Close Association Between Non-Alcoholic Fatty Liver Disease and Ossification of the Posterior Longitudinal Ligament of the Spine

Abstract

Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease of unknown etiology occurring frequently in individuals with metabolic disturbances. Obesity has been suggested as a potential risk factor for the severity of OPLL. We aimed to investigate whether non-alcoholic fatty liver disease (NAFLD) is associated with OPLL severity. We assessed the severity of NAFLD by a liver-to-spleen (L/S) ratio on computed tomography (CT) scans of 85 symptomatic OPLL patients at a single institution in Japan. We also assessed the severity of OPLL by CT reconstruction sagittal and axial images. The prevalence of NAFLD in middle-aged patients (age < 70 years, n = 50) was 80.3%, which was 2.5-8 times higher than that in the general Japanese population (9–30%). The ossification index of the spinal ligaments increased in proportion to the severity of fatty liver. The L/S ratio was revealed as a significant risk factor associated with the total ossification index (standardized β: -0.40, 95% confidence interval: -54.34 to -4.22). This study suggests the potential contribution of NAFLD to the progression of OPLL. The close association between NAFLD and OPLL demonstrated in this study warrants further study to elucidate the causal nature of this relationship.

Lumbar ossification of the ligamentum flavum reflects a strong ossification tendency of the entire spinal ligament

“…Considering that OLF is most likely to be observed in the thoracolumbar region 7 , the conventional hypothesis that mechanical stress is a factor in the development of OLF has some validity [8][9][10] . Recently, however, it was shown that patients with OPLL in the thoracic spine have a higher degree of obesity and a tendency toward diffuse heterotopic ossification of the entire spine, including OLF, compared to those with OPLL localized in the cervical spine 12,13,17 . In addition, patients with multilevel OLF tend to be more obese than those with localized OLF 14 .…”

Strong relationship between dyslipidemia and the ectopic ossification of the spinal ligaments

“…Recently, it has been reported that the severity of ossi cation of the entire spine in patients with symptomatic OPLL is associated with the severity of MAFLD rather than being associated with BMI. [24] The fact that patients with OPLL have a high frequency of comorbid lifestyle-related diseases also suggests that ossi ed lesions may be exacerbated by abnormal lipid metabolism related to visceral fat obesity, rather than by mere local instability or mechanical stimulation. [30][31][32] The mechanisms by which abnormal lipid metabolism causes ectopic ossi cation of spinal ligaments are speculative.…”

“…Subjects with OLF without concomitant C-OPLL or T-OPLL were classi ed as the OLF group. This classi cation was based on the following rationale: (1) C-OPLL has a comparatively high probability of occurring concomitantly with OLF; [9] (2) compared to C-OPLL, T-OPLL has distinct features, such as morbid obesity, early onset of symptoms, and diffuse ligament ossi cation of the entire spine, including OLF and C-OPLL; [12,15,24] and (3) OLF occurs mostly in the thoracic spine and rarely in the cervical or lumbar spine. [29] All subjects were also divided into the following two groups according to the presence or absence of concomitant dyslipidemia: DL(+) (n = 215), and DL(−) (n = 243).…”

“…[20][21][22] In recent years, the association of OPLL/OLF with obesity, malnutrition, genetic factors, and metabolic dysfunction-associated fatty liver disease (MAFLD) has become clear. [10][11][12][13][14][15][23][24][25][26] This suggests that metabolic disturbances related to spinal ligament ossi cation could affect systemic bone metabolism and trigger ectopic ossi cation. Despite the common features of dyslipidemia and spinal ligament ossi cation, no study has investigated their relationship in detail.…”