Incidence and Clinical Significance of Heterotopic Ossification After Partial Ray Resection

Published:February 24, 2016DOI:


      Heterotopic bone growth is a common finding after partial foot amputation that can predispose to recurrent wounds, osteomyelitis, and reamputation. Heterotopic ossification is the formation of excessive mature lamellar bone in the soft tissues adjacent to bone that is exacerbated by trauma or surgical intervention. The relevance of heterotopic ossification is dependent on its anatomic location. Its occurrence as a sequela of partial foot amputation can lead to prominence on the plantar aspect of the foot that can predispose the patient to recurrent neuropathic ulceration or preclude appropriate wound healing. Reulceration puts the high-risk patient who has already undergone local amputation at greater risk of recurrent infection and further amputation. The present study aimed to assess the incidence and risk factors for heterotopic ossification to further evaluate its role in partial foot amputation. A retrospective analysis of 72 consecutive patients who had undergone partial metatarsal resection was performed, with 90% of the cohort having peripheral neuropathy and 88% diabetes mellitus. Our findings revealed a heterotopic ossification incidence of 75% diagnosed radiographically. The initial onset of heterotopic ossification was not appreciated >10 weeks postoperatively. Ten patients (18.5%) exhibited heterotopic ossification-associated ulceration. The incidence of heterotopic ossification was 30% less in patients with peripheral vascular disease. These results indicate that heterotopic ossification is a common sequela of partial ray resection in an already high-risk patient population. The perioperative use of pharmacologic or radiation prophylaxis in an attempt to minimize amputation-related morbidity should be considered.

