Chronic Non-bacterial Osteomyelitis Treated With Pamidronate

Study Overview
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Brief Summary
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In a randomized double blind placebo controlled trial to investigate the effect of pamidronate in treatment of chronic non bacterial osteomyelitis. Main objective: Reduction of the inflammatory activity in the bone lesions measured by whole body MRI after 36 weeks. Healing of the inflammatory activity in the bone lesions measured by whole body MRI after 36 weeks. Secondary objectives: Changes in bone lesions in whole body MRI between baseline and week 12 and between week 12 and week 36 Changes in bone lesions of anterior chest-wall (adults) evaluated by CT scan between baseline and week 36. Changes in patient self reported outcome measures Changes in inflammatory markers and bone markers.

Detailed Description
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Chronic non-bacterial osteomyelitis is a multifocal inflammatory bone disorder. The pathogenesis is unknown. The disease is mainly diagnosed in childhood. There is a strong association with inflammatory disorders of the skin, mainly psoriasis. The disease is characterized by recurrent episodes of pain and disability. It is unclear if SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) might be the adult version of chronic non-bacterial osteomyelitis. The disease can persist in adulthood and course chronic bone deformations. Wholebody MRI is the most sensitive imaging for diagnosing and monitoring the non bacterial osteitis. The treatment of chronic non-bacterial osteomyelitis is largely empiric. First line treatment is NSAID (Non Steroidal Anti-Inflammatory Drug). When NSAID is inadequate the bisphosphonate pamidronate has been described relief pain in small cohorts in retrospective studies. In this research protocol, investigators seek to investigate if it is beneficial to use pamidronate in the treatment of chronic non bacterial osteomyelitis and the osteitis component in SAPHO syndrome. Primary outcome is whole body MRI. Secondary outcome is CT scan, patient measure reported outcome and biomarkers. A biobank may help us to understand the pathogenesis and future treatment targets of chronic non bacterial osteomyelitis.

Official Title
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Chronic Non-bacterial Osteomyelitis Treated With Pamidronate in a Randomised Placebo Controlled Trial

Conditions
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Immune System Disease, Musculoskeletal Disease

Intervention / Treatment
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* Drug: Pamidronatdinatrium
* Other: Natrium chloride 9mg/ml


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 9-65 years (inclusive) Fulfilling the diagnostic criteria for chronic non bacterial osteomyelitis: Mono-, oligo- or multifocal inflammatory bone lesions (osteomyelitis, osteitis, osteosclerosis) Diagnostic score according to A. Jansson criteria (2009) > 39 or malignancy and infection excluded by biopsy Symptoms > 6 weeks Volunteer, signed written informed content Exclusion Criteria: Age older than 65 years Age younger than 9 years Pregnant women or nursing (breastfeeding) mothers Hypersensitivity to pamidronate, bisphosphonate og additives in pamidronate Known history or current lymphoproliferative disease History of surgery on glandula thyroidea Known alcohol/medical abuse Poor dental status Low Vitamin D- status Liver/ kidney disease Abnormal laboratory screening for comorbidity

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pamidronatdinatrium 3mg/ml<br>Pamidronatdinatrium 1 mg/kg max 60 mg for 3 days every 3 month in total of 3 series (0,3,6 month). First day first series 0,5mg/kg max 30 mg. | Drug: Pamidronatdinatrium<br> <br> * Other names: Pamidronat, Pamifos, Aredia;|
| Placebo Comparator: Natrium chloride 9 mg/ml<br>Natrium chloride 9 mg/ml volume equals experimental drug | Other: Natrium chloride 9mg/ml<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wholebody MRI |  | Changes between baseline and week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CT scan of the anterior chestwall (adults) |  | Changes between baseline and week 36 | 
| Systemic inflammatory markers | TNF- α,IL-1 β, IL-8, IL-18, IL-17, INF-ƴ, IL-6, IL-10, IL-11, IL-21, MIP 1-alfa (CCL3, 22) and IL-1Ra | Changes between baseline and week 1, 4, 12, 24 and 36 | 
| Systemic bone markers | s-CTX og s-NTX, P1NP, C1NP, TRACP 5b, bone alkaline phosphatase | Changes between baseline and week 1, 4, 12, 24 and 36 | 
| Wholebody MRI |  | Changes between baseline and week 12 and changes between week 12 and 36 | 
| Changes in Health Assesment Questionnaire score |  | Changes between baseline and week 1, 4, 12, 24 and 36 | 
| Changes in Children Assesment Questionnaire score |  | Changes between baseline and week 1, 4, 12, 24 and 36 | 
| Changes in Visual Analog Score for pain |  | Changes between baseline and week 1, 4, 12, 24 and 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic non-bacterial osteomyelitis, Chronic recurrent multifocal osteomyelitis, Non- bacterial osteomyelitis, SAPHO syndrome, Whole body MRI, Pamidronate, Inflammatory bone disease, Autoinflammatory disease