Odontoiatric perspectives and osteonecrosis of the jaw as a possible adverse effect of bisphosphonates therapy in fibrous dysplasia and McCune-Albright syndrome

Tessaris, Daniele; Matarazzo, Patrizia; Lala, Roberto; Defabianis, Patrizia

doi:10.1515/jpem-2015-0300

Cited by 9 publications

(18 citation statements)

References 1 publication

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“…Another 309 articles were excluded in the title evaluation, and an additional 17 in the abstract review, making a total of 48 articles eligible for full-text evaluation; 1 article was added from the manual search. After the full-text review, 29 articles were included in the study that met the objectives of the systematic review [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ] ( Figure 1 ) ( Table 1 and Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…A total of 27.58% ( n = 8) of the articles did not show data to calculate the time involved in the use of antiresorptive therapy [ 35 , 36 , 43 , 50 , 51 , 53 , 54 , 55 ]. On the other hand, 68.96% ( n = 20) of the articles showed data for the time analysis, resulting in 4.21 years on average for 948 patients [ 37 , 38 , 39 , 40 , 41 , 42 , 44 , 45 , 46 , 47 , 48 , 49 , 52 , 56 , 58 , 59 , 60 , 61 , 62 , 63 ]. The lowest average of treatment time was 0.64 years [ 41 ] and the longest was 7.60 years [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

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Medication-Related Osteonecrosis of the Jaws (MRONJ) in Children and Young Patients—A Systematic Review

Rosales

Guevara

Requejo

et al. 2023

JCM

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Medication-related osteonecrosis of the jaw (MRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons (AAOMS) as the presence of an exposed bone area in the maxillofacial region, present for more than eight weeks in patients treated with the use of antiresorptive or antiangiogenic agents, with no history of radiation or metastatic disease. Bisphosphonates (BF) and denosumab (DS) are widely used in adults for the management of patients with cancer and osteoporosis, and recently there has been an increase in their use in child and young patients for the management of disorders such as osteogenesis imperfecta (OI), glucocorticoid-induced osteoporosis, McCune-Albright syndrome (MAS), malignant hypercalcemia, and others. There are differences between case reports in adults compared to child and young patients related to the use of antiresorptive/antiangiogenic drugs and the development of MRONJ. The aim was to analyze the presence of MRONJ in children and young patients, and the relation with oral surgery. A systematic review, following the PRISMA search matrix based on the PICO question, was conducted in PubMed, Embase, ScienceDirect, Cochrane, Google Scholar, and manual search in high-impact journals between 1960 and 2022, publications in English or Spanish, including randomized and non-randomized clinical trials, prospective and retrospective cohort studies, cases and controls studies, and series and case reports. A total of 2792 articles were identified and 29 were included; all of them published between 2007 and 2022, identifying 1192 patients, 39.68% male and 36.24% female, aged 11.56 years old on average, using these drugs mainly for OI (60.15%); 4.21 years on average was the therapy time and 10.18 drug doses administered on average; oral surgery was observed in 216 subjects, reporting 14 cases of MRONJ. We concluded that there is a low presence of MRONJ in the child and youth population treated with antiresorptive drugs. Data collection is weak, and details of therapy are not clear in some cases. Deficiencies in protocols and pharmacological characterization were observed in most of the included articles.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Medication-Related Osteonecrosis of the Jaws (MRONJ) in Children and Young Patients—A Systematic Review

Rosales

Guevara

Requejo

et al. 2023

JCM

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“…Although transient adverse events such as flu-like symptoms were seen in all cases after zoledronic acid infusion, long-term use side effects such as iatrogenic fracture and jaw necrosis were not seen (29). Five patients developed multiple physeal growth arrest lines warranting a regular follow-up with radiographs.…”

