Heterotopic Ossification and Total Knee Replacement - Dushan Atkinson FRCS Tr & Orth 5/9/2008

Heterotopic Ossification (HO) following primary Total Knee Replacement (TKR)


Occurs in 3-90% of TKRs (1-12)

3-grade classification system (2,11)

No correlation between HO and component alignment or component position (4)

Clinical findings similar to early infection

        Continuing low-grade fever

        Warm, swollen and erythematous knee

        Normal blood tests (7)

        Possibly an association with HLA-A2 and B18 (13)

        HO patients have worse KSS and function scores (6)


X-rays may not show abnormalities during the acute phase of erythema and swelling.

        Later radiographs (1-2 weeks after onset) often show only ST swelling.

        Starts to show on x-ray by a mean of 5 weeks (7)

        May take 8-14 months to reach maturity.

Triple-phase bone scanning technology preferred diagnostic test for earlier HO detection (12)


HO can require surgical excision (8) though should only be undertaken for clear functional goals.

        T o improve standing posture

        To improve ambulation

        When HO limits function and rehabilitation

        If HO significantly restricts joint ROM


Surgery is not undertaken until maturation of HO. May take 1-2 years.

Surgery is contraindicated in patients with clinical, laboratory, or radiographic evidence of active ossification.


Little evidence for giving prophylaxis treatment for HO to all primary arthroplasty patients (1)


Recurrence of HO after surgical excision unless prophylaxis is administered (5)


Prophylactic treatment in high risk patient (1)

            Radiotherapy 7-8 Gy pre (4 hours before surgery) or post-op (within 72 hours)

            Indomethacin 75mg daily for 6 weeks

            Etidronate disodium (EHDP) can prevent its recurrence


Patients at HIGH risk for developing HO after THR (Hip Arthroplasty)   (5)


        Bilateral hypertrophic osteoarthritis

        Patients with a history of HO in either hip

        Patients with posttraumatic arthritis characterized by hypertrophic osteophytosis

        Traumatic brain injury, spinal cord injury


Patients at MODERATE risk are

        Those with ankylosing spondylitis

        DISH (diffuse idiopathic skeletal hyperostosis)

        Paget's disease

        Unilateral hypertrophic osteoarthritis


Patients at HIGH risk for developing HO after TKR (Knee Arthroplasty) (5)

        Those with limited postoperative knee flexion

        Increased lumbar bone mineral density (BMD) on multivariate analysis (3)

        Hypertrophic arthrosis

        Excessive periosteal trauma

        Notching of the anterior femur

        Those who require forced manipulation after TKA

        47% in revision TKR surgery (6)

        Higher rates in revision TKR cases with infection (up to 76%) (6)


Preoperative measurement of spinal BMD may identify those patients at risk for HO (3)



Bone Joint Surg Br. 2007 Apr;89(4):434-40

The prophylaxis and treatment of heterotopic ossification following lower limb arthroplasty.

Board TN, Karva A, Board RE, Gambhir AK, Porter ML.

Wrightington Hospital, Wigan and the University of Manchester, Manchester, England.


Heterotopic ossification following joint replacement in the lower limb occurs in 3% to 90% of cases. Higher grades of heterotopic ossification can result in significant limitation of function and can negate the benefits of joint replacement. The understanding of the pathophysiology of this condition has improved in recent years. It would appear to be related to a combination of systemic and local factors, including over-expression of bone morphogenetic protein-4. There is currently little evidence to support the routine use of prophylaxis for heterotopic ossification in arthroplasty patients, but prophylaxis is recommended by some for high-risk patients. Radiotherapy given as one dose of 7 Gy to 8 Gy, either pre-operatively (< four hours before) or post-operatively (within 72 hours of surgery), appears to be more effective than indomethacin therapy (75 mg daily for six weeks). In cases of prophylaxis against recurrent heterotopic ossification following excision, recent work has suggested that a combination of radiotherapy and indomethacin is effective. Advances in our understanding of this condition may permit the development of newer, safer treatment modalities.

PMID: 17463108




Acta Orthop Scand. 1997 Feb;68(1):46-50.

Heterotopic ossification after total knee arthroplasty. 54/615 cases after 1-6 years' follow-up.

Rader CP, Barthel T, Haase M, Scheidler M, Eulert J.

Orthopedic Department, University of Würzburg, Germany.


We found heterotopic ossifications in 54 (9%) of 615 cases after total knee arthroplasty. The largest ossifications were located in the anterior distal femur. In 12 cases smaller ossifications were found in other knee regions. The development of heterotopic ossification showed a positive correlation with hypertrophic arthrosis and a negative correlation with rheumatoid arthritis. We propose a new 3-grade classification which refers only to the anterior distal femoral region. Grade III heterotopic ossifications occurred in 4 patients (4 knees) who had clinical symptoms; 2 were successfully reoperated with removal of the ossifications. Prophylaxis should be considered in patients with marked hypertrophic arthrosis or marked periosteal damage to the anterior distal femur.



