The association between sarcopenia and osteoporotic vertebral compression refractures.

Sarcopenia was reported to be significantly associated with osteoporosis. In this study, we reported for the first time that sarcopenia was an independent risk predictor of osteoporotic vertebral compression refractures (OVCRFs). Other risk factors of OVCRFs are low bone mass density T-scores, female sex, and advanced age. INTRODUCTION: The purpose of this study was to investigate the association between osteoporotic vertebral compression refractures (OVCRFs) and sarcopenia, and to identify other risk factors of OVCRFs. METHODS: We evaluated 237 patients with osteoporotic vertebral compression fracture who underwent percutaneous kyphoplasty (PKP) in our hospital from August 2016 to December 2017. To diagnose sarcopenia, a cross-sectional computed tomography (CT) image at the inferior aspect of the third lumbar vertebra (L3) was selected for estimating muscle mass. Grip strength was used to assess muscle strength. Possible risk factors, such as age, sex, body mass index (BMI), bone mineral density (BMD), location of the treated vertebra, anterior-posterior ratio (AP ratio) of the fractured vertebra, cement leakage, and vacuum clefts, were assessed. The multivariable analysis was used to determine the risk factors of OVCRFs. RESULTS: During the follow-up period, OVCRFs occurred in 64 (27.0%) patients. Sarcopenia was present in 48 patients (20.3%), including 21 OVCRFs and 27 non-OVCRFs patients. Sarcopenia was significantly correlated with advanced age, lower BMI, lower BMD, and hypoalbuminemia. Compared with non-sarcopenic patients, sarcopenic patients had higher OVCRFs risk. In univariate analysis, sarcopenia (p = 0.003), female (p = 0.024), advanced age (≥ 75 years; p < 0.001), lower BMD (p < 0.001), lower BMI (p = 0.01), TL junction (vertebral levels at the thoracolumbar junction) (p = 0.01), cardiopulmonary comorbidity (p = 0.042), and hypoalbuminemia (p = 0.003) were associated with OVCRFs. Multivariable analysis revealed that sarcopenia (OR 2.271; 95% CI 1.069-4.824, p = 0.033), lower BMD (OR 1.968; 95% CI 1.350-2.868, p < 0.001), advanced age (≥ 75 years; OR 2.431; 95% CI 1.246-4.744, p = 0.009), and female sex (OR 4.666; 95% CI 1.400-15.552, p = 0.012) were independent risk predictors of OVCRFs. CONCLUSIONS: Sarcopenia is an independent risk predictor of osteoporotic vertebral compression refractures. Other factors affecting OVCRFs are low BMD T-scores, female sex, and advanced age.

Contribution of presynaptic HCN channels to excitatory inputs of spinal substantia gelatinosa neurons.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pathological pain-associated voltage-gated ion channels. They are widely expressed in central nervous system including spinal lamina II (also named the substantia gelatinosa, SG). Here, we examined the distribution of HCN channels in glutamatergic synaptic terminals as well as their role in the modulation of synaptic transmission in SG neurons from SD rats and glutamic acid decarboxylase-67 (GAD67)-GFP mice. We found that the expression of the HCN channel isoforms was varied in SG. The HCN4 isoform showed the highest level of co-localization with VGLUT2 (23±3%). In 53% (n=21/40 neurons) of the SG neurons examined in SD rats, application of HCN channel blocker, ZD7288 (10µM), decreased the frequency of spontaneous (s) and miniature (m) excitatory postsynaptic currents (EPSCs) by 37±4% and 33±4%, respectively. Consistently, forskolin (FSK) (an activator of adenylate cyclase) significantly increased the frequency of mEPSCs by 225±34%, which could be partially inhibited by ZD7288. Interestingly, the effects of ZD7288 and FSK on sEPSC frequency were replicated in non-GFP-expressing neurons, but not in GFP-expressing GABAergic SG neurons, in GAD67-GFP transgenic C57/BL6 mice. In summary, our results represent a previously unknown cellular mechanism by which presynaptic HCN channels, especially HCN4, regulate the glutamate release from presynaptic terminals that target excitatory, but not inhibitory SG interneurons.