HETEROTOPIC OSSIFICATION
Mature Bone Formation in Soft Tissues
BROOKER CLASSIFICATION
Critical Must-Knows
- Brooker Grade III-IV = clinically significant (affects ROM)
- Prevention more effective than treatment (NSAIDs or radiation)
- Wait 6+ months for HO to mature before excision
- High-risk: head injury, burns, spinal cord injury, previous HO
- Recurrence rate significant without post-excision prophylaxis
Examiner's Pearls
- "Indomethacin 75mg daily x 6 weeks is classic prophylaxis regimen
- "Single-dose radiation (700cGy) within 72h is alternative to NSAIDs
- "Check ALP to confirm HO maturation before excision
- "Post-excision prophylaxis is MANDATORY to prevent recurrence
Clinical Imaging
Imaging Gallery
Critical Exam Concepts
Prevention is Key
Prophylaxis is far more effective than treatment. NSAIDs or radiation within 72h of surgery reduces HO by 80%. Know the regimens.
Wait for Maturity
Do NOT excise immature HO. Wait 6-12 months until bone is mature (normal ALP, cold bone scan). Early excision = high recurrence.
Brooker Classification
Grade III-IV = clinically significant. Only these grades typically affect function. Grade I-II usually observed.
Post-Excision Prophylaxis
Prophylaxis after excision is MANDATORY. Recurrence rate 50%+ without it. Same regimens as primary prevention.
Quick Decision Guide
| Scenario | Prevention | Treatment | Pearl |
|---|---|---|---|
| High-risk THA (previous HO, ankylosing spondylitis) | Indomethacin 75mg x 6 weeks OR radiation 700cGy | Excision if Grade III-IV | Start prophylaxis within 24-72h |
| Head injury with acetabular fracture | VERY high risk - prophylaxis mandatory | Wait 12+ months for maturity | Often bilateral, may be severe |
| Established HO Grade IV with ankylosis | Prophylaxis post-excision | Surgical excision when mature | Check ALP and bone scan before surgery |
| Asymptomatic Brooker I-II | None needed if primary prevention given | Observation only | Rarely progresses if stable at 6 months |
HABITRisk Factors for HO
Memory Hook:Patients with these HABITs are at high risk for growing bone where it shouldn't be!
1-2-3-4Brooker Classification
Memory Hook:1-Islands, 2-Big gap, 3-Small gap, 4-Fused (Think: the gap gets smaller as grade increases!)
RINDHO Prevention Protocol
Memory Hook:Use RIND to protect against bone growing in the wrong place - Radiation or Indomethacin for Necessary Duration!
Overview and Epidemiology
Definition
Heterotopic ossification (HO) is the formation of mature lamellar bone in extra-skeletal soft tissues (typically muscle and periarticular connective tissue). It is NOT dystrophic calcite or myositis ossificans traumatica (which involves muscle injury specifically).
Epidemiology
- Total hip arthroplasty: 10-50% radiographic, 3-5% symptomatic
- Acetabular fractures: 20-40%
- Elbow surgery: 3-20%
- Spinal cord injury: 20-30%
- Traumatic brain injury: 10-20%
- Males more commonly affected
High-Risk Groups
- Previous HO (strongest predictor - 50% recurrence)
- Traumatic brain injury
- Spinal cord injury
- Burns greater than 20% TBSA
- Ankylosing spondylitis
- Diffuse idiopathic skeletal hyperostosis (DISH)
- Hypertrophic osteoarthritis
Pathophysiology
The Pathogenesis Triad
HO requires three elements: (1) osteogenic precursor cells, (2) an inducing agent/signal, and (3) a permissive environment. Understanding this guides prevention strategies.
Osteogenic Precursor Cells
Source of bone-forming cells:
- Mesenchymal stem cells (MSCs) in muscle and connective tissue
- Circulating osteoprogenitor cells
- Local fibroblasts with osteogenic potential
- Endothelial cells via endothelial-to-mesenchymal transition
The differentiation pathway: MSCs differentiate into osteoblasts under appropriate signals, laying down osteoid which then mineralizes to form mature bone.
Why Does Head Injury Cause HO?
Multiple mechanisms: (1) Loss of inhibitory neural signals to bone turnover, (2) Release of brain-derived osteogenic factors into circulation, (3) Systemic inflammatory response, (4) Prolonged immobilization. Head-injured patients can develop HO at sites remote from any surgery or local trauma.
