Benefits and harms of antiresorptive therapy in men with non-metastatic prostate cancer on androgen deprivation therapy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND

Androgen deprivation therapy (ADT) is used as an adjuvant treatment in men with prostate cancer. It is associated with bone loss and increased fracture risk. In this systematic review and meta-analysis, we evaluated the effects of antiresorptives on bone health in men with non-metastatic prostate cancer (nmPCa) on ADT.

METHODS

We searched four databases until October 14th 2024 for randomized controlled trials (RCTs) of antiresorptives in men with non-metastatic prostate cancer on ADT.

FINDINGS: We included 26 RCTs: Intravenous bisphosphonates (N = 17), oral bisphosphonates (N = 5) or denosumab (N = 2). 2 RCTs included both oral bisphosphonate and denosumab. Oral bisphosphonates had no effect on fracture incidence at 12-months (RR = 0.57; 95%CI[0.10, 3.23]; very low certainty). Intravenous bisphosphonates had no effect on the risk of morphometric vertebral fractures at 36-months (RR = 1.06; 95%CI[0.57,1.98]; very low certainty). One trial showed that denosumab probably results in a large reduction in new morphometric vertebral fracture risk at 12 (RR = 0.15), 24 (RR = 0.31) and 36-months (RR = 0.38; 95%CI[0.19-0.78]). Treatment with bisphosphonates or denosumab for 12-months increased BMD at the hip (+1.5 to +3.9%) and lumbar spine (+4.0 to +6.8%) and decreased BTMs (-26 to -78%). Data on mortality is scarce. The most common adverse events were gastrointestinal across all antiresorptives. Acute phase reactions were common with Intravenous bisphosphonates, while jaw osteonecrosis occurred more rarely.

INTERPRETATION: Denosumab decreases morphometric vertebral fractures risk in men with nmPCa receiving ADT. Anti-resorptive treatment had a protective effect on BMD and decreased BTMs. Well-designed powered RCTs are needed to assess their effect on fracture risk.