Association of bone turnover biomarkers with severe intracranial and extracranial artery stenosis in type 2 diabetes mellitus patients

BACKGROUND Intracranial and extracranial artery stenosis is associated with cerebral infarction.Vascular calcification and atherosclerosis are the main causes of stenosis and major risk factors for cardiovascular and cerebrovascular events in patients with type 2 diabetes mellitus(T2DM).Bone turnover biomarkers(BTMs)are associated with vascular calcification,atherosclerosis,glucose,and lipid metabolism.AIM To investigate the association of circulating BTM levels with severe intracranial and extracranial artery stenosis in patients with T2DM.METHODS For this cross-sectional study including 257 T2DM patients,levels of the BTMs serum osteocalcin(OC),C-terminal cross-linked telopeptide of type I collagen(CTX),and procollagen type I N-peptide were measured by electrical chemiluminescent immunoassay,and artery stenosis was assessed by color Doppler and transcranial Doppler.Patients were grouped according to the existence and location(intracranial vs.extracranial)of artery stenosis.Correlations between BTM levels,previous stroke,stenosis location,and glucose and lipid metabolism were analyzed.RESULTS T2DM patients with severe artery stenosis had a higher frequency of previous stroke and levels of all three tested BTMs(all P<0.05)than patients without.Some differences in OC and CTX levels were observed according to the location of artery stenosis.Significant associations were also observed between BTM levels and some glucose and lipid homeostasis parameters.On multivariate logistic regression analysis,all BTMs were significant predictors of artery stenosis in T2DM patients with and without adjustment for confounding factors(all P<0.001),and receiver operating characteristic curve analysis demonstrated the ability of BTM levels to predict artery stenosis in T2DM patients.CONCLUSION BTM levels were found to be independent risk factors for severe intracranial and extracranial artery stenosis and were differentially associated with glucose and lipid metabolism in patients with T2DM.Therefore,BTMs may be promising biomarkers and potential therapeutic targets for artery stenosis.

Bone markers predict survival in castration-resistant prostate cancer patients treated with docetaxel

AIM: To investigate the relationship between clinicopathological features and bone turnover markers in castration-resistant prostate cancer(CRPC) patients treated with docetaxel.METHODS: Thirty-three patients were enrolled in this study. Serum levels of carboxyterminal cross-linked telopeptide of type 1 collagen generated by metalloproteinases(1CTP) and alkaline phosphatase(ALP) were measured at the start of docetaxel chemotherapy. We examined the relationship between clinicopathological features and serum levels of 1CTP and ALP levels in CRPC patients treated with docetaxel.RESULTS: For the total patient group, the mean ± standard deviation(SD) values for docetaxel chemotherapy dose, dose intensity, dosage interval, and num-ber of cycles were 59.3 ± 10.6 mg/m2, 13.9 ± 5.2 mg/m2 per week, 4.7 ± 1.2 wk, and 11.2 ± 7.4, respectively. Fourteen patients died from prostate cancer. Patients were divided into two groups according to mean + SD of serum 1CTP(8.2 ng/m L) and ALP(538.2 IU/L) levels at the start of docetaxel chemotherapy. Patients with lower levels of serum 1CTP and ALP had significantly better survivals than those with higher serum levels(P < 0.05).CONCLUSION: Serum levels of 1CTP and ALP are predictors of survival in patients with CRPC who are treated with docetaxel.

Mechanisms of treatment of cancer pain with a topical Chinese herbal formula in rats

Background Pain has a substantial impact on patients＇ activities and overall quality of life, but current conventional drugs have debilitating side effects, including gastrointestinal disorders. Thus there is a pressing need for new therapies with fewer side effects to alleviate cancer pain. We recently developed a topical herbal formula Xiaotan Tongluo analgesic gel （X＇I-IL gel） based on the principles of traditional Chinese herbalism, and we have received positive feedback from bone cancer pain patients. The aim of this study was to determine the analgesic effects and explore the mechanisms of XTI-L gel in a rat model of bone cancer pain. Methods The rat model of bone cancer pain was established by inoculating Walker-256 rat carcinoma cells directly into the right tibial medullary cavity of Wistar rats. The rats were randomly assigned to three groups （n=-10 per group）： （1） sham bone cancer control （sham group）： vehicle （PBS） inoculation without carcinoma cells plus topical administration of blank gel; （2） Sham treatment control （vehicle group）： Walker-256 cell inoculation plus topical administration of blank gel; （3） XTTL gel treatment （treatment group）： Walker-256 cell inoculation plus topical administration of XTTL gel. XTTL gel treatments were applied daily for 7 days starting on day 14 following inoculation. Outcomes were assessed 21 days after inoculation by mechanical allodynia, histological staining, and by measuring concentrations of type I collagen carboxy-terminal telopeptide （ICTP） and bone-specific alkaline phosphatase （BAP） in serum. Results Fourteen days after cancer cell incubation, significant mechanical allodynia in the ipsilateral hind paw and tumor growth in proximal end of the tibia were observed in the vehicle and treatment groups but not in the sham group. At day 21, mechanical withdrawal thresholds in treatment group rats were significantly higher （（4.8557±0.8336） g） compared with those of the vehicle group （（1.8630±1.4369） g, P 〈0.05）. ICTP and BAP levels increased significantly in vehicle group rats （（101.5176±11.0694） U/L and （370.7838±12.8273） U/L, respectively） compared with those of the sham group （（11.7553±1.1885） U/L and （185.7338±3.6761） U/L, respectively; P 〈0.05）. XTTL gel decreased the level of blood serum ICTP （（41.8998±6.4970） U/L, P 〈0.05） but had little effect on blood serum BAP （（365.5338±18.5361） U/L, P 〉0.05）. Conclusion Topical use of XTTL gel may have an analgesic effect on bone cancer pain, an effect mediated by lowering of ICTP levels and inhibiting bone resorption. Chin Med J 2009; 122（17）：2027-2031