Classification Systems
Brooker Classification (1973)
Most commonly used - for hip HO
| Grade | Description | Clinical Significance |
|---|---|---|
| Grade I | Islands of bone within soft tissues about the hip | Usually asymptomatic |
| Grade II | Bone spurs from pelvis or femur with gap greater than 1cm | Mild, usually asymptomatic |
| Grade III | Bone spurs from pelvis or femur with gap less than 1cm | Moderate - may affect ROM |
| Grade IV | Apparent bone ankylosis of the hip | Severe - significant functional impairment |
Clinical Rule: Grades I-II are usually observed. Grades III-IV typically require surgical consideration.
Clinical Assessment
History
- Previous surgery/trauma to area
- Risk factors (head injury, SCI, burns)
- Timeline of symptom development
- Previous HO at any site
- Current medications (esp. NSAIDs)
- Functional limitations
Examination
- Range of motion - key functional assessment
- Palpable firm mass (late finding)
- Local warmth and swelling (early/active phase)
- Pain on movement (especially at end-range)
- Skin changes over lesion
- Neurovascular status (rare compression)
Clinical Stages of HO Development
Natural History
Local warmth, swelling, pain. May mimic infection or DVT. X-ray usually negative. Bone scan may be positive.
Early mineralization begins. Soft tissue mass becomes palpable. X-ray shows faint calcification. ALP elevated.
Progressive ossification and organization. ROM progressively limited. X-ray shows maturing bone. ALP peaks then normalizes.
Bone fully mature with cortical margins. ALP normal. Bone scan cold or minimal uptake. This is the safe window for excision.
Differential Diagnosis Early HO
Early HO can mimic: DVT (swelling, warmth), Infection (local inflammation), Stress fracture, Tumor (mass lesion). Bone scan and serial X-rays help differentiate. Don't miss DVT - consider duplex if lower limb.
Investigations
Radiological Investigations
| Modality | Timing | Findings | Role |
|---|---|---|---|
| Plain X-ray | From 3-6 weeks | Calcification, bone formation, Brooker grading | Primary imaging, classification |
| CT scan | Mature HO | Precise anatomy, surgical planning | Pre-operative planning |
| Bone scan (Tc-99) | Early (1-2 weeks) | Increased uptake (hot) = active | Assess maturity for timing of surgery |
| MRI | Early phase | Soft tissue edema, early changes | Rarely needed, can show early HO |
Maturity for surgery: Bone scan should be "cold" (no increased uptake) or minimal activity. This indicates mature HO safe for excision.
Pre-Excision Workup
Before excising HO, confirm maturity with: (1) Normal ALP for at least 2-3 months, (2) Cold or inactive bone scan, (3) Cortical margins on X-ray, (4) Stable radiographic appearance on serial imaging. Operating on immature HO dramatically increases recurrence.
Prevention Strategies
Prevention is Far More Effective Than Treatment
Prophylaxis reduces HO incidence by 70-80%. Once HO is established, only surgical excision can restore motion, with significant morbidity and recurrence risk. Prevention is the key strategy.
NSAID Prophylaxis
Mechanism: Inhibits prostaglandin synthesis, blocking osteogenic signal.
| Drug | Dose | Duration | Notes |
|---|---|---|---|
| Indomethacin | 75mg daily (or 25mg TDS) | 6 weeks | Classic regimen - best evidence |
| Naproxen | 500mg BD | 6 weeks | Alternative if indomethacin not tolerated |
| Celecoxib | 200mg daily | 6 weeks | COX-2 selective - fewer GI effects |
| Aspirin | 600-900mg daily | 6 weeks | Less effective than other NSAIDs |
Contraindications: GI ulcer/bleed history, renal impairment, anticoagulant use, fracture healing concerns.
Starting time: Begin within 24-48 hours of surgery. Delayed start reduces efficacy.
NSAIDs vs Radiation - When to Choose Which?
NSAIDs preferred: Most common, convenient, cheap. Use when no contraindications. Radiation preferred: NSAID contraindications (GI, renal), fracture healing concerns, difficult-to-shield anatomy. Both equally effective: No significant difference in HO prevention rates (70-80% reduction).
Management
Non-Operative Management
Indications: Brooker Grade I-II, minimal functional limitation, still maturing.
