Views vary on adjacent segment degeneration

Genetics or biomechanics? It’s a question that can be asked about a number of musculoskeletal disease processes. At the Federation of Spine Associations Specialty Day, the question was applied to adjacent segment degeneration (ASD).

Taking the side of “It’s All Biomechanics” was Avinash G. Patwardhan, PhD. Noting that the etiology of ASD is controversial, he believes that the evidence supports the pre-eminent role of biomech-anical factors in the development of ASD and associated disease. He also acknowledged, however, the role of genetic and environmental factors in determining and regulating the course of ASD among affected persons.

Changes in biomechanics occur over a lifetime, Dr. Patwardhan said, and the effect an individual experiences varies. “Aging-related changes in the musculoskeletal structures in the neck region will lead to concordant degradation in the biomechanical characteristics of the segment that govern its ability to withstand physiologic loads without causing or aggravating injury to the soft tissue and bony elements,” he said. “The ability to adapt to these changes depends on a multitude of factors, including genetic predisposition, nutritional supply, and functional adequacy of the surrounding musculature.”

A person who has an adequate ability to adapt and who avoids traumatic injury may remain a-symptomatic, but often progressive degeneration and loss of disk height overload the facet joints, leading to facet arthrosis and cervical spondylytic phenomena. The resulting pain and neurologic dysfunction can severely limit a person’s ability to perform activities of daily living.

Surgical management: CDA or ACDF?
Dr. Patwardhan traced the progression of ASD and the role of biomechanics leading up to symptomatic segments and possible surgical management with anterior cervical diskectomy and fusion (ACDF) or cervical disk arthroplasty (CDA). He said the evidence favors artificial disk replacement.

Because abnormal biomechanics at the index level in the cervical spine will induce biomechanical changes at the adjacent segments, an inability to adapt to the altered biomechanics and restore homeostasis at the index level will result in progressive degeneration at the adjacent level. Studies comparing the effects of CDA and ACDF on cervical spine biomechanics have shown that ACDF results in increased motion, stress, and disk pressure on adjacent levels (Fig. 1).

Research has found that “patients subjected to ACDF have a significantly higher incidence of progression of disk degeneration than individuals who did not have surgery,” Dr. Patwardhan said. Studies have reported incidence values for developing adjacent level disease after cervical spine surgery ranging from 6.7 to 25.6 percent at 10 years postoperatively. In one series, adjacent segment disease that required subsequent additional surgery developed in 9 percent of patients who had posterior foraminotomy.

The incidence of symptomatic disease after cervical interbody fusion may be higher when radiographic evidence of asymptomatic disk degeneration is seen before surgery, Dr. Patwardhan said.

In contrast to the findings for fusion, he said, clinical studies show low rates of segment degeneration and reoperation following CDA. Such outcomes can be attributed to biomechanical factors, he said. “Clinical evidence shows that cervical spine motion at the operated level is restored to physiologic values after disk replacement surgery, and the physiologic angular and translational motion at the adjacent segments is preserved.”

But is it disease?
Offering a counterpoint to Dr. Patwardhan’s framework was F. Todd Wetzel, MD. He called his presentation “It’s All Genetics,” but to that title he appended “Actually, it’s survival and aging.”

Dr. Wetzel’s overall theme was one of caution and concerted skepticism. He questioned the assumptions about the significance of ASD itself. “Is it real? Is it imagined? Is it clinically significant? We must draw a distinction between adjacent segment degeneration and adjacent segment disease. If we prevent one, can we prevent the other?” he asked.

He expressed the view that measures to detect ASD—and subsequent interventions in response to finding it—may be misguided. “This is guilt by association. Bad timing leads to bad outcomes. You have to be careful to look at the context of the findings. Incidental findings are especially apparent when you attempt to ascribe significance to them.”

To gain a better understanding of ASD and the biomechanical factors that may or may not be significant, one must scrutinize the literature and its quality in terms of study level, length of follow-up, and, for the biomechanical issues, the use of clinically relevant parameters, Dr. Wetzel said. He contended that in all cases of in vitro studies, “any clinical implications are speculative.”

How biomechanical experiments are conducted is critical to their clinical relevance. He said that testing should involve a “realistic” loading paradigm, which consists of displacement control testing. In contrast to temporary static load-displacement analysis, simulated fusion with displacement control “simulates the mechanics of a patient trying to achieve a specific range of motion or activity,” Dr. Wetzel said.

He cited a cadaver study that used a more contemporary fusion model for C5-6 fusion and found no significant difference in preoperative and postoperative range of motion at C4-5 and a 14 percent increase in axial rotation at C6-7.

The parameters of measurement are also important in in vivo studies of the relationship between ASD and fusion, Dr. Wetzel said. He summarized a level III study in which 21 patients undergoing ACDF were examined with dynamic fluoroscopy and a “validated quantitative system.” No significant difference was found pre- and postoperatively for shear, flexion extension, or vertical displacement at the anterior or posterior disk space.

As to the significance of findings from imaging, Dr. Wetzel dissented from Dr. Patwardhan’s contention that radiologic evidence of disk degeneration preoperatively is indicative of disease. Such evidence “does not mean that it is symptomatic,” he said.

Quoting a colleague, John D. Loeser, MD, Dr. Wetzel quipped, “An MRI is a great way to tell someone’s age, but not what’s wrong with them.” He cited a long-term study of patients undergoing cervical fusion that found a radiographic incidence of ASD of 92 percent. But the study found no correlation between changes in Nurick scores (which measure spinal cord compression due to spondylosis) and radiographic degeneration in the most severely involved, myelopathic subgroup.

Even in the “contrarian” literature, the findings do not necessarily support a biomechanical rationale. Dr. Wetzel said. For example, one study examined patients with a “huge” (73 percent) incidence of ASD. Although 17 percent of patients had revision surgery, most of the revision group had pre-existing degeneration, so that less than 10 percent of the revision group had apparent adjacent segment changes de novo.

“What we are seeing,” Dr. Wetzel said, “is certainly biomechanics, but it’s clearly being overshadowed by natural history and the fact that humans are vertebrates and walk in an upright position.”

Dr. Wetzel noted that in all clinical fusion studies, the index fusion is assumed to be solid. “Clinically, this is a questionable assumption,” he said. “We all know that in the lumbar spine, there are varying rates of specificity and sensitivity for [evaluating] any technique. This is likely the case in the cervical spine.”

In one study, for example, the results in cervical fusion patients who had undergone re-exploration for various reasons were compared with results as measured by MRI, computed tomography, and planar radiography. At best, in 15 percent of patients, fusion status had been incorrectly evaluated.

The lesson of this finding in relation to the study of ASD, said Dr. Wetzel, is that because fusion status may not be determined correctly, “unless one reruns all the data with a worst-case scenario, including biomechanics, all conclusions must be approached with some caution.”

Disclosure information: Dr. Patwardhan—Spinal Kinetics; Dr. Wetzel—Relievant Medical, North American Spine Society, the McKenzie Institute, Spine, The Spine Journal, Pain Management.

Terry Stanton is senior science writer for AAOS Now. He can be reached at tstanton@aaos.org