Insulin secretory response is positively associated with the extent of ossification of the posterior longitudinal ligament of the spine

Background: Glucose intolerance is frequently found in patients with ossifi cation of the posterior longitudinal ligament of the spine. This study was undertaken to examine the relationship between glucose intolerance and the extent of ossification in patients with ossification of the posterior longi tudinal ligament. Methods: A total of 100 patients with ossification of the posterior longitu dinal ligament (the overall study group), including fifty-two inpatients wh o were scheduled to have an operation (the inpatient group) and forty-eight outpatients who had undergone an operation, were analyzed, Indices of gluc ose metabolism-fasting plasma glucose and serum insulin levels, hemoglobin A, level, and insulinogenic index (a ratio of the increment of the serum le vel of insulin to that of glucose)-as well as age and body-mass index were correlated with the extent of ossification, as determined by the number of vertebral levels affected with ossification of the posterior longitudinal l igament (extent of ossification), in the inpatient group. In addition, a si milar analysis was performed in twenty-eight inpatients (the selected inpat ient group) whose ages and body-mass indices were within one standard devia tion of the mean values of those of the inpatient group. Association of a p olymorphism in the gene of insulin receptor substrate-1, an essential subst rate in insulin signaling, with the extent of ossification was evaluated wi th genomic DNA extracted from the overall study group. Results: Multiple-regression analysis revealed direct correlations of age ( p = 0.038), body-mass index (p 0.006), and insulinogenic index (p = 0.0003) with the extent of ossification of the posterior longitudinal ligament in the inpatient group. The fasting plasma glucose level, the hemoglobin A, le vel, and the stage of glucose tolerance were not associated with the extent of ossification. In the analysis of the selected inpatient group, only the insulinogenic index was correlated with the extent of ossification (p = 0. 002), However, no significant association was seen between the insulin rece ptor substrate-1 polymorphism and the extent of ossification. Conclusions: The insulin secretory response was associated with the extent of ossification of the posterior longitudinal ligament. Since insulin recep tor substrate-1 is expressed both in the spinal ligament and in the tissues regulating glucose metabolism, we speculate that some other molecules rela ted to insulin signaling that are impaired only in the tissues regulating g lucose metabolism may be responsible for the progression of ossification. W e also speculate that the upregulation of insulin production due to the imp airment of insulin action may stimulate osteoprogenitor cells in the ligame nt to induce ossification. Clinical Relevance: The insulinogenic index may be useful as a serum marker for the prediction of progression of ossification of the posterior longitu dinal ligament. This study may serve as a stimulus for evaluation of the us e of various drugs that may improve the response to insulin in the tissues regulating glucose metabolism to prevent the progression of ossification.