For decades, ACDF has been regarded as the gold

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1 J Neurosurg Spine 14: , 2011 Heterotopic ossification after cervical total disc replacement: determination by CT and effects on clinical outcomes Clinical article Tsung-Hsi Tu, M.D., 1,2 Jau-Ching Wu, M.D., 1 3 Wen-Cheng Huang, M.D., Ph.D., 1,2 Wan-Yuo Guo, M.D., Ph.D., 2,4 Ching-Lan Wu, M.D., 2,4 Yang-Hsin Shih, M.D., 1 and Henrich Cheng, M.D., Ph.D Department of Neurosurgery, Neurological Institute, and 4 Department of Radiology, Taipei Veterans General Hospital; and 2 School of Medicine and 3 Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan Object. Heterotopic ossification (HO) after cervical total disc replacement (TDR) has been reported to impede artificial disc motion. In all previously reported cases of HO, assessment was based on plain radiographs. The authors hypothesized that CT scan is a more sensitive and accurate detector. The aims of this study were to assess the actual incidence of HO and its effect on outcome in a cohort of patients undergoing cervical TDR with the Bryan disc and to compare HO detection by means of plain radiographs and CT. Methods. The authors retrospectively assessed data from medical records, radiological studies, and clinical evaluations of patients who underwent 1- or 2-level cervical TDR with the Bryan disc and were followed up for more than 12 months. The presence and grading of HO according to the McAfee classification were assessed by CT scan, and these findings were compared with findings on plain radiographs. Thirty-six patients (mean age ± 7.24 years; range years; 21 men and 15 women) who underwent Bryan TDR at 52 levels were included in the study. The mean duration of CT follow-up was ± 4.64 months; the mean duration of clinical follow-up was ± 7.20 months. Results. On the basis of CT, HO was identified in 18 (50%) of 36 patients and 25 (48.1%) of 52 levels treated. Grade 1 HO was present in 9 of the levels treated (17.3%), Grade 2 in 13 levels (25.0%), Grade 3 in 2 levels (3.8%), and Grade 4 in 1 level (1.9%). Nineteen (76%) of the 25 affected levels were in patients who had undergone 2-level TDR. There was no significant association with patient sex or disc pathology. There was a tendency for HO development among older patients, but this finding was not statistically significant (mean age 48.8 ± 6.8 in patients with HO vs 44.4 ± 7.2 in those without HO, p = 0.065). Although HO was found in 25 levels, 96.2% of the treated levels (50 of 52) had segmental range of motion on dynamic (flexion and extension) radiographs. The concordance between HO grading by CT and radiography was high, with an intraclass correlation coefficient of (lower limit of 95% CI: 0.710, p < 0.001). Patients who had HO had the same clinical success rate as those who did not (94.4% vs 94.4%, p = 1.00). The visual analog scale scores for neck and arm pain were significantly improved in both the HO and the non-ho group. Conclusions. The rate of HO detected by CT scan in this cohort of patients undergoing cervical TDR with a Bryan disc was 48.1% per level treated and 50% per patient with minimal limitation of segmental motion (96.2% of levels remained mobile), but plain radiograph is an acceptable detection tool. Two-level surgery has a higher risk of HO, although development of HO does not affect clinical outcome. (DOI: / SPINE10444) Key Words heterotopic ossification total disc replacement Bryan disc cervical arthroplasty For decades, ACDF has been regarded as the gold standard of surgical intervention in treating cervical spondylosis and disc disease, producing excellent clinical outcomes. 4,5,10,14 Recently, there has been an emerging option of TDR, which is designed to preserve segmental motion and theoretically prevent ASD. 26,30 Whether ASD is a consequence of ACDF remains debatable. Abbreviations used in this paper: ACDF = anterior cervical discectomy and fusion; ASD = adjacent-segment disease; HO = heterotopic ossification; NSAID = nonsteroidal antiinflammatory drug; TDR = total disc replacement; VAS = visual analog scale. Several studies have shown that fusion of spinal motion segments alters cervical spinal biomechanics of the unfused adjacent levels. 7,8,17,33,36 Accelerated degeneration or subsequent ASD is postulated to relate to ACDF. 9,13,16,24,29 Recently, several prospective, randomized, controlled clinical trials of cervical TDR compared with ACDF have yielded promising results. 12,20,21 Very few complications or adverse events have been reported, and generally, these artificial discs retain segmental motion throughout the trial. However, as follow-up becomes longer, there are concerns about failure to maintain motion of the artificial disc or loss of protection from adjacent-level disease

