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Abstract. Vitamin K belongs to the family of fat-soluble vitamins and plays an important role in hemostasis, bone metabolism and may affect cerebral sphingolipid synthesis. It is a cofactor necessary for posttranslational γ-carboxylation of glutamyl residues in selected proteins such as the osteocalcin, and procoagulation factors II, VII, IX, X. Vitamin K deficient individuals appear to have more undercarboxylated proteins, which are functionally defective. The witamin K deficiency has been frequently documented in patients with cystic fibrosis. The main possible causes of this deficiency include: fat malabsorption due to pancreatic exocrine insufficiency, cholestatic or noncholestatic liver disease, reduced production of vitamin K by colonic flora related to chronic antibiotic treatments, bowel resections and increased mucous accumulation in the bowel. CF patients are more prone to osteopenia, caused by chronic vitamin K shortage, than to coagulopathy. Despite available evidence, which strongly suggests that all CF patients are at risk for developing vitamin K deficiency, its supplementation doses have not been established. Recent recom- mendations from Europe and the UK have suggested varied doses ranging from 0.3 mg/day to 10 mg/week. Further studies, both cross sectional and longitudinal interventional, are still required to determine routine and therapeutic supplementation doses.
Osteocalcin is synthesized by osteoblasts and incorporated into bone matrix. During bone resorption by osteoclasts, osteocalcin is released from bone matrix. Plasma osteocalcin level may be used as a bone turnover marker. The aim of the study was to assess a relationship between osteocalcin level in blood and forearm bone mineral density in women. Significant negative correlation between osteocalcin concentration and bone mineral density of forearm mid distal region was found.
The study was conducted on 40 women in the early postmenopausal period, aged 52.3±3.1 years with primary osteoporosis unmanageable in treatment, divided into 2 groups based on a randomized list. Group I (n-20) was administered orally fluoride 0.25 mg kg-1 24 h-1 with modified transdermal hormone therapy/HRT, and group II (n-20) was administered orally fluoride and supplement hormonal therapy(HST) in 21 therapeutic cycle. The serum concentrations of osteocalcin (OC), procollagen(PICP), insulin-like growth factor I (IGF-1), prolactin basic (PRL) and prolactin after metoclopramide (PRL/ MCP) 4 times by using radioimmunoassy methods, before treatment and after 1, 3, 12 months of treatment. Bone mineral density (BMD) L2 – L4 was determined before treatment and at 12 month with a dualenergy x-ray absorptiometry scanner (Lunar DPX-1Q). In group I women receiving fluoride and transdermal HRT IGF-1 increased significantly while the concentrations of OC and PICP significantly decreased after 3 and 12 months of treatment but no statistically significant changes in the PRL concentration occurred. In group II women receiving orally fluoride and HST, a significant decrease in the concentration of IGF-1, OC after 3 and 12 months and a significant increase in the concentration of PRL and PRL/ MCP after 1, 3 and 12 months of treatment compared with the baseline values appeared. The concentration of type I procolagen (PICP) showed no statistically significant changes. Increase in bone mineral density was statistically significant L1, L2 (p < 0.05), L3, L4 (p < 0.01) compared with the baseline in the group receiving transdermal HRT. In women receiving fluoride and orally HST increase in the bone mineral density for L1 and L2 was non-insignificant, whereas for L3 and L4 it was significantly higher compared with the baseline (p < 0.05).
Bone displays suppressed osteogenesis in inflammatory diseases such as sepsis and rheumatoid arthritis. However, the underlying mechanisms have not yet been clearly explained. To identify the gene expression patterns in the bone, we performed Affymetrix Mouse Genome 430 2.0 Array with RNA isolated from mouse femurs 4 h after lipopolysaccharide (LPS) administration. The gene expressions were confirmed with real-time PCR. The serum concentration of the N-terminal propeptide of type I collagen (PINP), a bone-formation marker, was determined using ELISA. A total of 1003 transcripts were upregulated and 159 transcripts were downregulated (more than twofold upregulation or downregulation). Increased expression levels of the inflammation-related genes interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) were confirmed from in the period 4 h to 72 h after LPS administration using real-time PCR. Gene ontogene analysis found four bone-related categories involved in four biological processes: system development, osteoclast differentiation, ossification and bone development. These processes involved 25 upregulated genes. In the KEGG database, we further analyzed the transforming growth factor β (TGF-β) pathway, which is strongly related to osteogenesis. The upregulated bone morphogenetic protein 2 (BMP2) and downregulated inhibitor of DNA binding 4 (Id4) expressions were further confirmed by real-time PCR after LPS stimulation. The osteoblast function was determined through examination of the expression levels of core binding factor 1 (Cbfa1) and osteocalcin (OC) in bone tissues and serum PINP from 4 h to 72 h after LPS administration. The expressions of OC and Cbfa1 decreased 6 h after administration (p < 0.05). Significantly suppressed PINP levels were observed in the later stage (from 8 h to 72 h, p < 0.05) but not in the early stage (4 h or 6 h, p > 0.05) of LPS stimulation. The results of this study suggest that LPS induces elevated expressions of skeletal system development- and osteoclast differentiation-related genes and inflammation genes at an early stage in the bone. The perturbed functions of these two groups of genes may lead to a faint change in osteogenesis at an early stage of LPS stimulation. Suppressed bone formation was found at later stages in response to LPS stimulation.
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