Anterior cervical discectomy and fusion (ACDF) commonly results in subsidence, which is reported in 19.3%–42.5% of cases and is characterized by graft or cage sinking into a vertebral body, affecting disk height, sagittal alignment, and clinical outcomes [1–5]. The aging population raises concerns about osteopenia-related complications in ACDF, as studies have suggested an increased risk of revision surgery and instrumentation failure in patients with osteopenia [6–9]. However, the literature lacks a unanimous stance on the osteopenia–subsidence link, with conflicting findings on cage subsidence rates in patients with osteoporosis [10].

Inconsistent data also surround the relationship between bone density and subsidence, with some studies linking lower preoperative Hounsfield units (HUs) to subsidence, whereas others report the lack of correlation [1,11–13]. Osteopenia, defined by bone density measurements, is diagnosed by dual-energy X-ray absorptiometry (DEXA), highlighting variations in trabecular bone density and mechanical bone strength across spinal regions [14–17]. This prompts further exploration of osteopenia diagnoses and bone density differences in the cervical spine.

Given the disparity in the current literature, this study aimed to investigate the correlation between preoperative computed tomography (CT)-derived HUs as a measure of bone density and subsidence following ACDF. Furthermore, osteopenia diagnosis and its correlation with CT-derived HUs and subsidence were analyzed. Lastly, whether a history of osteopenia corresponds to lower HU measurements in the cervical spine was explored.

This study included 131 patients with a total of 244 levels fused. The mean age for the entire cohort was 53.6±10.9 years. Patients underwent one-level (n=41; 31%), two-level (n=67; 51%), or three-level (n=23; 18%) fusions. Of the 131 patients, 27 (20.6%) had a prior diagnosis of osteopenia. Of the 27 patients included in the osteopenia group, 14 had DEXA scans, and the remaining 13 had a chart history (within the past medical history or problem list sections of EPIC) of osteopenia or osteoporosis. The mean age was higher for patients with a prior diagnosis of osteopenia (59.5 years vs. 52.1 years, p=0.001) (Table 1). The median follow-up for patients with osteopenia was 13.4 months (range, 6–37 months) and 11.9 months (range, 5–61 months) for patients without osteopenia (Table 1).

No significant associations were found between a diagnosis of osteopenia and either anterior (p=0.633) or posterior (p=0.751) subsidence (Table 2). In multivariable linear regression model, osteopenia (β, −0.023; 95% confidence interval [CI], −0.507 to 0.461) was not significantly correlated with anterior subsidence (p=0.926). Similarly, no correlation was observed between osteopenia (β, −0.020; 95% CI, −0.397 to 0.358) and posterior subsidence (p=0.918) (Table 3).

The subgroup of patients with preoperative CT scans included 28 patients with 54 levels fused. Nine patients (32%) had a prior diagnosis of osteopenia. The average age for the subgroup was 54.1±9.8 years. Patients underwent one-level (n=8; 29%), two-level (n=14; 50%), or three-level (n=6; 21%) fusion. Patients received allograft (n=8; 29%), titanium (n=8; 29%), PEEK (n=5; 18%), and zero-profile (n=2; 7%) cages. The median follow-up was 11.6 months (range, 5.3–44.9 months) (Supplement 1).

No correlation was found between anterior subsidence and endplate HUs of the superior vertebrae at the fusion level (β, −0.273; 95% CI, −3.001 to 2.455; p=0.842) or endplate HUs of the inferior vertebrae at the fusion level (β, −0.787; 95% CI, −3.686 to 2.111; p=0.588). Anterior subsidence was not associated with the full vertebrae or ellipse HUs of the superior and inferior vertebrae. Similarly, no relationship was observed between posterior subsidence and endplate HUs of the superior vertebrae (β, −0.483; 95% CI, −2.294 to 1.328; p=0.595) or endplate HUs of the inferior vertebrae at the fusion level (β, −0.310; 95% CI, −2.242 to 1.623; p=0.749). Endplate HU, full vertebrae HU, and ellipse HU measurements were not correlated with anterior or posterior subsidence (Fig. 2, Supplements 2–4).

In a multivariable linear regression, no difference was observed in the amount of anterior subsidence based on endplate HUs of the superior vertebrae at the fusion level (β, 1.807; 95% CI, −3.077 to 6.691; p=0.460), endplate HUs of the inferior vertebrae at the fusion level (β, −2.583; 95% CI, −7.658 to 2.491; p=0.311), full vertebrae HUs of the superior and inferior vertebrae, and elliptical HUs of the superior and inferior vertebrae at the fusion level. In addition, no relationship was observed between posterior subsidence and endplate HUs of the superior vertebrae (β, −1.015; 95% CI, −4.511 to 2.482; p=0.562), endplate HUs of the inferior vertebrae (β, 0.498; 95% CI, −3.135 to 4.131; p=0.784), full vertebrae HUs of the superior and inferior vertebrae, and elliptical HUs of the superior and inferior vertebrae at the fusion level (Table 4).