2 T. H. Tu et al. Osseous fusion after cervical arthroplasty was first reported by Parkinson and Sekhon in Several month later, Bartels and Donk 2 reported 2 other cases of bony fusion after cervical arthroplasty with the Bryan disc. These were the earliest reports that referred to heterotopic ossification (HO) after cervical TDR. Still later in 2005, the first prospective, multicenter clinical trial specifically aimed at determining the clinical significance of HO following cervical TDR was reported by Leung and colleagues. 15 The data came from the original Bryan Disc Study by the European Consortium, a multicenter, prospective, observational study involving 7 centers in 6 European countries (Belgium, England, France, Germany, Italy, and Sweden). They demonstrated a 17.8% incidence of HO (HO occurring in 16 of 90 patients) 12 months postoperatively, with 11% (10/90) of the implanted Bryan disc prostheses failing to show segmental motion by radiography. Heterotopic ossification is one of the major causes of a limited range of motion at the index level after cervical TDR. 2,11,15,19 However, reported rates vary, and most have been assessed by plain radiography. With the hypothesis that the 2D overlapping image on plain radiographs has a high chance of underestimation, the authors of the present study aimed to retrospectively investigate the incidence of HO as determined by multidetector CT scan with image reconstruction, which is common in spine practice. This study is the first CT-based report on the rate of HO after cervical TDR with the Bryan artificial disc. In addition, it includes comparisons with plain radiographs. Methods Forty-six consecutive cases involving patients who underwent 1- or 2-level TDR with the Bryan cervical disc (Medtronic Spine and Biologics) were included in this study. Surgical indications included subaxial (C3 7) cervical disc herniation with radiculopathy or myelopathy, degenerative disc disease with intractable axial pain, or symptomatic cervical spondylosis with failure of medical treatments for at least 6 months and preservation of range of motion at the proposed treatment level as demonstrated by dynamic (flexion-extension) radiography. The general exclusion criteria were infection, osteoporosis (T score of -3.5), malignancy, metabolic bone disease, severe systemic disease, and traumatic disc disease with ligament injury. The specific exclusion criteria were moderate to severe cervical spondylosis with bridging spur formation, loss of more than 50% of disc height, or loss of segmental mobility (due to spur and facet degeneration); target segment instability (> 2 mm translational instability or > 11 angular motion); incompetent facet joints; ossification of the posterior longitudinal ligament; and diffuse idiopathic skeletal hyperostosis. The study was approved by the ethics committee of Taipei Veterans Hospital, and all patients provided informed consent. Surgical Techniques and Postoperative Management Standard anterior cervical discectomy via a right-sided anterolateral approach was followed by TDR with the Bryan cervical disc. Generous decompression of neural elements, including resection of the posterior longitudinal ligament and bilateral uncovertebral joints, was performed prior to implant insertion with the surgical aim of resecting all of the spurs and uncovertebral joints around the exiting nerve roots, even those on the asymptomatic side. During decompression, special care was taken to preserve the milled socket-shaped endplate. The operative field was copiously irrigated with normal saline during the entire process of milling and drilling. Aggressive hemostasis was achieved by bipolar coagulation for venous hemorrhage and bone wax for the cancellous bone. A closed-system drainage catheter was routinely placed before wound closure. Each patient was encouraged to walk after the operation without use of a soft neck collar. Perioperative NSAIDs were routinely prescribed for 1 week if not contraindicated. Evaluations Standard anterior-posterior and flexion-extension plain radiographs were obtained at 3 days and at 3, 6, and 12 months after surgery, with clinical outcomes assessed at the same time points. Measurements of segmental motion at the functional spinal unit were