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        • Martini F.
        • Sell S.
        • Reize P.
        • Jani R.
        • Küsswetter W.
        Perioperative side effects of preventative measures against heterotopic ossification: diclofenac versus irradiation.
        Aktuelle Rheumatol. 1995; 20: 61-65
        • Bremen-Kühne R.
        • Stock D.
        • Franke C.
        Z Orthop Ihre Grenzgeb. 1997; 135 ([in German]): 422-429
        • Kölbl O.
        • Knelles D.
        • Barthel T.
        • Raunecker F.
        • Flentje M.
        • Eulert J.
        Preoperative irradiation versus the use of nonsteroidal anti-inflammatory drugs for prevention of heterotopic ossification following total hip replacement: the results of a randomized trial.
        Int J Radiat Oncol Biol Phys. 1998; 42: 397-401
        • Kienapfel H.
        • Koller M.
        • Wust A.
        • Sprey C.
        • Merte H.
        • Engenhart-Cabillic R.
        • Griss P.
        Prevention of heterotopic bone formation after total hip arthroplasty: a prospective randomised study comparing postoperative radiation therapy with indomethacin medication.
        Arch Orthop Trauma Surg. 1999; 119: 296-302
        • Chao S.T.
        • Joyce M.J.
        • Suh J.H.
        Treatment of heterotopic ossification.
        Orthopedics. 2007; 30: 457-464
        • Burd T.A.
        • Lowry K.J.
        • Anglen J.O.
        Indomethacin compared with localized irradiation for the prevention of heterotopic ossification following surgical treatment of acetabular fractures.
        J Bone Joint Surg Am. 2001; 83-A: 1783-1788
        • Schafer S.J.
        • Schafer L.O.
        • Anglen J.O.
        • Childers M.
        Heterotopic ossification in rehabilitation patients who have had internal fixation of an acetabular fracture.
        J Rehabil Res Dev. 2000; 37: 389-393
        • Moore K.D.
        • Goss K.
        • Anglen J.O.
        Indomethacin versus radiation therapy for prophylaxis against heterotopic ossification in acetabular fractures: a randomised, prospective study.
        J Bone Joint Surg Br. 1998; 80: 259-263
        • Kölbl O.
        • Knelles D.
        • Barthel T.
        • Kraus U.
        • Flentje M.
        • Eulert J.
        Randomized trial comparing early postoperative irradiation vs. the use of nonsteroidal anti-inflammatory drugs for prevention of heterotopic ossification following prosthetic total hip replacement.
        Int J Radiat Oncol Biol Phys. 1997; 39: 961-966
        • Sell S.
        • Willms R.
        • Jany R.
        • Esenwein S.
        • Gaissmaier C.
        • Martini F.
        • Bruhn G.
        • Burkhardsmaier F.
        • Bamberg M.
        • Küsswetter W.
        The suppression of heterotopic ossifications: radiation versus NSAID therapy—a prospective study.
        J Arthroplasty. 1998; 13: 854-859
        • Knelles D.
        • Barthel T.
        • Karrer A.
        • Kraus U.
        • Eulert J.
        • Kölbl O.
        Prevention of heterotopic ossification after total hip replacement: a prospective, randomised study using acetyl-salicylic acid, indomethacin and fractional or single-dose irradiation.
        J Bone Joint Surg Br. 1997; 79: 596-602
        • Thomas B.J.
        • Amstutz H.C.
        Prevention of heterotopic bone formation: clinical experience with diphosphonates.
        Hip. 1987; : 59-69
        • Lee K.B.
        • Cho Y.J.
        • Park J.K.
        • Song E.K.
        • Yoon T.R.
        • Seon J.K.
        Heterotopic ossification after primary total ankle arthroplasty.
        J Bone Joint Surg Am. 2011; 93: 751-758
        • Choi W.J.
        • Lee J.W.
        Heterotopic ossification after total ankle arthroplasty.
        J Bone Joint Surg Br. 2011; 93: 1508-1512
        • Angthong C.
        • Adams S.B.
        • Easley M.E.
        • Nunley J.A.
        Heterotopic ossification following total ankle replacement: clinical significance and factors affecting its formation.
        J Surg Orthop Adv. 2014; 23: 203-213
        • Boffeli T.B.
        • Pfannenstein R.P.
        • Thompson J.C.
        Radiation therapy for recurrent heterotopic ossification prophylaxis following partial metatarsal amputation.
        J Foot Ankle Surg. 2015; 54: 345-349
        • Vahvanen V.
        • Piirainen H.
        • Kettunen P.
        Resection arthroplasty of the metatarsophalangeal joints in rheumatoid arthritis: a follow-up study of 100 patients.
        Scand J Rheumatol. 1980; 9: 257-265
        • Matsumoto T.
        • Kadono Y.
        • Nishino J.
        • Nakamura K.
        • Tanaka S.
        • Yasui T.
        Midterm results of resection arthroplasty for forefoot deformities in patients with rheumatoid arthritis and the risk factors associated with patient dissatisfaction.
        J Foot Ankle Surg. 2014; 53: 41-46
        • Coughlin M.J.
        Rheumatoid forefoot reconstruction: a long-term follow-up study.
        J Bone Joint Surg Am. 2000; 82: 322-341
        • Ross M.H.
        • Pawlina W.
        Bone: cells of bone tissue.
        in: Histology: A Text and Atlas, With Correlated Cell and Molecular Biology. ed 6. Lippincott, Williams & Wilkins, Philadelphia2009: 223-231
        • Buring K.
        On the origin of cells in heterotopic bone formation.
        Clin Orthop Relat Res. 1975; 110: 293-302
        • Tonna E.A.
        • Cronkite E.P.
        Autoradiographic studies of cell proliferation in the periosteum of intact and fractured femora of mice utilizing DNA labeling with H3-thymidine.
        Proc Soc Exp Biol Med. 1961; 107: 719-721
        • Burd T.A.
        • Hughes M.S.
        • Anglen J.O.
        Heterotopic ossification prophylaxis with indomethacin increases the risk of long-bone nonunion.
        J Bone Joint Surg Br. 2003; 85: 700-705
        • Vavken P.
        • Castellani L.
        • Sculco T.P.
        Prophylaxis of heterotopic ossification of the hip.
        Clin Orthop Relat Res. 2009; 467: 3283-3289
        • Blokhuis T.J.
        • Frolke P.M.
        Is radiation superior to indomethacin to prevent heterotopic ossification in acetabular fractures: a systematic review.
        Clin Orthop Relat Res. 2009; 467: 526-530
        • Mavrogenis A.
        • Soucacos P.
        • Papagelopoulos P.
        Heterotopic ossification revisited.
        Orthopedics. 2011; 34: 177
        • Craven P.L.
        • Urist M.R.
        Osteogenesis by radioisotope labelled cell populations in implants of bone matrix under the influence of ionizing radiation.
        Clin Orthop Relat Res. 1971; 76: 231-233
        • Lo T.C.
        • Pfeifer B.A.
        • Smiley P.M.
        • Gumley G.J.
        Case report: radiation prevention of heterotopic ossification after bone and joint surgery in sites other than hips.
        Br J Radiol. 1996; 69: 673-677
        • Eggli S.
        • Woo A.
        Risk factors for heterotopic ossification in total hip arthroplasty.
        Arch Orthop Trauma Surg. 2001; 121: 531-535
        • Morbach S.
        • Quante C.
        • Ochs H.R.
        • Gaschler F.
        • Pallast J.M.
        • Knevels U.
        Increased risk of lower-extremity amputation among Caucasian diabetic patients on dialysis.
        Diabetes Care. 2001; 24: 1689-1690
        • Balboni T.A.
        • Gobezie R.
        • Mamon H.J.
        Heterotopic ossification: pathophysiology, clinical features, and the role of radiotherapy for prophylaxis.
        Int J Radiat Oncol Biol Phys. 2006; 65: 1289-1299
        • Ayers D.C.
        • Evarts C.M.
        • Parkinson J.R.
        The prevention of heterotopic ossification in high-risk patients by low-dose radiation therapy after total hip arthroplasty.
        J Bone Joint Surg Am. 1986; 68A: 1423-1430
        • Parkinson J.R.
        • Evarts C.M.
        Heterotopic bone formation after total hip arthroplasty.
        Adv Orthop Surg. 1984; 8: 17
        • Healy W.L.
        • Lo T.C.
        • DeSimone A.A.
        • Rask B.
        • Pfeifer B.A.
        Single-dose irradiation for the prevention of heterotopic ossification after total hip arthroplasty: a comparison of doses of five hundred and fifty and seven hundred centigray.
        J Bone Joint Surg Am. 1995; 77: 590-595
        • Haubner F.
        • Ohmann E.
        • Pohl F.
        • Strutz J.
        • Gassner H.G.
        Wound healing after radiation therapy: review of the literature.
        Radiat Oncol. 2012; 7: 162-171
        • Macfarlane R.J.
        • Ng B.H.
        • Gamie Z.
        • El Masry M.A.
        • Velonis S.
        • Schizas C.
        • Tsiridis E.
        Pharmacological treatment of heterotopic ossification following hip and acetabular surgery.
        Expert Opin Pharmacother. 2008; 9: 767-786