Diffuse Sclerosing Osteomyelitis

Diffuse sclerosing osteomyelitis is a chronic, non-suppurative, diffuse sclerosing disease of the mandible, with relapsing pain and swelling. It involves large areas, often the entire body and ramus, and seldom has a clear infective focus.

It affects young to middle aged adults and some children, women a little more than men. It sits in the spectrum of chronic non-bacterial osteomyelitis and the SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis).

Pathophysiology. The cause is unclear. Cultures are mostly negative, and an autoinflammatory process, with raised IL-1 and TNF-alpha, is favoured over infection.

Low virulence organisms may play a part, and anaerobes and Actinomyces have been reported. Bone shows sclerosis with chronic inflammatory change but no abscess.

Episodic pain, swelling and tenderness of the jaw lasting weeks, with trismus, and quiet intervals. Some have fever, malaise and neck lymphadenopathy. There is usually no pus, sinus or sequestrum, and teeth are often healthy.

Ask about skin pustulosis, acne, palmoplantar pustulosis, joint pain, anterior chest wall pain and bone pain at other sites, which suggest SAPHO or multifocal disease.

• Panoramic radiograph and CT: diffuse sclerosis of the mandible with cortical thickening, mixed lucent areas and periosteal new bone, and generalised expansion without sequestra.
• MRI: marrow oedema and enhancement in active disease. Bone scintigraphy or whole body MRI to look for other sites.
• Bloods: C-reactive protein and ESR (often mildly raised), full blood count, calcium, alkaline phosphatase, and HLA-B27 when spondyloarthropathy is suspected.
• Bone biopsy with histology and culture to exclude infection and malignancy. Histology: sclerotic bone with chronic inflammation and fibrosis.
• Examination of skin, joints and chest wall for SAPHO.

Differential diagnosis.

• Chronic suppurative and sclerosing osteomyelitis
• Chronic recurrent multifocal osteomyelitis
• Paget disease
• Fibrous dysplasia
• Florid cemento osseous dysplasia
• Osteosarcoma and Ewing sarcoma
• Langerhans cell histiocytosis

• Anti-inflammatory therapy first: naproxen 500 mg orally twice daily with food and a proton pump inhibitor for 2 to 6 weeks, or ibuprofen 400 to 600 mg three times daily, avoided in renal impairment, peptic ulcer, and anticoagulant use. Review at 2 to 4 weeks.
• A short course of prednisolone 0.5 mg/kg (maximum 40 mg) daily for 1 to 2 weeks, tapered, for severe flares.
• Antibiotics for 4 to 6 weeks, with amoxicillin 500 mg to 1 g three times daily and metronidazole 400 mg three times daily, or clindamycin 300 to 450 mg four times daily, if infection is suspected. Response is variable and evidence is limited.
• Bisphosphonate for refractory pain: pamidronate 1 mg/kg (maximum 60 mg) intravenously over 4 hours every 4 weeks for 3 to 6 doses, or zoledronic acid 4 mg intravenously once, repeated at 6 months if needed. Check creatinine (avoid when eGFR is under 35 for zoledronic acid), calcium, vitamin D and dental health before treatment, with calcium and vitamin D replacement, and warn of the risk of osteonecrosis of the jaw. Evidence is from case series.
• Denosumab, methotrexate 10 to 15 mg once weekly with folic acid 5 mg once weekly, sulphasalazine or anti-TNF therapy, selected by the specialist team for refractory or multifocal disease.
• Surgery: decortication or limited resection for persistent disease. Radical surgery has high rates of recurrence and is avoided.
• Hyperbaric oxygen, with limited evidence.

Monitoring. Review every 4 to 6 weeks at first and then every 3 months, with pain scores, C-reactive protein, and imaging at 6 to 12 months. Renal function, calcium and dental review with bisphosphonates.

Referral and escalation. Refer to oral and maxillofacial surgery and rheumatology. Urgent referral for fracture, rapid progression, or any destructive or mass like change.