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Heterotopic Ossification: Incidence and Prevention

May 17, 2012 Dr. Kristi Wood. Heterotopic Ossification: Incidence and Prevention. Introduction. Definition: ectopic bone formation within muscles and connective tissues. Background. First described in 1883 by Reidel Acquired many names Paraosteoarthropathy Myositis ossificans

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Heterotopic Ossification: Incidence and Prevention

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  1. May 17, 2012 Dr. Kristi Wood Heterotopic Ossification:Incidence and Prevention

  2. Introduction Definition: ectopic bone formation within muscles and connective tissues

  3. 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

  4. Etiology Trauma Frequent complication following THA and acetabular surgery Abductor compartment most commonly involved Neurologic injury Genetic abnormality

  5. 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

  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.

  7. 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.

  8. 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)

  9. Brooker Classification Grades: 1 – islands of bone 2 – bony spurs, > 1 cm gap between bony ends 3 – gap < 1 cm 4 – apparent ankylosis

  10. 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.

  11. Presentation Typically asymptomatic Presents with: Impingement Instability Decrease ROM/ankylosis Nerve irritation Trochanteric bursitis Pain uncommon

  12. 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

  13. Prevention MAINSTAYS NSAIDs Radiotherapy NEW THERAPEUTIC MODALITIES – under investigations

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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)

  20. 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

  21. Combination NSAIDs + radiation Lowest risk of HO Especially useful in prophylaxis against recurrent HO after excision

  22. 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

  23. New therapeutic modalities Under investigation Noggin BMP type 1 receptor inhibition Nuclear retinoic acid receptor g (RAR-g)1 Retinoic acid signalling is a strong inhibitor of chondrogenesis RAR-g agonists are potent inhibitors of HO (in mice) Free radical scavengers 1-Shimono et al. (2011) Nat Med. 17:454

  24. 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.

  25. 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

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