title: Denosumab in treatment-naïve and pre-treated with zoledronic acid postmenopausal women with low bone mass: Effect on bone mineral density and bone turnover markers.
abstract: OBJECTIVE
  To compare denosumab-induced changes in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD), bone markers and free soluble receptor activator of nuclear factor kappaB ligand (sRANKL) between treatment naïve postmenopausal women with low bone mass (naïve group) and those who were previously treated with a single zoledronic acid infusion (post-Zol group).
  
  
  METHODS
  Procollagen type 1N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTx) and sRANKL levels were measured in serum samples obtained at baseline and 3, 6 and 12months after denosumab initiation. LS and FN BMD were measured at baseline and 12months.
  
  
  RESULTS
  LS and FN BMD increased significantly in both naïve and post-Zol group (p<0.001 and p=0.025 vs. p<0.001 and p=0.017, respectively). Despite the higher P1NP and CTx levels in naïve patients at baseline (both p<0.001), denosumab caused comparable decreases in both groups at month 3, which returned to post-Zol group baseline levels at month 6 and 12 in all patients. Similarly, sRANKL levels decreased significantly at month 3 in both groups and returned to baseline levels at months 6 and 12.
  
  
  CONCLUSIONS
  In patients previously treated with zoledronic acid, sequential denosumab treatment is effective in terms of BMD increases and bone turnover suppression. Despite the lower baseline levels in patients pre-treated with zoledronic acid, bone markers are similarly decreased in both groups following denosumab administration and maintain their reversibility. Denosumab reversibly suppresses endogenous free sRANKL levels in both naïve and zoledronic acid pre-treated patients.
authors.affiliation: Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece. Electronic address: anastath@endo.gr.
authors.forename: Athanasios D
authors.initials: AD
authors.lastname: Anastasilakis
authors.affiliation: Second Medical Clinic, Department of Medicine, Aristotle University of Thessaloniki, Ippokration General Hospital, Thessaloniki, Greece.
authors.forename: Stergios A
authors.initials: SA
authors.lastname: Polyzos
authors.affiliation: Department of Endocrinology, "Hippokration" General Hospital of Thessaloniki, Thessaloniki, Greece.
authors.forename: Zoe A
authors.initials: ZA
authors.lastname: Efstathiadou
authors.affiliation: 1st Department of Orthopaedics, 424 General Military Hospital Thessaloniki, Greece.
authors.forename: Matthaios
authors.initials: M
authors.lastname: Savvidis
authors.affiliation: Department of Rheumatology, 424 General Military Hospital, Thessaloniki, Greece.
authors.forename: Grigorios T
authors.initials: GT
authors.lastname: Sakellariou
authors.affiliation: Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, Athens, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papatheodorou
authors.affiliation: Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, Athens, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kokkoris
authors.affiliation: Department of Endocrinology and Diabetes, 251 Hellenic Air Force & VA General Hospital, Athens, Greece.
authors.forename: Polyzois
authors.initials: P
authors.lastname: Makras
mesh_terms: D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D016723:Bone Remodeling / Q000187:drug effects*; D024042:Collagen Type I / Q000097:blood; D000069448:Denosumab / Q000008:administration & dosage*; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D017698:Postmenopause / Q000187:drug effects; D011347:Procollagen / Q000097:blood; D053245:RANK Ligand / Q000097:blood; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D053245:RANK Ligand; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D000069448:Denosumab; D000077211:Zoledronic Acid
keywords: Bone markers; Bone mineral density; Denosumab; RANKL; Zoledronic acid