that it acts on mature bone resorbing osteoclasts after 3 months of treatment, whereas, after 1 year, it diminishes their formation by reducing their precursors and serum RANKL.


BACKGROUND
Osteoclasts are the target cells of bisphosphonates, though the most drug-sensitive steps of their formation and activity have not been determined. The present study evaluates the effect of alendronate on osteoclastogenesis, cytokine production, and bone resorption in postmenopausal women.


METHODS
The study was conducted on 35 osteoporotic women; 15 were pretreated with alendronate 70 mg/week, whereas, 20 were treated with calcium 1 g/day and vitamin D 800 IU/day. After 3 months, 30 received alendonate 70/mg, vitamin D 2800 IU/week, and calcium 1 g/day for 12 months (combined therapy), whereas, the other five patients remained on calcium 1 g/day and vitamin D 800 IU/day. The following parameters were assessed before and after therapy: changes in bone resorption markers, circulating osteoclast precursors, formation of osteoclasts in peripheral blood mononuclear cell cultures, their viability, and variations in cytokines production.


RESULTS
After 3 months of alendronate, there was no significant reduction in the number of osteoclast precursors, osteoclast formation and viability, and cytokine levels, whereas, there was a significant reduction of bone resorption markers. One year of the combined therapy, on the other hand, reduced osteoclast precursors, osteoclast formation, and serum RANKL, whereas, calcium plus vitamin D alone had no effect.


CONCLUSIONS
We suggest that alendronate mainly acts on mature bone resorbing osteoclasts in the short term, whereas, its long-term administration diminishes their formation by reducing their precursors and serum RANKL.
D'Amelio
P
P
Gerontology Section, Department of Surgical and Medical Disciplines, University of Torino, Corso Bramante 88/90, 10126, Torino, Italy. patrizia.damelio@unito.it
Grimaldi
A
A
Cristofaro
M A
MA
Ravazzoli
M
M
Molinatti
P A
PA
Pescarmona
G P
GP
Isaia
G C
GC
D000368:Aged; D019386:Alendronate / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D001862:Bone Resorption / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D002118:Calcium / Q000627:therapeutic use; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008875:Middle Aged; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D053245:RANK Ligand / Q000097:blood; D013234:Stem Cells / Q000187:drug effects; D014807:Vitamin D / Q000627:therapeutic use
D050071:Bone Density Conservation Agents; D016207:Cytokines; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D014807:Vitamin D; D002118:Calcium; D019386:Alendronate