Diffuse Idiopathic Skeletal Hyperostosis

Diffuse idiopathic skeletal hyperostosis is a non-inflammatory condition of unknown cause in which the ligaments and entheses ossify, especially the anterolateral longitudinal ligament of the thoracic spine. It produces flowing bony bridging over at least four contiguous vertebrae, with preserved disc height and normal sacroiliac joints and facet joints.

It affects about 25% of men and 15% of women over 50 years in some white populations (the prevalence rises with age and is lower in Asian and African populations). It is associated with obesity, type 2 diabetes, metabolic syndrome, hyperuricaemia and gout, dyslipidaemia, high vitamin A intake or long term retinoid use, and acromegaly. Most patients have mild stiffness; many are found by chance on a radiograph.

Complications:

• Spinal stiffness and pain.
• Dysphagia from cervical anterior osteophytes (up to 17% of patients with prominent cervical osteophytes).
• Hoarseness and airway obstruction (rare).
• Cervical or thoracic myelopathy and spinal stenosis (often with ossification of the posterior longitudinal ligament).
• Unstable fractures through the ossified spine after minor trauma, which can be missed.

Pathophysiology.

New bone forms at the entheses through dysregulated osteoblast activity driven by metabolic and growth factors (insulin, insulin like growth factor 1, leptin, transforming growth factor beta). The ossified anterior longitudinal ligament acts as a rigid lever, which is why a fracture through the ankylosed spine behaves like a long bone fracture. Disc height is preserved, which separates the condition from degenerative disc disease and ankylosing spondylitis.

Gradual stiffness of the thoracic and lumbar spine, mild back pain, neck stiffness, and reduced range of motion that is worse in the morning for a short period. Extra-spinal enthesopathy gives heel pain, elbow pain and hip or shoulder pain. Symptoms of dysphagia (food sticking in the throat), hoarseness, snoring or sleep apnoea may appear. Myelopathy gives clumsy hands, gait imbalance and sphincter dysfunction.

Examine posture, spinal range (reduced extension and rotation), neck, swallowing, voice, neurological state (including the legs), and peripheral entheses. Check for diabetes and gout.

• Radiographs of the thoracic and lumbar spine (lateral): flowing ossification along the anterolateral aspect of at least four contiguous vertebral bodies, with preserved disc space height, absence of apophyseal joint ankylosis, and normal sacroiliac joints. Cervical lateral view for anterior osteophytes.
• CT for fractures through the ossified spine and for the extent of ossification of the posterior longitudinal ligament; MRI for cord or root compression and for occult fracture.
• Blood tests: fasting glucose or HbA1c, lipids, uric acid, and CRP and ESR (normal or mildly raised); HLA-B27 is not needed.
• Videofluoroscopic swallow study and endoscopy for dysphagia; sleep study if airway symptoms.

Differential diagnosis.

• Ankylosing spondylitis (sacroiliac fusion, disc involvement, younger age) and psoriatic spondylitis.
• Degenerative spondylosis with osteophytes.
• Ossification of the posterior longitudinal ligament alone.
• Fluorosis, acromegaly and retinoid related ossification.

There is no treatment that stops ossification. Care is aimed at symptoms, metabolic risk factors and complications.

General measures. Education, regular exercise and stretching, physiotherapy to maintain mobility, weight loss, treatment of diabetes (target HbA1c set for the patient, usually 53 to 58 mmol/mol), gout and dyslipidaemia, and avoidance of retinoids and vitamin A supplements where possible.

Medication.

• Paracetamol 1 g orally every 6 hours as needed (maximum 4 g daily; 3 g daily when weight is under 50 kg, with chronic alcohol use or hepatic impairment).
• For flares of up to 2 to 4 weeks, use one NSAID:
  • Naproxen 500 mg orally every 12 hours with food (maximum 1000 mg daily).
  • Or ibuprofen 400 mg orally every 8 hours with food (maximum 1200 mg daily).
  • Or celecoxib 200 mg orally once or twice daily (maximum 400 mg daily).
• Add omeprazole 20 mg orally once daily in patients over 65 or with ulcer risk.
• Avoid NSAIDs with eGFR under 30 mL/min/1.73 m2, peptic ulcer, heart failure, uncontrolled hypertension or anticoagulant use.
• NSAIDs may also help reduce progression in some patients, but the evidence is limited.
• Local corticosteroid injection for enthesitis (methylprednisolone acetate 40 mg); avoid repeated injections near tendons.
• Neuropathic pain from stenosis: gabapentin 300 mg orally at night, increased by 300 mg every 1 to 3 days to 300 to 600 mg three times daily (maximum 3600 mg daily; reduce at creatinine clearance under 60 mL/min).

Dysphagia. Dietary modification (soft food, small bites, head turning), speech and swallow therapy, treatment of reflux (omeprazole 20 to 40 mg once daily), and surgical resection of anterior cervical osteophytes for severe or progressive dysphagia, airway compromise or aspiration; recurrence of ossification can occur.

Surgery. Decompression (with instrumented fusion) for myelopathy or symptomatic stenosis. Fractures in the ossified spine are managed with long segment posterior instrumentation (two to three levels proximal and distal to the fracture), because the construct fails otherwise.

Perioperative care:

• Cefazolin 2 g intravenously (3 g when weight is 120 kg or over) within 60 minutes before incision.
• Tranexamic acid 15 mg/kg (maximum 1 g) intravenously over 10 minutes before incision.
• Enoxaparin 40 mg subcutaneously once daily from 24 to 48 hours after surgery (20 mg at creatinine clearance under 30 mL/min).
• Plan for a difficult airway because of cervical ossification.

Analgesia after surgery. Paracetamol 1 g orally every 6 hours; oral morphine 5 to 10 mg every 4 hours as needed for up to 3 to 5 days (start 2.5 to 5 mg with age over 75 or eGFR under 30 mL/min/1.73 m2); laxative.

Monitoring. Review yearly for pain, mobility, swallowing and neurological symptoms; metabolic control (glucose, lipids, urate) at 3 to 6 months. Imaging only when symptoms change. After any trauma, however minor, a patient with spinal ossification who has new pain needs CT.

Referral and escalation. Refer to a spinal surgeon for myelopathy, progressive neurological deficit or spinal fracture; to ear, nose and throat or upper gastrointestinal surgery for dysphagia with weight loss, aspiration or airway symptoms; to rheumatology if inflammatory disease is possible. Emergency referral for any suspected fracture with neurological symptoms, or airway obstruction.

Special groups.

• Trauma patients: regard the spine as unstable until imaging excludes fracture; keep the spine in its usual alignment during transfers (do not force a neutral position).
• Diabetes and obesity: strict metabolic control; bariatric measures when appropriate.
• Older adults and kidney impairment: avoid NSAIDs, reduce gabapentin and morphine doses.
• Patients on retinoids (isotretinoin, acitretin): review the need for continued therapy if ossification develops.