Radiotherapy, Osteoporosis and Osteonecrosis of the Jaw

MRONJ- Medication Related Osteonecrosis of the Jaw

ORNJ - Osteoradionecrosis of the Jaw

ONJ- Osteonecrosis of the Jaw

What is ONJ?

ONJ is a rare complication associated with radiotherapy and the use of anti-resorptive as well as anti-angiogenic medications in cancer management and osteoporosis.

It happens when poor healing of bone occurs after a dental extraction or any other procedure that involves the bone structure of the mouth, such as implant placement. Diagnosis of ONJ is made only 8 weeks after the procedure.

MRONJ

MRONJ is defined as exposed bone that can be probed through an intra-oral and extra-oral fistula, in the maxillofacial region, that has persisted for more than 8 weeks in patients with a history treatment with anti-resorptive or anti-angiogenic drugs and where there has been no history of radiation therapy to the jaws or no obvious metastatic disease to the jaws (1,2).

1. Anti resorptive medications

   Examples with common brand names: Alendronic acid (Fozamax), zoledronic acid (Zometa), ibandronic acid (Bonviva), risedronate sodium (Actonel), denosumab (Prolia)

   
   

   Bone is constantly being remodelled by the action of osteoblasts, which create bone tissue, and osteoclasts which break down (resorb) bone tissue. Anti-resorptive drugs prevent osteoclast differentiation and function, causing decreased bone resorption. The jaw is known to have an increased remodelling rate compared to other bones in our body. Hence, the viability of bone in this region may be adversely affected by the action of these drugs.

   
   

   There are two main types of anti-resorptive drugs that have been associated with osteonecrosis of the jaw, the bisphosphonates and denosumab. These are used in the management of osteoporosis and other non-malignant and malignant conditions. Anti-resorptive drugs can have a significantly positive effect on the

   quality of life of patients by reducing or delaying onset of disease or treatment complications, such as bone fractures and bone pain.

   
   

   A) Bisphosphonates

   These reduce bone resorption by inhibiting enzymes that help osteoclasts function. They have a high affinity for hydroxyapatite and remain in our bones for a long time. Half life of alendronic acid is 10years. They can also inhibit angiogenesis (formation of new blood vessels) and delay soft tissue healing.

   Bisphosphonates are usually used for the treatment of metastatic cancers, osteoporosis, Paget’s disease, osteogenesis imperfecta and fibrous dysplasia. (3)

   
   

   B) Denosumab

   Denosumab is a fully human monoclonal antibody which inhibits osteoclast function and associated bone resorption by binding to the receptor activator nuclear factor κB ligand (RANKL) (4)

   
   

   Denosumab is indicated for the prophylaxis and treatment of osteoporosis and to reduce skeletal-related events related to metastasis. Denosumab is administered subcutaneously every six months in osteoporosis patients, with a higher dose given monthly in patients with metastatic disease. Denosumab does not bind to bone and its effects on bone turnover diminish within nine months of treatment completion.

   
   

2. Anti-angiogenic medications

Anti-angiogenic drugs prevent the formation of new blood vessels hence restrict tumour vascularisation and proliferation.

The vascular endothelial growth factor (VEGF) inhibitors bevacizumab and aflibercept and the receptor tyrosine kinase (RTK) inhibitor sunitinib have been associated with osteonecrosis of the jaw (5).

Anti-angiogenic drugs can be used in combination with the bisphosphonates in the management of cancer and there is some evidence that this results in a greater MRONJ risk

ORNJ

ORN is a serious, late-onset complication of radiation therapy, characterized by bone death (necrosis) in areas previously exposed to radiation, often in the jaws. This happens because irradiation causes blood vessels to shut down. After dental extractions, if blood supply is poor, healing is impaired. With radiation induced osteonecrosis, patients are more at risk years after, as fibrosis progresses (5)

SYMPTOMS

• pain

• swelling

• a sore, or ulcer, in the mouth or on the jaw

• difficulty opening the jaw

• an abnormal opening, or fistula, between the jaw and the surface of the body

• less feeling in the mouth or jaw, or even a complete loss of sensation in the area

• infection

• jaw fracture not related to an accident or other trauma

• exposed bone inside the mouth

• bone sticking out through the skin, which is called sequestrum

• Loose teeth

What increases your risk of MRONJ and ORNJ?

1. Dental extractions

2. Cancer surgery/ biopsies

3. Denture irritations

4. Accidents

5. Gum disease

   
   

Discussing management of ONJ is beyond the scope of this article.

Our Recommendations

Let your dentist know if you are about to start any treatment for cancer or osteoporosis (or any other condition). They can liaise with your doctor to make sure that you are not at risk of developing ONJ at a later stage.

If you think that you fall in the categories above and have not visited your dentist for your regular check ups, please book yourself in. Stabilisation of oral health is key to preventing more serious complications.

If you are taking the above medications or have undergone radiation therapy to the head and neck areas, we have to absolutely avoid dental extractions or any procedure involving the bone tissues of the jaws.

References:

1) Ruggiero SL, Dodson TB, Fantasia J, et al. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw - 2014 update. Journal of Oral and Maxillofacial Surgery. 2014;72(10):1938-1956.

2) Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. Journal of Bone and Mineral Research. 2015;30(1):3-23.

3) Lee SH, Chang SS, Lee M, Chan RC, Lee CC. Risk of osteonecrosis in patients taking bisphosphonates for prevention of osteoporosis: a systematic review and meta-analysis. Osteoporosis International. 2014;25(3):1131-1139.

4) Qi WX, Tang LN, He AN, Yao Y, Shen Z. Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: a meta-analysis of seven randomized controlled trials. International Journal of Clinical Oncology. 2014;19(2):403-410.

5)MHRA. Bevacizumab and sunitinib: risk of osteonecrosis of the jaw. Drug Safety Update.

Jan 2011;4(6):A

5) S. Nabil, N Samman. Incidence and prevention of osteoradionecrosis after dental extraction in irradiated patients: a systematic review. International Journal of Maxillofacial Surgery.2011 Mar;40(3):229-43