Overview of Etiology and Pathogenesis
Toshihiko Taguchi
The posterior longitudinal ligament extends from the skull to the sacrum. This ligament is more fi rmly attached to the discs than to the vertebral bodies. It displays two strata of fi bers. The superfi cial, longer strands form a distinct strap whose fi laments bridge several vertebral bodies. A second, deeper stratum spans only two vertebral bodies and forms a lateral curving extension of fi bers that pass along the dorsum of the disc and out through the intervertebral foramen.
The posterior longitudinal ligament differs consider- ably from the anterior longitudinal ligament with respect to the clinical signifi cance of its relation to the neural elements, including the spinal cord and nerve roots [1].
Ossifi cation of the posterior longitudinal ligament (OPLL) was fi rst diagnosed in an autopsy case reported by Tsukimoto in 1960 [2]. Since then there have been many reports from Japan in which OPLL causes myelop- athy [3–5]. At fi rst, this disease was called calcifi cation of the longitudinal ligament. After pathological exami- nation revealed that the longitudinal ligament is ossi- fi ed in these cases, the disease was renamed OPLL. As there were only a few reports of OPLL from countries other than Japan, OPLL was once known as a “Japanese disease.” The disease came to be recognized as the con- ditions associated with ankylosing skeletal hyperostosis reported by Forestier and Lagier [6]. In 1976 Resnick and Niwayama [7] described the entity diffuse idio- pathic skeletal hyperostosis (DISH) and regarded OPLL as a type of DISH. Its clinical features were reported in detail by Nakanishi et al. [8] and Ono et al. [9]. Research- ers have not yet fully clarifi ed why the longitudinal liga- ment becomes ossifi ed.
Over the past decades a considerable number of studies have been conducted regarding the factors related to the occurrence and development of OPLL, including many environmental, systemic, and local factors. One environmental factor is the diet. An example of systemic factors is the genetic background, with the metabolic or endocrinological characteristics
of an individual (i.e., hereditary transmission, hor- monal abnormality, abnormal calcium metabolism, an association with diabetes mellitus). Common local factors include mechanical stress to the cervical spine (a form of local dynamic stress) or chronic trauma to the cervical spine.
It is clear that OPLL has a genetic background [10–
14]. This is supported by family studies, twin studies, and HLA haplotype analysis. The pathological gene for OPLL has not yet been determined. Identifying this gene probably requires the study of families with OPLL using linkage analysis. In a previous family study, the incidence of OPLL in blood relatives in second-degree relationships was 23.2%. Because of this high incidence, it is easier to collect sibling pairs with OPLL, investi- gating many such pairs using nonparametric linkage analysis.
As there are racial differences in the incidence of OPLL, one of the causes of OPLL is thought to be life environment, especially the diet. There are reports that patients with OPLL prefer vegetable protein to animal protein, in contrast to controls [15,16], but this hypoth- esis has not been confi rmed by well-designed control studies.
The relationship between vitamin A and OPLL has been investigated [17,18]. It is possible that taking an excess of vitamin A puts one at risk for OPLL, but there is no conclusive proof of this.
A high incidence of OPLL has been reported in patients with metabolic and endocrinological disorders.
Such disorders include calcium metabolic abnormality, hypoparathyroidism, vitamin D-resistant hypophos- phatemic rickets, disturbances in glucose metabolism, and growth hormone secretion or action.
There have been many studies of the correlation between calcium metabolic abnormality and OPLL [19–22]. These study results suggest that calcium meta- bolic abnormality is related to the occurrence and development of OPLL.
In an investigation of the relation between OPLL and hypoparathyroidism, many patients with hypoparathy- roidism were found to have OPLL [23]. There is no general agreement concerning the relation between OPLL and hypoparathyroidism.
Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1 Minami Kogushi, 1-Chome, Ube 755- 8505, Yamaguchi, Japan
29
30 T. Taguchi
Vitamin D-resistant hypophosphatemic rickets [24]
is well known to be associated with OPLL. The occur- rence of OPLL is suspected to be related to a derange- ment in calcium and phosphate metabolism, but the incidence of OPLL combined with vitamin D-resistant hypophosphatemic rickets is obscure because the sample of patients is small.
A considerable number of studies have been con- ducted regarding the relation between OPLL and diabe- tes mellitus [23,25–28]. Summarizing these studies, we concluded that diabetes mellitus does not directly take part in osteogenesis, but obesity and disturbances in glucose metabolism do induce OPLL.
Acromegaly is sometimes reported to accompany OPLL. It is possible that changes in growth hormone secretion or its actions infl uence the development of OPLL [19].
The above-mentioned factors related to OPLL are not fully supported by high-grade evidence because most studies on the etiology and pathogenesis of OPLL were experimental studies. Such studies are diffi cult to perform as randomized controlled trials (RCTs).
Pathology studies of OPLL indicate that the damaged parts of the spinal cord show tissue softening and necrosis. Myelopathy is induced by static compression of the spinal cord by an ossifi ed mass. Ono et al. [9]
reported that Japanese patients with an anteroposterior (AP) dimension of the cervical canal that has decreased by more than 40% on cervical spine fi lms can develop severe spinal cord symptoms. Kawaguchi et al. [29]
reported that some patients have slight symptoms with the AP dimension decreased by more than 40%. An ossifi ed mass, however, does not always correlate with the severity of the myelopathy. Some reports indicate that severe myelopathy can be induced by minor cervi- cal trauma in patients with OPLL [24,30]. These fi nd- ings show that cervical myelopathy due to OPLL results from dynamic factors in the spinal cord as well as static factors.
References
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Overview of Etiology and Pathogenesis 31
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