Tooth Extraction Socket Healing in Pediatric Patients Treated with Intravenous Pamidronate

doi:10.1016/j.jpeds.2008.05.003

The Journal of Pediatrics

Volume 153, Issue 5, November 2008, Pages 719-720

https://doi.org/10.1016/j.jpeds.2008.05.003 Get rights and content

Osteonecrosis of the jaw (ONJ) has been described as a complication of bisphosphonate therapy in adults. In the present study, we did not find a case of ONJ among 278 pediatric patients who had received intravenous pamidronate during childhood or adolescence.

Section snippets

Methods

Between October 1992 and December 2006, 338 pediatric patients received at least 1 cycle of intravenous pamidronate at the Shriners Hospital for Children in Montreal. For the purpose of the present study, we were able to contact 278 of these patients (142 females; 136 males). The majority of the patients had a diagnosis of osteogenesis imperfecta (n = 221); other diagnoses included fibrous dysplasia (n = 20), idiopathic juvenile osteoporosis (n = 14), neuromuscular disorders (n = 11), bone

Results

None of the 278 patients who could be contacted had a history of ONJ. Dental extractions had been performed on 113 patients during or after pamidronate treatment. None of the patients or their parents recalled postoperative complications after these extractions.

Chart data from the treating dentist could be obtained for 66 patients (25 females, 41 males; median age at follow up, 14.0 years; range, 2 to 30 years). The median cumulative dose of pamidronate before dental extraction was 40 mg/kg

Discussion

In this study, we found no cases of ONJ among 278 patients who had received pamidronate at our institution, even though this group of patients had a number of risk factors for developing ONJ, such as dental extraction and prolonged exposure to intravenous pamidronate at relatively high doses. This exposure profile is similar to that of adult cancer patients who developed ONJ;⁵ however, a large majority of those adult patients also received treatment with chemotherapy and other concomitant

References (12)

F. Rauch et al.
Osteogenesis imperfecta
Lancet
(2004)
T. Mavrokokki et al.
Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia
J Oral Maxillofac Surg
(2007)
R. Weitzman et al.
Critical review: updated recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patients, May 2006
Crit Rev Oncol Hematol
(2007)
J.T. Grbic et al.
Incidence of osteonecrosis of the jaw in women with postmenopausal osteoporosis in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once-Yearly Pivotal Fracture Trial
J Am Dent Assoc
(2008)
A. Badros et al.
Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors
J Clin Oncol
(2006)
A. Bamias et al.
Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors
J Clin Oncol
(2005)

There are more references available in the full text version of this article.

Cited by (56)

