What are the treatment options for heterotopic ossification (HO)?

Treatment Options for Heterotopic Ossification

For acquired heterotopic ossification (HO) following trauma or surgery, prophylaxis with NSAIDs—specifically indomethacin 25 mg three times daily for at least 3 weeks starting the first postoperative morning—or single-dose radiation therapy (7 Gy) are the most effective interventions, while established HO requires surgical excision only after bone maturation is confirmed by serial bone scanning. 1, 2, 3, 4

Prophylactic Treatment (Prevention)

First-Line: NSAIDs

• Indomethacin 25 mg three times daily for 7 days minimum (up to 3 weeks) starting on the first postoperative morning is the most effective prophylactic regimen 2, 3, 4
• Treatment for 7 days appears equally effective as 14 days for preventing severe HO 3, 4
• Even delaying initiation up to 5 days postoperatively does not result in severe HO development 3
• Alternative NSAIDs with proven efficacy include ibuprofen and diclofenac 2
• Selective COX-2 inhibitors are as effective as nonselective NSAIDs with fewer gastrointestinal side effects 2

First-Line Alternative: Radiation Therapy

• Single-dose 7 Gy postoperatively is the most commonly used and effective regimen 2, 4
• Fractionated 4 × 3 Gy is also effective but less convenient 4
• Single-dose 5 Gy is significantly less effective and should be avoided 4
• Radiation is particularly recommended for patients with contraindications to NSAIDs or those with previous HO after prior operations 4

Second-Line: Bisphosphonates

• Diphosphonates such as ethane-1-hydroxy-1-diphosphate (etidronate) can be used as prophylaxis 1
• Less commonly prescribed than NSAIDs or radiation but may be considered in specific circumstances 5

Treatment of Established HO

Timing of Surgical Intervention

• Surgical resection is the only definitive treatment for established HO but must be delayed until bone maturation to prevent recurrence 1, 2
• Serial quantitative bone scans are essential to determine bone maturity before surgical excision 1
• Premature resection before maturation leads to recurrent and potentially progressive HO 1

Medical Management During Maturation Phase

• Continue NSAIDs to reduce inflammation and potentially slow progression 5
• Bisphosphonates may be used as adjunctive therapy 5
• Physical therapy to maintain range of motion is a mainstay of treatment during the waiting period 5

Diagnostic Confirmation

Imaging Approach

• Triple-phase bone scan is the confirmation test to distinguish HO from cellulitis, osteomyelitis, or thrombophlebitis 1, 5
• Plain radiographs using Brooker classification (grades I-IV) for staging 2
• CT scan provides superior visualization and quantification of established heterotopic bone formation 6
• Serial bone scans are used to assess bone maturity before surgical resection 1

Laboratory Testing

• Bone metabolic turnover markers have been tested but none are clinically relevant for prevention or diagnosis 2

Special Considerations for Fibrodysplasia Ossificans Progressiva (FOP)

This is a distinct genetic condition requiring completely different management:

Acute Flare Management

• Brief 4-day course of high-dose corticosteroids combined with NSAIDs started within 24 hours of flare-up may reduce inflammation 7
• Preventative management focuses on avoiding trauma, falls, and viral infections 7

Critical Contraindications in FOP

• Any trauma, including positioning for imaging or procedures, can trigger new ossification 7, 6
• Intramuscular injections are absolutely contraindicated 7
• Surgical excision of HO is contraindicated as it triggers more extensive ossification 7

Common Pitfalls to Avoid

• Do not use acetylsalicylic acid (aspirin) for HO prophylaxis—it is significantly less effective than indomethacin or radiation 4
• Do not use single-dose 5 Gy radiation—it results in significantly more ossification than 7 Gy 4
• Do not perform surgical excision before bone maturation—this leads to recurrence and progression 1
• Be aware of NSAID contraindications including active peptic ulcer disease, renal insufficiency, and bleeding disorders before prescribing 3
• Always provide gastroprotection when prescribing indomethacin 4
• Do not confuse acquired HO (trauma/surgery-related) with genetic FOP—management is completely different 7

Risk Stratification for Prophylaxis

Prophylaxis is particularly indicated for:

• Hip ankylosis patients 2
• Male gender 2
• Previous history of HO 2
• Traumatic brain injury or spinal cord injury patients (neurogenic HO) 5
• Total hip arthroplasty patients (15-90% develop HO without prophylaxis) 2