Osteoporosis International

, Volume 26, Issue 10, pp 2521–2527 | Cite as

Denosumab versus zoledronic acid in patients previously treated with zoledronic acid

  • A. D. AnastasilakisEmail author
  • S. A. Polyzos
  • A. Gkiomisi
  • Z. G. Saridakis
  • D. Digkas
  • I. Bisbinas
  • G. T. Sakellariou
  • A. Papatheodorou
  • P. Kokkoris
  • P. Makras
Original Article



Denosumab and zoledronic acid are potent antiresorptives. In this study in patients pre-treated with zoledronic acid, denosumab achieved similar increases with zoledronic acid in lumbar spine BMD despite the more prominent reduction of bone turnover markers. Denosumab reversibly reduced endogenous RANKL.


We aimed to compare yearly changes in lumbar spine (LS) bone mineral density (BMD), bone turnover markers, free soluble receptor activator of nuclear factor kappaB ligand (sRANKL) and sclerostin levels between denosumab and zoledronic acid.


Postmenopausal women with low bone mass previously treated with zoledronic acid for 1 year were assigned to denosumab injection (n = 32) or zoledronic acid infusion (n = 26). Procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTx), sRANKL, and sclerostin levels were measured in serum samples obtained at baseline and 3, 6, and 12 months after denosumab injection or zoledronic acid infusion. LS BMD was measured at baseline and 12 months.


The mean LS increase was 4.5 and 4.4 % with denosumab and zoledronic acid, respectively (p = 0.560). Denosumab caused a larger decrease in CTx at 3 months (p < 0.001) and P1NP at 3 (p < 0.001), 6 (p = 0.021), and 12 months (p = 0.042). Denosumab significantly decreased sRANKL by 87.4 % at 3 months (p < 0.001). Sclerostin levels were not changed with either intervention (p = 0.162 and p = 0.214, respectively).


In patients previously treated with zoledronic acid, denosumab reduces bone turnover more than zoledronic acid, but the increases in LS BMD are comparable. Furthermore, denosumab administration results in reversible inhibition of the metabolically significant endogenous free soluble RANKL levels. Serum sclerostin is not affected by either agent.


Bone mineral density Bone turnover markers Denosumab RANKL Sclerostin Zoledronic acid 



We thank Roche Diagnostics Hellas for providing us the kits for the measurements of CTx, P1NP, PTH, and 25(OH)D.

Conflicts of interest

Athanasios D. Anastasilakis has received lecture fees and research grant from Amgen and lecture fees from Lilly; Stergios A. Polyzos has received lecture fee and research grant from Amgen; Athina Gkiomisi, Zacharias G. Saridakis, Dimitrios Digkas, Ilias Bisbinas, Grigorios T. Sakellariou, Athanasios Papatheodorou, and Panagiotis Kokkoris have nothing to declare. Polyzois Makras has received lecture fees and research grants from Amgen, and lecture fees from Glaxo, Lilly, Pfizer, Leo, Genesis, ELPEN, VIANEX. Neither Amgen nor Novartis had any implication in any stage of this study (study’s conception and design, analysis and interpretation of data, drafting, or revising the manuscript).


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2015

Authors and Affiliations

  • A. D. Anastasilakis
    • 1
    Email author
  • S. A. Polyzos
    • 2
  • A. Gkiomisi
    • 3
  • Z. G. Saridakis
    • 4
  • D. Digkas
    • 4
  • I. Bisbinas
    • 5
  • G. T. Sakellariou
    • 6
  • A. Papatheodorou
    • 7
  • P. Kokkoris
    • 7
  • P. Makras
    • 8
  1. 1.Department of Endocrinology424 General Military HospitalThessalonikiGreece
  2. 2.Second Medical Clinic, Department of Medicine, Ippokration General HospitalAristotle University of ThessalonikiThessalonikiGreece
  3. 3.Department of Obstetrics and Gynaecology424 General Military HospitalThessalonikiGreece
  4. 4.Hellenic Military School of MedicineThessalonikiGreece
  5. 5.1st Department of Orthopaedics424 General Military HospitalThessalonikiGreece
  6. 6.Department of Rheumatology424 General Military HospitalThessalonikiGreece
  7. 7.Department of Medical Research251 Hellenic Air Force & VA General HospitalAthensGreece
  8. 8.Department of Endocrinology and Diabetes251 Hellenic Air Force & VA General HospitalAthensGreece

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