Rheumatology Advance Access originally published online on February 4, 2008
Rheumatology 2008 47(3):383; doi:10.1093/rheumatology/kem387
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Comment on: Bisphosphonates and osteonecrosis of the jaw
1Bone Metabolism Unit, Istituto Auxologico Italiano, Milano, Italy and 2Department of Propedeutic Pediatrics and Bone Metabolic Diseases, Medical University of Lodz, Lodz, Poland
Correspondence to: M. L. Bianchi, Istituto Auxologico Italiano IRRCS, Bone Metabolism Unit, via L. Ariosto 13, 20145 Milano Italy. E-mail: ml.bianchi{at}auxologico.it
SIR, We read the editorial by Shenker and Jawad [1] on bisphosphonates (BPs) and osteonecrosis of the jaw (ONJ) with great interest, and we would like to express our concern also regarding the younger patients treated with BPs. Currently, both i.v. and oral BPs are increasingly also used for long-term treatment in children and adolescents affected by conditions like osteogenesis imperfecta (OI), fibrous dysplasia or secondary osteoporosis due to chronic diseases and/or glucocorticoid (GC) treatment. Until now, there are no published reports on the occurrence of ONJ in young patients treated with BPs, but we deem it very important to be aware of this possible problem, considering also the special metabolic conditions of bone during growth and development.
As a cautionary measure, soon after reading the first reports on BP-related ONJ [2, 3], we began to regularly examine the oral cavity in the 38 young patients (17 girls, 21 boys; aged 4–22 yrs) on BP treatment followed at our department, looking for any abnormal sign. These patients had OI (11 cases), fibrous dysplasia (1 case) or secondary osteoporosis with recurrent fractures (26 cases); in this last group, 20 patients were on long-term GC therapy (mean duration 58 ± 9 months). In many cases, dental problems such as dentinogenesis imperfecta in OI (6 cases) and misalignment (13 cases) were diagnosed before starting BP therapy. At the beginning of this study, 18 patients had received i.v. pamidronate in 4-month cycles for 3–6 yrs (1.5–3 mg/kg/cycle) and 20 patients oral alendronate (5–10 mg/daily) for 2.5–4 yrs.
This group of young BP-treated patients could be considered potentially at risk of ONJ, considering the use of i.v. BPs (18 cases, 47.4%), the length of treatment (2.5–6 yrs) and the local problems possibly related to misalignment correction devices (9 cases, 23.7%) or to dental extractions (4 cases).
During more than 3 yrs of follow-up, all the patients continued to take the same drugs. We made, and are still making, an accurate examination of the oral cavity in all patients every 6 months. The patients and their parents have been instructed to maintain a good oral hygiene, to immediately report any suspect sign or symptom and to keep us informed about any intervention of a dentist. All the patients’ dentists were contacted and informed of the BP-related ONJ problem, and were asked to accurately check the oral cavity of these patients in case of any intervention, emphasizing the need for dental care and the use of oral anti-microbial rinses (chlorhexidine 0.12%) and antibiotics (penicillin or erythromycin) before, during and after any major oral intervention. During the study, 4 patients had dental extractions, 15 caries repair, 5 misalignment correction and 7 dental prophylaxis.
Until now, no pain, mucosal swelling, altered sensations in the area, erythema, ulceration or other sign or symptom of BP-related ONJ have been reported by the patients or found on examination at our department or by dentists. Panoramic dental radiographs, performed in 15 patients for a deeper evaluation, were also negative.
The fact that we did not find any sign of ONJ is encouraging but, of course, not conclusive, given the low frequency of this complication and the small sample.
We would strongly suggest that children and adolescents on long-term treatment with BPs deserve special attention regarding the risk of BP-related ONJ. The fact that no cases of BP-related ONJ have been reported in young patients until now should stimulate the maximum effort for prevention, as well as promote an updating of the current guidelines for the use of BPs in children.
Prospective studies, in cooperation between doctors, dentists and surgeons, are required to better evaluate the risk of BP-related ONJ, and to study the best prevention strategy, also in young patients.
Children and adolescents on BP treatment should be educated to keep a good oral hygiene and to report any oral problem or discomfort immediately. Oral and dental examination should be made in all new patients before starting BPs, and are an essential part of the follow-up [4]. Radiographic exams, particularly panoramic radiographs, may be useful [5].
Notwithstanding the apparently low risk, it is very important that both patients and doctors be aware of this potential severe complication of BP use.
Disclosure statement: The authors have declared no conflicts of interest.
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- Shenker NG, Jawad ASM. Bisphosphonates and osteonecrosis of the jaw. Rheumatology (2007) 46:1049–51.
[Free Full Text] - Marx RE. Pamidronate (Aredia) and zolendronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg (2003) 61:1115–8.[CrossRef][Web of Science][Medline]
- Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaw associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg (2004) 62:527–34.[CrossRef][Web of Science][Medline]
- Ficarra G, Beninati F. Bisphosphonate-related osteonecrosis of the jaws: the point of view of the oral pathologist. Clin Cases Min Bone Metabol (2007) 4:53–7.
- Bagan JV, Jimenez Y, Murillo J, et al. Jaw osteonecrosis associated with bisphosphonates: multiple exposed areas and its relationship to teeth extractions. Study of 20 cases. Oral Oncol (2006) 42:327–9.[CrossRef][Web of Science][Medline]
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  N. G. Shenker and A. S. M. Jawad Comment on: Bisphosphonates and osteonecrosis of the jaw: reply Rheumatology, March 1, 2008; 47(3): 383 - 384. [Full Text] [PDF]
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