Spontaneous medication-related osteonecrosis of the jaws in a 23-year-Old
2023, Oral and Maxillofacial Surgery Cases
Medication-related osteonecrosis is a well-documented yet rare complication of antiresorptive treatment. The risk of MRONJ is well established in the adult population but has yet to be established in the pediatric population. Additionally, the risk to this population in adulthood following many years of antiresorptive use is unknown. This case report describes a patient who received long-term antiresorptive medication as an adolescent and spontaneously developed MRONJ at age 23. To the authors’ knowledge, this is the youngest patient with MRONJ reported in the literature.
Antiresorptive and anti-angiogenic drug therapy in the pediatric population with reference to medication-related osteonecrosis of the jaw
2023, International Journal of Oral and Maxillofacial Surgery
The objective of this study was to identify the prevalence of osteonecrosis of the jaw in a pediatric population with systemic therapeutic exposure to an antiresorptive, anti-angiogenic, and/or immunomodulating drug (ARAID), and in particular in the subgroup of patients who had undergone invasive dental treatment. This was a retrospective cohort study performed at a single center. The investigation included pediatric patients who had undergone systemic therapy with ARAIDs and who began receiving ARAID therapy at ≤16 years of age. The study included 482 patients who received ARAIDs between January 2011 and January 2021. The most common medication class was bisphosphonates (45.0%), followed by mTOR inhibitors (30.1%) and anti-angiogenics (17.8%). No diagnosis of osteonecrosis of the jaw was observed. From this population, 26 patients were noted to have undergone invasive dental treatment. The duration from treatment to the invasive procedure ranged from 0 to 5.9 years. Medication-related osteonecrosis of the jaw is extremely rare among the pediatric population – much less common when compared to the adult population. Prospective cohort studies and continued evaluation will help determine the incidence and prevalence of medication-related osteonecrosis of the jaw in pediatric patients.
Management of bisphosphonate preparation-treated children in the field of pediatric dentistry
2022, Japanese Dental Science Review
Since most of the reports of BRONJ onset are adults, in order to clarify the current situation of BRONJ onset in children, it is necessary to search for articles and report on the current status and actual conditions of surgical treatment of children with BP preparations who are being followed up in our clinic.
In previous reports both inside and outside Japan, there was no mention of jaw bone necrosis during tooth extraction or surgery in children who were receiving or had a history of BP administration.
There were 15 children with a history of BP administration who manage the oral cavity in our clinic. No unpleasant events in the extraction of deciduous teeth were confirmed in medical records. It is necessary to intervene early on oral management of pediatric BP-administered children, especially BP-and steroid-administered children, obtain plaque control to keep the oral cavity cleaner, respond early to infectious diseases, and manage to prevent inflammation from spreading to the jawbone. When surgical treatment is unavoidable, it is important to consider reducing the invasion as much as possible and to cooperate with the medical department such as administration of antibiotics to prevent infection.
Medication-Related Osteonecrosis of the Jaws in the Pediatric Population
2022, Journal of Oral and Maxillofacial Surgery
Citation Excerpt :
A difficulty in providing dental recommendations for this population is that many pediatric patients treated with antiresorptives start treatment at a very young age. In our study, the average age at the start of antiresorptive treatment was 8.18 years, similar to previous reports.8-11 In the absence of known or reported cases of MRONJ in the pediatric population, we agree with Chahine et al that dental extractions should not be withheld because of previous antiresorptive exposure.10
Few reports have investigated medication-related osteonecrosis of the jaws (MRONJ) in the pediatric population. The study purpose was to measure the frequency of MRONJ in pediatric patients receiving antiresorptive medications at our institution.
This retrospective case series was granted an exemption by the University of Texas Southwestern Medical Center Institutional Review Board. The primary outcome variable was the presence or absence of MRONJ. Other variables of interest included 1) age at first dose of antiresorptive; 2) sex; 3) antiresorptive medication received; 4) reason for antiresorptive; 5) dental records available; 6) dental extractions that occurred after the start of antiresorptive; 7) exposure to immunosuppressants/chemotherapy; 8) time interval from the last dose of antiresorptive to dental extractions; and 9) longest follow-up after starting antiresorptive. Frequencies and proportions were calculated for categorical data. Medians, means, and standard deviations were calculated for continuous data.
The study sample was composed of 122 subjects. We observed 0 cases of MRONJ during the study interval. At the start of antiresorptive treatment, the average age was 8.18 years (range 0.02-17; standard deviation (SD) 5.15). There were 67 males (55%) and 55 females (45%). The reason for antiresorptive treatment was osteogenesis imperfecta in 36 patients, malignancy in 6 patients, and other in 80 patients. Thirty patients received pamidronate, 72 received zoledronate, 17 received a combination, and 3 received only denosumab. A total of 16 patients had exposure to immunosuppressants and/or chemotherapy. The average follow-up time was 4.89 years (median 4 years). Twenty-six patients underwent dental extractions of 74 teeth following antiresorptive treatment.
