Four studies reported risks of ALOD after 2 years: 1 RCT using the patient as the unit of measure evaluating ACDF with anterior plates compared with TDR9; 2 single-arm studies evaluating only ACDF with anterior plating using adjacent levels as the unit of measure10,12; and 1 single-arm study assessed NIF, also using adjacent levels as the unit of measure.13 Among the 3 studies evaluating ACDF using anterior plates, the risk of ALOD ranged from 64% (the proportion in patients) to 41% (proportion of levels) (Figure 2). The risk of ALOD after TDR in 1 study was 24% (proportion in patients)9 and after NIF in 1 study, 6% (proportion of levels).13
One RCT used a single site's data from a multicenter Investigational Device Exemption Food and Drug Administration trial to determine whether ALOD occurs more frequently in patients undergoing fusion with plate fixation than it does in patients undergoing total disc arthroplasty.9 Pre- and postoperative radiographs were read by 2 independent spine fellows blinded to the treatment. The surgical level was blacked-out through photo editing, making blind assessment possible. ALOD was rated using the following classification system10: Grade 1, ossification occupying less than 50% of the adjacent disc space height; Grade 2, ossification extending beyond 50% of the adjacent disc space height; and Grade 3, bridging of 100% of the adjacent disc space with bone (Figure 3). The fusion group had significantly higher ossification grades than the arthroplasty group at both the 2-year (P = 0.003) and the 4-year follow-up interval (P = 0.004). The proportion of patients who developed any ALOD was greater after anterior plate fusion, 64% versus 24%, respectively (risk difference, 40%; 95% CI, 14%–66%; P = 0.006; number needed to harm, 2.5).
Two studies assessing fusion with anterior plates reported on the risk of ALOD based on whether the ossification developed cranially or caudally to the fused segment. Both reported a 2-fold higher risk of ALOD in the cranial adjacent segment compared with the caudal (59% vs. 29%11 and 58% vs. 28%12) (Table 3). The single study on NIF reported 4.8% cranial ossification compared with 1.2% caudal.13
Risk Factors for ALOD
Two studies reported on the relationship between PDD and risk of ALOD,9,10 and 1 study evaluated the progression of ALOD stratified by PDD.11 Park et al10 in 2005, reviewed 118 patients who had solid fusion after anterior fusion with a plate for a degenerative cervical condition. Follow-up was for a minimum of 1 year. Eighteen caudal adjacent-level segments were not included in the analysis because of inadequate visualization on radiographs. They determined a higher risk of any ALOD when the plate was less than 5 mm away from the disc compared with greater than 5 mm: 58.6% of the levels versus 11.5% (risk ratio, 5.1; 95% CI, 2.5–10.4). When the investigators looked at the moderate to severe cases of ossification (grade 2 or 3), the risk in the group with a PDD less than 5 mm was 16.6% of the levels compared with 5.0% in the group with a PDD of 5 mm or more (risk ratio 3.3; 95% CI, 0.8–13.4; P = 0.076). Similarly, the post hoc analysis by Garrido et al9 described earlier reported a higher risk of any ALOD when the PDD was less than 5 mm versus 5 mm or more: 95% and 50% of patients, respectively. Park et al,11 in 2007, studied 62 patients, most of whom had developed ALOD after anterior fusion and plating, and retrospectively evaluated the progression of the ossification over time. They determined that progression from no or mild ossification (grade 0 or 1) in adjacent levels by 3, 6, or 12 months to moderate or severe ossification (grade 2 or 3) was 2 to 2.7 times more likely in patients with a PDD less than 5 mm compared with patients with a PDD of 5 mm or more (Figure 4).
Single-Level Anterior Cervical Corpectomy and Fusion Versus 2-Level ACDF
Park et al,12 in 2010, reviewed the lateral cervical radiographs of 97 patients who had a solid fusion after a single-level anterior cervical corpectomy and fusion (ACCF) or 2-level ACDF for the treatment of cervical spondylosis. All patients underwent anterior fusion using allograft and screw-plate fixation. The choice of operation was based on the presence of retrovertebral compression. A corpectomy was used if the decompression could be performed more easily using that procedure. The risk of ALOD was higher in the single-level ACCF group compared with the 2-level ACDF group at final follow-up (24 mo), 50% of the levels versus 33% (risk ratio, 1.5; 95% CI, 0.99–2.27; P = 0.051).
