Scintigraphic evaluation of mandibular bone turnover in patients with solid tumors receiving zoledronic acid

Abstract

Bisphosphonates (BP) have been associated with the occurrence of osteonecrosis of the jaw (ONJ), possibly by causing an excessive bone turnover inhibition. However, little in vivo evidence exists to support this theory. The (99m)Tc-medronate scintigrams of patients with skeletal metastases and BP use (n=40) were individually matched with cancer patients without BP exposure (n=40) and controls with neither malignancy nor BP use (n=40). Patients with established ONJ or intense focal abnormalities in the studied regions were excluded. Mandibular (MBT) bone turnover was quantified relative to the femur by defining regions-of-interest with correction for background activity. The patients with BP exposure (34 female, 6 male) had a median age of 63 years (range 25-81) and received a median number of 11 zoledronic acid administrations (range 1-44). Most patients suffered from breast cancer (n=30). The mean ratio of the MBT in cancer patients with BP use over non-users was 0.88 (95% CI 0.80-0.96; p=0.003), and 0.83 (95% CI 0.73-0.94; p=0.001) when BP using oncological patients were compared with controls without malignancy or BP use. The ratio of MBT's between BP naive patients was 0.95 (95% CI 0.83-1.07; p=0.8). No dose-response effect between the number of BP administrations and MBT could be demonstrated (r=0.02; p=0.9). These findings suggest that, relative to the femur, BP exert a stronger effect on mandibular bone turnover, which strengthens the hypothesis that the inhibition of bone turnover may be important in the pathophysiology of ONJ.