Components:
- Pain management
- Physiotherapy to maintain ROM (gentle - not forced)
- Monitor with serial X-rays
- Wait and watch - some HO resorbs partially
Note: Aggressive physiotherapy does NOT cause HO (old myth) BUT forced ROM through established HO can cause fracture or bleeding.
Post-Excision Prophylaxis is MANDATORY
The surgical field is highly osteogenic after excision. Without prophylaxis, recurrence rate exceeds 50%. Both NSAIDs and radiation are effective. Begin within 24-72 hours of surgery.
Surgical Technique Considerations
Hip HO Excision
Approach selection:
- Use same approach as index surgery if possible
- Lateral/anterolateral for most THA HO
- Consider dual approaches for circumferential HO
Technical pearls: Identify and protect neurovascular structures first (sciatic nerve at risk posteriorly). Excise HO to restore bone-capsule plane. Release contracted capsule. Ensure full ROM before closure.
Complications
Complications of HO and Its Treatment
| Complication | HO-Related | Surgery-Related | Management |
|---|---|---|---|
| Ankylosis | Grade IV HO | - | Surgical excision when mature |
| Neurovascular compression | Rare but serious | - | Urgent excision may be needed |
| Recurrence | - | 20-30% with prophylaxis | Re-excision possible |
| Neurovascular injury | - | During excision (sciatic, ulnar) | Careful identification, protect |
| Fracture | - | During manipulation | Gentle technique, staged if needed |
| Bleeding/hematoma | - | Promotes recurrence | Meticulous hemostasis, drain |
Sciatic Nerve and Hip HO
Sciatic nerve injury is a real risk during hip HO excision, especially for posterior/circumferential HO. Nerve may be encased in bone. Identify nerve early, trace proximally from known anatomy, and protect throughout. Neuromonitoring is advisable for complex cases.
Postoperative Care
Post-Excision Rehabilitation
Rehabilitation Protocol
Begin CPM if available. Active-assisted range of motion exercises. Maintain drains until output minimal.
Active ROM exercises. Physiotherapy daily initially. Focus on maintaining surgical gains. Weight bearing as tolerated (unless concurrent fracture).
Continue prophylaxis for full 6 weeks. Progressive strengthening. Functional training. Monitor ROM closely.
Ongoing home exercise program. Serial X-rays to monitor for recurrence. Return to functional activities.
CPM After HO Excision
Continuous passive motion (CPM) may help maintain ROM gains after excision, especially for elbow HO. Evidence is mixed but commonly used. Start immediately post-operatively. Goal is to maintain ROM achieved at surgery.
Outcomes and Prognosis
Prognostic Factors
Good Prognosis:
- Isolated HO without neurological cause
- Good ROM before HO developed
- Mature HO at time of excision
- Prophylaxis given post-excision
- Motivated patient for rehabilitation
Poor Prognosis:
- Neurogenic HO (TBI, SCI)
- Previous recurrence
- Circumferential HO
- Poor pre-HO ROM baseline
- Non-compliance with physiotherapy
Evidence Base and Key Trials
Fransen Meta-Analysis - NSAIDs for HO Prevention
- Meta-analysis of 18 RCTs, 4,763 patients
- NSAIDs reduce HO after hip surgery by 60-70%
- Indomethacin most studied and effective
- 6-week course standard
Burd Meta-Analysis - Radiation for HO Prevention
- Meta-analysis comparing radiation vs NSAIDs
- Both equally effective (70-80% reduction)
- Single dose 700cGy as effective as fractionated
- Pre-op and post-op radiation equally effective
Pakos Meta-Analysis - NSAIDs and Fracture Healing
- NSAIDs may delay fracture healing
- Short-term use (less than 2 weeks) probably safe
- 6-week course for HO prophylaxis controversial in fractures
- Consider radiation if fracture healing is concern
Vavken Review - HO in Total Hip Arthroplasty
- Comprehensive review of HO after THA
- Incidence 10-50% radiographic, 3-5% symptomatic
- Risk factors clearly defined
- Prophylaxis recommended for high-risk patients
Garland Review - Neurogenic HO
- Classic description of neurogenic HO
- SCI and TBI patients at very high risk
- Can occur at sites remote from trauma
- Wait 12+ months for maturity in neurogenic cases
Exam Viva Scenarios
Practice these scenarios to excel in your viva examination
Scenario 1: Post-THA Patient with Stiffness
"A 62-year-old man is 4 months post total hip arthroplasty. He had a history of ankylosing spondylitis. He now presents with progressive stiffness of the hip and reduced range of motion from 100 degrees flexion at 6 weeks to 60 degrees now. How would you assess and manage this patient?"
