Multiparametric assessment of bone health in metastatic hormone-sensitive prostate cancer patients receiving androgen deprivation + enzalutamide ± zoledronic acid (BonEnza study)

Androgen deprivation therapy has a negative effect on bone mineral density and trabecular bone score in prostate cancer patients. The addition of androgen receptor pathway inhibitors can result in worsened skeletal fragility.BonEnza is a prospective phase II trial in which metastatic hormone sensitive prostate cancer patients were randomized to receive androgen deprivation therapy plus enzalutamide with (EZ arm) or without (E arm) the addition of zoledronic acid. Bone quantity and quality parameters were evaluated by dual-energy x-ray absorptiometry (DXA) scan at baseline and after 18 months of therapy. Alkaline phosphatase (ALP) and C-terminal telopeptide of type I collagen (CTX) were assessed at baseline and after 18 months of treatment.Eighty-nine patients had paired DXA evaluation at both timepoints. After 18 months of treatment femoral neck and lumbar spine bone mineral density significantly decreased in E arm (−8.6% and − 9.26% respectively; p < 0.001), while improved in EZ arm (+1.83%, p 0.019; and + 5.47%, p < 0.001). Trabecular bone score significantly worsened in E arm (−3.35%, p < 0.001) and improved in EZ arm (+3.01%, p 0.004).Both ALP and CTX showed marked reduction overtime among patients receiving zoledronic acid (−35.6%, p < 0.0001, and − 58.9%, p < 0.0001, respectively), while remaining stable (−0.6%, p 0.934) or significantly increasing (39.5%, p 0.011) respectively among patients from E arm.The addition of zoledronic acid to enzalutamide and androgen deprivation improved bone mineral density, trabecular bone score, and reduced bone turnover markers. Future studies in mHSPC should consider the use of lower doses of bone protecting agents and regard the reduction in morphometric fractures by DXA as a primary endpoint.