Jaw complications in breast and prostate cancer patients treated with zoledronic acid

Recently, many authors have described osteonecrosis of the jaw (ONJ) occurring in patients with bone metastases from different cancers treated with intravenous (i.v.) bisphosphonates, particularly with zoledronic acid [1–4]. Durie reported an incidence of ONJ of 6.8% in 904 myeloma patients and 4.3% in 299 breast cancer patients [4].

The incidence of ONJ associated with long-term bisphosphonate therapy appears to be growing. Certainly, there is a broader focus on this problem but also a possible bias in diagnosis. In fact there is no common definition of ONJ and no consensus on diagnostic criteria: many reports consider ONJ as a single wide nosological entity that includes various dental complications, such as osteonecrosis, osteomyelitis, exposed bone, bone necrosis, sequestrum and impaired healing after dental procedures, requiring various treatments with different clinical outcomes.

We assessed the incidence of jaw complications, ONJ and infections, in 178 (52 prostate and 126 breast cancer) patients with bone metastases treated with monthly i.v. zoledronic acid 4 mg and concomitant standard hormone and/or chemotherapy at our Institute between January 2002 and May 2005. Overall, 13 of 178 patients (7.3%) experienced jaw complications; five of 13 were ONJ (Table I).

Table I.  Incidence of jaw complications. ONJ: osteonecrosis of the jaw

	breast cancer n = 126	prostate cancer n = 52	total patients (%) n = 178
ONJ	2	1	3 (1.7)
INFECTIONS	3	5	8 (4.5)
ONJ + INFECTIONS	0	2	2 (1.1)
Total ONJ complications	2/126 (1.6%)	3/52 (5.8%)	5/178 (2.8)
Total jaw complications	5/126 (4.0%)	8/52 (15.4%)	13/178 (7.3)

In breast cancer patients, median number of zoledronic acid administrations was 12 (range 1–33) and no correlation was found between number of administrations and jaw complications (Mann–Whitney test: p = 0.095).

In prostate cancer patients, median number of zoledronic acid administrations was eight (range 1–32) and a significant correlation between number of administrations and jaw complications was found (Mann–Whitney test: p = 0.021). All jaw complications occurred in patients receiving a median of 18 (range 6–24) administrations (24 for ONJ and 16 for infections). None of these jaw complications were associated with metastatic disease. All patients presenting with jaw complications discontinued zoledronic acid and received conservative treatment and only 4 of 5 breast cancer patients were able to restart zoledronic acid after jaw healing. Nevertheless 8 of 13 (62%) patients had persistent dental symptoms at last follow-up visit.

Bisphosphonates are an important component in the management of patients with multiple myeloma and carcinoma bone metastases. Current guidelines suggest that, once initiated, bisphosphonates should be continued until deterioration of quality of life because of progressing disease. The worrisome incidence of potentially serious jaw complications justifies efforts to elucidate causative relationships, associations with other clinical variables, and prevention guidelines. To minimize the risk of jaw complications, we now include a dental examination, panoramic radiographs and tooth extractions when needed as baseline procedures for our patients candidates to treatment with bisphosphonates. Patients are then regularly followed-up during treatment.

In conclusion, ONJ remains poorly understood and its frequency is variable in literature reports. Based on our data, we believe that patients with metastatic bone disease deriving benefits from bisphosphonates have a risk of dental complications that is acceptable. The high incidence in prostate cancer patients (5.7%) and the positive association with the number of zoledronic acid administrations deserve additional studies.