Ossification of the Posterior Longitudinal Ligament: An Update on Its Biology, Epidemiology, and Natural History

Abstract

Abstract SIGNIFICANT PROGRESS HAS been achieved in basic research during the past decade on the pathogenesis of ossification of the posterior longitudinal ligament (OPLL), a multifactorial disease in which complex genetic and environmental factors interact. A review of the literature was conducted to update recent findings on the biology, epidemiology, natural history, and related diseases of OPLL. Gene analysis studies found specific polymorphisms that may be associated with OPLL in several collagen genes, which encode for extracellular matrix proteins. Polymorphisms in the nucleotide pyrophosphate gene, which is involved in regulation of calcification in chondrocytes, may also be associated with OPLL. However, the results of the gene analysis studies have not always been consistent. Involvement of many growth factors and cytokines, including bone morphogenic proteins and transforming growth factor-β, has been demonstrated in various histochemical and cytochemical analyses. Several transcription factors involved in cellular differentiation may also have a role. Recent epidemiological studies reaffirmed an earlier finding that diabetes mellitus is a distinct risk factor for OPLL. The long-term follow-up studies of OPLL patients are disclosing the natural history, as well as the frequency and rate of progression, of OPLL after surgical intervention. Further knowledge on the factors responsible for progression of OPLL may predict its behavior in each patient, and treatment may be tailored accordingly. The coexistence of OPLL with other diseases of ectopic ossification of the spine, such as ossification of the ligamentum flavum and diffuse idiopathic skeletal hyperostosis, is not uncommon. Scientific breakthrough in those diseases may, in turn, give insights into the pathogenesis of OPLL.