title: Long-term disuse osteoporosis seems less sensitive to bisphosphonate treatment than other osteoporosis.
abstract: We sought to determine whether risedronate can preserve cortical bone mass and mechanical properties during long-term disuse in dogs, assessed by histomorphometry and biomechanics on metacarpal diaphyses. Risedronate slowed cortical thinning and partially preserved mechanical properties, but it was unable to suppress bone loss to the degree seen in other osteoporoses.
  
  
  BACKGROUND
  Disuse induces dramatic bone loss resulting from greatly elevated osteoclastic resorption. Targeting osteoclasts with antiresorptive agents, such as bisphosphonates, should be an effective countermeasure for preventing disuse osteoporosis.
  
  
  METHODS
  Single forelimbs from beagles (5-7 years old, n = 28) were immobilized (IM) for 12 months. Age-matched, non-IM dogs served as controls. One-half the animals received either risedronate (RIS, 1 mg/kg) or vehicle daily. Histomorphometry was performed on second metacarpal mid-diaphyses. Cortical mechanical properties were determined by testing third metacarpal diaphyses in four-point bending.
  
  
  RESULTS
  IM caused marked reduction in cortical area (-42%) and cortical thinning (-40%) through endocortical resorption, extensive intracortical tunneling, and periosteal resorption; both bone resorption and formation were significantly elevated over control levels on all envelopes. IM also decreased maximum load and stiffness by approximately 80% compared with controls. RIS reduced both periosteal bone loss and marrow cavity expansion; however, cortical area remained significantly lower in RIS-treated IM animals than in untreated non-IM controls (-16%). RIS also increased resorption indices in all envelopes compared with nontreated IM, indicating that RIS suppressed osteoclast activity but not osteoclast recruitment. RIS did not affect bone formation. RIS treatment conserved some whole bone mechanical properties, but they were still significantly lower than in controls. There were no significant differences in tissue level material properties among the groups.
  
  
  CONCLUSIONS
  RIS treatment reduces cortical bone loss at periosteal and endocortical surfaces caused by long-term immobilization, thus partially conserving tissue mechanical properties. This modest effect contrasts with more dramatic actions of the bisphosphonate in other osteoporoses. Our results suggest that risedronate impairs osteoclastic function but cannot completely overcome the intense stimulus for osteoclast recruitment during prolonged disuse.
authors.affiliation: Leni and Peter W. May Department of Orthopaedics, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
authors.forename: Chao Yang
authors.initials: CY
authors.lastname: Li
authors.forename: Christopher
authors.initials: C
authors.lastname: Price
authors.forename: Kemesha
authors.initials: K
authors.lastname: Delisser
authors.forename: Philip
authors.initials: P
authors.lastname: Nasser
authors.forename: Damien
authors.initials: D
authors.lastname: Laudier
authors.forename: Mariza
authors.initials: M
authors.lastname: Clement
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Jepsen
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Schaffler
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use*; D004285:Dogs; D004351:Drug Resistance; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005552:Forelimb / Q000473:pathology; D007103:Immobilization; D010024:Osteoporosis / Q000188:drug therapy*; D000068296:Risedronic Acid
chemical_list: D002121:Calcium Channel Blockers; D004164:Diphosphonates; D000068296:Risedronic Acid; D012968:Etidronic Acid