Systematic review
The effect of radiotherapy, and radiotherapy combined with bisphosphonates or RANK ligand inhibitors on bone quality in bone metastases. A systematic review

https://doi.org/10.1016/j.radonc.2016.03.001Get rights and content

Abstract

Purpose

The role of radiotherapy in stabilizing metastatic bones is unclear. This systematic review assessed the effects of (1) radiotherapy, (2) radiotherapy combined with bisphosphonates, and (3) radiotherapy combined with RANK ligand (RANKL) inhibitors on bone quality and bone strength in bone metastases originating from solid tumors.

Methods

Pubmed, EMBASE and the Cochrane Library were searched. Any type of study design and type and dose of radiotherapy, bisphosphonates and RANKL inhibitors were allowed.

Results

39 articles were identified. Animal studies showed that radiotherapy had similar effects on bone quality and strength as receiving no treatment, whereas adding bisphosphonates to radiotherapy restored bone quality and strength. In patient studies, bone density increased after radiotherapy and radiotherapy combined with bisphosphonates. However, due to the often non-optimal study design and study quality, it was unclear whether this increase could be attributed to these treatments. There was insufficient evidence to assess the additional effect of bisphosphonates or RANKL inhibitors.

Conclusion

Despite the clinical experience that radiotherapy is an effective treatment for bone metastases, there was no sufficient evidence for a positive effect on bone quality and fracture risk. Animal studies showed that adding bisphosphonates to radiotherapy restored bone quality and strength, whereas this was not proven in patients. There were no studies addressing the adjunct effect of RANKL inhibitors to radiotherapy. Although associated with several methodological, practical and ethical challenges, randomized controlled trials are needed.

Section snippets

Search strategy

PubMed, EMBASE and the Cochrane Library were searched (last search performed November 26th, 2015). No limits were used for PubMed and the Cochrane Library. The search in EMBASE was limited to articles, errata, and reviews. The search strategy included search terms and their synonyms for bone metastases, radiotherapy, bisphosphonates, RANKL inhibitors, bone mineral density, bone quality and bone strength. The search strategy was developed in collaboration with information specialists from the

Study selection

The search strategy retrieved 3273 unique records. Subsequent selection procedure resulted in 37 eligible articles. Two additional relevant articles were found via cross-referencing. Thus, 39 studies [17], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66] were included in this systematic review (Fig. 1). Vassiliou et al.

Discussion

We conducted this study to systematically review all studies on the effect of (1) radiotherapy, (2) radiotherapy combined with bisphosphonates, and (3) radiotherapy combined with RANKL inhibitors on bone quality and bone strength parameters in bone metastases originating from solid tumors.

In clinical practice, patients are often treated with a combination of local radiotherapy and systemic treatments. These systemic treatments include e.g. anticancer treatments with chemotherapy or hormonal

Conclusion

Based on this systematic review, it can be concluded there was no sufficient evidence that radiotherapy had a positive effect on bone quality and fracture risk. In addition, animal studies showed that the addition of BPs to radiotherapy restored bone quality and bone strength to that of healthy bone, whereas this is not yet proven in patients. Furthermore, there were neither animal nor patient studies addressing the effect of RANKL inhibitors as an adjunct to radiotherapy on bone quality and

Author contributions

All authors have made substantial contributions to all three of the following sections:

  • 1)

    The conception and design of the study, or acquisition of data, or analysis and interpretation of data;

  • 2)

    Drafting the article or revising it critically for important intellectual content; and

  • 3)

    Final approval of the version to be submitted.

Conflicts of interest statement

No conflict of interest

Acknowledgments

We greatly appreciate the help of Elmie Peters and Alice Tillema from the Radboud University Nijmegen Library of Medical Sciences with developing the search strategy. This study was funded internally by the Radboudumc.

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