performed with the quantitative measurement analysis software SmartIris (Taiwan Electronic Data Processing Co.), which used extrapolative algorithms to determine the intersecting angle between 2 lines drawn by investigators. Cervical CT was performed at follow-up more than 12 months after the operation for detection and grading of HO. The protocol used for the CT scan was spiral thincut (1-mm) axial sections from C-2 to T-1 with sagittal and coronal reconstruction in 2-mm thickness. For plain radiographs, each image, including dynamic and static studies, was reviewed to determine segmental mobility and the presence of HO. Grading of HO was defined by the classification proposed by McAfee et al. 18 Loss of segmental motion was defined by failure to demonstrate more than 2 of motion on dynamic radiographs. Two independent radiologists and 2 neurosurgeons made all of the radiological interpretations. Discussion and voting were conducted to attain consensus in cases of any ambiguity. Clinical outcomes were assessed using a VAS for arm and neck pain, as well as by means of the Odom outcome classification. 23 Clinical success was defined as patient report of excellent or good in the Odom rating system. The following variables were analyzed to determine their association with HO: age, sex, pathological types of disc disease, clinical outcome, and number of levels treated. Any discrepancy on HO grading by CT and radiographic images was reported, and reliability analysis was conducted using intraclass correlation of HO grading. The Student t-test was used for continuous variables and the chi-square test for categorical data. Significance was accepted at the 5% level. All statistical analyses were performed using the SPSS software (Version 17.0; SPSS, Inc.). 458

3 Heterotopic ossification after cervical total disc replacement Demographic Characteristics Of the 46 consecutive patients who fulfilled the inclusion criteria, 36 who completed the clinical and radiological evaluations were included in the study. The other 10 were excluded due to inadequate evaluation, lack of informed consent, or loss to follow-up. Fifty-two cervical levels in 36 patients were evaluated; 20 (55.6%) of 36 patients had 1-level TDR, and 16 (44.4%) had 2-level TDR. The mean CT follow-up time was ± 4.64 months (range months), and the mean patient age at the time of surgery was ± 7.24 years (range years). The group included 21 men and 15 women. The mean clinical follow-up time was ± 7.20 months (range months). All 36 patients completed 12 months of postoperative clinical follow-up, and 25 were available at 24 months postoperatively for clinical outcome assessments. Radiculopathy was the most common presentation (50.0%), and the disc pathology was soft herniation in the majority of cases (61.1%) (Table 1). Of the 52 disc levels treated, 2 were C3 4, 13 were C4 5, 32 were C5 6, and 5 were C6 7 (Table 2). TABLE 1: Clinical and demographic characteristics in 36 patients* Characteristic Value sex male 21 (58.3) female 15 (41.7) age (yrs) mean ± 7.24 range duration of CT follow-up (mos) mean ± 4.64 range duration of clinical follow-up (mos) mean ± 7.20 range level op 20 (55.6) 2-level op 16 (44.4) disc pathology soft disc herniation 22 (61.1) spondylosis w/ spur formation 14 (38.9) presentation radiculopathy 18 (50.0) myelopathy 5 (13.9) myeloradiculopathy 7 (19.4) axial neck pain 6 (16.7) result (per Odom criteria) excellent/good 27/7 (94.44) fair /poor 2/0 (5.56) * Values represent numbers of patients (%) unless otherwise indicated. Means are given ± SDs. One patient had Grade 1 HO, the other did not have HO. Results Of the 36 patients enrolled, 20 underwent 1-level cervical TDR with the Bryan disc and 16 underwent 2-level TDR. Of the 52 levels treated, 25 levels (48.1% of the 52 levels) in 18 patients (50% of the 36 patients) had HO formation detected by CT scans. Six patients who had undergone single-level TDR had HO at the treated level. Twelve patients who had undergone 2-level TDR also had HO at one level in 5 patients and at both levels in 7, for a total of 19 levels with HO in patients who had undergone 2-level TDR. According to the McAfee grading criteria, there were 9 levels with Grade 1 HO; 13 with Grade 2 HO; 2 with Grade 3 HO; and 1 with Grade 4 HO (36%, 52%, 8%, and 4% of the 25 HO levels; 17.3%, 25.0%, 3.8%, and 1.9% of all 52 treated levels, respectively) (Table 3). The distribution of the treated levels and HO presence is shown in Fig. 1. The clinical success rate was 94.41% (27 patients had