Bisphosphonate Treatment in Chronic Recurrent Multifocal Osteomyelitis

doi:10.1016/j.jpeds.2007.08.047

The Journal of Pediatrics

Volume 152, Issue 4, April 2008, Pages 571-575

https://doi.org/10.1016/j.jpeds.2007.08.047 Get rights and content

Objective

To test the safety and efficacy of biphosphonates in chronic recurrent multifocal osteomyelitis (CRMO).

Study design

Five patients with CRMO, all of whom had ongoing pain and loss of function despite conventional treatment with non-steroidal anti-inflammatory agents, were treated with pamidronate (1 mg/kg/dose with a dosing frequency of 2 to 4 monthly for a total treatment duration of 12 to 42 months).

Results

Pain decreased after the first infusion for 4 of 5 patients, with symptomatic improvement maintained with time. Significant improvement was seen in radiological lesions for these 4 patients.

Conclusion

Bisphosphonates appear to be a useful and safe adjunctive treatment in CRMO when simple therapies such as anti-inflammatory agents fail to control symptoms or cases in which lesion expansion continues.

Section snippets

Case Histories

Clinical details and pamidronate dosing for each patient are summarized in Table I. Radiological changes are summarized in Table II.

Discussion

In this case series of pamidronate use in CRMO, objective evidence of reduction in lesion size has been demonstrated. One earlier case series of children with the related SAPHO syndrome has shown symptomatic improvement only, with no objective change in lesion size.¹⁶ Earlier case reports of CRMO have shown response to treatment in individual patients. Four of our 5 patients showed clinical response, with some radiographic changes in all 4 patients. The fifth patient may have had some minimal

