Heterotopic Ossification:Incidence and Prevention

May 17, 2012Dr. Kristi Wood

Introduction

Definition:• ectopic bone formation within muscles and connective

tissues

Background

• First described in 1883 by Reidel• Acquired many names

– Paraosteoarthropathy– Myositis ossificans– Periarticular new bone formation– Periarticular ectopic ossification– Neurogenic osteoma– Neurogenic ossifying fibromyopathy– Heterotopic calcification

Etiology

• Trauma– Frequent complication following THA and acetabular

surgery• Abductor compartment most commonly involved

• Neurologic injury• Genetic abnormality

Incidence

• 3-90% following THR– 42-57% average1

• 3-7% clinically significant, up to 25%

• Increased risk following hip resurfacing (RR 1.6)2

• Following TKA: low (0.9%)3

1-Spinarelli et al (2011) Musculoskelet Surg. 95:1-5.

2-Smith et al (2010) Acta Orthopaedica. 81(6):684-695.

3-Atamaz et al (2006) Acta Orthop Traumatol Turc. 40(3):202-6

Risk Factors

• Male• Old age• Hx HO in ipsi > contra hip• Hip fusion• Hypertrophic arthritis• Ankylosing spondylitis• Diffuse idiopathic skeletal hyperostosis• Paget’s disease• Post-traumatic arthritis• Osteonecrosis• Rheumatoid arthritis

1-Board et al (2007) J Bone Joint Surg [Br]. 89-B:434-40.

Risks related to surgical technique

• Extent of soft tissue dissection• Bone trauma• Persistence of bone debris

– Reamings, marrow or dust• Hematoma• Lateral approach1

– Lower risk with posterior2 (vs anterolateral/transtrochanteric)

• ? Increased risk with Cemented1 vs uncemented3

• Psoas tendon release

1-Pavlou et al (2012) Hip Int. 22(1):50-5.

2-Ashton et al (2000) J Orthop Surg. 8:53-7.

3-Spinarelli et al (2011) Musculoskelet Surg. 95:1-5.

Theories of Pathophysiology

• Inappropriate differentiation of pluripotent mesenchymal stem cells– Interplay b/w local and systemic factors

• Over-expression of BMP-4

• PG-E2

• COX-2 pathway (vs Warfarin)

Brooker Classification

Grades:1 – islands of bone2 – bony spurs, > 1 cm gap

between bony ends3 – gap < 1 cm4 – apparent ankylosis

Brooker Classification

• Grades 1-2– Does not influence the outcome of THR

• Grades 3-4– Less favourable outcome

Puhl et al (2005) Strahlenther Onkol 181:529-33.

Presentation

• Typically asymptomatic

• Presents with:– Impingement– Instability– Decrease ROM/ankylosis– Nerve irritation– Trochanteric bursitis

• Pain uncommon

Investigations

• Xray – no abnormality for 4-6 weeks– Increased uptake on bone scan as early as 3 weeks

post-op

• Rises in osteoclastic and osteoblastic markers as early as 1 week

• Extensive bone formation within 3 months but full maturation takes up to 1 year

Prevention

MAINSTAYS• NSAIDs• Radiotherapy

NEW THERAPEUTIC MODALITIES – under investigations

NSAIDs

• Reduce incidence of HO by 1/2 - 2/3

• S/E– GI bleeding– Renal impairment– Exacerbation of asthma– ?Risk of bleeding from anti-platelet effect

NSAIDs – Which one?

• Indomethacin remains gold standard1

– Only drug proven effective after acetabular surgery• Naproxen, diclofenac equally as effective1

• Ibuprofen– Decreased HO but no change in clinical outcome– Increased major bleeding complications

• Rofecoxib2,3/celecoxib1

– equally effective with significantly less GI s/e– ? Safety of COX-2 inhibitors re: cardiovascular

1-Macfarlane et al (2008) Expert Opin Parmacother. 9(5):767-86.

2-van der Heide et al (2007) Acta Orthop 78(1):90-4.

