%0 Journal Article
%T Radium-223 Treatment Produces Prolonged Suppression of Resident Osteoblasts and Decreased Bone Mineral Density in Trabecular Bone in Osteoblast Reporter Mice.
%A Lin SC
%A Yu G
%A Corn PG
%A Damasco J
%A Lee YC
%A Song JH
%A Navone NM
%A Logothetis CJ
%A Melancon MP
%A Panaretakis T
%A Lin SH
%J Cancers (Basel)
%V 16
%N 14
%D 2024 Jul 21
%M 39061241
%F 6.575
%R 10.3390/cancers16142603
%X Radium 223 (Ra-223) is an α-emitting bone-homing radiopharmaceutical that targets tumor-induced osteoblasts and is used to reduce bone pain and prolong overall survival in men with bone-metastatic, castrate-resistant prostate cancer. However, increased fracture risk in skeletal sites with no bone metastasis has been observed in patients treated with Ra-223. Both luciferase- or green fluorescence protein (GFP)-labeled osteoblast reporter mice were used to monitor the effect of Ra-223 on resident osteoblasts and normal bone structure. Upon Ra-223 treatment, 70% of resident osteoblasts were reduced within 2 days, and the osteoblast reduction lasted for at least 18 weeks without detectable recovery, as measured by in vivo bioluminescent imaging. In GFP-labeled osteoblast reporter mice, Ra-223 mainly reduced osteoblasts localized in the trabecular bone areas; the osteoblasts in the growth plates were less affected. Micro-computed tomography analyses showed that Ra-223 significantly reduced bone mineral density and bone microstructure in the trabecular area of femurs but not in the cortical bone. Tumor-induced bone was generated by inoculating osteogenic TRAMP-BMP4 prostate cancer cells into the mouse femurs; Ra-223 treatment significantly reduced tumor-induced osteoblasts. Our study shows that Ra-223 affects bone structures that are not involved in bone metastasis. Strategies that improve bone health may reduce fracture risk in patients receiving Ra-223.