Association between serum leptin and bone metabolic markers, and the development of heterotopic ossification of the spinal ligament in female patients with ossification of the posterior longitudinal ligament

Abstract

Obesity is a risk factor for ossification of the posterior longitudinal ligament (OPLL) of the spine, which is characterized by heterotopic bone formation in the posterior longitudinal spinal ligament. Hyperleptinemia is a common feature of obese people and leptin is believed to be an important factor in the pathogenesis of OPLL. However, the association between leptin and bone metabolism and the development of OPLL is not understood fully. The objective of the present study was to determine the association between serum leptin concentration and bone metabolic markers and the extent of heterotopic ossification of the spinal ligament in patients with OPLL. The serum concentrations of leptin, insulin, fructosamine, bone-specific alkaline phosphatase, and carboxyterminal propeptide of type I procollagen, urine deoxypyridinoline levels, and the number of vertebrae with OPLL involvement were measured in 125 (68 males and 57 females) patients with OPLL. The correlation between leptin and these other factors was then examined. Serum leptin and insulin concentrations were increased significantly in OPLL females compared to non-OPLL female controls. In the females with OPLL, serum leptin concentrations corrected for body mass index correlated positively with the number of vertebrae with OPLL involvement. In females, serum leptin levels were significantly higher in patients in whom OPLL extended to the thoracic and/or lumbar spine than in patients in whom OPLL was limited to the cervical spine. Our results suggest that hyperleptinemia, in combination with hyperinsulinemia, may contribute to the development of heterotopic ossification of the spinal ligament in female patients with OPLL.

The predisposing factors for the heterotopic ossification after cervical artificial disc replacement

“…Previously, Musha [35] reported that serum estrogen levels were higher in OPLL male patients than in controls, suggesting that sex hormone imbalance is responsible for the development of OPLL. In female patients, hyperlipidemia and leptin are believed to be important factors in the pathogenesis of OPLL [36]. In such females with OPLL, serum leptin concentrations corrected for body mass index were shown to be positively correlated with the number of vertebrae with OPLL involvement.…”

Leptin accelerates the pathogenesis of heterotopic ossification in rat tendon tissues via mTORC1 signaling

“…Scale bar, 50 µm (Ben-Eliezer, Phillip, & Gat-Yablonski, 2007;Fan et al, 2007;Handschin et al, 2007). In addition, the effect of leptin on HO had also been studied (Chauveau et al, 2008;Ikeda et al, 2011;Xu et al, 2009;Yamamoto & Kosaka, 2009) A previous study had shown that leptin exerted pivotal endocrine effects on energy homeostasis and intracellular functions (Gautron & Elmquist, 2011). Recent investigations have revealed its positive role in osteogenesis and angiogenesis (Delle Monache et al, 2016;Lanier et al, 2016;Xu, Wu, Zhou, Yang, & Liu, 2016;Yang et al, 2016), as well as the inflammatory reaction (Drosos et al, 2016;Vuolteenaho et al, 2009), implying its potential roles in mediating HO formation.…”

Metabolic Factors in Diffuse Idiopathic Skeletal Hyperostosis – A Review of Clinical Data

“…Japanese female patients with OSL, but not males have elevated leptin, which correlates with elevated insulin levels [ 74 ]. There is a positive correlation with extent and severity of ligamentous ossification in OSL [ 75 ]. The leptin receptor is expressed in human spinal ligaments, although in vitro studies did not show increased collagen synthesis after exposure to leptin [ 74 ].…”