title: Time course of bone mineral density changes with denosumab compared with other drugs in postmenopausal osteoporosis: a dose-response-based meta-analysis.
abstract: OBJECTIVE
  Our objective was to compare the time course of bone mineral density (BMD) changes at the lumbar spine (LS) and total hip (TH) in postmenopausal women during treatment with denosumab, bisphosphonates, selective estrogen receptor modulators, PTH, or calcitonin.
  
  
  METHODS
  Data were extracted from 142 randomized controlled trials for prevention or treatment of postmenopausal osteoporosis representing over 113,000 women.
  
  
  METHODS
  The percent change from baseline in BMD was analyzed using a nonlinear least-squares random-effects meta-regression analysis. The dose-response relationship of BMD changes was well characterized by a maximal effect (EMax) model with a different EMax for LS and TH for each drug class. The ratio of LS and TH BMD changes was significantly different across the different drug classes. The time course of BMD changes was well characterized by an exponential onset with a different rate for LS and TH for each drug class. The dose-response relationship for denosumab showed that the approved dosing regimen of 60 mg every 6 months resulted in maximal BMD changes.
  
  
  CONCLUSIONS
  This exploratory analysis shows that 3 years of treatment with denosumab resulted in bigger changes in LS and TH BMD compared with 3 years of treatment with 10 mg/d oral alendronate, 5 mg/y i.v. zoledronic acid, 5 mg/d oral risedronate, 150 mg/mo oral ibandronate, 3 mg i.v. ibandronate every 3 months, 60 mg/d oral raloxifene, and 200 IU/d calcitonin. Treatment with PTH resulted in larger changes in LS BMD compared with denosumab; however, denosumab treatment provided larger changes in TH BMD.
authors.affiliation: Quantitative Solutions (J.W.M.), Menlo Park, California 94025; Amgen Inc (J.Z., C.L.), Thousand Oaks, California 91320; and Amgen (J.J.P.R.), 46530 Puzol, Valencia, Spain.
authors.forename: Jaap W
authors.initials: JW
authors.lastname: Mandema
authors.forename: Jenny
authors.initials: J
authors.lastname: Zheng
authors.forename: Cesar
authors.initials: C
authors.lastname: Libanati
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Perez Ruixo
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D002116:Calcitonin / Q000008:administration & dosage; D000069448:Denosumab; D004164:Diphosphonates / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D016018:Least-Squares Analysis; D008159:Lumbar Vertebrae / Q000473:pathology; D008875:Middle Aged; D017711:Nonlinear Dynamics; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000473:pathology; D010281:Parathyroid Hormone / Q000008:administration & dosage; D011237:Predictive Value of Tests; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D016032:Randomized Controlled Trials as Topic; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D010281:Parathyroid Hormone; D053245:RANK Ligand; D020845:Selective Estrogen Receptor Modulators; D000069448:Denosumab; D002116:Calcitonin