What is the best management approach for chronic non-bacterial osteomyelitis (Non-Bacterial Osteomyelitis)?

Management of Chronic Non-Bacterial Osteomyelitis (CNO)

The best management approach for chronic non-bacterial osteomyelitis (CNO) follows a stepwise algorithm starting with NSAIDs/COXIBs as first-line therapy, advancing to intravenous bisphosphonates or TNF inhibitors as second-line options, and referral to specialized centers for third-line treatments in refractory cases. 1

Diagnosis and Initial Assessment

• CNO is characterized by sterile bone inflammation that may affect multiple sites
• Key diagnostic imaging:
  • MRI is the preferred initial imaging modality
  • Alternative: CT combined with nuclear imaging
  • Consider whole-body imaging for diagnostic and prognostic purposes 1
• Rule out infection through appropriate cultures if fever or significantly elevated inflammatory markers are present
• Bone biopsy is not routinely recommended unless there is suspicion of malignancy or infectious osteomyelitis 1

Treatment Algorithm

First-Line Treatment

• NSAIDs/COXIBs at maximum tolerated and approved dosage
• Options include naproxen, indomethacin, ibuprofen, celecoxib, etoricoxib, piroxicam, and meloxicam
• Evaluate response at 2-4 weeks:
  • If sufficient response: continue and re-evaluate at 12 weeks
  • If sustained improvement at 12 weeks: consider tapering to on-demand treatment
  • If insufficient response: consider NSAID/COXIB rotation or advance to second-line treatment 1

Special Considerations for First-Line Treatment

• Consider directly advancing to second-line treatment in patients with:
  • Spinal bone lesions with risk of vertebral collapse
  • Significant accumulated skeletal damage 1

Second-Line Treatment

• Preferred option: Intravenous bisphosphonates (IVBP)
• Alternative: TNF-α inhibitors (TNFi)
• Choice between IVBP and TNFi should be individualized based on:
  • Presence of additional inflammatory features
  • Patient-specific factors
• Evaluate response at 3-6 months:
  • If sufficient response: consider tapering after 6-12 months of sustained improvement
  • If insufficient response: add or replace with the alternative second-line option (TNFi if on IVBP or vice versa) 1

Third-Line Treatment

• Refer patients with insufficient response to both IVBP and TNFi to an expert center
• Various third-line options may be considered based on individual patient characteristics 1

Supportive Measures Throughout All Treatment Stages

• Patient education and lifestyle recommendations
• Consider physiotherapy to maintain function and mobility
• Dental examination (particularly important with bisphosphonate therapy)
• Short courses of oral prednisolone or intra-articular glucocorticoid injections may be used as bridging options
• Avoid long-term use of glucocorticoids 1

Monitoring and Follow-Up

• Treatment success assessment:
  • Pain reduction and improved function
  • Radiological assessment (MRI or CT combined with nuclear imaging)
  • Laboratory monitoring of inflammatory markers if previously elevated 1
• Be aware of potential complications:
  • Neurovascular complications in patients with anterior chest wall involvement
  • Risk of vertebral fractures in patients with spinal involvement
  • Monitor for adverse treatment effects according to established guidelines 1

Treatment Efficacy and Prognosis

• NSAIDs are effective in many patients, with studies showing symptom-free status in up to 43% after 6 months 2
• Radiological relapses may occur in up to 41% of patients, but approximately two-thirds of these may be clinically silent 2
• For NSAID-refractory cases, bisphosphonates have shown disease remission in some patients, while TNF inhibitors (etanercept, infliximab, adalimumab) have demonstrated effectiveness in cases with inadequate response to bisphosphonates 3

Pitfalls and Caveats

• CNO is often underdiagnosed or misdiagnosed as bacterial osteomyelitis, leading to unnecessary antibiotic treatment
• Long-term NSAID use can cause gastrointestinal, renal, and cardiovascular adverse effects, especially in elderly patients 4
• Relapses and new radiological lesions can occur at any time and at any site in the skeleton, necessitating ongoing monitoring even during periods of clinical remission 2
• The disease may be self-limiting in some cases, but more aggressive treatment may be needed to prevent long-term bone damage 5