Scintigraphic evaluation of mandibular bone turnover inhibition by bisphosphonates in patients with solid tumors

Abstract

9519 Background: Bisphosphonates (BP) have been associated with the occurrence of osteonecrosis of the jaw (ONJ), possibly by causing an excessive inhibition of local bone turnover. However, little in vivo evidence currently exists to support this theory. Methods: Whole-body scintigrams acquired after administration of 99mTc labeled medronate of 120 patients were studied. Patients with skeletal metastases from a solid tumor (n=40) were individually matched with cancer patients without BP exposure (n=40) and controls with neither a malignancy nor BP use (n=40). Controls were matched for age, gender, malignancy, steroid and hormonal therapy use, where appropriate. Patients with established ONJ or intense focal abnormalities in the studied regions were excluded. Mandibular bone turnover (MBT) was quantified relative to the femurs by defining regions-of-interest on the scintigrams with correction for background activity. The study had a power of 90% to detect a 10% reduction in MBT after BP use. Results were analyzed using a repeated-measures ANOVA with a two-sided significance level of p<0.05. Results: The patients with BP exposure (34 female, 6 male) had a median age of 62 years (range 25–80) and received a median number of 11 zoledronic acid administrations (range 1–48). Malignancies included: breast (n=30), prostate (n=4), colon (n=2) and bladder cancer (n=2); and neuroendocrine carcinoma (n=2). The mean MBT was significantly lower in BP using cancer patients (2.59) compared with matched controls from oncological patients without BP use 3.01 (difference 0.42; 95% CI 0.13 - 0.72; p=0.006), or patients without cancer or BP exposure 3.09 (difference 0.50; 95% CI 0.21 - 0.78; p=0.001). In contrast, there was no significant difference in MBT between non-BP users (difference 0.08; 95% CI -0.31 - 0.46; p=0.7). Likewise, no correlation between MBT and the number of BP administrations could be demonstrated (r2=0.01; p=0.4), suggesting a stochastic rather than a deterministic effect. Conclusions: This in vivo data suggests that BP cause a higher inhibition of bone turnover in the mandible relative to the femur, which strengthens the hypothesis that the inhibition of bone turnover may be important in the pathophysiology of ONJ. [Table: see text]