1. Dr Sarah Constantine MBBS, FRANZCR
Bisphosphonate-Related Osteonecrosis of the Mandible: Case Report and Radiological Appearances.
Dr Sarah Constantine MBBS, FRANZCR

2. Case Report
An 84 year old female presented with unilateral swelling of the left side of the face.
The swelling had been worsening over the past 3 months.
Her face was not painful, although was mildly tender to palpation.
Intra-orally there was a draining sinus distal to left mandibular premolars.
Past history of osteoporosis, on Fosamax for 8 years.
Previous sequestrum removed from right mandible 4 years previously, previous retained root in left mandible removed.

3. Orthopantomogram (OPG).
OPG showed moth-eaten, permeative lesions involving both sides of the mandible, but more extensive on the left.

4. Computed Tomography (CT) Scan
The soft tissue swelling is obvious on the left.

5. CT Scan
There is bilateral bony destruction involving both sides of the mandible.

6. CT Scan
There is extensive circumferential periosteal reaction around the affected bone on the left.

7. CT Scan
There are gas bubbles in the medullary cavity.

8. CT Scan
There are sclerotic bone fragments (sequestrum) within the affected area.

9. Diagnosis: Osteonecrosis of the mandible due to long term oral bisphosphonate use.

10. Bisphosphonate-Related Osteonecrosis of the Mandible
Bisphosphonate-Related Osteonecrosis of the Mandible (BROM) was first recognised in oncology patients receiving intravenous (IV) bisphosphonates as part of chemotherapy for multiple myeloma or other cancers with bone metastases.
The first cases reports appeared in the literature in 2003.
Dental-related problems in a patient receiving oral alendronate (Fosamax) were first reported in
BROM was first reported in association with oral bisphosphonates taken for osteoporosis in

11. Aetiopathogenesis
The exact mechanism by which bisphosphonates cause osteonecrosis is unknown.
The main pharmacological effect of bisphosphonates is the inhibition of bone resorption by suppressing osteoclast function.2
The half-life of bisphosphonates in blood is a few hours, but in bone is many months to years.2, 3
Bisphosphonate-related osteonecrosis almost exclusively occurs in the jaws, and has never been reported outside the head or neck. The reason for this is also still unclear, but the close proximity to oral bacteria is being postulated as a factor.1, 2, 4
There is a strong similarity in the clinical presentation and treatment resistance to “fossy-jaw”, a condition seen in workers using white phosphorus to make matches in the late 19th century.1, 2

12. Epidemiology
BROM is more common in women than men (M : F = 1 : 3 - 8).2, 4, 5
The mean age of patients at presentation is years.2, 4, 5
These figures represent the common age groups in which cancers occur, and the more common occurrence and detection of osteoporosis in women compared to men.
There is a history of recent dental surgery or extraction in up to 80% of patients.2, 6
The mandible is involved more than twice as often as the maxilla.3, 4, 5, 6

13. Clinical Features Patients present with any or all of: Pain Swelling
Paraesthesia
Draining sinuses to the mouth or skin
Bleeding
- or may be asymptomatic.

14. Radiological Appearances
The radiological hallmark of the condition is osteosclerosis.7
The only indication of early osteonecrosis may be a focal increase in density of the affected alveolar bone.8
More advanced disease shows patchy areas of sclerosis associated with the bone destruction.

15. Radiological Appearances
The molar region is most commonly involved, followed by the premolar region. boon
Bone destruction may be patchy and mild to advanced with pathological fracture.
Periosteal reaction is common but not universal to the diagnosis. This is best seen with CT scanning.
Soft tissue swelling is also variable, but especially common with draining sinuses.

16. Differential Diagnosis
The radiological differential diagnosis includes:
Chronic sclerosing osteomyelitis (of Garré)
Osteoradionecrosis
Metastases
Paget’s disease

17. Management
The treatment of BROM is very difficult. This may be due to the long half life of bisphosphonates in bone, meaning that withdrawal of the drug is very prolonged.
A combination of bisphosphonate cessation, antibiotic treatment and surgery in selected cases is used.9, 10
Recurrence is common, and treatment is not always successful.6, 9, 10
Most authors recommend a dental examination including OPG prior to commencing IV bisphosphonates. The incidence in patients taking oral bisphosphonates is low, and the cost of pre-treatment screening in the osteoporotic population may be preclusive.
Dental hygiene in this group of patients is also very important.

18. Conclusion
Bisphosphonate-associated osteonecrosis of the mandible can occur in patients receiving either IV or oral bisphosphonates.
The radiological appearances are characteristic, and should prompt the radiologist to enquire about the use of bisphosphonates in an elderly patient, especially if female, or a patient with a known malignancy.
The treatment of bisphosphonate-associated osteonecrosis of the jaw is difficult, and radiological recognition is important to enable early drug withdrawal and treatment.

19. References
Pickett FA. Bisphosphonate-Associated Osteonecrosis of the Jaw: A Literature Review and Clinical Practice Guidelines. J Dent Hyg Summer; 80(3). Epub 2006 Jul 1.
Walter C, Grötz KA, Kunkel M, Al-Nawas B. Prevalence of bisphosphonate associated osteonecrosis of the jaw within the field of osteonecrosis. Support Care Cancer 2007 Feb;15(2):
Pongchaiyakul C et al. Bisphosphonate-Related Osteonecrosis of the Jaws (ONJ): a report of two cases. J Med Assoc Thai Nov; 90(11):
Pazianis M et al. A review of the literature on osteonecrosis of the jaw in patients with osteoporosis treated with oral bisphosphonates: prevalence, risk factors, and clinical characteristics. Clin Ther Aug; 29(8):
Estefanía Fresco R et al. Bisphpsphonates and oral pathology II. Osteonecrosis of the jaws: review of the literature before Med Oral Patol Oral Cir Bucal 2006 Nov 1; 11(6): E
Boonyapakorn T et al. Bisphosphonate-induced osteonecrosis of the jaws: Prospective study of 80 patients with multiple myeloma and other malignancies. Oral Oncol. 2008; doi: /j.oraloncology
Phal PM et al. Imaging findings of bisphosphonate-associated osteonecrosis of the jaws. AJNR Am J Neuroradiol Jun - Jul; 28(6):
Bisdas S et al. Biphosphonate-induced osteonecrosis of the jaws: CT and MRI spectrum of findings in 32 patients. Clin Radiol Jan; 63(1):
Magopoulos C et al. Osteonecrosis of the jaws due to bisphosphonate use. A review of 60 cases and treatment proposals. Am J Otolaryngol May - Jun; 28(3):
Lobato JV et al. Jaw avascular osteonecrosis after treatment of multiple myeloma with zoledronate. J Plast Reconstr Aesthet Surg. 2008; 61(1):
Thanks to Dr. P. Duke, Oral Surgeon, for his feedback about this case.