Time Course for the Development of ALOD
Three studies reported risks of ALOD over time, and 1 study evaluated the progression of ALOD over time (Figure 5). One study observed an increased risk in the prevalence for ALOD from 64% of patients at 2-year follow-up to 84% at 4-year follow-up when performing fusion with plates.9 The same study also observed an increased prevalence for ALOD using a TDR, with the prevalence increasing from 25% of patients at 2 years to 52% at 4 years. Park et al,12 in 2010, noted that 5% of the levels developed adjacent-level ossification as early as 6 weeks after anterior plate fusion that rose to 41% of the levels at the 24-month follow-up. The third study in patients undergoing NIF reported a small risk of ossification that remained relatively constant at the 6-, 12-, and 24-month follow-ups.13
In the Park et al11 2007 study described earlier, the authors noted that the absence of ossification in the early postoperative period was no guarantee of avoiding advanced ossification later. They reported that 23.5% and 14.9% of adjacent levels in patients without ossification 3 and 6 months after anterior fusion and plating progressed to moderate or severe (grade 2 or 3) ALOD by the 24-month follow-up. Among patients without ossification at the 12-month follow-up, only 1.8% of the adjacent levels went on to develop moderate or severe ALOD. Among patients with grade 0 or 1 ossification 24 months after surgery, none of the 80 levels progressed to grade 2 or 3 ossification.
ALOD and Outcomes
We determined no clinical studies assessing outcomes or rates of reoperation comparing patients with ALOD with patients without ALOD.
The overall strength of evidence evaluating the absolute risk of ALOD after anterior fusion with a plate or total disc arthroplasty is “low,” that is, we have low confidence in the absolute estimate and further research may change the estimate. The overall strength of evidence evaluating the absolute risk of ALOD after NIF is “insufficient,” that is, the evidence does not permit a conclusion. The overall strength of evidence evaluating the PDD as a risk factor for ALOD is “moderate,” meaning that we have moderate confidence that the evidence reflects the true effect, although further research may change the estimate. The overall strength of evidence for key question 3 evaluating the timing of ALOD and key question 4 evaluating the outcomes and reoperation rates of ALOD are “low” (low confidence in the evidence reflecting the true effect) and “insufficient” (the evidence is not available), respectively (Table 4).
On the basis of our systematic review, anterior cervical fusion with a plate and decreased PDD (<5 mm) demonstrated higher rates of ALOD. Although the etiology of ALOD is not known, anterior cervical plates and specific plating technique seem to play a role in its development. This is evidenced by higher rates of ALOD seen in plated ACDF compared with noninstrumented ACDF and total disc arthroplasty.9,10,12,13 In addition, when plates are applied less than 5 mm from the adjacent levels, the risk for the development of ALOD was 2 to 5 times higher.9,10 Thus, in theory, ALOD may be caused by an inflammatory reaction between the plate and anterior longitudinal ligament leading to ossification.
Although both ALOD and ASP can result in bone formation, there are differences between the 2. It has been our experience that patients with ALOD typically have better preservation of disc height compared with patients with ASP. In addition, patients with ASP are more likely to have disc protrusions, facet arthrosis, spondylolisthesis, endplate sclerosis, and/or osteophyte formation. Because ALOD in its severest stages causes ankylosis and a decrease in motion, the result is a “relative protection” of the adjacent level from degenerative changes. Also, ALOD forms nonmarginal bone, caused by ossification of the anterior longitudinal ligament, as opposed to degeneration of the adjacent motion segment where you get marginal osteophyte formation. Finally, it is not clear whether ASP is due to surgery or the natural history of degenerative disease. ALOD, on the contrary, seems to be an iatrogenic problem that has a high likelihood of developing if the plate is placed too close to the adjacent segment (Figure 6).
There is insufficient evidence to suggest a role for surgical treatment of ALOD and no study has examined or verified inferior outcomes with its development. Although this may question the clinical significance of ALOD, current outcomes-based questionnaires are not designed specifically for assessing the consequences of ALOD. Range-of-motion analysis is necessary to define the effect of ALOD on adjacent-segment motion. Thus, meticulous surgical technique, with care to minimize adjacent-level encroachment by a plate, should be used.
On the basis of moderate evidence, we determined that plates increase the risk of ALOD and the risk is increased if the plate is placed less than 5 mm away from the adjacent disc. Therefore, we recommend that the surgeons make every effort to keep the plate as far away from the adjacent disc as possible.
Strength of Statement: Strong
- Instrumentation with an anterior plate increases the risk of ALOD compared with NIFs of the cervical spine.
- A PDD of more than 5 mm is recommended to minimize the risk for the development of ALOD.
- ALOD occurs more commonly in ACDF compared with TDR.
The authors thank Ms. Nancy Holmes, RN, for her administrative assistance.
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