excellent and 7 had good outcomes based on the Odom criteria; Table 4). For patients without HO, the mean VAS arm pain score improved from preoperatively to and postoperatively (at 12 and 24 months, respectively), while the mean VAS neck pain score improved from preoperatively to and postoperatively. For patients with HO, the mean VAS arm pain score improved from preoperatively to and postoperatively (12 and 24 months, respectively), while the mean VAS neck pain score improved from preoperatively to and postoperatively. There were significant reductions (p < 0.001) in both VAS arm pain and neck pain scores at the 12- and 24-month follow-up compared with the preoperative scores. However, there were no significant differences between the group with and the group without HO at any time point (Fig. 2). There was no C-5 palsy in any of the 13 patients who underwent C4 5 surgery. Anterior migration of the Bryan disc was identified in one patient 6 months postoperatively. This patient had undergone 1-level surgery without associated symptoms and required no revision surgery. There were no other complications, such as instrument failure, wound infections, or neural injury. Comparisons of the 2 groups of patients 18 patients with identified HO and 18 without HO were made. The mean age was 4.4 years greater in the HO group, but this difference was not statistically significant (48.8 ± 6.8 vs 44.4 ± 7.2, p = 0.065). Sex distribution also showed no significant differences (p = 0.735). The types of disc pathology had no significant effect (p = 0.494) upon HO formation, but the HO group had a significantly higher TABLE 2: Distribution of levels treated Levels No. of TDRs (%) C3 4 2 (3.8) C (25.0) C (61.5) C6 7 5 (9.6) 459

4 T. H. Tu et al. TABLE 3: Distribution by number of levels treated and grade of HO* Variable No. of Levels w/ HO (%) No. of Patients w/ HO (%) 1-level TDR, HO in treated level 6 (24) 6 (33.3) 2-level TDR HO in 1 treated level 5 (20) 5 (27.8) HO in both treated levels 14 (56) 7 (38.9) McAfee grading Grade 1 9 (36) Grade 2 13 (52) Grade 3 2 (8) Grade 4 1 (4) * Heterotopic ossification was identified in 25 of 52 levels and in 18 of 36 patients treated. Percentage values are based on the overall number of levels or patients with HO. McAfee criteria applied only to discs. rate of 2-level surgery than the non-ho group (66.67% vs 22.22%, p = 0.02). The success rates, defined by excellent or good according to the Odom criteria, were the same in both groups (94.4%, p = 1.000) (Table 5). In most (96.0%) of the levels at which HO developed, it was graded as less than Grade 3, indicating preserved segmental motion in most cases with existing HO. Dynamic radiography demonstrated loss of segmental motion (< 2 ) in 2 treated levels (3.8%). One of the immobilized levels had Grade 4 HO, whereas the other one had Grade 2 HO. Plain radiographic examination had 80% sensitivity and 88.89% specificity in detecting the presence of HO. Concordance between HO grading by means of CT scans and plain radiographs was excellent, with an intraclass correlation coefficient (ICC) of (95% CI Fig. 1. Bar graph showing distribution of treated levels and presence of HO by level. TABLE 4: Clinical outcome according to the Odom criteria Outcome Description No. of Patients excellent all preop symptoms relieved, neurological deficit 27 improved good minimal persistence of preop symptoms, neuro- 7 logical deficit unchanged or improved fair some preop symptoms improved, others un- 2* changed or slightly improved poor preop symptoms unchanged or exacerbated 0 * One had Grade 1 HO, the other did not have HO , p < 0.001). For Grades 0 2 HO, plain radiographs underestimated 5 and overestimated 4 levels (ICC 0.713, p < 0.001). On the other hand, plain radiographs and CT had high agreement on Grades 3 and 4 HO (Table 6). Discussion The conceptual goal of cervical TDR is the preservation of segmental motion close to the physiological kinematics of the cervical spine after discectomy. Thus, many kinds of cervical artificial discs with different designs share the common feature of motion preservation, and disc replacement with an artificial disc has become one of the options other than ACDF in spine care. Several prospective, randomized controlled studies have shown neurological success rates for cervical TDR comparable to those achieved with conventional ACDF. 2,12,20,21,31,32 The question of whether cervical TDR reduces resultant ASD after ACDF is still debatable, although Robertson et al. 29 concluded, based on their