Overweight/obesity and underweight are both risk factors for fractures at different sites. Fracture risk assessment may be improved if fracture sites are taken into account and BMI is categorized.

Purpose: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that has various roles in tumor development and progression. We previously reported that expression of MCP-1 is associated with macrophage infiltration and tumor vessel density in human gastric carcinomas. The present study was undertaken to obtain direct evidence that MCP-1 participates in recruitment of macrophages and induction of angiogenesis. Experimental Design:We did transfection experiments to analyze the role of MCP-1 in tumorigenicity and angiogenesis in gastric carcinoma in nude mice. The human MCP-1 gene cloned into the BCMGS-Neo expression vector was transfected into the human gastric carcinoma TMK-1 cell line. We examined tumor volumes with the ectopic s.c. xenograft model and tumorigenicity with the orthotopic gastric xenograft model. We determined intratumor microvessel counts and tumor-infiltrating macrophage counts by immunohistochemical staining. Results: There was no difference in in vitro proliferation between MCP-1-transfected TMK-1 cells and mock-transfected (control) cells; however, MCP-1 transfectants induced tumor growth in ectopic xenografts and increased tumorigenicity and induced lymph node metastases and ascites in orthotopic xenografts. In both ectopic and orthotopic xenograft models, strong infiltration of macrophages was observed within and around the tumors after implantation of MCP-1 transfectants whereas fewer macrophages were seen after inoculation of control cells. The microvessel density was significantly higher in tumors produced by MCP-1 transfectants than in control tumors. Conclusions: MCP-1 produced by gastric carcinoma cells may regulate angiogenesis via macrophage recruitment. MCP-1 may be a potential target for antiangiogenic therapy for gastric carcinoma.

Advanced glycation end products (AGE) in collagen have been reported to decrease the mechanical property of bone. However, there are no available data on the relation between fracture risk and levels of glycoxidative (nonenzymatic) cross-links of collagen in clinical samples. A total of 432 Japanese elderly women who were not receiving any drug treatment for osteoporosis were selected and followed for 5.2 +/- 3.3 (mean +/- SD) years for this observational study. Vertebral fractures and bone mineral density were assessed at baseline and then at 1- to 2-year intervals or at indication of any symptom. Two types of collagen metabolites were measured at baseline: urinary N-terminal telopeptide of type I collagen (NTX), a marker of pyridinium cross-link, and urinary pentosidine, a nonenzymatic collagen cross-link produced by AGEs. A total of 97 incident vertebral fractures on 72 subjects were observed. Simple regression analysis using Cox's hazards model showed that log-transformed urinary NTX and pentosidine are significant risk factors for time-dependent incidence of vertebral fractures, in addition to the traditional risk factors (age, lumbar bone mineral density, and number of prevalent vertebral fractures). However, urinary excretion of pentosidine (hazard ratio, 1.33; 95% CI, 1.01-1.76, P = 0.04) was a significant predictor of incident vertebral fracture after adjustment for other traditional risk factors. The present data suggest that AGE-related collagen cross-link is a novel risk for vertebral fracture.

The spread of tumor cells to regional lymph nodes is an early event of gastric cancer metastasis. In our study, we assessed the expression of lymphangiogenic factors and lymphatic endothelial markers in gastric carcinoma tissues and compared expression levels with the status of lymph node metastasis. We also examined the correlation between lymphatic vessel density (LVD) in primary tumors and lymph node metastasis. Paired biopsy samples (tumor and corresponding normal mucosa) of gastric tissue were obtained from 39 patients with gastric carcinoma. The expression of VEGF-C, VEGF-D, VEGFR-3 and podoplanin mRNAs was assessed by real-time quantitative PCR. The expression of VEGF-C (but not of VEGF-D) was significantly greater in patients with lymph node metastasis than in those without metastasis. The expression of lymphatic endothelial markers VEGFR-3 and podoplanin was also significantly greater in the node-positive group. LVD, as assessed by immunohistochemistry for podoplanin, was correlated with lymph node metastasis. These results indicate that quantitative analysis of lymphangiogenic markers in gastric biopsy specimens may be useful in predicting metastasis of gastric cancer to regional lymph nodes. ' 2005 Wiley-Liss, Inc.

Once-weekly preventive administration of hPTH(1-34) increased the total contents of immature and mature enzymatic cross-links, which contributed significantly to vertebral cancellous bone strength.