J Arthroplasty. 1995 Aug;10(4):413-9

Heterotopic ossification following primary total knee arthroplasty.

Furia JP, Pellegrini VD Jr.

Department of Orthopaedics, University of Rochester Medical Center, New York, USA.


Ninety-eight consecutive primary total knee arthroplasties (TKAs) in 70 patients were retrospectively evaluated for heterotopic ossification (HO). A radiographic classification was devised based on the extent and location of the ectopic bone. Twenty-five knees (26%) in 19 patients developed HO. Eight of 11 patients (73%) with preexisting heterotopic bone at other sites developed HO in the index knee. Multivariate analysis demonstrated that advanced HO was associated with restricted knee motion. Eight knees with advanced HO had a mean 14 degrees decrease in postoperative, as compared with preoperative, knee flexion (P < .05). For all patients with HO, mean lumbar spine bone mineral density (BMD) was significantly elevated compared with a matched control group not developing HO (P < .05). Heterotopic ossification following primary TKA correlates with a limitation of postoperative knee flexion and is predicted by increased lumbar BMD. Preoperative measurement of spinal BMD may identify those patients at risk for HO and allow for the institution of preoperative prophylaxis and modification of postoperative rehabilitation to optimize functional outcome following TKA.

PMID: 8522997



Arch Orthop Trauma Surg. 2005 Apr;125(3):188-92. Epub 2005 Feb 2.

Limited range of motion caused by heterotopic ossifications in primary total knee arthroplasty: a retrospective study of 27/191 cases.

Sterner T, Saxler G, Barden B.

Department of Orthopaedic Surgery, University of Essen, Pattbergstr. 1-3, 45239 Essen, Germany.


INTRODUCTION: Heterotopic ossification (HO) following primary total knee arthroplasty is a rare complication and may be symptomatic if massive enough. Especially the range of motion (ROM) is essential for the function and durability of the implant. The aim of the study was to evaluate the influence of HO on ROM using clinical and radiological parameters. MATERIALS AND METHODS: We reviewed 191 primary total knee arthroplasties according to the clinical preoperative and postoperative parameters of the Knee Society Score with special interest paid to the ROM. Standardized radiographs were taken at three levels and the implant position compared. The patients were divided into group 1 (with HO) and group 2 (without HO). The clinical and radiological parameters were compared. RESULTS: We found an incidence of HO in 14.1% (n = 27). Group 1 showed a decreased ROM postoperatively (p = 0.003) and worse flexion contracture (p = 0.04) compared with group 2. The evaluated radiological parameters showed no significant difference between the two groups. CONCLUSION: We found a significant limitation of ROM because of HO in our study. We found no correlation between HO and component alignment or component position. Local irritation has to be considered the main reason for limited ROM.



J Am Acad Orthop Surg. 2002 Nov-Dec;10(6):409-16.

Heterotopic ossification after hip and knee arthroplasty: risk factors, prevention, and treatment.

Iorio R, Healy WL.

Department of Orthopaedic Surgery, Lahey Clinic Medical Center, Burlington, MA, USA.


Symptomatic heterotopic ossification (HO) after total hip arthroplasty (THA) and total knee arthroplasty (TKA) is relatively rare. Patients at high risk for developing HO after THA include men with bilateral hypertrophic osteoarthritis, patients with a history of HO in either hip, and patients with posttraumatic arthritis characterized by hypertrophic osteophytosis. Patients at moderate risk are those with ankylosing spondylitis, diffuse idiopathic skeletal hyperostosis, Paget's disease, or unilateral hypertrophic osteoarthritis. Patients at high risk for developing HO after TKA include those with limited postoperative knee flexion, increased lumbar bone mineral density, hypertrophic arthrosis, excessive periosteal trauma and/or notching of the anterior femur, and those who require forced manipulation after TKA. Preoperative radiation is effective for preventing HO after THA, as are post-operative prophylactic drug regimens and single-dose radiation treatments. Recurrence of HO after surgical excision should be expected unless prophylaxis is administered. Prophylactic measures against HO after THA and TKA should be administered before the fifth postoperative day, optimally within 24 to 48 hours.



Clin Orthop Relat Res. 2002 Nov;(404):208-13.

Heterotopic ossification after revision total knee arthroplasty.

Barrack RL, Brumfield CS, Rorabeck CH, Cleland D, Myers L.

Department of Orthopaedic Surgery, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.


