**5.1 Method of application**

The way of medication administration is an important factor in assessing the risk of developing osteonecrosis. Bisphosphonates taken orally have been shown to be more benign than bisphosphonates administered intravenously [3, 39]. The prevalence of medication related osteonecrosis in oral bisphosphonates is much lower (ranging from 0.1% to 0.05%) than the prevalence of intravenous bisphosphonates and denosumab (ranging from 2% to 10). Prevalence increases after invasive surgical procedure and also increases with the duration of therapy. The largest prevalence of medication-related osteonecrosis has been described in patients with multiple myeloma [22, 40].
