Ossification of the posterior longitudinal ligament (OPLL) was first described by Aston C Key [1] in 1838 as a disease that causes paraplegia. Two male patients with OPLL suffered from bladder disturbance and paraplegia, followed by septicemia. The autopsies revealed a narrowed cervical canal due to OPLL. However, the condition then went without notice for a long time. Oppenheimer [2] reported 18 cases of calcification or ossification of the anterior and posterior longitudinal ligaments over 100 years after OPLL was first described by Key. Most of these cases were ossification of the anterior longitudinal ligament. He did not recognize the clinical significance of OPLL.

In Japan, a similar case to Key’s was reported in 1960 by Dr. Hirokuni Tsukimoto [3]. A 47-year-old male with finger clumsiness and sensory disturbance in both arms and legs underwent posterior surgery and achieved transient recovery. However, he suffered from pneumonia 3 months after the operation following tetraparesis and pressure sore formation on the sacrum. The autopsy revealed ectopic bone formation adjacent to the vertebral body, which was presumed to have changed from the posterior ligament (Fig. 1.1). The author speculated that the etiology involved repeated minor trauma to the neck, such as whiplash injury, inducing this ectopic bone formation. The author noted that vascular factors are also related to the acceleration of myelopathy. Following this report, many studies have been enthusiastically conducted in Japan.

Fig. 1.1
figure 1

The first reported case of cervical OPLL showed ectopic bone formation (a) just behind the vertebral body (b). Reprinted with permission from 3)

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In 1975, the government launched a research grant to conquer intractable diseases that have continued up to the present. Eight investigation committees have been organized for this disease. Table 1.1 shows the names of the chief researchers of each group and their main topics.

Table 1.1 Names of chief researchers and their main topics in the investigation committee of research groups
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The PLL ossifies spontaneously and increases in length and thickness year by year, resulting in compression of the spinal cord. Minor trauma can easily cause deterioration of paresis or induce spinal cord injury. Although ectopic bone formation in ligamentous tissue has been presumed to occur in association with diabetes mellitus or certain foods and other metabolic diseases, the precise mechanism has remained unclear [4, 5].

Although epidemiology, natural history, diagnosis, and treatment were common topics of each period, the development of imaging techniques, such as CT and magnetic resonance imaging, enabled the addition of new information. Reconstructed CT images of the cervical to lumbar spine can be easily obtained within a few minutes. Such whole-spine reconstructed images indicated that ossification of the yellow ligament in the thoracic and lumbar spine was more frequently observed in patients with cervical OPLL than expected. Moreover, cervical OPLL was detected in males three-times more frequently than in females, but thoracic OPLL showed an opposite trend. Additionally, the ossification of other spinal ligaments, such as the anterior, supraspinal, and yellow ligaments, was observed [6,7,8]. These facts indicate that genetic factors strongly contribute to the development of the ossification of all spinal ligaments. This advancement in imaging also made it easy to evaluate the ossified bone volume in a 3D fashion. Analysis revealed an annual increase in the ossified bone volume and the suppression of ossification after surgical fusion [9, 10]. These studies provide valuable information for the selection of an operative method.

The pathology of ectopic ossification in the spinal ligaments has been studied for a long time. Ossification of the spinal ligaments is ectopic, with hypertrophy of the ligament, proliferation of cartilaginous cells in the ligament, and the release of cytokines related to bone formation (bone morphogenetic protein and transforming growth factor beta) during the ossification process [11]. Recent genetic studies have provided more advanced knowledge of the pathogenesis. A sib-pair study and a genome-wide association study were conducted to identify the susceptibility gene(s) for ectopic bone formation of the spinal ligaments [12, 13]; there were six susceptible loci for OPLL. Ectopic ossification of the spinal ligaments is more likely to develop in middle-aged adults with such genetic factors. The function of some candidate genes has since been studied. This splendid progression in basic research suggests that it is not unreasonable to expect a drug to be available in the future to control the development of ectopic ossification.

Until now, the main treatment for OPLL has been surgery. Many kinds of laminoplasty have been developed in Japan [14, 15]. However, the basic concept of wide and simultaneous decompression of the spinal cord has been mandatory in posterior surgical treatment since the report by Kirita [16]. Anterior cervical corpectomy and fusion (ACCF) is also available for this disease. Yamaura’s floating method, in which the ossified ligament is not removed but thinned carefully, has gradually prevailed to avoid intraoperative neurological complications [17]. Comparative studies between these two types of surgery indicated similar outcomes 2 and 3 years postoperatively; however, subsequently, neurological symptoms in patients treated with laminoplasty can deteriorate because of the gradual progression of kyphotic alignment or ossification [18]. The newly proposed K-line is quite useful in the determination of a surgical method. The K-line is defined as the line connecting the midpoints of the spinal canal at the C2 and C7 levels on lateral cervical X-ray examination. When the ossification is large enough to exceed this line toward the spinal cord, anterior surgery will be preferred. The relationship between the ossification and the line depends on the sagittal profile of the cervical spine and the thickness of the ossification [19]. This concept has rapidly prevailed globally in helping to decide on the surgical approach used for each patient.

The concomitant use of posterior instrumentation with laminoplasty was recently proposed to avoid alignment changes [20]. Fusion of the spinal segments may also suppress ossification development. Thus, surgical fusion with either an anterior or posterior approach could help to maintain a good outcome over the long term in the treatment of this disease [21,22,23].

For thoracic OPLL, laminectomy with posterior instrumentation has become popular [24]. Prospectively collected data from multiple spine centers nationwide have shown that abnormal wave changes occurred in more than 40% of cases. Although most of the patients showed spontaneous recovery until the end of the surgery, some of them remained paralyzed postoperatively. The cause of this critical complication is presumed to be not a technical problem but due to the prone position during surgery [25].

Above all, recent progress in this area has been achieved by great support from governmental research grants. Most of these results were obtained by the collaboration of nationwide spine centers and the research committee organized by the Japanese Orthopaedic Association. Details of the studies are available in this textbook.