Scenario 2: Prevention Discussion
"You are performing a total hip arthroplasty on a 58-year-old woman who had previous heterotopic ossification after her contralateral THA which required excision. What would be your prophylaxis strategy?"
Scenario 3: Head Injury and Elbow HO
"A 28-year-old man who sustained a severe traumatic brain injury 8 months ago now presents with gradually worsening elbow stiffness bilaterally. He has a functional arc of only 30-80 degrees flexion on the right and the left elbow is nearly ankylosed. X-rays show extensive heterotopic ossification at both elbows. How would you manage this patient?"
MCQ Practice Points
Brooker Classification Question
Q: What is the Brooker Grade III classification for heterotopic ossification of the hip? A: Bone spurs from pelvis or femur with a gap of less than 1 cm. Grade I = islands, Grade II = gap greater than 1cm, Grade III = gap less than 1cm, Grade IV = ankylosis.
Prevention Regimen Question
Q: What is the standard NSAID prophylaxis regimen for prevention of heterotopic ossification after high-risk hip surgery? A: Indomethacin 75mg daily (or 25mg TDS) for 6 weeks, starting within 24-48 hours of surgery. Reduces HO by 70-80%.
Timing of Excision Question
Q: When is the optimal timing for surgical excision of heterotopic ossification? A: Minimum 6 months after formation, when ALP has normalized and bone scan is cold. For neurogenic HO (TBI/SCI), wait 12+ months. Early excision of immature HO leads to high recurrence.
Risk Factors Question
Q: What is the strongest risk factor for developing heterotopic ossification after hip surgery? A: Previous HO at any site (50% recurrence risk). Other major risk factors: TBI, SCI, burns, ankylosing spondylitis, DISH.
Radiation Dose Question
Q: What is the recommended single-dose radiation protocol for HO prophylaxis? A: 700-800 cGy within 72 hours of surgery (preferably within 24h). Single dose is as effective as fractionated. Pre- or post-operative delivery equally effective.
Post-Excision Question
Q: What is the recurrence rate after surgical excision of HO without prophylaxis? A: Greater than 50%. With prophylaxis (NSAIDs or radiation), recurrence is 20-30%. Post-excision prophylaxis is mandatory.
Australian Context
Practice Patterns
- NSAID prophylaxis more common than radiation
- Radiation access may be limited in regional areas
- Indomethacin is PBS-listed
- Most excisions done at major centers
Training Requirements
- HO prevention is SET competency
- Classification and management expected knowledge
- Excision techniques typically advanced fellowship level
- High-risk patient identification important
Medicolegal Considerations
Document risk factors and prophylaxis decision. High-risk patients should receive prophylaxis - failure to offer may be considered breach of standard of care. Consent for HO excision should include recurrence risk and need for ongoing prophylaxis.
HETEROTOPIC OSSIFICATION
High-Yield Exam Summary
Key Facts
- •10-50% radiographic after THA, 3-5% symptomatic
- •Brooker III-IV = clinically significant
- •Prevention reduces incidence by 70-80%
- •Previous HO = strongest risk factor (50% recurrence)
Brooker Classification
- •Grade I: Islands of bone in soft tissue
- •Grade II: Bone spurs, gap greater than 1cm
- •Grade III: Bone spurs, gap less than 1cm
- •Grade IV: Apparent ankylosis
Prevention
- •Indomethacin 75mg daily x 6 weeks
- •OR Radiation 700cGy within 72h
- •Start within 24-48 hours of surgery
- •Both equally effective
Surgical Excision
- •Wait 6+ months for maturity (12+ for neurogenic)
- •Confirm normal ALP, cold bone scan
- •Post-excision prophylaxis MANDATORY
- •Recurrence 20-30% with prophylaxis, 50%+ without
Risk Factors (HABIT)
- •Head injury / Hypertrophic OA
- •Ankylosing spondylitis / DISH
- •Burns / Bilateral hip OA
- •Previous HO / Invasive surgery
- •Trauma / Spinal cord injury