Anterior bone loss (ABL) is a relatively easily neglected condition after cervical disc replacement (CDR). Whether this phenomenon is a radiological anomaly or a complication remains controversial. Several studies have reported the clinical characteristics of ABL and speculated on the pathogenic mechanism based on a certain type of artificial disc, while the overall understanding of ABL is lacking.

To describe the prevalence, impacts, and risk factors of ABL after CDR.

We searched the PubMed, Cochrane Library, and Excerpta Medica databases using the terms “bone loss” or “bone remodeling” or “bone absorption” or “osteolysis” or “implant loosening” or “implant migration” or “hypersensitivity” or “hyperreactivity”, “cervical disc replacement” or “cervical disc arthroplasty” or “total disc replacement”. Eligible manuscripts on the prevalence and impacts of ABL were reviewed by the authors. Data extraction was performed using an established extraction form. The results of the included studies were described narratively.

Six studies met the inclusion and exclusion criteria. One was a prospective study and the others were retrospective studies. A total of 440 patients with 536 segments were included. The artificial cervical discs included Bryan, Baguera-C, Discocerv, and Mobi-C. The prevalence of ABL ranged from 3.13% to 91.89%, with a combined overall prevalence of 41.84%. ABL occurred within 6 mo and stopped 12 mo after surgery. Several cases were noted to have a self-healing process. Severe ABL resulted in segmental kyphosis, implant subsidence, and persistent neck pain. ABL may be related to heterotopic ossification. Multilevel surgery may be one of the risk factors for ABL.

ABL is a common condition after CDR. The underlying mechanisms of ABL may include stress concentration and injury to nutrient vessels. ABL should be considered a complication after CDR as it was associated with neck pain, implant subsidence, and heterotopic ossification.

Anterior cervical discectomy and fusion (ACDF) is recognized as the standard procedure for cervical degenerative disc disease. However, concerns such as non-union, pseudarthrosis, and acceleration of adjacent segment degeneration have been raised[1-4]. Compared with ACDF, cervical disc replacement (CDR), a motion preservation technique, can reduce intervertebral disc pressure in adjacent levels and better simulate the physiological condition of the cervical spine[5,6]. Studies have shown that CDR and ACDF have equivalent efficiency in clinical outcomes such as symptom relief[7,8]. However, CDR is better in some respects, such as faster recovery, higher patient satisfaction, and is more cost-effective[9,10].

Although CDR is widely performed and patients have benefited due to its satisfying results, it has some implant-related complications, such as heterotopic ossification (HO), implant migration, and implant subsidence[11-16]. With regard to these complications, in-depth studies have been performed to determine the potential risk factors and clinical impacts[17-20]. In contrast to excessive bone formation (which is HO), anterior bone loss (ABL) is another implant-related condition after CDR and has gained more attention in recent years[21]. ABL is the process of bone rebuilding in the ventral part of vertebral bodies, and can usually be recognized from lateral radiographs. Peri-prosthetic bone loss has been extensively described in large joint arthroplasty. However, ABL is easily ignored in cervical disc arthroplasty.

The prevalence of ABL after CDR varies from 3.13% to 91.89% and differs greatly among different types of artificial cervical discs[22-27]. Several studies have reported the clinical characteristics of ABL and speculated the pathogenic mechanism based on a certain type of artificial disc, while the overall understanding of ABL after CDR is lacking. In addition, it remains controversial whether ABL is a radiological anomaly or a complication. Therefore, we performed this systematic review of currently available clinical data to comprehensively describe the prevalence, impacts, and risk factors of ABL after CDR.

A comprehensive literature search was carried out in PubMed, Cochrane Library, and the Excerpta Medica databases. Studies before May 2019 were included. The following keywords were used in the search: “bone loss” or “bone remodeling” or “bone absorption” or “osteolysis” or “implant loosening” or “implant migration” or “hypersensitivity” or “hyperreactivity”, “cervical disc replacement” or “cervical disc arthroplasty” or “total disc replacement”. Articles published in English that involved peri-prosthetic bone absorption after CDR were specifically identified. The references of all identified papers were manually reviewed to identify further potentially relevant studies.

