Safety Alerts
Osteonecrosis of the jaw (ONJ) associated with bisphosphonates
19 April 2010
Audiences
Healthcare professional
Industry member
Product-type
Therapeutic Products
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The Vigilance Branch of HSA would like to remind healthcare professionals of the risk of osteonecrosis of the jaw (ONJ) associated with the use of oral and intravenous bisphosphonates and also provide an update on the local cases of ONJ that HSA has received with bisphosphonates.
Bisphosphonates are inhibitors of osteoclastic bone resorption, indicated for the treatment of postmenopausal and corticosteroid induced osteoporosis; Paget's disease; hypercalcemia associated with malignancy and osteolysis and bone pain associated with metastatic bone disease.The bisphosphonates registered locally include alendronate, risedronate, clodronate, etidronate, ibandronic acid, pamidronate and zoledronic acid.
Bisphosphonate-related osteonecrosis of the jaw
ONJ, a severe and disabling bone disorder of the jaw, has been reported with the use of bisphosphonates in the medical literature since 2003.1 To-date, many reports of ONJ from the literature implicate both the intravenous and oral bisphosphonates.2-4 According to a recent study published in the Journal of Oral Maxillofacial Surgery in 2009, the risk of bisphosphonates-related ONJ is between 1 in 10,000 and 1 in 100,000. This incidence may increase to 1 in 300 after dental extraction.3 In another article investigating the prevalence of oral bisphosphonate-related ONJ in Asian population, the estimated prevalence of oral bisphosphonate-related ONJ was found to be 0.05% to 0.07%.4
The mechanism underlying ONJ is unknown, but it has been postulated that bisphosphonates may inhibit new vessel formation, thereby resulting in impaired healing of the jawbone tissue. Well documented risk factors for ONJ includes a diagnosis of cancer, concomitant therapies (e.g. chemotherapy, radiotherapy, corticosteroids) and co-morbid conditions (e.g. anaemia, coagulopathies, infection, pre-existing oral disease). The typical signs and symptoms include severe jaw pain, soft-tissue swelling and infection, loosening of teeth, and exposed bone.
Local situation
To date, the Vigilance Branch of HSA has received one report of possible osteomyelitis with zoledronic acid use and 11 reports of osteonecrosis associated with several types of bisphosphonates – four after intravenous bisphosphonate use, and seven after oral alendronate use.Of the four reports of osteonecrosis concerning intravenous bisphosphonates, three of the reports implicated zoledronic acid and one implicated pamidronate. More details of these 12 reports are listed in table 1 below.
HSA's advisory
An article was previously published in the December 2004 issue of the HSA ADR bulletin highlighting osteonecrosis of the jaw with bisphosphonate use. 5 In view of the local reports of bisphosphonate-related ONJ and the fact that its complications may result in significant chronic pain, dysfunction and disfigurement, healthcare professionals are reminded to be aware of the potential risk of ONJ when prescribing bisphosphonates to their patients. Warnings on the risk of ONJ have been highlighted in the local package inserts for all bisphosphonates registered locally.
Healthcare professionals should consider the need for dental examination with appropriate preventive dentistry for patients with concomitant risk factors for ONJ (eg, cancer, chemotherapy, corticosteroids, and poor oral hygiene) before bisphosphonate treatment. Additionally, physicians are advised to inform patients to avoid invasive dental procedures if possible, while on treatment with bisphosphonates. Dental surgery may exacerbate the condition in patients who develop ONJ while on bisphosphonate treatment.
Healthcare professionals are encouraged to report adverse reactions suspected to be associated with the use of bisphosphonates to the Vigilance Branch of HSA.
Table 1: Cases of Osteonecrosis associated with bisphosphonates use reported to HSA since 2004
Table caption
No | Age, Gender | Bisphosphonate used | Indication for bisphosphonate | Description of ADR | Date of onset |
|---|---|---|---|---|---|
1 | 71 , Male | Zometa (zoledronate) | Multiple myeloma | Experiences jaw pain, X-rays and CT scan of mandible showed lytic lesion but no periosteal reaction. Query osteomyelitis | 24/05/2004 |
2 | 71, Female | Zometa (zoledronate) | Multiple myeloma | Osteonecrosis of anterior maxilla after extraction that progressed to osteomyelitis | 20/09/2004 |
3 | 66, Male | Zometa (zoledronate) | Multiple myeloma | Osteonecrosis of anterior maxilla and right mandible. Osteomyelitis | 17/03/2004 |
4 | 64, Female | Pamidronate | Bone metastasis to rib/spine | Osteonecrosis/ osteomyelitis of left maxiila. | 01/08/2001 |
5 | 58, Female | Fosamax (Alendronate) | Osteoporosis | Osteonecrosis with secondary osteomyelitis of left mandible. | 12/01/2005 |
6 | 76, Male | Zometa (zoledronate) | Bone metastasis due to prostate cancer | Osteonecrosis of anterior maxilla, stable, 0.5mm exposed | 08/07/2004 |
7 | Unknown | Fosamax (Alendronate) | unk | Osteonecrosis of the jaw | 01/01/2007 |
8 | Unknown | Fosamax (Alendronate) | unk | Osteonecrosis of the jaw; gingival swelling | 01/01/2007 |
9 | 85, Female | Fosamax Plus (Alendronate, Cholecalciferol (Vit D3)) | Osteoporosis | Alendronate therapy was discontinued in Nov 06 when patient experienced bilateral femur shaft fracture. On 18 September 2007, patient was suspected to have developed osteonecrosis of jaw and was referred to a dentist for follow up. The reporter felt that the osteonecrosis of jaw was not related to therapy with alendronate since therapy with alendronate has been discontinued for a long time. | 18/09/2007 |
10 | 82, Female | Fosamax (Alendronate), Fosamax Plus (Alendronate, Cholecalciferol (Vit D3)) | Osteoporosis | Patient started therapy with alendronate sodium for treatment of osteoporosis in 2002 and in 2005, switched therapy to Alendronate + Colecalciferol (Vit D3). The patient complained to reporting physician that she has chronic ulcer in the gum for a year and biopsy indicated finding consistent with ulcer with infection which was subsequently diagnosed as bisphosphonate-related osteonecrosis of the jaw by an ENT specialist | 01/01/2007 |
11 | 70, Unknown | Fosamax Plus (Alendronate, Cholecalciferol (Vit D3) | Osteoporosis | Osteonecrosis of jaw | 01/01/2008 |
12 | Unknown | Fosamax (Alendronate) | Osteoporosis | Osteonecrosis of jaw | 01/10/2008 |
References
J Oral Maxillofac Surg 2003; 61: 1104 -7
J Oral Maxillofac Surg 2003; 61: 1115-7.
J Oral Maxillofac Surg 2009 May; 67 (5 suppl): 35-43
Osteoporosis International 2009 Jul 25.
HSA ADR News Bulletin. December 2004, Vol 6; No 3