Bone atrophy and its related fragility fractures are frequent, late side effects 
of radiotherapy in cancer survivors and have a detrimental impact on their 
quality of life. In another study, we showed that parathyroid hormone 1-34 and 
anti-sclerostin antibody attenuates radiation-induced bone damage by 
accelerating DNA repair in osteoblasts. DNA damage responses are partially 
regulated by the ubiquitin proteasome pathway. In the current study, we examined 
whether proteasome inhibitors have similar bone-protective effects against 
radiation damage. MG132 treatment greatly reduced radiation-induced apoptosis in 
cultured osteoblastic cells. This survival effect was owing to accelerated DNA 
repair as revealed by γH2AX foci and comet assays and to the up-regulation of 
Ku70 and DNA-dependent protein kinase, catalytic subunit, essential DNA repair 
proteins in the nonhomologous end-joining pathway. Administration of bortezomib 
(Bzb) reversed the loss of trabecular bone structure and strength in mice at 4 
wk after focal radiation. Histomorphometry revealed that Bzb significantly 
increased the number of osteoblasts and activity in the irradiated area and 
suppressed the number and activity of osteoclasts, regardless of irradiation. 
Two weeks of Bzb treatment accelerated DNA repair in bone-lining osteoblasts and 
thus promoted their survival. Meanwhile, it also inhibited bone marrow 
adiposity. Taken together, we demonstrate a novel role of proteasome inhibitors 
in treating radiation-induced osteoporosis.-Chandra, A., Wang, L., Young, T., 
Zhong, L., Tseng, W.-J., Levine, M. A., Cengel, K., Liu, X. S., Zhang, Y., 
Pignolo, R. J., Qin, L. Proteasome inhibitor bortezomib is a novel therapeutic 
agent for focal radiation-induced osteoporosis.