Injury to peripheral tissue leads to hyperalgesia that appears to be partly mediated by functional changes at the level of the spinal cord. Glutamate receptors are thought to play a role in acute and short-term (minutes to hours) spinal cord nociceptive responses and may be involved in prolonged or chronic pain (hours to days). We used in situ hybridization to examine AMPA/kainate (GluR1, GluR2, and GluR3) and NMDA (NR1) receptor gene expression in spinal cord following induction of prolonged inflammation by a unilateral intraarticular injection of lipopolysaccharide (LPS; 10 micrograms) into the hindpaw. In control rats, GluR1 expression was prominent throughout the layers of the gray matter of the spinal cord. Microscopic examination revealed labeling of neuronal cell somata in all major nuclei. GluR2 was abundant in substantia gelatinosa and motor nuclei; emulsion-dipped sections exhibited intense labeling over densely packed neurons in the superficial laminae of dorsal horn and individual motoneurons of ventral horn. GluR3 and NR1 were expressed at low levels throughout spinal cord gray matter. One day after LPS injection, when joint swelling was maximal, GluR1 expression was bilaterally decreased by 25% in the substantia gelatinosa at the level of the lumbar cord. In contrast, no significant change was apparent in GluR2, GluR3, or NR1 expression in any nucleus of the cord. At 72 hr after injection, when joint diameter approached control values, all four transcripts were expressed at near control levels. These findings provide evidence for a specific decrease in GluR1 expression in the cord in response to joint inflammation.

The study evaluates the serum levels of Trimethylamine N-Oxide (TMAO), a gut microbial metabolite, in 286 postmenopausal women with hip fracture. From January 1, 2018 to December 31, 2018, eligible patients were included. Same women without fracture mated age were enrolled. TMAO serum levels were tested by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The serum levels of TMAO were significantly higher in patients with hip fracture than in those controls (P<0.001). The serum levels of TMAO were also higher in patients with hip fracture only than in those who also had upper limb fracture (P=0.001). High level of TMAO was proved a predictor of both hip fracture and had upper limb fracture combined hip fracture, after the adjustment of other existing risk factors [e.g., for each 1 uM increase of TMAO, odd ratio 1.16 (95% CI, 1.07-1.25), P < 0.001; and 1.12 (95% CI, 1.03-1.26), P=0.008, respectively]. In summary, increased TMAO serum levels associated with high risk of hip fracture, suggesting that increase TMAO may contribute to osteoporosis and fracture in postmenopausal women.

PurposeThere is limited information on the prevalence of vitamin D deficiency among patients diagnosed with hip fracture in the Chinese Han population. Therefore, the aim of this study was to assess the effects of change in the serum levels of 25-hydroxyvitamin D [25(OH) D] and intact parathyroid hormone (iPTH) among postmenopausal women in North China with confirmed hip fracture.MethodsThis study was done from May 1, 2012 to April 30, 2014. Three hundred and forty-nine postmenopausal women who were diagnosed with first-ever hip fracture and 349 matched controls without fracture were used for this study. The 25(OH) D, iPTH, alkaline phosphatase, calcium, and phosphorus levels were measured in fasting venous blood samples collected from the subjects. A predesigned questionnaire was used to collect information on covariates for multivariate analyses to evaluate the hypothesized relationship between vitamin D deficiency and fracture risk.ResultsThe serum 25(OH) D levels were found to be significantly (P < 0.0001) lower in hip fracture patients than in the controls [37.0 (interquartile range [IQR] 28.0–48.0) nmol/L vs. 41.3 (IQR 32.0–54.5) nmol/L; P < 0.0001], and the iPTH levels were significantly higher in the former group [10.2 (IQR 6.3–14.9) pmol/L vs. 5.8 (IQR 4.1–6.6) pmol/L; P < 0.0001]. Further, a 25(OH) D level ≤50 nmol/L was found to independently indicate the occurrence of hip fracture [odds ratio (OR), 3.023; 95 % confidence interval (CI) 2.154–4.298], as well as hip fracture with concomitant upper limb fracture (OR 4.473; 95 % CI 2.984–10.532). Similarly, a serum iPTH level ≥6.8 pmol/L independently indicated the development of hip fracture (OR 2.498; 95 % CI 1.764–3.942), as well as hip fracture with concomitant upper limb fracture (OR 3.254; 95 % CI 1.998–7.984).ConclusionsVitamin D insufficiency and secondary hyperparathyroidism were found to be common problems in the sample of postmenopausal women who had experienced hip fracture. Monitoring the alterations in the serum levels of 25(OH) D and iPTH could be applied clinically as independent risk factors for hip fracture.

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