title: Denosumab significantly increases bone mineral density and reduces bone turnover compared with monthly oral ibandronate and risedronate in postmenopausal women who remained at higher risk for fracture despite previous suboptimal treatment with an oral bisphosphonate.
abstract: Managing osteoporotic patients suboptimally adherent to bisphosphonates (BPs) is difficult. Such patients who remained at higher risk for fracture (≥1 risk factor) were transitioned to denosumab or a monthly oral BP. Denosumab-treated subjects had significantly greater increases in bone mineral density and decreases in bone turnover in this 12-month study.
  
  
  BACKGROUND
  A clinical need exists to manage patients who are suboptimally adherent to oral BPs and remain at higher risk for fracture. Here, we compare the effects on bone mineral density (BMD) and bone turnover of transitioning such patients to denosumab or monthly oral BP (ibandronate or risedronate).
  
  
  METHODS
  In two previous multicenter, open-label studies, postmenopausal women ≥55 years previously treated with, though suboptimally adherent to, a daily or weekly BP were randomized to denosumab 60 mg subcutaneously every 6 months (N = 852) or oral BP 150 mg monthly (N = 851) for 12 months. In this combined post-hoc analysis, a subset of higher risk subjects was identified, and the percentage changes from baseline in BMD and serum C-telopeptide of type I collagen (sCTX-1) were assessed.
  
  
  RESULTS
  In the overall population, denosumab was associated with greater gains in BMD at 12 months than monthly oral BP at the total hip, femoral neck, and lumbar spine (p < 0.0001 for all). In higher risk subjects, denosumab led to greater gains in BMD than oral BPs at the total hip (2.2 vs 0.8 %), femoral neck (1.8 vs 0.3 %), and lumbar spine (3.7 vs 1.4 %) (p < 0.0001 for all). Denosumab also led to greater decreases in sCTX-1 in the overall population and higher risk subjects at months 1 and 6 (p < 0.0001 for both). Adverse events and serious adverse events were generally similar between treatment groups.
  
  
  CONCLUSIONS
  Transitioning to denosumab was well tolerated and more effective in increasing BMD and reducing bone turnover than cycling to a monthly oral BP treatment in subjects who remained at higher fracture risk despite suboptimal BP treatment.
authors.affiliation: CHU de Québec Research Centre and Laval University, Room S-763, 2705 Laurier Boulevard, Quebec City, QC, G1V 4G2, Canada, jacques.brown@crchul.ulaval.ca.
authors.forename: J P
authors.initials: JP
authors.lastname: Brown
authors.forename: C
authors.initials: C
authors.lastname: Roux
authors.forename: P R
authors.initials: PR
authors.lastname: Ho
authors.forename: M A
authors.initials: MA
authors.lastname: Bolognese
authors.forename: J
authors.initials: J
authors.lastname: Hall
authors.forename: H G
authors.initials: HG
authors.lastname: Bone
authors.forename: S
authors.initials: S
authors.lastname: Bonnick
authors.forename: J P
authors.initials: JP
authors.lastname: van den Bergh
authors.forename: I
authors.initials: I
authors.lastname: Ferreira
authors.forename: P
authors.initials: P
authors.lastname: Dakin
authors.forename: R B
authors.initials: RB
authors.lastname: Wagman
authors.forename: C
authors.initials: C
authors.lastname: Recknor
mesh_terms: D000284:Administration, Oral; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D024042:Collagen Type I / Q000097:blood; D000069448:Denosumab; D004164:Diphosphonates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D012968:Etidronic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D006621:Hip Joint / Q000503:physiopathology; D006801:Humans; D000077557:Ibandronic Acid; D007279:Injections, Subcutaneous; D008159:Lumbar Vertebrae / Q000503:physiopathology; D055118:Medication Adherence; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D058866:Osteoporotic Fractures / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D010455:Peptides / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D000068296:Risedronic Acid; D012307:Risk Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000069448:Denosumab; D000068296:Risedronic Acid; D012968:Etidronic Acid; D000077557:Ibandronic Acid