maintenance of motion following arthroplasty can be hindered by the development of heterotopic ossification ( ho ) , whose causes remain uncertain.1,2,3,4,5 whether the formation of ho following cervical disc arthroplasty is of clinical or functional importance is also unknown .
the aims of this study are to investigate the rate of ho at a longer follow - up ( mean 3 years ) , to determine if the presence of ho negatively affects functional outcome and to identify factors that may precipitate the formation of ho following cervical disc arthroplasty .
what is the incidence of ho following cervical arthroplasty ? does the development of ho negatively influence the clinical outcome in patients receiving arthroplasty ?
inclusion criteria : patients suffering from radiculopathy , myelopathy or myeloradiculopathy secondary to soft disc hernia and/or mild degree spondylosis operated between october 2004 and december 2006 .
1 ) thirty - nine patients suffering from cervical radiculopathy and/or myelopathy treated with anterior disc replacement ( adr ) were selected .
nine patients were excluded from this analysis because of insufficient outcome data at different time intervals ( n  =  7 ) or were not available for follow - up ( n  =  2 ) .
outcomes and analysis evidence of ho using the mcafee grading system6 ( table 1 ) .
rom was calculated by using two lines parallel to the prodisc - c keels , or to the endplates of the prestige lp , and measuring the intervening angle in flexion and extension on lateral radiographs .
lordosis was assigned a negative value and kyphosis a positive one ; the difference between the two values gave the final rom .
ct scan on patients with grade two or higher ho to assess localization of ho .
a comparison of scores was made between those who developed ho and those who did not using a two - sided student t - test .
all images were independently reviewed by both a radiologist and a neurosurgeon not directly involved in the surgical procedures .
forty - five disc prostheses ( seven prestige - lp and 38 prodisc - c ) were implanted in 30 patients ( 18 males ) ranging in age from 2863 years ( mean age 40.9 ) .
the underlying disease included radiculopathy ( n  =  13 ) , myelopathy ( n  =  4 ) or myeloradiculopathy ( n  =  13 ) , secondary to soft - disc hernia ( n  =  17 ) , spondylosis ( n  =  8) or a combination of disc hernia and spondylosis ( n  =  5 ) .
nineteen patients received one - level disc replacement , seven patients received two - level and four patients received three level disc replacement .
the following distribution of prostheses / level was recorded : c34:5 ; c45:4 ; c56:23 ; c67:13 ( table 2 ) . the incidence rate of ho using the number of prostheses as the denominator was 42.2% ( 19 levels in 16 patients , fig .
the risk of a patient developing ho after receiving one or more prostheses was 53.3% ( 16/30 ) .
ten patients showed progressive ossification over time : in six patients de novo ho was demonstrated at 2346 months ( mean 33.3 ) postoperatively ( figs . 2 , 3 ) .
among the 16 patients with ho , 15 ( 93.8% ) demonstrated a range of motion 3 ( fig .
comparison of pre- and postoperative sf-36 and ndi scores revealed functional improvement from baseline to follow - up at 3 , 6 , 12 , 18 , 24 , and 36 months .
there was no significant difference in functional scores between those who did and those who did not develop ho , p  >  .05 ( fig .
risks and relative risks by factor related to patient characteristics associated with ho formation were analyzed : males tended to develop ho more than females ( twice as likely ) , though this did not reach statistical significance ( table 3 ) .
no patients required revision surgery for adjacent segment disease or persisting / recurrent symptoms .  
patient population and intervention   double - level arthroplasty with prodisc - c at c56 and c67 .
absence of ho at 1 month after surgery ( left ) , presence of grade two ho 1 year postoperatively ( middle ) and of grade three ho ( right ) 3 years postoperatively , respectively .  
note the progression of ho at the c45 disc space at 1 month ( left ) , 12 ( middle ) and 48 ( right ) months , respectively , postoperatively ( arrow ) .  
flexion and extension x - rays ( same patient as in fig 3 ) showing mobile disc prostheses at 48-months follow - up despite the presence of heterotopic ossification .
our rate of grade two and three ho ( 42.2% ) is consistent with that previously reported.7 it is higher than in other series8,9 but lower than sola 's et al.10 ho is prevalent on the anterolateral surface of vertebral bodies ( fig .
strengths : this study reports 3 years mean follow - up data , to date the longest available . for all included patients complete follow - up data are available .
furthermore , we have shown that a delayed progression , or de novo onset , of ho is possible .
limitations : this study was not conducted prospectively and is based on a relatively small albeit consecutive sample size .
lack of potential prognostic factors available for analysis and a 77% follow - up rate are further limitations .