Of the 54 fused levels with measured HUs, 22 (40.7%) were in patients diagnosed with osteopenia. In a t-test, no correlation was found between a diagnosis of osteopenia and upper endplate HUs (p=0.735), lower endplate HUs (p=0.693), upper full vertebrae HUs (p=0.686), lower full vertebrae HUs (p=0.735), upper elliptical bone HUs (p=0.501), and lower elliptical bone HUs at the fusion level (p=0.465) (Supplement 5).

Although previous studies have linked reduced bone density to an increased risk of revision surgery and instrumentation failure in cervical spine surgery, the relationship between prior osteopenia and subsidence remains unclear [6,21]. Some studies have indicated that cage subsidence is not related to osteopenia, whereas other studies have reported correlations between lower preoperative HU measurements and increased risk of postoperative subsidence [10–13]. The present study investigated the effect of prior osteopenia diagnosis and preoperative CT HUs on subsidence following ACDF.

The results showed no significant association between prior osteopenia diagnosis and subsidence following ACDF. Osteopenia has rarely been associated with cervical subsidence in previous studies [22]. Opsenak et al. [22] found a 56% incidence of cage subsidence in their study, and lower bone density was significantly linked with a higher incidence of subsidence. Despite these findings, some studies have indicated that osteopenia is not always associated with subsidence after ACDF. Zhang et al. [10] analyzed 42 patients who underwent single-level ACDF and found no differences in cage subsidence rates at the 3-year follow-up between patients who had osteopenia and those who did not. The present study adds to this growing body of research as our results suggest that a prior diagnosis of osteopenia is not significantly associated with subsidence in our institutional cohort of patients undergoing ACDF. Therefore, a preoperative diagnosis of osteopenia may not increase the risk of subsidence.

The present study also showed no significant association between HU measurements and subsidence following ACDF. Anderson et al. [23] demonstrated the utility of CT-derived HU as a measure of bone mineral density. Interestingly, the cervical spine literature generally points to a significant relationship between HU measurements and postoperative subsidence. Ji et al. [24] retrospectively analyzed 73 patients who underwent single-level ACDF and found a significant correlation between lower global cervical HUs in patients with cage subsidence. Lee et al. [11] retrospectively reviewed 235 patients who underwent one- or two-level ACDF procedures and found that lower HUs were associated with higher subsidence rates. Other studies have found that lower preoperative CT-derived HUs are associated with cage subsidence in ACDF [11,12]. For instance, Wang et al. [12] determined that lower preoperative CT-derived HUs were associated with cage subsidence in patients undergoing single-level ACDF. Taking together the results of these studies, measures of bone mineral density, such as HU, have predictive clinical power for determining the degree and rate of subsidence following ACDF [11–13]. However, Brenke et al. [13] did not find a correlation between bone mineral density and subsidence risk but concluded that subsidence depends on cage geometry and varies with the operative procedure [11,12]. Our results indicate that HU measurements using the endplate, vertebrae, and ellipse methods were not significant predictors of cage or allograft subsidence. Our results may differ from those of previous studies owing to the sample size and differences in the diagnostic criteria for osteopenia. Furthermore, the majority of our patients underwent ACDF of ≥2 levels, and the complexity of multilevel surgeries may introduce additional factors that either obscure or reduce the visibility of osteopenia’s effect on subsidence, contributing to our finding of the lack of correlation between HU and subsidence. Although previous studies have evaluated HU measurements or preoperative osteopenia diagnosis, the present study compares both in a single institutional dataset.

Osteopenia is diagnosed primarily based on bone mineral density measurements taken during DEXA of the lumbar spine, hip, and forearm [14,25]. A radiographic study by Ahmed et al. [26] assessed the referral letters of 3,479 women who were referred for bone mineral density screening and concluded that radiographic osteopenia is an excellent predictor of low bone mass. Jha et al. [27] reviewed the differential diagnosis of low bone density and osteoporosis and concluded that these two variables should be differentiated from one another when diagnosing patients. Several studies have reported differences in bone density within the C3–C7 vertebrae [28,29]. Moreover, Anderst et al. [30] reported significant variations in the bone density of the cervical vertebrae based purely on anatomical location, suggesting differences in the regional bone mechanical properties.

The results of this study suggest the lack of correlation between an osteopenia diagnosis and HUs within the cervical spine. This lack of correlation between osteopenia and cervical spine bone density may be linked to the fact that osteopenia is diagnosed using DEXA throughout the body. The World Health Organization defines osteoporosis according to the following guidelines: a T-score within 1 standard deviation of the young adult mean indicates normal bone density, a T-score of 1–2.5 standard deviations below the young adult mean indicates osteopenia, and T-score of ≥2.5 standard deviations below the young adult mean indicates osteoporosis [14,25]. DEXA may not be the best measure of localized cervical spine bone quality. Furthermore, bone mineral density scores taken at the lumbar spine, hip, and forearm are not necessarily reflective of the cervical spine bone quality. Although this study reports on a small sample of patients with preoperative CT, the use of HUs allows for bone density assessment across different cervical vertebral levels. This provides an improved assessment of the cervical spine bone density compared with DEXA, which reports a single value at the lumbar spine level. Our results support this theory as we found that a prior diagnosis of osteopenia was not significantly associated with HUs within the cervical spine, indicating that surgeons should not assume that a patient with osteopenia will have reduced HUs in their cervical spine. This study represents a real-world analysis of osteopenia diagnosis as DEXA scans are not always available preoperatively. Given that many patients do not present for surgery with DEXA results and the increasing role of preoperative planning using CT, understanding the correlation between HU and subsidence is significant.

