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Denosumab treatment for giant-cell tumor of bone: a systematic review of the literature

  • Orthopaedic Surgery
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Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

Abstract

Background

Denosumab is a human monoclonal antibody (mAb) that specifically inhibits tumor-associated bone lysis through the RANKL pathway and has been used as neoadjuvant therapy for giant-cell tumor of bone (GCTB) in surgical as well as non-surgical cases. The purpose of this systematic review of the literature, therefore, is to investigate: (1) demographic characteristics of patients affected by GCTBs treated with denosumab and the clinical impact, as well as, possible complications associated with its use (2) oncological outcomes in terms of local recurrence rate (LRR) and development of lung metastasis, and (3) characteristics of its treatment effect in terms of clinical, radiological, and histological response.

Methods

A systematic review of the literature was conducted using PubMed, EMBASE, and COCHRANE search including the following terms and Boolean operators: “Denosumab” AND “primary bone tumor”, “denosumab” AND “giant cell tumor”, “denosumab” AND “treatment”, and finally, “denosumab” AND “giant cell tumor” AND “treatment” since 2000. After applying inclusion and exclusion criteria, a total of 19 articles were included. The quality of the included studies was assessed using STROBE for the assessment of observational studies.

Results

A total of 1095 patients were included across all 19 studies. Across all the studies included, there were 615 females and 480 males. The mean patient age was 33.7 ± 8.3 years when starting the denosumab treatment. The pooled weighted local recurrence rate was 9% (95% CI 6–12%) and the pooled weighted metastases rate was 3% (95% CI 1–7%). The most common adverse event was fatigue and muscular pain. Radiologic response was estimated to occur in 66–100% of the patients. A significant reduction in pain under denosumab treatment was reported in seven studies and additional improvement in function and mobility was reported by several authors. Only two studies reported musculoskeletal tumor society (MSTS) scores which were better after denosumab treatment.

Conclusions

The use of denosumab as an adjuvant treatment of GCTB has shown a positive but variable histological response with consistent radiological changes and several types of adverse effects. There is a positive clinical response in terms of pain relief with decrease on the morbidity of surgical procedures to be performed. Finally, oncological outcomes are disparate with neither effect on metastatic disease nor local recurrence rates.

Level of evidence

IV.

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Funding

The authors, their immediate family, and any research foundation with which they are affiliated did not receive any financial payments or other benefits from any commercial entity related to the subject of this article. All authors significantly contributed to the document and have reviewed the final manuscript.

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Authors and Affiliations

  1. Hospital Universitario 12 de Octubre, Madrid, Spain

    Gonzalo Luengo-Alonso, Maria Mellado-Romero & Luis Ramos-Pascua

  2. Musculoskeletal Oncology Division, Department of Orthopedics, Miller School of Medicine, University of Miami, Miami, FL, USA

    Juan Pretell-Mazzini

  3. Department of Orthopedic Surgery, Rabin Medical Center, Petach Tikva, 49100, Israel

    Shai Shemesh

  4. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel

    Shai Shemesh

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  1. Gonzalo Luengo-Alonso
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Correspondence to Juan Pretell-Mazzini.

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Luengo-Alonso, G., Mellado-Romero, M., Shemesh, S. et al. Denosumab treatment for giant-cell tumor of bone: a systematic review of the literature. Arch Orthop Trauma Surg 139, 1339–1349 (2019). https://doi.org/10.1007/s00402-019-03167-x

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