prospective study, that maintaining motion rather than fusion will prevent ASD at 2-year follow-up. Nonetheless, any factor that can compromise motion preservation in cervical TDR should be addressed because preservation of motion constitutes the main rationale for TDR. Heterotopic ossification is one of the notorious causes of limited segmental motion after cervical TDR. Traditionally described in the orthopedic literature, HO refers to bone formation in tissues that normally do not have features of osteogenesis. Several risk factors, including male sex, hypertrophic osteoarthritis, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis, have been reported in orthopedic experience. 1,6,22,28,35,37 However, the heterotopic ossification addressed in the current study only refers to the undesirable bone formation after TDR that precludes the motion preservation for which the artificial discs are designed. It is characterized by ectopic bone formation anywhere around the implant (anteriorly, posteriorly, or laterally). When HO occurs at the intervertebral space, it will not only limit the function of the artificial disc but also cause compression of the neural tissue. The true etiology of HO after cervical TDR is unique and remains unknown. Heterotopic ossification after cervical TDR was first reported by Parkinson and Sekhon in 2005, 25 who reported fusion after cervical TDR in a 55-year-old woman 460

5 Heterotopic ossification after cervical total disc replacement Fig. 2. Mean VAS scores for neck and arm pain. Error bars represent SDs. Asterisk represents significant difference compared with preoperative level for both the HO and the non-ho groups (p < and p < 0.001, respectively). There were no significant between-group differences at 12 and 24 months after surgery. who had undergone implantation of a Bryan disc at the C5-6 level. Both plain radiographs and CT documented the bony bridging around the artificial disc. Dynamic radiographs also confirmed the loss of mobility. Later, Bartels and Donk 2 reported 2 other cases of bony fusion after cervical TDR with the Bryan disc. One involved a 30-year-old man with bony fusion around the Bryan disc, with loss of segmental motion at the C5 6 level 2 years postoperatively. The other involved a 49-year-old woman who had radiographic evidence of a bone spur at the C5-6 level 1 year postoperatively and bony fusion 2 years postoperatively. These 3 patients all had clinical improvement compared with their preoperative condition and required no further surgical treatment. The incidence of HO after cervical TDR varies greatly in the literature, from as high as two-thirds of patients to none. A rate of 67.1% at 2-year follow-up was reported by Beaurain et al. 3 for 76 cervical levels (68 patients) treated by means of TDR with Mobi-C. Mehren et al. 19 reported a 66.2% HO occurrence rate at 1-year follow-up in the Prodisc-C series with 77 discs in 53 patients. They noted significantly higher rates in multilevel cases and reported that the grade of HO does not correlate with clinical outcomes. A 29% HO occurrence rate was reported by Heidecke et al. 11 in a series of 59 Bryan discs in 54 patients at 2-year follow-up; loss of motion was observed in 12% of the implanted discs, mostly due to high-grade HO. Leung et al. 15 reported a 17.8% rate at 1-year followup in 90 patients who had undergone single-level disc replacement with a Bryan disc; in that patient group, older age and male sex were the 2 significant factors associated with HO formation. There was also a strong association of the development of HO with subsequent loss of motion of the implanted discs. These 4 studies involved different perioperative NSAID uses, including duration and types. Postoperative NSAID tends to reduce HO formation. In the Mobi-C trial by Beaurain et al., 3 the choice of post- TABLE 5: Analysis of factors related to HO formation* Group Variables Total HO Non-HO p Value no. of patients (50.0) 18 (50.0) mean age (yrs) ± ± ± sex male (52.4) 10 (47.6) female 15 7 (46.7) 8 (43.3) disc pathology soft disc herniation (55.6) 12 (66.7) spondylosis w/ spur formation 14 8 (44.4) 6 (33.3) no. of levels treated (30.0) 14 (70.0) (75.0) 4 (25.0) success rate (%) * Data are given as number of patients (%) unless otherwise indicated. Statistically significant. Percentage of patients with excellent or good outcome. 461

