Etiology and Pathogenesis

Abstract

Ossifi cation of the posterior longitudinal ligament (OPLL) in an autopsy case was fi rst described by Tsukimoto [1] in 1960. Since then a number of clinical and pathological studies of this disease have been reported [2–6]. Increased recognition of OPLL led the Ministry of Public Health and Welfare of Japan to appoint, in 1974, a special study group, the Investigation Committee on OPLL, to make extensive studies ranging from basic research to clinical investigation. To date, various systemic and regional factors have been reported concerning the etiology and pathogenesis of OPLL. The pathogenesis of OPLL has two aspects: the pathogenesis of ossifi cation of the posterior longitudinal ligament and the pathogenesis of the myelopathy induced when OPLL compresses the spinal cord. It is not fully understood why the posterior longitudinal ligament becomes ossifi ed, although it is clear that the occurrence of OPLL has a genetic background [7–11]. This is supported by family studies, twin studies, and HLA haplotype analysis. The pathological gene of OPLL has not yet been identifi ed. Details of the genetic background of OPLL are described in another part of this book. The occurrence and development of OPLL involve many environmental, systemic, and local factors. One environmental factor is dietary life. An example of a systemic factor is the metabolic or endocrinological background of an individual, and a common local factor is mechanical stress on the cervical spine. There are racial differences in the incidence of OPLL. OPLL used to be called a Japanese disease because it was rarely found in other countries. Because of this, one of the causes of OPLL is thought to be life style, especially dietary factors. There are reports that patients with OPLL prefer vegetable protein to animal protein, in comparison with controls [12,13], but this hypothesis has not been confi rmed by well-designed control studies. The relation between vitamin A and OPLL has been investigated. Tosti and colleagues [14] reported a patient on long-term vitamin A therapy who had an increased tendency to develop hyperostosis and who developed OPLL. Imamura et al. [15] radiographically evaluated nine patients who were treated with etretinate for disorders of keratinization. Five patients showed ossifi cation of the cervical spinal ligament and developed ossifi cation during therapy. 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 derangements in mineral metabolism such as hypoparathyroidism and vitamin D-resistant hypophosphatemic rickets, disturbances in glucose metabolism, and growth hormone secretion or actions. There have been many studies of the correlation between calcium metabolic abnormality and OPLL. Patients with OPLL were reported to show an increase in systemic bone mineral density [16]. Bone alkaline phosphatase and osteocalcin also were investigated in OPLL patients [17,18], but the authors of these studies did not reach a defi nite conclusion. Seichi et al. noted that patients with OPLL showed a signifi cantly low response to the oral calcium tolerance test. This result suggests that the development of OPLL is associated with decreased intestinal calcium absorption [19]. In an investigation of the relation between OPLL and hypoparathyroidism, Okazaki et al. reported that 9 of 12 patients with hypoparathyroidism were found to have OPLL [20], although there was a case report that a patient with hyperparathyroidism also had OPLL. There is no general agreement concerning the relation between OPLL and hypoparathyroidism. Vitamin D-resistant hypophosphatemic rickets [21] is well known to be associated with OPLL. The occurrence of OPLL is suspected to be related to a derangement 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. These study results suggest that calcium metabolic abnormality is related to the occurrence and development of OPLL. Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1 Minami Kogushi, 1-Chome, Ube 7558505, Yamaguchi, Japan