In radiation oncology, little is known about possible difficulties in patients with Osteogenesis Imperfecta (OI). Because radiotherapy can cause various side-effects including bone, soft tissue and cardiovascular toxicities, we foresee that patients with OI may experience even more acute and late side-effects due to pre-existing problems. We present two cases of radiotherapy in patients with OI, measured the effects of radiation on their bone mineral density and provide clinical recommendations for patient tailored radiotherapy strategies in patients with OI.