Is Bone Turnover of Jawbone and Its Possible Over Suppression by Bisphosphonates of Etiologic Importance in Pathogenesis of Bisphosphonate-Related Osteonecrosis?

Abstract

The pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is not completely understood. The most popular hypothesis has suggested that the bone turnover (BT) in the jawbone is greater than that in other sites and that this turnover will be overly suppressed by bisphosphonates. Using bone scintigraphy, a simple tool for the quantitative evaluation of bone metabolism and blood flow, the goals of the present study were to determine whether the rate of bone remodeling is greater in the jaw and whether the bone BT in the jaw is differentially altered after bisphosphonate intake compared with that in other skeletal sites. The bone scintigraphies of 90 female patients with breast cancer were retrospectively analyzed (n= 45 with bisphosphonate intake; n= 45 without bisphosphonate intake [control group]). All patients in the study group had undergone bone scintigraphy before therapy and during the treatment (course after 12 and 24months). The data were quantitatively analyzed using 6 predetermined regions of interest. The bone BT of the mandible was similar to that of the femur and significantly reduced compared with that of the maxilla (P < .01). None of the investigated bone regions (including the mandible and maxilla) were significantly altered after bisphosphonate administration (P > .05). The finding that the mandible had significantly lower bone BT than that of the maxilla and that two thirds of BRONJ cases occur in the mandible were inconsistent with the investigated hypothesis. Furthermore, the bone BT in the jawbone was not overly suppressed by bisphosphonates. Thus, it is unlikely that over suppression of bone BT is the exclusive causation playing a role in the pathomechanism of BRONJ.