a longer follow - up is necessary to assess whether arthroplasty can reach the goal of maintaining motion and if development of high - grade ho at the target level infers an increased risk of adjacent segment degeneration .
clinical and functional improvement following cervical disc arthroplasty is maintained despite the presence of ho .
preventative measures such as prophylactic nonsteroidal medications , local application of bone wax or intentional early range of motion measures were not routinely utilized in our study . while these are interesting factors ,
axial ct scan showing the presence of laterally sited ho ( arrows ) at c45 level ( a ) and at c67 level ( b )   number of ossified levels and stratification for mcafee ossification grades ( ho : heterotopic ossification )   differences of pre- and postoperative functional outcome in the two groups
disc replacement offers a new interventional option and long - term data on the potential complications to artificial disc replacement compared with fusion are very much needed .
this prospective study 's contribution to the literature regarding heterotopic ossification ( ho ) following cervical arthroplasty is appreciated .
as the authors note , the causes of ho in disc arthroplasty remain unclear and are probably multifactorial .
ho frequency : the authors report a ho rate of 42% following artificial disc replacement in 32 patients , a higher overall rate than is reported in most other studies .
ho rates in the may 2008 ebss special edition on cervical arthroplasty were summarized as follows : there were no ho cases reported in two rcts , with follow - up of 24 months in one study and other being a preliminary report with most patients having only 12-months follow - up .
ho was , however , common in two case series with one reporting an overall 18% rate or 7% cases when restricted to grades iii or iv .
the other series of patients with 1 , 2 , or 3 level disease reported that 8% of segments had grade i , 39% of segments had grade 
 ii , 10% had ho leading to restricted movement and 9% experienced spontaneous fusion .
there are several factors which may partially explain discrepancies in ho rates across studies , aside from differences in length of follow - up .
it is possible that increased attention to radiographic detail may go hand in hand with increased reporting . grading the severity of ho is not an exact science .
there is some subjectivity which may translate into difficulty in distinguishing between adjacent grades ( eg , between grades 2 and 3 ) and overlap in classification .
the grading of ho has so far not been subjected to inter- and intra - observer reliability evaluation and is not known to correlate with any health - related quality of life ( hrqol ) outcomes measures .
study specifications and protocols : use of structured measures and protocols in a prospective study , which are consistently applied to all patients , is important to decrease study bias . while the authors suggest that structured protocols were used , no details were provided .
reporting detail about protocols assists in determining the extent to which various factors may or may not have influenced the results . for studies of ho , important protocol details should include whether or not bone waxing was done at the osteotomy site as well as specifics for radiographic measurements and use of antiinflammatory medications .
it is unclear whether early initiation of range of motion creates an inflammatory response which contributes to ho formation or if it facilitates functional outcome .
strengths : the use of validated outcomes measures ( ndi and sf-36 ) is commendable as is the authors ' acknowledgment of small sample size and a relatively low follow - up rate 
 ( 77% ) as study limitations .
 study design :  retrospective cohort study.objective :  to analyze the presence and clinical relevance of heterotopic ossification ( ho ) at 3 years mean follow-up.methods :  thirty patients suffering from cervical radiculopathy and/or myelopathy treated with anterior disc replacement ( adr ) were studied . 
 ho was classified using the mcafee grading system . 
 range of motion was measured from flexion and extension x - rays . 
 short - form 36 and neck disability index ( ndi ) assessed functional outcome.results :  forty - five prostheses were implanted in 30 patients with cervical radiculopathy and/or myelopathy , mean age 40.9 years . 
 nineteen patients received 1 level and 11 patients received multilevel disc replacement . 
 the incidence rate of ho was 42.2% ( 19 levels ) . 
 segmental range of motion was 3 in 93.8% of patients with ho . 
 there was no significant difference in functional scores between those who did and those who did not develop ho . 
 males tended to develop ho more frequently than females , though this was not statistically significant . 
 the indication for surgery ( soft disc hernia or spondylosis ) was not associated with the formation of ho.conclusions :  functional improvement is maintained despite the presence of ho following cervical disc arthroplasty . 
 indications for arthroplasty should not be halted by the risk of ho.methods evaluation and class of evidence ( coe)methodological principle : study design :  prospective cohort  retrospective cohort  case - control  case seriesmethods  patients at similar point in course of treatment  follow - up 85%  similarity of treatment protocols for patient groups  patients followed for long enough for outcomes to occur  control for extraneous risk factors*evidence class : iii*authors must provide a description of robust baseline characteristics , and control for those that are potential prognostic factors.the definiton of the different classes of evidence is available on page 83 . 