Subsidence following ACDF is a common radiographic finding; however, its clinical implications, particularly regarding patient-reported outcomes, are nuanced. Several studies have investigated the correlation between subsidence and clinical outcomes. Lee et al. found that subsidence occurred in 46.8% of patients 12 months after ACDF; however, no significant difference was found in clinical outcomes, such as neck and arm pain, between patients with and without subsidence. This suggests that subsidence does not adversely affect short-term clinical outcomes [31]. Milczynska et al. [32] reported a subsidence rate of 23% with the use of a novel titanium cage and similarly found no significant effect on health-related quality of life outcomes, including the Visual Analog Scale (VAS) for neck and arm pain, EuroQol-five dimension five-level, EuroQol VAS, and Neck Disability Index scores. This further supports the notion that subsidence does not necessarily correlate with worse patient-reported outcomes [32]. In a long-term follow-up study, Ryu et al. [33] found that subsidence occurred in 45.2% of patients; however, it did not significantly influence radiological or clinical outcomes, provided that adequate foramen decompression was achieved. This indicates that a proper surgical technique may mitigate the potential negative effects of subsidence [33]. According to Wu et al. [34], although subsidence was common (19.1%), it did not significantly affect long-term clinical outcomes, emphasizing the importance of cervical lordosis improvement over subsidence in determining patient outcomes. Although subsidence is a frequent occurrence following ACDF, current evidence suggests that it does not significantly affect patient-reported outcomes, provided that other surgical goals, such as maintaining cervical alignment and adequate decompression, are achieved.

In addition to patient-specific factors, accurate cage placement during ACDF is essential for minimizing the risk of subsidence. Ensuring proper alignment and choosing an appropriate surgical technique, as well as utilizing fixation materials that complement the patient’s pathology, are critical steps to achieving optimal outcomes. Studies have demonstrated that precise cage positioning and the use of suitable surgical techniques can significantly reduce subsidence [3,35]. Although our analysis did not identify a strong association between reduced bone density and subsidence, factors such as surgical technique and the quality of the bone–implant interface as well as patient anatomy may be critical in determining the long-term success of ACDF. In addition to the alignment and surgical technique, the advancement of biomaterials for ACDF implants may have affected ACDF subsidence in patients with osteopenia. Recent advancements, particularly with PEEK and titanium-coated PEEK cages, have shown promise in reducing subsidence, particularly in patients with osteopenia [13]. These materials, with their elastic modulus closer to the bone, enhance stability and osseointegration. In addition, novel porous implant designs such as gyroid structures help distribute mechanical loads more evenly, further minimizing subsidence [36]. Coating technologies, such as bioceramic, also improve the implant–bone interaction, enhancing the overall outcomes for patients with compromised bone quality [37]. This study did not evaluate the effect of the surgical technique or patient anatomy on subsidence. However, we did control for cage material in our regression analyses using a heterogeneous cohort of patients with PEEK, titanium, ceramic, and allograft spacers.

Several limitations must be considered when interpreting this study. As a single-institution retrospective study, our results may not be generalizable to other institutions and patient cohorts in other geographic locations. Second, differences in patient positions during radiographic collection may be attributed to some measurement variations. Furthermore, changes in disk height measurements may be due to causes other than subsidence, such as cage settling, bone resorption at the surgical site, or graft collapse [38]. Other potential causes of low bone density, such as osteomalacia and chronic kidney disease, can further contribute to subsidence [27]. In addition, because our bone density analysis subgroup was significantly smaller than the osteopenia analysis group we began with, our bone density data may be underpowered. To that same point, although we controlled for variables including age, sex, smoking status, and cage type, the study does not have adequate statistical power to control for all variables of clinical interest. Although our regression analysis is limited by the sample size, a strength of this study is the measurement of subsidence as a continuous variable rather than a binary variable, which decreases the sample size necessary to produce meaningful results. Owing to the limited sample size, patients with osteoporosis were categorized as osteopenic rather than subcategorized in their own group. Finally, although this study primarily focused on the analysis of HU and its correlation with subsidence, osteopenia diagnosis was determined via chart review of physician notes and DEXA results, which introduces variability and likely underrepresents the prevalence of osteopenia.

This study suggests that a prior diagnosis of osteopenia does not increase the risk of subsidence following ACDF. Further, no relationship was observed between bone density as measured by HU in preoperative CT scans and subsidence risk. This lack of relationship could reflect the diagnostic methods for osteopenia, which rely on bone density measurements in skeletal regions that do not include the cervical spine, and differences in surgical technique and patient anatomy play a larger role in subsidence development. These results highlight the multifactorial nature of subsidence, and osteopenia and HU may not independently predict subsidence following ACDF.