The search produced 1460 published articles. We then systematically assessed the selected articles. The inclusion criteria were as follows: (1) peri-prosthetic bone loss occurred in the surgical segment after CDR; and (2) bone remodeling occurred in the anterior/ventral part of vertebral bodies. The exclusion criteria were as follows: (1) Peri-prosthetic bone loss occurred in another part of the vertebral bodies, (2) Case reports, (3) Reviews, (4) Commentaries, and (5) Cadaveric or experimental studies. The results of the literature search are shown in Figure 1.

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Figure 1 Preferred reporting items for systematic reviews. Preferred reporting items for systematic reviews flow diagram for selection of studies based on inclusion criteria during systematic review.

The screening of titles and abstracts was performed by two reviewers (Wang XF and Meng Y) independently. Articles that met the eligibility criteria on the first screening were further assessed by reading the full text. After screening, six clinical studies were included in the systematic review. The two reviewers (Wang XF and Meng Y) then performed data extraction and rated the level of evidence of each article independently using the published guideline[28]. The results of this study were described narratively.

One randomized controlled study and five retrospective studies were included in this review[22-27]. A total of 440 patients with 536 segments were included. The mean age of these patients ranged from 45.3 to 50.1 years, and the mean follow-up time ranged from 32.3 to 74.4 mo. The artificial cervical discs included Bryan, Baguera-C, Discocerv, and Mobi-C. The surgical procedure included single-level CDR, double-level CDR, triple-level CDR, and hybrid surgery. Study information and level of evidence are listed in Table 1. Detailed information on ABL including the prevalence, course, effects, and outcomes are summarized in Tables 2-4 and Figure 2.

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Figure 2 Summarized grading systems of the included studies. ABL: Anterior bone loss, colored in gray; VAS: Visual analogue score; NDI: Neck disability index.

Peri-implant bone loss has been widely reported in large joint arthroplasty[29-31]. However, studies on bone loss after CDR are lacking. By reviewing the literature, we classified the mechanism of ABL into three major hypotheses: stress shielding, micromovement, and injury to nutrient vessels.

The stress shielding effect has been documented as one of the factors of bone loss in hip and knee replacement[29]. In CDR, this term may be more accurately named as stress concentration. Physiologically, the axial loads transfer evenly and gently from one vertebra to the intervertebral disc, then to another vertebra. However, this mechanical system is altered after disc arthroplasty; the axial loads would transfer through the implant. Therefore, the stress would concentrate on where the implant is located. On the one hand, some artificial discs show obvious stress concentration in the anterior part of the endplates[32,33]. The hyper-pressure in the anterior region can activate the process of bone resorption[34]. On the other hand, the artificial disc does not cover the endplate sufficiently[35,36]. For the non-keel designed artificial disc, for instance, Discocerv and Baguera-C, the anterior part of the endplates cannot be covered, which may lead to hypo-pressure in this region. Based on Wolff’s law, the anterior vertebral hypo-pressure from the artificial disc would initiate bone resorption. Consistent with this hypothesis, previous finite element studies showed that stress was distributed in the covered area of the endplates at the surgical level[37,38]. In addition, Wang et al[21] noted that patients with ABL showed a significantly more lordotic disc angle (which may shift the axial load posteriorly), compared with those who developed anterior HO. Accordingly, stress concentration may be one major reason for the development of ABL.

Micromovement of the implant into the vertebra may induce mechanical damage to the peri-implant bone and subsequent bone loss[22,23]. On the other hand, micromotion may cause artificial discs to produce friction and wear debris, which may induce an inflammatory response and peri-implant bone loss[29,39,40]. Basic studies have proved that the wear debris can initiate bone loss via the RANK/RANKL/OPG pathway, and the inhibition of inflammation or RANK/RANKL pathway has protective effects on peri-implant osteolysis[41-43]. In addition, debris can also induce innervation and pain factor production[42].

Although wear debris-induced osteolysis is widely accepted in large joint arthroplasty, this hypothesis is flawed with regard to two aspects in CDR. First, bone loss caused by wear debris is not confined to the anterior portion of the vertebra, but is around the surface of the implant. For instance, Devin et al[44] reported wear debris-induced bone loss after lumbar disc replacement. Massive osteolysis was noted in the central and posterior region of the vertebral body, and debris was scattered in the adjacent bones. Veruva et al[45] described the presence of osteolytic cysts distributed around artificial lumbar discs caused by the debris. These findings suggest that wear debris-induced bone loss is different to ABL in phenotype. Second, ABL was observed within 3 mo in most cases, and had a self-limited course. In contrast, debris-induced osteolysis may be evident on radiographs after a longer time and may be progressive, which was reported by Tumialán et al[46]. They described bone loss which was noted 9 mo after Prodisc-C implantation. The osteolytic process did not stop until the implant was removed. To sum up, wear debris is not a likely cause of ABL.

