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

Abstract

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.

Carbon-Ion Beam Irradiation Alone or in Combination with Zoledronic acid Effectively Kills Osteosarcoma Cells

“…In addition, treatment with carbon-ion beam irradiation combined with ZOL increased the number of cells in the G2/M phase, compared to the case for treatment with carbon-ion beam irradiation and ZOL alone, suggesting that the combination treatment significantly attenuated cell cycle progression. These findings are partially consistent with previous reports stating that ZOL augments the X-ray or γ-ray radiosensitivity of fibrosarcoma and nasopharyngeal carcinoma cells [22][23][24][25][26], indicating that ZOL not only enhances low LET photon beam radiosensitivity, but also high LET carbon-ion beam radiosensitivity in OSA cells.…”

“…However, although carbon ion beam radiotherapy treatment has yielded promising results, the prognosis of OSA still remains unsatisfactory; developing novel combinational therapeutic strategies to further improve overall survival is required.Bisphosphonates comprise the most important class of osteoclast-mediated bone resorption inhibitors and are used extensively for treating skeletal diseases such as postmenopausal osteoporosis and tumor-induced osteolysis [20,21]. Zoledronic acid (ZOL), a third-generation nitrogen-containing bisphosphonate, is an inhibitor of osteoclast-mediated bone resorption that has demonstrated efficacy in treating bone metastases in cancer patients with breast, prostate, lung, and other solid tumors [22][23][24]. ZOL significantly enhances radiation-induced apoptosis and decreases cell viability, suggesting that it may exhibit radiosensitizing effects [25][26][27][28][29][30][31][32][33].…”

Limited short-term effect of palliative radiation therapy on quantitative computed tomography-derived bone mineral density in femora with metastases

“…First, it should be noted that concurrent treatment with bisphosphonates may enhance the effect of RT on BMD 11, 12, 13. Although we did not find any interaction with medication, it may potentially have caused biased effects in the earlier studies that did not test this 8, 10.…”

“…Additionally, some studies report a beneficial effect of RT on bone mineral density (BMD),8, 9, 10, 11, 12 which is also the clinical experience of medical specialists. In contrast, this beneficial effect was not confirmed in a recent systematic review 13 . Moreover, the relationship between pain relief and BMD is unclear.…”

The role of radiotherapy in bone metastases: A critical review of current literature

“…A systemic review regarding the effect radiotherapy alone or combined with bisphosphonates for bone metastases was published in 2016 (Groenen et al., ). An increased of bone density was observed with radiotherapy alone and with the combination of bisphosphonates.…”