Introduction

Heterotopic ossification (HO) is the abnormal formation of mature lamellar bone within soft tissues where bone does not normally exist. It most commonly develops after musculoskeletal trauma, fractures, burns, spinal cord injury, traumatic brain injury, or orthopaedic surgical procedures, particularly around major joints. Although the exact mechanism remains incompletely understood, inappropriate differentiation of mesenchymal stem cells into osteoblasts following tissue injury is believed to be the underlying process.

HO may be asymptomatic in its early stages but can progressively cause pain, joint stiffness, loss of function, nerve compression, and ankylosis if left untreated.

Epidemiology

• Common after major trauma and orthopaedic surgery.

• Frequently occurs following total hip arthroplasty and acetabular fracture fixation.

• Increased incidence after traumatic brain injury and spinal cord injury.

• More common in young adults following high-energy trauma.

• Males are affected more frequently than females due to greater exposure to traumatic injuries.

Etiology

Heterotopic ossification develops following local tissue injury combined with abnormal activation of bone-forming pathways.

Common causes include:

• Fractures

• Joint dislocations

• Total hip arthroplasty

• Elbow surgery

• Acetabular surgery

• Spinal surgery

• Traumatic brain injury

• Spinal cord injury

• Severe burns

• Blast injuries

• Repeated muscle trauma

Rare hereditary causes include:

• Fibrodysplasia ossificans progressiva

• Progressive osseous heteroplasia

Pathophysiology

Following trauma or surgery, tissue injury triggers an inflammatory response with the release of cytokines, prostaglandins, and bone morphogenetic proteins (BMPs). These signalling molecules stimulate mesenchymal stem cells within injured muscles and connective tissues to differentiate into osteoblasts rather than regenerating normal soft tissue. Progressive osteoid formation is followed by mineralization and maturation into lamellar bone through endochondral ossification, resembling normal skeletal bone development. This ectopic bone gradually enlarges over several weeks to months and may bridge adjacent bones, restricting joint movement and causing pain, stiffness, and functional impairment.

Risk factors

• Major fractures

• Hip and acetabular fractures

• Total hip arthroplasty

• Elbow trauma

• Traumatic brain injury

• Spinal cord injury

• Severe burns

• Prolonged immobilization

• Delayed rehabilitation

• Previous heterotopic ossification

• Male sex

Classification

According to etiology

• Traumatic heterotopic ossification

• Neurogenic heterotopic ossification

• Genetic heterotopic ossification

Brooker classification (hip)

Grade I

Small isolated islands of bone within soft tissues.

Grade II

Bone spurs with more than 1 cm between opposing surfaces.

Grade III

Bone spurs leaving less than 1 cm between opposing surfaces.

Grade IV

Complete ankylosis of the affected joint.

Clinical presentation

Symptoms usually develop several weeks after injury or surgery.

Patients may present with:

• Progressive pain

• Reduced range of motion following trauma or surgery

• Joint stiffness

• Swelling

• Local warmth

• Tenderness

• Palpable firm mass

• Difficulty with rehabilitation

• Functional limitation

Bone formation usually becomes visible on plain radiographs 4–6 weeks after the initial injury or surgical procedure.

Advanced disease may present with:

• Joint ankylosis

• Nerve compression

• Difficulty walking

• Difficulty performing activities of daily living

Diagnostic criteria

Diagnosis is based on compatible clinical features together with imaging evidence of ectopic bone formation.

Diagnosis is supported by:

• History of trauma, neurological injury, burns, or recent surgery

• Progressive pain and restriction of joint movement

• Local swelling or palpable hard mass

• Imaging demonstrating heterotopic bone formation

• Exclusion of infection, fracture, tumour, or prosthetic complications

Investigations

Laboratory investigations

Laboratory tests are primarily supportive.

• Complete blood count (CBC)

• Erythrocyte sedimentation rate (ESR)

• C-reactive protein (CRP)

• Serum alkaline phosphatase (may be elevated during active bone formation)

• Serum calcium and phosphate (usually normal)

Imaging

Plain X-ray

First-line imaging.

Findings include:

• Mature ectopic bone

• Peripheral mineralization

• Usually visible 4–6 weeks after injury

Triple-phase bone scan

Most sensitive investigation during the early stage before radiographic ossification becomes apparent.

CT scan

Useful for:

• Surgical planning

• Assessing maturity and extent of ectopic bone

• Defining relationship to neurovascular structures

MRI

Limited role but may help exclude:

• Infection

• Soft tissue tumour

• Muscle injury

Ultrasound

May detect early soft tissue calcification before radiographic ossification.

Differential diagnosis

• Septic arthritis

• Osteomyelitis

• Cellulitis

• Deep vein thrombosis

• Soft tissue sarcoma

• Calcific tendinitis

• Myositis ossificans

• Prosthetic joint infection

Management

Treatment aims to:

• Relieve pain

• Preserve joint motion

• Prevent progression

• Improve functional recovery

• Restore mobility

Non-pharmacological management

• Early physiotherapy with gentle range-of-motion exercises

• Avoid aggressive stretching during the acute inflammatory phase

• Early mobilization where appropriate

• Occupational therapy

• Functional rehabilitation

• Walking aids if required

• Regular clinical follow-up

Pharmacological treatment

According to the current Standard Treatment Guidelines:

Indomethacin

• 75–150 mg orally per day administered as a single daily dose or in two divided doses every 12 hours.

Surgical management

Surgical excision is indicated for patients with:

• Severe restriction of joint movement

• Persistent pain

• Functional impairment

• Neurovascular compression

• Failure of conservative management

According to the current guideline:

• Surgery should be delayed for approximately 6 months after the initial trauma or surgery to allow maturation of the ectopic bone and development of a distinct fibrous capsule, thereby reducing recurrence and facilitating complete excision.

Postoperative physiotherapy should begin early to maintain joint mobility.

Rehabilitation

• Progressive range-of-motion exercises

• Muscle strengthening

• Gait training

• Occupational therapy

• Functional training

• Prevention of contractures

• Gradual return to normal activities

Monitoring and follow-up

Patients should be monitored for:

• Pain severity

• Joint range of motion

• Functional recovery

• Progression of ossification on imaging

• Adverse effects of NSAID therapy

• Recurrence following surgical excision

Complications

• Permanent joint stiffness

• Ankylosis

• Chronic pain

• Functional disability

• Nerve entrapment

• Vascular compression

• Pressure ulcers in immobilized patients

• Recurrence after surgical excision

Prognosis

The prognosis depends on the severity of the initial injury, the extent of ectopic bone formation, and the timing of treatment. Mild cases often remain stable or improve with conservative management and rehabilitation. Severe heterotopic ossification may cause permanent limitation of joint movement and require delayed surgical excision. Early recognition, appropriate prophylaxis in high-risk patients, and structured rehabilitation improve functional outcomes and reduce long-term disability.