title: Risedronate reduces osteoclast precursors and cytokine production in postmenopausal osteoporotic women.
abstract: This paper studies the effect of oral risedronate on osteoclast precursors, osteoclast formation, and cytokine production in 25 osteoporotic women. Risedronate is effective in reducing the number of osteoclast precursors, their formation, vitality, and activity and the level of RANKL and TNF-alpha in cultures.
  
  
  BACKGROUND
  Bisphosphonates inhibit bone resorption by acting against osteoclasts. Some in vitro studies suggest that they induce osteoclast apoptosis; others suggest that they exert an effect on the production of pro-osteoclastogenic cytokines. The effect of risedronate on osteoclastogenesis by peripheral blood mononuclear cells (PBMCs) in postmenopausal osteoporosis has not been previously studied. This paper examined the influence of risedronate on the formation of osteoclast precursors and cytokine production within the compass of osteoclastogenesis in osteoporosis.
  
  
  METHODS
  This study was conducted on 38 osteoporotic women; 25 patients were treated with risedronate 5 mg/d, whereas 13 were treated with calcium 1 g/d and vitamin D 800 UI/d. The following parameters were assessed: changes in bone turnover, circulating osteoclast precursors, formation of osteoclasts in PBMC cultures, their activity and vitality, and variations in the production of pro-osteoclastogenic cytokines before and after therapy.
  
  
  RESULTS
  After 3 mo of risedronate, there was a significant reduction in the number and degree of differentiation of osteoclast precursors, osteoclast formation, vitality and activity, and in the level of RANKL and TNF in cultures and of TNF and osteoprotegerin (OPG) in serum, whereas in the group treated with calcium and vitamin D, there were no significant changes.
  
  
  CONCLUSIONS
  Our data show that risedronate is effective in lowering the number of circulating osteoclast precursors, their formation, vitality, and activity in cultures, and in reducing the level of pro-osteoclastogenic cytokines in culture supernatants and in serum.
authors.affiliation: Department of Internal Medicine, University of Torino, Torino, Italy. patrizia.damelio@unito.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: D'Amelio
authors.forename: Anastasia
authors.initials: A
authors.lastname: Grimaldi
authors.forename: Stefania
authors.initials: S
authors.lastname: Di Bella
authors.forename: Cristina
authors.initials: C
authors.lastname: Tamone
authors.forename: Stefano Z M
authors.initials: SZ
authors.lastname: Brianza
authors.forename: Marco G A
authors.initials: MG
authors.lastname: Ravazzoli
authors.forename: Paola
authors.initials: P
authors.lastname: Bernabei
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Cristofaro
authors.forename: Gian Piero
authors.initials: GP
authors.lastname: Pescarmona
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Isaia
mesh_terms: D000368:Aged; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D002118:Calcium / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D015663:Osteoporosis, Postmenopausal / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D053244:Osteoprotegerin / Q000096:biosynthesis; D017698:Postmenopause / Q000097:blood / Q000187:drug effects; D053245:RANK Ligand / Q000378:metabolism; D000068296:Risedronic Acid; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D050071:Bone Density Conservation Agents; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D; D000068296:Risedronic Acid; D012968:Etidronic Acid; D002118:Calcium