High index of suspicion for early diagnosis of alendronate‐induced stage zero osteonecrosis of jaw in thalassaemia major

Osteopenia-osteoporosis syndrome (OOS) is a significant cause of bone morbidity that affects 60–80% of thalassaemia major (TM) patients worldwide, causing fracture, bone pain and hospital admissions (Terpos & Voskaridou, 2010; Chatterjee et al, 2012). It is multifactorial in origin and the pathology still poorly understood. It is principally a high bone turnover disease due to transfusional haemosiderosis, chelation therapy (desferrioxamine-induced skeletal dysplasia) and hypogonadotrophic hypogoandism (HH; Chatterjee et al, 2012). In TM, bisphosphonates are used intravenously (pamidronate, zolendronic acid) or orally (alendronate), with or without sex steroids, with successful outcome of increased bone mass (Terpos & Voskaridou, 2010; Chatterjee et al, 2012). However, bisphosphonates may be associated with a potentially serious side effect, bisphosphonate-related osteonecrosis of the jaw (BONJ), which is well reported in malignant and non-malignant bone diseases (Assael, 2009) but not in TM. We report for the first time three TM individuals (2 females; 1 male) with OOS presenting with clinical and radiological features of BONJ (Table I). All 3 had received alendronate 70 mg/week for 4–6 years. Case 2 had received IV pamidronate 60 mg/month for 3 years prior to oral alendronate. Cases 1 and 2 presented with clinical features of nonexposed BONJ, such as gingival and jaw bone pain with swelling, sinus tract and minimal bone loss whilst the third patient had frank trans-mucosal necrotic bone exposure. All were managed symptomatically with antibiotics and analgesics for infection and pain control. At the 1-year follow-up, there was stable BONJ with no signs of progression in two individuals whilst the third patient experienced severe uncontrolled pain, secondary infection of exposed necrotic bone, and further development of multiple osteonecrotic areas to jawbones. Although this is the first report of BONJ in TM, BONJ after oral bisphosphonates was first reported in 2003 (Marx, 2003; Koka et al, 2007). BONJ is a potentially severe and a debilitating complication of bisphosphonate. It typically manifests clinically as painful infected areas of necrotic jawbone and can lead to severe chronic pain, facial disfigurement, compromised eating and speech, and reduced quality of life. It is estimated that 8–10% of patients with malignancy taking bisphosphonate can develop BONJ, although the incidence varies widely, from 0–27% (K€ uhl et al, 2012). Recent reports have shown a much higher frequency of BONJ (4–7 8%; Benlidayi & Guzel, 2013; Otto et al, 2012) in patients taking oral bisphosphonate, such as alendronate sodium. It is difficult to accurately determine the prevalence of BONJ due to the following factors: Firstly, there is wide variation of patients presenting with this pathology. Secondly, the self-limiting nature of the condition and, most importantly, the lack of awareness of physicians caring for TM patients could possibly contribute to its under diagnosis. Conventionally, BONJ is defined according to the Task force of American Society of Bone and Mineral research as an exposed area of bone in the maxillofacial area which fails to heal within 8 weeks after its identification by a health care professional, in a patient who was currently receiving or had been previously exposed to a bisphosphonate and did not have radiotherapy to the craniofacial area. All our TM patients fulfilled the criteria of the updated definition of American society of Mineral research for BONJ (Benlidayi & Guzel, 2013), as used at our institution, which states that patients must meet all 3 criteria to be considered for BONJ: