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Update on denosumab in postmenopausal osteoporosis—recent clinical data

Densoumab bei postmenopausaler Osteoporose – rezente klinische Daten

Wiener Medizinische Wochenschrift volume 162, pages 374–379 (2012)Cite this article

An Erratum to this article was published on 20 December 2012

Summary

Denosumab, a fully human monoclonal antibody against the key osteoclastogenic factor RANK ligand, is currently approved for the treatment of postmenopausal osteoporosis. Denosumab differs from bisphosphonates in many aspects, for example, its ability to act in the extracellular compartment and its likelihood to be distributed throughout the skeleton. In contrast, bisphosphonates have to be internalized by osteoclasts and are mainly located across bone surfaces. This could explain why patients with osteoporosis, who are already treated with bisphosphonates, might experience further benefit when switching to denosumab. Head-to-head studies revealed that transition to denosumab resulted in a greater increase of bone mineral density (BMD) and a greater reduction of bone turnover than did continued alendronate. Additional analyses of the phase 3 FREEDOM trial demonstrated that fracture reduction was particularly high in cortical bone, such as the wrist. In addition, denosumab treatment for a 5- and 8-year period showed sustained reduction in fracture risk, increase in BMD and continued to be well tolerated. The 7-year extension study of FREEDOM and a phase 3 trial evaluating denosumab for the treatment of male osteoporosis are still ongoing and will provide supportive data in the near future.

Zusammenfassung

Denosumab, ein voll-humaner monoklonaler Antikörper gegen den zentralen Osteoklastenfaktor RANK Ligand, ist derzeit zur Behandlung der postmenopausalen Osteoporose zugelassen. Denosumab unterscheidet sich von Bisphosphonaten in vielerlei Hinsicht, unter anderem darin, dass Denosumab seine Wirkung im extrazellulären Raum entfaltet und sich wahrscheinlich im gesamten Skelett verteilt. Im Gegensatz dazu müssen Bisphosphonate von Osteoklasten aufgenommen werden und verteilen sich überwiegend an den Knochenoberflächen. Dies könnte erklären, warum Osteoporose-Patienten, die bereits mit Bisphosphonaten behandelt wurden, weitere klinische Verbesserungen aufweisen, wenn ihre Therapie auf Denosumab umgestellt wird. Direkte Vergleichsstudien zeigten, dass eine Umstellung auf Denosumab zu einem größeren Anstieg der Knochenmineraldichte (BMD) und größerer Reduktion des Knochenumbaus führte, als eine Weiterbehandlung mit Alendronat. Zusätzliche Analysen der Phase 3 FREEDOM Studie belegten, dass die Verringerung der Frakturen besonders hoch bei kortikalen Knochen war, beispielsweise in den Handgelenksknochen. Zusätzlich zeigte die Denosumab Behandlung über fünf und acht Jahre eine anhaltende Verringerung des Frakturrisikos, einen weiteren Anstieg der BMD und eine anhaltend gute Verträglichkeit. Die über sieben Jahre laufende Verlängerungsstudie von FREEDOM und eine Phase 3 Studie zur Wirkung von Denosumab bei männlichen Osteoporose Patienten laufen derzeit und werden in näherer Zukunft weitere Daten liefern.

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Conflict of interest

All authors serve/served as primary or coordinating investigators for the FREEDOM study in Austria.

Christian Muschitz has received speaker honoraria from Amgen, Novartis, Servier, Eli Lilly, Nycomed/Takeda, and has received educational grants/research support from Roche Austria, Eli Lilly Austria and Amgen Austria.

Astrid Fahrleitner-Pammer has received speaker honoraria from Amgen, Biomedika, Daichii, Roche, Novartis, Merck, MSD, Sanofi-Aventis, Eli Lilly, Takeda, Servier and has received educational grants.

Johannes Huber has no conflict of interest concerning this paper.

Elisabeth Preisinger has no conflict of interest.

Stefan Kudlacek has no conflict of interest.

Heinrich Resch has received speaker honoraria from Amgen, Novartis, Servier, Eli Lilly, Nycomed/Takeda, Merck (MSD), and has received educational grants/research support from Eli Lilly and Roche.

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Affiliations

  1. VINFORCE Study Group, St. Vincent Hospital, Medical Department II, Academic Teaching Hospital, Medical University of Vienna, Stumpergasse 13, 1060, Vienna, Austria

    Christian Muschitz MD & Heinrich Resch MD

  2. Division of Endocrinology and Metabolism, Medical University Graz, Graz, Austria

    Astrid Fahrleitner-Pammer MD

  3. Clinic for Gynecology and Obstetrics, Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria

    Johannes Huber MD, PhD

  4. Deptartment of Physical Medicine and Rehabilitation, Hietzing Hospital and Neurology Center Rosenhuegel, Vienna, Austria

    Elisabeth Preisinger MD

  5. Department of Internal Medicine, Hospital Barmherzige Brueder Vienna, Vienna, Austria

    Stefan Kudlacek MD

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  1. Christian Muschitz MD
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  2. Astrid Fahrleitner-Pammer MD
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  3. Johannes Huber MD, PhD
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  4. Elisabeth Preisinger MD
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  5. Stefan Kudlacek MD
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  6. Heinrich Resch MD
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Correspondence to Christian Muschitz MD.

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Muschitz, C., Fahrleitner-Pammer, A., Huber, J. et al. Update on denosumab in postmenopausal osteoporosis—recent clinical data. Wien Med Wochenschr 162, 374–379 (2012). https://doi.org/10.1007/s10354-012-0116-x

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  • DOI: https://doi.org/10.1007/s10354-012-0116-x

Keywords

  • Postmenopausal osteoporosis
  • Denosumab
  • Fractures
  • Bone mineral density
  • Review

Schlüsselwörter

  • Postmenopausale Osteoporose
  • Denosumab
  • Frakturen
  • Knochenmineraldichte
  • Review