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Chronic Recurrent Multifocal Osteomyelitis
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Chronic nonbacterial monoarticular osteomyelitis of the elbow
2022, JSES Reviews, Reports, and Techniques
Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory disease of unknown etiology. Patients typically present with slow onset, recurring sterile bone lesions that produce pain and affect sleep. Active disease may be unifocal or multifocal and combined with swelling and reduced range of motion in the affected area. The metaphyses of long bones are most commonly affected, although reports of lesions in the shoulder, jaw, clavicle, and spine have also been described. Diagnosing CNO requires exclusion of other differential diagnoses, namely infection, and cancer. This entails a thorough clinical and physical examination, radiological imaging, and potentially a surgical biopsy. Timely diagnosis of CNO is critical for the prevention of long-term sequelae associated with this condition, such as spondyloarthropathy, arthritis, and diminished quality of life. Standardized treatment remains controversial and is mainly based on small case series or case reports. The present report outlines an intriguing case of CNO of the elbow. This case augments our understanding of the disease by expanding the possible anatomic sites of involvement to the proximal ulna and supports favorable treatment options pertaining to CNO of the elbow.
TNF-inhibitors or bisphosphonates in chronic nonbacterial osteomyelitis? - Results of an international retrospective multicenter study
2022, Clinical Immunology
Citation Excerpt :
While most data confirm predisposition for this complication in older patients with underlying malignancy [59,60,62], no published evidence exists that may suggest occurrence of Bisphosphonate-related osteonecrosis of the jaw (BRONJ) in the context of CNO or in children and adolescents with other bone disease like osteogenesis imperfecta [62–64]. While in the present and additional large cohorts no osteonecrosis of the jaw was seen during follow-up, awareness of possible long-term complications, including osteonecrosis, is necessary [43,65,66]. In this cohort, 3/91 (3.2%) patients exhibited a refractory disease course and neither responded to bisphosphonates nor TNFi.
Chronic nonbacterial osteomyelitis (CNO) can cause significant morbidity, including bone pain and damage. In the absence of clinical trials, treatments include non-steroidal anti-inflammatory drugs, corticosteroids, TNF-inhibitors (TNFi) and/or bisphosphonates. In a retrospective chart review in the United Kingdom and Germany, we investigated response to TNFi and/or pamidronate. Ninety-one patients were included, receiving pamidronate (n = 47), TNFi (n = 22) or both sequentially (n = 22). Patients with fatigue [p = 0.003] and/or arthritis [p = 0.002] were more frequently treated with TNFi than pamidronate. Both therapies were associated with clinical remission at 6 months, and reduction of bone lesions on MRI at 12 months. While not reaching statistical significance, pamidronate resulted in faster resolution of MRI lesions. Fewer flares were observed with TNFi. Failure to respond to pamidronate was associated with female sex [p = 0.027], more lesions on MRI [p = 0.01] and higher CRP levels [p = 0.03]. Randomized clinical trials are needed to confirm observations and generate evidence.
Chronic recurrent multifocal osteomyelitis in paediatrics in a tertiary centre
2022, Revista Colombiana de Reumatologia
La osteomielitis crónica multifocal recurrente (OCMR), también conocida como osteomielitis crónica no bacteriana, es una enfermedad autoinflamatoria caracterizada por afectación ósea, de curso en brotes y en ausencia de aislamiento microbiológico. El diagnóstico es de exclusión y el pilar fundamental del tratamiento son los antiinflamatorios no esteroideos (AINES). El objetivo del estudio es describir nuestra experiencia de tres niñas diagnosticadas de OCMR, destacando la presentación clínica, los hallazgos en las pruebas complementarias, el tratamiento y la evolución de la enfermedad.
Revisión retrospectiva de historias clínicas de niños diagnosticados de OCMR en los últimos cinco años, en seguimiento en consulta de reumatología pediátrica de un hospital terciario.
Presentamos tres pacientes diagnosticadas de OCMR, todas ellas mujeres adolescentes, con media de edad de 11 años. Consultaron por dolor e impotencia funcional, dos en una única localización y la otra por varios focos de dolor, a nivel cervical y lumbar, asociando debilidad de miembros superiores e inferiores. Con respecto al tratamiento, dos recibieron tratamiento antibiótico. Una niña respondió a antiinflamatorios; otra precisó asociar corticoides, y la restante, además de antiinflamatorios y corticoides, necesitó pamidronato intravenoso.
Con este estudio y a pesar del pequeño tamaño muestral, se pretende resaltar la importancia de esta patología, en muchos casos desconocida e infradiagnosticada, e insistir en la importancia de establecer un protocolo diagnóstico y terapéutico para su correcto abordaje.
Chronic recurrent multifocal osteomyelitis (CRMO), also called chronic non-bacterial osteomyelitis, is an autoinflammatory disease characterised by bone involvement, recurrent flare-ups, and the lack of microbiological isolation. It is a diagnosis of exclusion, and the fundamental basis of treatment is non-steroidal anti-inflammatory drugs. The objective of the study is to describe our experience as a result of three girls diagnosed with CRMO, highlighting the clinical presentation, the findings in the complementary tests, the treatment, and the evolution of the disease.
Retrospective chart review of children with CRMO in the last 5 years, being followed-up in a paediatric rheumatology clinic in a tertiary centre.
