Effect of Bisphosphonates on Skeletal Related Events in Long Bone Metastases of Renal Cell Carcinoma: A Review

Bone metastases (BMs) in patients with renal cell carcinoma (RCC) are lytic lesions which are prone to skeletal related events (SREs) such as (pending) pathological fractures or bone pain requiring radiotherapy or surgery. The aim of this review is to assess whether the use of bisphosphonates in patients with RCC and BMs in the long bones results in reduced SRE rate. A systematic review of literature was conducted, using PubMed, Embase, Medline, Web of Science, Cochrane, and Google Scholar (date 1971 till June 2021). All clinical studies on bisphosphonates in patients with RCC and BMs in long bones were retr ieved. Pr imary outcome measure was SRE rate of BMs in long bones. Secondary outcome was fracture rate of BMs in long bones. Fourteen relevant articles were selected. Bisphosphonates reduced the mean skeletal morbidity rate by 0.4-0.95 SREs/year and had a pooled SRE rate of 38.3% (95% confidence interval [CI] 28.4%-49.3%). When bisphosphonates were added to radiotherapy the pooled SRE rate was 18.4% (95% CI, 10.5%-30.3%). In addition, pooled effect sizes showed a significant SRE risk reduction (RR 0.45, 95% CI, 0.24-0.85) in the bisphosphonates combined with radiotherapy group. There was limited reported data on rate of pathological fractures. In general, bisphosphonates reduce the SRE rate in RCC patients with BMs. The level of evidence for the effect of bisphosphonates on the rate of pathological fractures in patients with long BMs of RCC is low.