The third major hypothesis of ABL is the injury to nutrient vessels of the anterior vertebrae. The anatomic study by Dunbar et al[47] demonstrated the abundant nutrient blood supply in the anterior part of the cervical spine[48]. These vessels pass over the longus colli, and penetrate vertebrae mainly on the anterior surface of the cervical vertebrae. Usually, these nutrient vessels are coagulated to reduce intraoperative bleeding, and this may cause avascular necrosis of the anterior part of the endplate. The anterior nutrient foraminae are mainly located in the superior third of the vertebrae, leaving the inferior portion hypo-vascular. Therefore, theoretically, the inferior portion of vertebrae would be at a higher risk of avascular necrosis, and this is consistent with the clinical findings of Kieser et al[27]. Consequently, ABL may be related to avascular necrosis caused by injury to nutrient vessels.

Kieser et al[26] showed that the more levels operated, the higher the risk of developing ABL. A possible explanation for this might be that multilevel surgery would change the biomechanical properties of the cervical spine leading to hyper- or hypo-pressure in the anterior region of the vertebrae, as described earlier. Additionally, we believe the design of artificial discs is another risk factor in the development of ABL. The prevalence of ABL was different among artificial discs, and this could be attributed to the discrepancy in stress distribution of the endplates of different types of artificial discs.

Some authors consider that heat necrosis due to the burring and milling process could inactivate osteocytes of the anterior vertebra, and result in a direct osteolytic insult. However, the findings of Heo et al[25] and Kieser et al[26,27] do not support this assumption. Even though the anterior cortex of the vertebra was carefully preserved during surgery, ABL still occurred. In addition, Wang et al[21] found that the anterior milling ratio and milling angle were comparable between patients with ABL or anterior bone formation. Therefore, heat necrosis may not be the most important risk factor for ABL.

Usually, patients with ABL do not have clear clinical and radiological effects, while severe ABL may produce segmental kyphosis and local pain[23-25]. Due to the self-limited process, most cases do not require intervention. However, we hold the view that early interventions including rehabilitation exercise and pain relief are necessary for these patients. In our center, we have seen patients with ABL complain of persistent neck pain for one year after surgery. Early interventions can improve the satisfaction of surgery and quality of life. In addition, the impacts of ABL on the adjacent segments remain unknown. Further studies with long-term follow-up are needed to clarify the relationship between ABL and adjacent segment degeneration.

Currently, ABL is observed on lateral radiographs. Notwithstanding this method is simple and easy, but it may increase the false positive rate of ABL. Occasionally, the inappropriate irradiation direction of X-rays may give us a false impression that ABL has occurred. For this reason, computed tomography scans are better in evaluating the prevalence of ABL[25]. Moreover, to prevent and identify ABL early, further studies on the mechanism and risk factors of ABL after CDR are needed.

There are several limitations in our study. The major limitation is the small sample size of each included study. Studies with large sample size are needed to determine the precise prevalence of ABL. As diverse evaluation systems for ABL were used in the included studies, it is difficult to make accurate assessments on the impacts of ABL. In addition, most studies only used non-keeled artificial discs; thus, ABL in keeled artificial discs, such as Prodisc-C and Prestige-LP, is unknown. Finally, we focused on prospective and retrospective studies, and may have missed a wider discussion on the underlying mechanism of ABL in some case reports or case series. Further studies are required to elucidate these limitations.

ABL is common in CDR. ABL occurs within 3-6 mo, and stops 12 mo after surgery. Several cases were noted to have a self-healing process. ABL does not have obvious clinical or radiological effects in most patients, while severe ABL may result in segmental kyphosis and persistent pain. ABL may be related to HO; however further studies are required to confirm this. Multilevel surgery is recognized as a potential risk factor for ABL, and the underlying mechanisms include stress concentration and injury to nutrient vessels. ABL should be considered a complication after CDR as it was associated with neck pain, implant subsidence, and HO.

We wish to thank Dr. Ying-Jun Guo and Dr. Jun-Bo He for advice on the discussion.