The cases are presented of 3 patients diagnosed with CRMO, all of them young girls, with a mean age of 11 years, who consulted due to pain and functional impotence. It was in single location in two cases, and the other with several sources of pain, at cervical and lumbar level, associated with weakness of the upper and lower limbs. Two of the cases received antibiotic treatment. One girl responded to treatment with anti-inflammatory drugs and another required combining corticosteroids. The remaining case, in addition to anti-inflammatory drugs and corticosteroids, required intravenous pamidronate.
With this study, and despite the small sample size, the aim was to highlight the importance of this, in many cases unknown and underdiagnosed, pathology, and to stress the importance of establishing a diagnostic and therapeutic protocol for the correct approach to this disease.
Effect of bisphosphonates on healing of tooth extraction wounds in infectious osteomyelitis of the jaw
2021, Bone
Citation Excerpt :
When the mandible is involved, it is considered as DSO (or PCO) of the mandible [32]. Anti-inflammatory therapy was the main treatment for CRMO; however, bisphosphonates in combination with a nonsteroidal anti-inflammatory drug have recently become a common approach to treat CRMO [33]. Bisphosphonate treatment rapidly alleviates the clinical symptoms of CRMO.
Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) and infectious osteomyelitis of the jaw (OMJ) in antiresorptive-naïve patients are different disease entities. Although osteoclast inhibition is at the center of the pathogenesis of ARONJ, the role of osteoclast inhibition in infectious OMJ is unknown. The objective of this study was to determine the effect of bisphosphonate osteoclast inhibition in infectious OMJ.
Osteomyelitis was induced in mice by S. aureus inoculation. The establishment of OMJ was verified by the culture of bone marrow samples obtained from the mandible. Infected animals received either zoledronic acid (ZA) or saline starting at week-2. Treated animals along with non-infected animals underwent tooth extractions at week-4 post-infection. Healing was assessed every week using in vivo micro-computed tomography and intraoral photos. Animals were euthanized at week-8 and cervical lymph nodes were assessed for lymphatic and blood vessels.
Tooth extraction wounds did not heal in animals with OMJ. These wounds were characterized by incomplete soft tissue coverage, sporadic bone fill in the sockets, and inflammatory cell accumulation in the connective tissue at 4 weeks after tooth extractions. Conversely, the majority of tooth extraction wounds in the infected animals treated with ZA had improved healing with better bone fill than even non-infected control animals. Consistently, atrophic lymphatic vessels were noted in the draining lymph nodes in animals with OMJ. However, infected animals treated with ZA had lymphatic vessels that were unaltered and showed a similar appearance to those in non-infected control animals.
ZA treatment promoted wound healing in the jaw with infectious osteomyelitis. Clearly, antiresorptive therapy is contraindicated in patients with ARONJ. However, our finding suggests that osteoclast inhibition is potentially an effectual remedy for infectious OMJ in antiresorptive-naïve patients.
Treatment of chronic recurrent multifocal osteomyelitis with bisphosphonates in children
2020, Revue du Rhumatisme (Edition Francaise)
Évaluation de l’efficacité des bisphosphonates dans le traitement de l’ostéomyélite multifocale chronique récidivante (OMCR) réfractaire aux anti-inflammatoires non stéroïdiens (AINS).
Analyse rétrospective de dossiers de patients traités pour une ostéomyélite multifocale chronique récidivante entre 2012 et 2018.
Entre 2012 et 2018, notre service a diagnostiqué une ostéomyélite multifocale chronique récidivante chez 76 enfants et adolescents. Des AINS ont été administrés à tous les patients en première instance, aboutissant à une rémission dans 46 % des cas. Quarante-et-un patients, sept garçons et 34 filles, n’ont pas répondu aux AINS. L’âge moyen à l’apparition de la maladie était de dix ans. La douleur était le plus souvent localisée dans le pied, la clavicule et la hanche. Le groupe présenté a reçu du pamidronate par intraveineuse à raison de 1 mg/kg/jour pendant trois jours. Six séquences (1 à 17) de traitement ont été administrées en moyenne, avec un intervalle moyen de dix semaines (4 à 14). Nous avons observé une diminution rapide de l’intensité des symptômes après la première dose et une récidive de la douleur après trois à quatre semaines. La fréquence des doses de pamidronate était adaptée aux symptômes des patients. Aucun effet indésirable grave n’a été rapporté. Nous avons arrêté le traitement lorsque la rémission des symptômes était complète et le remodelage osseux total sur les clichés d’imagerie. Sur les 41 patients de ce groupe, 32 sont en rémission et neuf toujours sous traitement. Les patients du groupe de rémission ont reçu en moyenne sept séquences de pamidronate sur une période moyenne de 20 mois.
Le pamidronate est un traitement sûr et efficace de l’OMCR, en particulier chez les patients réfractaires aux AINS. Le traitement par pamidronate permet à la fois le soulagement des symptômes et la normalisation de la morphologie osseuse.

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Original articleBisphosphonate Treatment in Chronic Recurrent Multifocal Osteomyelitis

Objective

Study design

Results

Conclusion

Section snippets

Case Histories

Discussion

Hum Pathol

J Pediatr

J Pediatr

J Pediatr

Int J Oral Maxillofac Surg

Oral Surg Oral Med Oral Pathol Oral Radiol Endod

Lancet

Subacute and symmetrical osteomyelitis

Ann Radiol

Chronic recurrent multifocal osteomyelitis in children

Ped Infect Dis J

Chronic non-bacterial osteomyelitis in children

Ann Rheum Dis

Chronic recurrent multifocal osteomyelitis: two cases of sacral disease responsive to corticosteroids

Clin Infect Dis

Original article
Bisphosphonate Treatment in Chronic Recurrent Multifocal Osteomyelitis