Chronic Non-bacterial Osteomyelitis Treated With Pamidronate

Phase 2

Brief Summary: In a randomized double blind placebo controlled trial to investigate the effect of pamidronate in treatment of chronic non bacterial osteomyelitis.

Main objective:

1. Reduction of the inflammatory activity in the bone lesions measured by whole body MRI after 36 weeks.

2. Healing of the inflammatory activity in the bone lesions measured by whole body MRI after 36 weeks.

Secondary objectives:

1. Changes in bone lesions in whole body MRI between baseline and week 12 and between week 12 and week 36

2. Changes in bone lesions of anterior chest-wall (adults) evaluated by CT scan between baseline and week 36.

3. Changes in patient self reported outcome measures

4. Changes in inflammatory markers and bone markers.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Age: 9-65 years (inclusive)
Fulfilling the diagnostic criteria for chronic non bacterial osteomyelitis:
1. Mono-, oligo- or multifocal inflammatory bone lesions (osteomyelitis, osteitis, osteosclerosis)
2. Diagnostic score according to A. Jansson criteria (2009) > 39 or malignancy and infection excluded by biopsy
3. Symptoms > 6 weeks
Volunteer, signed written informed content

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Pamidronatdinatrium 3mg/ml	Pamidronatdinatrium	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.
Natrium chloride 9 mg/ml	Natrium chloride 9mg/ml	Natrium chloride 9 mg/ml volume equals experimental drug

Primary Outcome Measures

Name	Time	Method
Wholebody MRI	Changes between baseline and week 36

Secondary Outcome Measures

Name	Time	Method
Systemic inflammatory markers	Changes between baseline and week 1, 4, 12, 24 and 36	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
CT scan of the anterior chestwall (adults)	Changes between baseline and week 36
Systemic bone markers	Changes between baseline and week 1, 4, 12, 24 and 36	s-CTX og s-NTX, P1NP, C1NP, TRACP 5b, bone alkaline phosphatase
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