A consecutive series of revision total knee arthroplasties done at two centers was evaluated for the presence of heterotopic ossification on radiographs taken before and after revision using the classification system of Harwin et al. Knee Society scores were obtained preoperatively and at annual intervals postoperatively. The patients' demographics and clinical scores were correlated with the incidence and grade of heterotopic ossification. Minimum 2-year followup was obtained in 135 of 151 patients who had revision total knee arthroplasty during this period (89%). The incidence of heterotopic ossification before revision surgery was 23%, which increased to 56% at most recent followup (mean, 30 months; range, 24-48 months). The only risk factor identified for the development of heterotopic ossification was the presence of infection (76%), which was significantly higher than the 47% incidence of heterotopic ossification in patients who did not have an infection. The average postoperative Knee Society score was lower in patients with heterotopic ossification compared with patients without heterotopic ossification (129 points versus 148 points). Patients with heterotopic ossification had significantly lower functional scores particularly on stair climbing but did not have a significantly decreased range of motion. Parameters not associated with subsequent development of heterotopic ossification included gender (males), patient size (body mass index), surgical time, operative approach, or number of prior knee procedures.




Arch Orthop Trauma Surg. 2002 Jun;122(5):274-8. Epub 2002 Jan 25

Heterotopic ossification around distal femur after total knee arthroplasty.

Hasegawa M, Ohashi T, Uchida A.

Department of Orthopaedic Surgery, Mie University Faculty of Medicine, 2-174 Edobashi, Tsu City, Mie 514-8507, Japan.


Heterotopic ossification after total knee arthroplasty is not well recognized. We found heterotopic ossification around the distal femur in 10 (5%) of 221 knees after primary total knee arthroplasty and evaluated clinical findings as well as risk factors. The duration of follow-up ranged from 1 to 5 years. Most patients with heterotopic ossification showed clinical findings that were suspected of being early infection after surgery such as continuing low-grade fever and erythematous, warm, and swollen knees, whereas blood examinations were normal. Heterotopic ossification developed by a mean period of 5 weeks, and the size increased for a mean period of 9 weeks. The maximum size of the ossification was <5 cm in 9 knees and >5 cm in 1 knee. After that, the size decreased without any treatment in all knees, and the ossification finally disappeared in 2 knees. Osteoarthrosis and the presence of postoperative effusion were the significant risk factors in the development of heterotopic ossification. Although it is difficult to draw valid conclusions from our small study, heterotopic ossification at the distal femur after total knee arthroplasty needed no treatment and was not progressive, nor did it affect the short-term outcome in this study.




Am J Orthop. 1996 Aug;25(8):559-61

Heterotopic ossification following total knee arthroplasty requiring surgical excision.

Freedman EL, Freedman DM.

Department of Orthopaedic Surgery, UCLA Medical Center, USA.


We present a case of progressive heterotopic ossification (HO) after cementless total knee arthroplasty causing painful stiffness that was treated with surgical excision. The patient had few risk factors associated with HO, including minimal anterior notching and dissection of the distal femoral cortex. The patient did undergo manipulation; however, this occurred after the diagnosis of HO was made. This report documents a rare case of HO following total knee arthroplasty that required surgical excision.

PMID: 8871754



J Arthroplasty. 2004 Jun;19(4):447-52

The incidence of heterotopic ossification after total knee arthroplasty.

Dalury DF, Jiranek WA.

Orthopaedic Associates, Baltimore, Maryland 21204, USA.


Five hundred consecutive patients undergoing primary cemented knee arthroplasties were prospectively followed up and evaluated for the presence of heterotopic ossification. Of the patients studied, 95% had osteoarthritis and 5% had inflammation. A radiographic grading system was devised based on the size and location of the heterotopic bone. The overall incidence of heterotopic ossification in this group was 15%. The patients who developed HO tended to be heavier than the average and were more likely to be men. This is the most comprehensive prospective study of the incidence of HO in primary cemented knee arthroplasty. Other than a small subset of the patients (4 of 500), HO does not appear to have a major influence on the outcome of knee arthroplasty.

PMID: 15188102



J Arthroplasty. 1993 Apr;8(2):113-6

Heterotopic ossification following primary total knee arthroplasty.

Harwin SF, Stein AJ, Stern RE, Kulick RG.

Department of Orthopaedic Surgery, Albert Einstein College of Medicine, New York, New York.


Heterotopic ossification is a rare complication following primary total knee arthroplasty and may be symptomatic if massive enough. The authors retrospectively reviewed 158 primary total knee arthroplasties from 1985 to 1989 and found 6 cases (3.8%) of heterotopic ossification. Patients were graded before and after surgery according to the Hospital for Special Surgery total knee arthroplasty score and their histories were reviewed for the presence of recognized risk factors for heterotopic ossification and whether a manipulation under anesthesia was performed. This report describes the incidence of, appearance of, and clinical risk factors for heterotopic ossification following primary total knee arthroplasty in this series. A radiographic grading system is proposed.

PMID: 8478626


12) Tanaka T, Rossier AB, Hussey RW. Quantitative assessment of para-osteo-arthropathy and its maturation on serial radionuclide bone images. Radiology. Apr 1977;123(1):217-21.


13) G. Sessa, L. Costarella, R. Mollica, V. Pavone, Heterotopic ossification after total hip replacement and the HLA system in the Sicilian population. 2002;2(3):125-8.

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