3-Grohs et al (2007) Acta Orthop. 78(1):95-8.

NSAIDs – Which one?

• Indomethacin– Effective in reducing HO after hip arthroscopy

• Especially in male patients undergoing osteoplasty for correction of FAI

1-Bedi et al (2012) Am J Sports Med. 40(4):854-63.

NSAIDs – Dose/Duration

• Indomethacin – typically 25 mg PO TID x 5-6 weeks1

– Increased rate of non-union of long bones• Concern with trochanteric osteotomy or

uncemented components• At least 7 days2,3

1-Board et al (2007) J Bone Joint Surg [Br]. 89-B:434-40.

2-Fijn et al (2003) Pharm World Sci. 25(4):138-45.

3-van der Heide et al (2007) Acta Orthop 78(1)90-4.

Radiotherapy

• Marginally more effective than NSAIDs at preventing Brooker grades 3-4

• Dose: variable, many doses studied– 7-8 Gy given in a single dose seems both efficacious

and convenient1

• Timing/duration:– Pre-op (< 4 hours before) or post-op (within 72 hrs)1

1-Board et al (2007) J Bone Joint Surg [Br]. 89-B:434-40.

Radiotherapy

• Side effects– Testis very radiosesitive

• Decreased sperm count with > 0.2 Gy– dose 0.11 Gy with testicular shield (safe)

– Slowed # healing• trochanteric nonunion• Uncemented implants (shielding?)

• No documentation of radiation-induced tumours in HO prophylaxis-no radiation induced tumour with receiving < 30 Gy

(50 yr review)

Radiotherapy – Non-hip surgery

• For patients at high risk for developing further HO, prophylactic RT appears to be a safe and effective adjunct to surgery in prevention of HO recurrence (30 patients)1

– Elbow– MCP– Knee

1-Mishra et al (2011) J Med Imaging Radiat Oncol. 55(3):333-6

Combination NSAIDs + radiation

• Lowest risk of HO• Especially useful in prophylaxis against recurrent HO

after excision

NSAIDs vs Radiotherapy

• No significant difference between NSAIDS or radiation in prevention of HO (statistically or clinically) (Systematic review and meta-analysis)1

• Risks: no significant difference, but wide 95% CI so ? differences possible in future studies1

• Costs (Medicare data)2: – NSAIDS - 19.71 – Radiation therapy - 898.55

1-Vavken et al (2009) Clin Orthop Relat Res. 467:3283-3289

2-Strauss et al (2008) Int J Radiat Oncol Biol Phys. 71:1460-64

New therapeutic modalities

Under investigation• Noggin• BMP type 1 receptor inhibition• Nuclear retinoic acid receptor (RAR-)1

– Retinoic acid signalling is a strong inhibitor of chondrogenesis

– RAR- agonists are potent inhibitors of HO (in mice)• Free radical scavengers

1-Shimono et al. (2011) Nat Med. 17:454

Current recommendations

• 2007 JBJS [Br] – no indication for prophylactic treatment following routine replacement1

– Primary prevention for ‘high risk’ • Defiinition varies

– Prophylaxis for those undergoing excision of HO• 2012 J Ortho Trauma - Italian multicentre trial – findings

favour routine administration of prophylaxis after THA2

– Used celecoxib 200 mg BID for 14-20 days– 23% vs 55% HO (treated vs untreated, p<0.0001)– Treated-no Brooker 3-4 vs untreated-Brooker 3-4

8.9%

1-Board et al (2007) J Bone Joint Surg [Br]. 89-B:434-40.

2-Barbato et al (2012) J Orthopaed Traumatol. Published online.

Conclusions

• HO is common after THA, moreso with resurfacing• NSAIDs are effective, safe, cost-wise option to prevent

HO• Gold standard is indomethacin but

celecoxib/naproxen/diclofenac are alternatives– Indomethacin – 25 mg PO TID x 5-6 weeks

• Consider radiotherapy in pt’s undergoing HO excision– 7-8 Gy single dose 4 hrs before-72 hrs after OR