Bisphosphonates (BPs) are widely used as bone-stabilizers in the treatment of osseous metastases, osteoporosis, and Paget’s disease due to their ability to inhibit osteoclast activity . Over 20 million BPs are prescribed annually in the USA . Side effects of BP therapy include acute renal failure, gastrointestinal disorders, hypocalcaemia, and bisphosphonate-related osteonecrosis of the jaw (BRONJ) . BRONJ is defined as the presence of exposed, nonvascularized, and necrotic bone tissue in the oral cavity and is frequently combined with inflammation of the surrounding tissue and pain .

Although several studies have quoted the estimated incidence of BRONJ to be 8–12% , the actual frequency is unclear. BRONJ is largely resistant to antibiotics, so its management remains difficult and includes surgical procedures to eradicate the necrotic bone .

The mandible appears to be more frequently affected by BRONJ than the maxilla . Isolated cases of maxillary BRONJ have been described in which a simultaneous sinusitis maxillaris was diagnosed . Sinusitis is characterized by quantitative and qualitative changes in mucus biosynthesis that contribute to sinus disease. Sinusitis can be classified etiologically as rhinogenic (60–80%) or ontogenic (20–40%).

The odontogenic origins of sinusitis may be periapical abscesses or periodontal disease, as well as infections following sinus perforation during tooth extractions or dislocation of foreign bodies after endodontic therapy . Chronic, focal alveolar osteitis or maxillary osteomyelitis can cause irritation and a subsequent sinus infection .

Functional and aesthetic deterioration resulting from maxillary BRONJ, as well as respiratory obstruction and pain due to an associated sinusitis, may compromise the patient’s quality of life. Due to immunosuppression following combined chemotherapy and corticosteroid treatment, sinusitis may spread to adjacent tissues, such as the orbit, the meninges, and the brain, resulting in life-threatening complications. Therefore, early diagnosis and prompt initiation of therapy are essential.

The aim of the present consecutive study was to determine the frequency of maxillary BRONJ, with special attention to coincidental sinusitis maxillaries, and to evaluate possible therapeutic outcomes.

Materials and methods

All patients presenting with BRONJ of the maxilla between January 2005 and July 2008 were evaluated in terms of frequency and therapeutic outcome, with special attention paid to patients with an associated sinusitis maxillaris.

All patients who met the following criteria were included: a history of BP therapy, intraoral lesion (e.g. exposed bone, purulent discharge, or fistulae) that persisted for more than 8 weeks or an extraoral manifestation of swelling or fistulae and no history of radiation therapy to the jaw. One additional patient (No. 3) with pain but intact mucosa was included after radiological confirmation of BRONJ (irregularly shaped radiolucencies). Malignant lesions of the maxillofacial region were considered an exclusion criterion.

All patients were examined clinically (including dental status and tooth sensibility, Fig. 1 ) and radiologically with digital volume tomography (DVT, Fig. 2 ). Using a standardized questionnaire, data were collected on BP therapy, its duration, and the manner of application ( Table 1 ). The anamnesis included questions related to symptoms of sinusitis such as facial pain, purulent nasal discharge and nasal obstruction. When anamnestic and/or clinical indications of sinusitis maxillaris were found, a computed tomography (CT) scan was performed ( Fig. 3 ).

Image of the exposed necrotic bone in the maxillary area.

DVT scan with BRONJ-related brightening of the right maxillary area and shading of the ipsilateral sinus maxillaris.

Table 1

Patient characteristics.

Patient no.	Sex	Age	Primary diagnosis	Underlying diseases	Oral surgery	Chemo-therapy
1	F	71	Breast cancer	–	+	+
2	F	55	Breast cancer	Smoking, alcohol abuse	+	+
3	F	58	Breast cancer	–	−	+
4	F	66	Breast cancer	–	−	+
5	F	74	Breast cancer	–	−	−
6	M	65	Breast cancer	HT, NIDDM II	−	+
7	M	70	Lung cancer	–	−	+
8	F	78	Multiple myeloma	–	+	+
9	M	69	Multiple myeloma	HT, hypothyreosis, gastric ulcer	−	+
10	M	72	Multiple myeloma	HT	−	+
11	F	66	Multiple myeloma	CHF, arrhythmia	−	+ (SCT)
12	F	63	Multiple myeloma	HT, renal failure	+	+
13	F	48	Multiple myeloma	–	−	+
14	F	76	Multiple myeloma	HT, systemic scleroderma, MI	+	+
15	F	67	Multiple myeloma	Pulmonary embolism	+	+
16	M	66	Prostate cancer	–	+	−
17	F	74	Rectal cancer	–	+	+
18	F	56	Renal cancer	–	+	+
19	F	85	Osteoporosis	HT, IDDM II, anaemia, renal failure, dementia	−	−
20	F	80	Osteoporosis	HT, CIHD, hypercholesterolaemia, depression	−	−
21	F	91	Osteoporosis	AMI, dementia, amaurosis	−	−

 

Abbreviations used: No., patient number; F, female; M, male; HT, hypertension; IDDM II, insulin-dependent diabetes mellitus type II; CIHD, chronic ischaemic heart disease; CHF, chronic heart failure; MI, mitral insufficiency; NIDDM II, non-insulin-dependent diabetes mellitus type II; AMI, acute myocardial infarction; and SCT, stem cell transplantation.

CT scan with BRONJ-related brightening of the maxilla and complete shading of the ipsilateral sinus maxillaris.

Management and outcome

Management was based on the results of BRONJ staging. All patients received antibiotics (2 g of amoxicillin plus 200 mg of clavulanic acid intravenously (i.v.) every 8 h) in combination with an intraoral chlorhexidine rinse at least 14 days prior to any intervention. In Stage 0 or I cases, surgical intervention was restricted to debridement of soft tissue. In Stage II or III cases, a segmental bone resection under general anaesthesia was performed. In all of the surgically treated cases, histological findings confirmed BRONJ without evidence of malignant infiltration ( Fig. 4 ). Patients with sinusitis were treated with antibiotics according to the protocol given above. If the sinusitis persisted after five days of antibiotic treatment an antrotomy was performed. A follow-up included clinical and radiological examinations every six months with special attention paid to the recurrence of BRONJ and sinusitis maxillaris. In case of recurrence i.v. antibiotics were administrated and a surgical revision was performed.

Photomicrograph displaying regions of necrotic bone with empty lacunae (haematoxylin–eosin stain, original magnification ×100).