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| Journal of the New Zealand Medical Association,
01-December-2006, Vol 119 No 1246
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Jaw osteonecrosis associated with
bisphosphonates
Jodie Battley, Sisira Jayathissa, Eric Seneviratne
Osteonecrosis of the jaw (ONJ) is a disabling and
potentially incurable condition in which localised vascular insufficiency of the
mandible or maxilla renders the bone unable to meet increased repair needs
following tooth removal, infection, and simply the day-to-day physiological
stress of mastication.1
Since 2003, an increasing number of cases of ONJ in patients
using long-term intravenous or oral bisphosphonates have been reported in the
literature.1
Case reportA 73-year-old New Zealand European man with multiple myeloma
presented in July 2005 with a 1-year history of gradual decline in health.
Myeloma was diagnosed in early 2001; initial therapy included melphalan and
alternate day prednisone, with subsequent weekly cyclophosphamide and monthly
pamidronate 90 mg IV infusions, later changed to zolendronate 4 mg IV infusions
in October 2001.
Despite multiple adjustments to medications, his
musculoskeletal symptoms persisted and he was commenced on thalidomide 1 month
prior to presentation. During admission, he was noted to have a painless area of
exposed bone and necrosis in the left maxillary alveolar ridge (Figure 1); and
the clinical and radiological diagnosis of osteonecrosis of the jaw (ONJ) was
made.
Figure 1. Osteonecrosis of the maxillary
alveolar ridge
 Zolendronate infusions were stopped. His dentures were
removed, with soft linings used for mealtimes, and he was treated with a course
of oral amoxycillin plus antibacterial mouth rinses and regular dental reviews.
He had no recent history of invasive dental procedures. Following discharge, he
declined any further dental follow-up and later died due to complications of
myeloma.
DiscussionBisphosphonates are powerful osteoclast inhibitors with
anti-tumour and antiangiogenic properties widely used in the management of
osteoporosis, Paget’s disease, multiple myeloma, metastatic bone
disease, and hypercalcaemia of malignancy.2,3
Etidronate, alendronate, pamidronate, and zolendronate are
bisphosphonates that are currently available in New Zealand. Etidronate has not
been associated with ONJ. Although ONJ occurs more commonly with IV
bisphosphonates, oral alendronate has also been implicated. It is anticipated
that use of alendronate in New Zealand will increase after recent widening of
access by New Zealand’s Pharmaceutical Management Agency (PHARMAC).
The Centre for Adverse Reactions Monitoring (CARM) in
Dunedin has received reports of three other cases of ONJ: one with pamidronate
and two with zolendronate. All three patients had some form of bony
malignancy.
The pathogenesis of osteonecrosis is thought to be related
to over-inhibition of osteoclastic function leading to inability to replace
dying osteocytes and maintain the capillary
network.1 ONJ is known to be associated with
radiotherapy, chronic osteomyelitis, major dental surgery, poor oral hygiene,
and corticosteroid therapy.4 Coexistent
thalidomide therapy, diabetes mellitus, and peripheral vascular disease are
thought to confer additional risk.2, 4
Effective management of ONJ remains unclear, and it appears
that the disease may progress despite surgery or cessation of therapy. In
established cases, palliation and control of secondary infection are the main
goals of treatment.3
ONJ progression has been shown to be limited with short
courses of antibiotics for secondary infection, chlorhexidine mouthwash, minor
debridement, and wound irrigation.3 Radical
resection of necrotic bone is of limited benefit, and may aggravate the
condition.2, 5 Hyperbaric oxygen does not
appear to offer any benefit.3, 6
Current recommendations prior to commencing long-term
bisphosphonates are that patients be fully informed of the risk of ONJ, and
undergo dental review for assessment and treatment of underlying dental disease.
Due to increasingly widespread use of bisphosphonates for
osteoporosis and cancers, it is essential that medical professionals are aware
of this potential complication. In addition, more research is required to
further define the aetiology, to determine which patients are at increased risk,
and to provide guidelines for safe length of bisphosphonate treatment.
Author information: Jodie Battley, House
Surgeon; Sisira Jayathissa, Consultant Physician; Eric Seneviratne, Consultant
Physician; Hutt Hospital, Lower Hutt
Correspondence: Jodie Battley, Relieving
House Surgeon, Hutt Hospital, Private Bag 31-907, Lower Hutt. Fax: (04) 570
9335; email: jodie_battley@yahoo.com
References:
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