6 T. H. Tu et al. TABLE 6: Agreement of HO grading by means of CT scans and plain radiographs* By CT Scan By Radiograph Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Grade Grade Grade Grade Grade * Values represent numbers of levels. operative NSAID used was left to the surgeon; 64% of patients with HO did not receive any NSAID and 60% of those without HO did receive postoperative NSAIDs. In the ProDisc-C series reported by Mehren et al., 19 the fusion rate of cervical TDR differed in two different participating centers. The fusion rate was higher in the center that did not routinely use NSAIDs. Such results may be attributable to NSAID use because the studies involved the same surgical technique and patient inclusion criteria. On the other hand, data from the 2-year follow-up of the Bryan FDA investigational device exemption trial showed no spontaneous fusion at 2 years. 12 The authors attributed the excellent mobility of the artificial discs to the prescription of NSAIDs for 2 weeks postoperatively, as well as patient selection to exclude those with severe spondylosis, in whom fusion was more likely. In the current study, 1-week postoperative NSAID treatment was chosen as a balance between HO prevention and NSAID side effects. However, to date, there is still no solid evidence regarding the effect of postoperative NSAID therapy on preventing HO. The choice and duration of NSAID treatment vary in most published studies. Fig. 3. Plain radiographs and CT images obtained in a 59-year-old female patient. A and B: Preoperative anterior-posterior (A) and neutral lateral (B) radiographs showing a normal cervical lordotic curve and alignment. C and D: Postoperative lateral extension (C) and flexion (D) radiographs demonstrating Grade 4 HO at the C4 5 level (white arrow) with loss of segmental mobility and Grade 2 HO at the C5 6 level (black arrowhead) with preserved segmental mobility. E and F: Right (E) and left (F) sides of the sagittal reformatted CT imaging study obtained 18 months after C4 5 and C5 6 TDR. G and H: The axial CT images at the C4 5 (G) and C5 6 (H) levels confirming the ventral and dorsal bridging ossification, HO (Grade 4), and showing the dorsal Grade 2 HO (black arrow) at the C5 6 level, which was not seen on plain radiographs. 462

7 Heterotopic ossification after cervical total disc replacement Several caveats must not be overlooked on the issue of HO development after cervical TDR. First, all previous reports are based on radiographs, which have some ambiguities in terms of interpretation due to their 2D overlapping character. Using plain radiographs to detect HO is convenient in most clinical scenarios but may inherently allow errors. The difficulty is less problematic when looking at high-grade HO, but critical in low-grade HO. Axial CT with reformatted sagittal and coronal images facilitates closer scrutiny of the details of bony structure, which is crucial in determining the presence of HO and its grading. Second, there is no standard protocol for the perioperative use of NSAIDs, so the timing, dosage, and regimen of NSAID treatment varies greatly. Third, the selection of patients for cervical TDR is an important factor in the development of HO. Because the severity of spondylosis can vary tremendously in each study, the tendency for postoperative spontaneous fusion (HO development) changes. Fourth, the biomechanical design of artificial discs also varies. Each disc has unique features of allowed range of motion, location of the rotator center, wearing properties, and insertion techniques. These variables, in conjunction with different surgical techniques, may influence HO development. In this study, HO developed in 48.1% of the surgically treated levels, with statistically significant higher rates of HO in 2-level TDR and a trend toward older age. Postoperative CT to determine HO is currently the most accurate examination modality. Our rate of HO development in almost half of the patients or levels is comparable to reports based on plain radiography in literature. Moreover, radiological findings in the present study, either by CT or plain radiographs, demonstrate good concordances. Therefore, the findings corroborate the existence of HO after cervical TDR and provide a basis for comparing the two imaging modalities. Most of the patients (94.4%) in the present study had excellent or good clinical outcomes (based on the Odom criteria), irrespective of HO formation. Segmental motion was preserved in 50 (96.2%) of 52 operated levels despite the relatively high rate of HO development. These results for preservation of motion compare favorably to those of Leung et al. 15 (89%) and Heidecke et al. 11 (88%). One of the two fused levels in this current study was due to high-grade HO (Fig. 3), whereas the other was due to facet fusion (Fig. 4). The explanation is that most of the HO formed in the series was low-grade (lower than Grade 2), which is intrinsically less likely to interfere with motion. As in most of the referenced studies, HO development generally did not have any adverse effect on clinical outcome. This may seem reasonable because, even in the worst case, high-grade HO or complete fusion of spinal segments, the functional result will be just like that of an interbody graft in ACDF. The present study demonstrates that a higher rate of HO is found in patients undergoing 2-level Bryan disc TDR, which can be explained in various ways. Patients requiring 2-level TDR generally have more severe spondylotic changes and are thus more likely to have autofusion. Whether biomechanical features of 2-level cervical TDR cause HO remains unclear. However, the similar Fig. 4. Dynamic plain radiographs and CT scans obtained in a 40-year-old female patient 20 months after C5 6 and C6 7 TDR. A and B: Lateral extension (A) and flexion (B) radiographs showing loss of segmental mobility at the C6 7 level and Grade 2 HO (black arrows). C E: Sagittal (C) and coronal (D) reformatted CT scan and axial CT scan (E) demonstrating arthrodesis in the left C6 7 facet (white arrows) with immobilization of the C6 7 segment. rates of HO per level treated in 1-level TDR (24%) and 2-level TDR (20%) imply that HO development can be an issue of idiosyncrasy. It is not impossible that there are some genetic predisposing factors that require further investigation. Some have proposed that HO formation is due to 463

8 T. H. Tu et al. residual bone dust left over in the operative site during milling and excessive muscle damage. The higher rate of HO formation in 2-level TDR supports the theory. Copious irrigation during the procedure may help eliminate the dispersed bone dust during endplate preparation and should be performed routinely. Meticulous dissection of the longus colli muscles with minimal cauterization may prevent myositis ossificans. The extent of coverage of the endplate by the prosthesis may also reduce HO, because it is assumed that the larger prosthesis can share more weight-bearing forces, and ossification can be precluded at the bony margin by the metallic shell. Ideally, the position of the prosthesis in the disc space should be as symmetrical and centered as possible to mimic the natural center of rotation. However, whether different prosthetic designs have different effects on HO is also unknown. The current suggestions of copious local irradiation or use of NSAIDs are based on experience gained from large joint arthroplasties by orthopedic surgeons. Therefore, future studies are necessary as the use of TDR increases. There are limitations in this retrospective cohort study. The relatively small case number lowers the power of the study to recognize any significant correlation between different variables and the formation of HO. A longer follow-up period of more than 5 years in patients who underwent cervical TDR is mandatory to evaluate the preservation of motion, occurrence of HO, and their effect on the adjacent segment disease. 34 Conclusions The rate of HO detected by CT scan in this cohort of patients receiving the Bryan disc is 48.1% per disc level and 50% per patient, with minimal effect on limitation of motion (96.2% of levels remain mobile). Two-level surgery has a higher risk for HO, although the development of HO does not affect clinical outcomes. Plain radiograph remains an acceptable tool for detecting HO. Disclosure This study was supported by grant VGH 99-S6-001 from Taipei Veterans General Hospital to Dr. H. Cheng. The authors report no conflict of interest concerning the materials or methods used in this study, or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: JC Wu, Tu. Acquisition of data: Tu. Analysis and interpretation of data: Tu, Huang, Guo, CL Wu. Drafting the article: JC Wu, Tu. Critically revising the article: JC Wu. Reviewed final version of the manuscript and approved it for submission: all authors. Statistical analysis: Tu, Administrative/technical/material support: Huang, Cheng. Study supervision: Huang, Shih, Cheng. Acknowledgment The authors acknowledge the editorial assistance of Gene Alzona Nisperos, M.D. References 1. Ahrengart L, Lindgren U: Heterotopic bone after hip arthroplasty. 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