While there were no reported cases of MRONJ in the present study, it is advisable to monitor pediatric patients who have received antiresorptive treatment closely. When possible, appropriate dental treatment should be completed prior to starting antiresorptive therapy. In the absence of reported MRONJ cases, dental extractions should not be withheld because of previous antiresorptive exposure and antiresorptive medication dosing need not be altered in the pediatric population.
Bisphosphonate-related osteonecrosis of the jaws and dental surgery procedures in children and young people with osteogenesis imperfecta: A systematic review
2020, Journal of Stomatology, Oral and Maxillofacial Surgery
Citation Excerpt :
The antibiotic prophylaxis was not always performed, and the follow-up largely varied and was not always specified. Schwartz et al. [24] and Chahine et al. [37] administered prophylactic antibiotics in 65% and 16.4% of the subjects respectively, but both omitted to report the reasons to administer the antibiotic therapy, nor specified the antibiotic used or the dosage. Differently, Milano et al. in their case report defined the use of IV ampicillin 50 mg/kg immediately prior to surgery, due to the numerous dental extraction the patients underwent under general anaesthesia [20], as similarly referred by Ierardo et al, who administered 50 mg/kg per os/IV amoxicillin/ampicillin or 20 mg/kg per os/IV clindamycin single dose 30–60 min before surgical procedures [42], while Ngan et al. prescribed a 5-day course of amoxicillin to prevent post-operative infection [38].
Bisphosphonates (BPs) contrast the bone fragility and improve bone density in some metastatic cancers and bone diseases, such as Osteogenesis Imperfecta (OI). BPs use has been associated with osteonecrosis of the jaws (BRONJs) in adults needing for invasive dental procedures.
To conduct a systematic review on BRONJ occurrence after dental surgery in paediatric population under BPs therapy for OI, so as to identify the pre-surgical protocols adopted.
According to PRISMA guidelines, Pubmed, Web of Science (WoS) and Cochrane were investigated on September 2018, and re-checked on July 2019. Inclusion criteria were English-language papers on children/young adults (until 24 years old) reporting dental/oral surgery procedures.
Totally, 60 articles were found. After title/abstract reviews and duplicates exclusion, 22 eligible titles underwent full-text evaluation. Finally, 10 studies were included.
The lack of BRONJ occurrence in paediatric population suffering OI and treated with BPs, was confirmed, but the reasons are still debated, being the BPs therapies and the surgical strategies various and not standardized. Longitudinal studies should evaluate what happens to those former children once adult, to evaluate the delayed BRONJs onset associated with the occurrence of comorbidities during the adulthood.
Can children be affected by bisphosphonate-related osteonecrosis of the jaw? A systematic review
2020, International Journal of Oral and Maxillofacial Surgery
Citation Excerpt :
Only one article was rated as having a high risk of bias. All of the aspects assessed can be found in Table 423–29. The articles selected for this systematic review were retrospective cohort studies, case-series studies, and prospective studies.
Knowledge of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is mostly based on adult cases, however bisphosphonates are also currently recommended for different paediatric diseases resulting in osteoporosis. The aim of this study was to review the literature on the risk of developing BRONJ in children and adolescents. The PubMed, LILACS, Web of Science, Scopus, and Cochrane databases were searched using the key words “bisphosphonates”, “osteonecrosis”, “jaw”, and “children”. Literature reviews, case reports, abstracts, theses, textbooks, and book chapters were excluded. Studies involving children and young adults (younger than 24 years of age) were included. A total of 56 publications were identified. After applying the eligibility criteria, only seven articles remained. Although no cases of osteonecrosis were identified, all studies had weaknesses such as a limited sample size or the absence of risk factors for the development of osteonecrosis. There is general consensus that this subject should be of concern and that further studies should be conducted before any definitive opinion is reached. It is believed that patients with secondary osteoporosis who use bisphosphonates continuously should be followed up during adulthood, since bone turnover decreases over the years.

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: Supported by the Shriners of North America and the Fonds de la Recherche en Santé du Québec. F.G. is a consultant for Novartis, Inc. F.R. is a Chercheur-Boursier Clinician of the Fonds de la Recherche en Santé du Québec.

: No reprints are available from the authors.

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Clinical and laboratory observationTooth Extraction Socket Healing in Pediatric Patients Treated with Intravenous Pamidronate

Section snippets

Methods

Results

Discussion

Lancet

J Oral Maxillofac Surg

Crit Rev Oncol Hematol

J Am Dent Assoc

Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors

J Clin Oncol

Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors

J Clin Oncol

Clinical and laboratory observation
Tooth Extraction Socket Healing in Pediatric Patients Treated with Intravenous Pamidronate