Section: Figure 7 | the Child Inmentioning

confidence: 88%

Response to Zoledronic Acid Infusion in Children With Fibrous Dysplasia

et al. 2020

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Objective: This retrospective study evaluated the outcome and safety of long-term treatment with zoledronic acid, in both polyostotic and mono-ostotic fibrous dysplasia (FD) of children.Methods: The case records of children and adolescents with symptomatic FD who received zoledronic acid (0.1 mg/kg IV infusion over 1 h) and have completed at least 2 years follow-up were analyzed. The relevant details were recorded in a predesigned chart. Clinical assessment [pain assessment by visual analog scale (VAS) and incidence of new fracture], radiological changes (cortical thickening, ossification, and decrease in the diameter of the osteolytic lesions) and biochemical parameters [alkaline phosphatase (ALP)] were used to evaluate the improvement.Results: The mean age of presentation was 9.1 years, with four males and six females. All patients had symptomatic FD in the lower limb with complaints of pain, tenderness, swelling, or deformity. Four children had associated pathological fracture. The radiological evaluation with bone scan revealed polyostotic involvement in eight patients and mono-ostotic involvement in two patients. Three patients had associated systemic features like café-au-lait spots or precocious puberty. The fracture united within 3 months and the radiological improvement was evident in the form of filling of the osteolytic defect. The pain score in six patients showed significant improvement (VAS < 3). The ALP level decreased to 544.12 ± 47.35 IU/L from an initial value of 895.75 ± 79.64 IU/L (p = 0.04) at 12 months. One patient had symptomatic hypocalcaemia after zoledronic acid infusion.Conclusion: The clinical and radiological response of zoledronic acid treatment in FD of children is promising. Further randomized control trials with a larger sample size are required to establish this drug as a first-line medical treatment in FD.

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“…Despite the frequent use of bisphosphonates in FD patients, there are no reports in the literature describing ONJ. This has led to postulation that patients with FD may be at lower risk for ONJ in comparison to the general population of patients treated with bisphosphonates [18]. Here we describe three patients in the NIH FD/MAS natural history study who developed ONJ subsequent to bisphosphonate treatment.…”

Section: Introductionmentioning

confidence: 98%

“…Early case reports and small series described subjective improvements in pain and variable effects on the radiographic appearance of FD lesions [13-15]; however, a placebo-controlled trial of the oral bisphosphonate alendronate showed no effects on pain or FD lesion appearance [16]. At present, there is little evidence to support an effect of bisphosphonates on FD quality or lesion expansion; however, intravenous formulations are generally considered beneficial for FD-related bone pain, and are frequently prescribed for this indication [2, 17, 18]. …”

Section: Introductionmentioning

confidence: 99%

Fibrous Dysplasia and Medication-Related Osteonecrosis of the Jaw

Metwally

Burke

Tsai

et al. 2016

Journal of Oral and Maxillofacial Surgery

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Purpose Osteonecrosis of the jaw (ONJ) is an established side effect of intravenous bisphosphonates and other anti-resorptive medications. Although bisphosphonates are frequently prescribed for patients with the skeletal disorder fibrous dysplasia (FD), there are no reports of ONJ in this population. This has led some to conclude that FD patients are at low risk for the development of bisphosphonate-related ONJ. Patients and Methods Patients were evaluated as part of a longstanding FD natural history study at the NIH. Results Out of 76 FD patients who were treated with bisphosphonates, four developed ONJ (5.4%). Three patients developed ONJ in areas of FD bone, and one in an area of normal bone. All four patients had features known to be associated with ONJ in the general population, including long-term, high dose, intravenous bisphosphonate treatment, periodontal and endodontic infections, and dentoalveolar surgical procedures. Conclusions These cases establish ONJ as a potential complication of bisphosphonate treatment in patients with FD. The presence of established risk factors for ONJ in this group of FD patients suggests that high risk individuals may be identified prior to the development of ONJ. Clinicians should use caution in prescribing bisphosphonates to FD patients, and should do so only for established indications.

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Odontoiatric perspectives and osteonecrosis of the jaw as a possible adverse effect of bisphosphonates therapy in fibrous dysplasia and McCune-Albright syndrome

Abstract: No patient developed ONJ. None of them showed radiological signs different from jaw FD. In spite of the low number of patients enrolled, results confirm that, in this population, ONJ can be ruled out as a chronic adverse side effect of bisphosphonate therapy.

Cited by 9 publications

References 1 publication

Medication-Related Osteonecrosis of the Jaws (MRONJ) in Children and Young Patients—A Systematic Review

Medication-Related Osteonecrosis of the Jaws (MRONJ) in Children and Young Patients—A Systematic Review

Response to Zoledronic Acid Infusion in Children With Fibrous Dysplasia

Fibrous Dysplasia and Medication-Related Osteonecrosis of the Jaw

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