Osteonecrosis of jaws related to intravenous bisphosphonates: the experience of a Jordanian teaching hospital

Abstract

Ann R Coll Surg Engl 2010; 92: 489-494 489Bisphosphonate-related osteonecrosis of the jaws (BRONJ), first described by Marx, 1 is defined as jaw necrosis occurring either spontaneously or, more commonly, after simple dento-alveolar surgery in patients on bisphosphonates, commonly with the intravenous (i.v.) form of the drug. Bisphosphonates are non-metabolised analogues of pyrophosphate that localise to bone inhibiting the dissolution of hydroxyapatite crystals preventing bone resorption.2,3 Other effects include reducing blood flow and antiangiogenic properties, 4 contributing to the ischaemic changes noted in the affected jawbones. Bisphosphonates are preferentially deposited in bones with high turn-over rates, since the maxilla and mandible are sites of significant remodelling, it is possible that the levels of the drug within the jaw are selectively elevated.2 BRONJ is a multifactorial event with multicellular impairments, resulting in altered wound healing. 5Cancer patients with metastatic or primary bone lesions often develop sequential skeletal complications and hypercalcaemia of malignancy.6 Intravenous bisphosphonates are primarily used in the management of cancer-related hypercalcaemia and skeletal-related events associated with bone metastases including pain, pathological fracture, spinal cord compression, mostly with solid tumours such as breast, prostate and lung cancers.6 They are also effective in the management of lytic lesions in the setting of multiple myeloma; 7 multiple myeloma patients appear to have a uniquely elevated risk for the development of the condition as the disease itself is present in bone. 8 The most prevalent and common indication for oral bisphosphonates is osteoporosis. RESULTS Of the 41 patients, four developed BRONJ, two in maxilla, one in mandible and one bimaxillary. Patients with BRONJ were older; mean age was 69.3 ± 3.1 years compared to 62.8 ± 12.5 years (P = 0.022). Dental co-morbidities were more commonly present in patients with the disease (P = 0.038). Patients who developed BRONJ were on treatment for a longer duration of time; the mean duration of treatment was 23.5 ± 8.4 months compared to 11.9 ± 13.4 months (P = 0.10). CONCLUSIONS The results of this case series demonstrated that age and poor oral health status are significant risk factors of BRONJ for oncology patients on long-term frequent dosing schedule of i.v. bisphosphonates.

Treatment strategies and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with characterization of patients: a systematic review

“…27,41,174,179 There is considerable discussion in the literature regarding whether ageing plays a significant role in the development of BRONJ. Some studies have found no statistically significant correlation between ageing and BRONJ, 180,181 whereas others have included advanced age as a BRONJ co-factor 80,159,182 ; this could be related to the physiological effects of ageing, including inflammatory issues, 183 immune dysfunction, 184 a reduction in blood flow and remodelling ability, 185,186 and increased oxidative stress. 187 In fact, these features are all implicated in the pathogenesis of BRONJ and could explain why the disease is not reported in young patients, even those with other associated risk factors.…”

Medication Related Osteonecrosis of the Jaw: 2015 Position Statement of the Korean Society for Bone and Mineral Research and the Korean Association of Oral and Maxillofacial Surgeons

“…[ 5 ] The prevalence was reported to be 0% to 0.186% for patients with bone metastases who have been treated with high dose bisphosphonates. [ 6 7 8 ]…”

Relationship between disease stage and renal function in bisphosphonate-related osteonecrosis of the jaw

“…On the other hand, Baqain et al32 and Vahtsevanos et al33 reported no statistically significant correlation between aging and BRONJ stage. In the present study, patient age did show a statistically significant association with the BRONJ stage.…”