This minireview briefly surveys the complexity of regulations governing the bone metabolism. The impact of clinical studies devoted to osteoporosis is briefly summarized and the emphasis is put on the significance of experimental mouse models based on an extensive use of genetically modified animals. Despite possible arising drawbacks, the studies in mice are of prime importance for expanding our knowledge on bone metabolism. With respect to human physiology and medicine, one should be always aware of possib le limitations as the experimental results may not be, or may be only to some extent, transposed to humans. If applicable to humans, results obtained in mice provide new clues for assessing un foreseen treatment strategies for patients. A recent publication representing in our opinion the important breakthrough in the field of bone metabolism in mice is commented in detail. It provides an evidence that skeleton is endocrine organ that affects energy metabolism and osteocalcin, a protein specifically synthesized and secreted by osteoblasts, is a hormone involved. If confirmed by other groups and applicable to humans, this study provides the awaited connection of long duration between bone disorders on one hand and obesity and diabetes on the other., O. Raška, K. Bernášková, I. Raška Jr., and Obsahuje seznam literatury
The aim of the study was to compare the bone mineral density (BMD) and body composition between ambulatory male MS patients and control subjects and to evaluate the relationships among body composition, motor disability, glucocorticoids (GC) use, and bone health. Body composition and BMD were measured by dual-energy X-ray absorptiometry in 104 ambulatory men with MS (mean age: 45.2 years) chronically treated with low-dose GC and in 54 healthy age-matched men. Compared to age-matched controls, MS patients had a significantly lower total body bone mineral content (TBBMC) and BMD at all measured sites except for the radius. Sixty five male MS patients (62.5 %) met the criteria for osteopenia and twenty six of them (25 %) for osteoporosis. The multivariate analysis showed a consistent dependence of bone measures (except whole body BMD) on BMI. The total leg lean mass % was as an independent predictor of TBBMC. The Expanded Disability Status Scale (EDSS), cumulative GC dose and age were independent determinants for BMD of the proximal femur. We conclude that decreasing mobility in male MS patients is associated with an increasing degree of osteoporosis and muscle wasting in the lower extremities. The chronic low-dose GC treatment further contributes to bone loss., V. Zikán ... [et al.]., and Obsahuje seznam literatury
The peak bone mass and the rate of bone loss are in part genetically determined. It has been suggested that bone mineral density (BMD) may be related to allelic variation in the apolipoprotein E (ApoE) gene locus. ApoE is important in the receptor-mediated clearance of chylomicron particles from the plasma, Apo E4 having the highest and Apo E2 the lowest receptor affinity. Chylomicrons are the main carrier of vitamin K in the plasma; vitamin K plays an important role in the carboxylation of osteocalcin. We have tested the hypothesis that persons with E4 variant would have lower BMD and increased bone turnover than those with E2 variant. A total of 18 ApoE 2/2 and ApoE 4/4 homozygotes were selected from 873 patients who were examined for the ApoE genotype. BMD in lumbar vertebral, femoral neck and distal forearm was measured and plasma concentrations of osteocalcin and C-terminal fragments of collagen (CTx) were determined. BMD values (expressed as T-score) at the three specified sites were -0.12± 1.72, -0.52± 1.32 and -0.52± 0.81 in ApoE 2/2 group and -0.24± 1.22, 0.00± 0.84 and -0.17± 1.07 in the ApoE 4/4 group. Plasma osteocalcin and CTx were within normal limits in both groups. In conclusion, we did not observe any association of ApoE genotype with BMD and biochemical markers of bone metabolism in ApoE 2/2 and ApoE 4/4 homozygotes., T. Štulc, R. Češka, A. Hořínek, J. Štěpán., and Obsahuje bibliografii
Osteoporosis is a bone disease characterized by low bone mineral density (BMD) and impaired bone microarchitecture due to the abnormal activity of osteoclasts. Cathelicidins are antimicrobial peptides present in the lysosomes of macrophages and polymorphonuclear leukocytes. LL-37, a cathelicidin, induces various biological effects, including modulation of the immune system, angiogenesis, wound healing, cancer growth, as well as inflammation, and bone loss. A previous study reported direct involvement of LL-37 suppressing osteoclastogenesis in humans. Here, we examined the role of LL-37 in the treatment of osteoporosis using an ovariectomy (OVX) rat model. Our results showed that LL-37 significantly reduced bone loss and pathological injury in OVX rats with osteoporosis. Furthermore, we found that LL-37 significantly increased the activity of the Wnt/β-catenin pathway in OVX rats with osteoporosis, including the increased expression of β-catenin, Osterix (Osx), and Runt-related transcription factor 2 (Runx2), whereas XAV-939, an inhibitor of the Wnt/β-catenin pathway, significantly blocked the effects of LL-37 on bone loss and abnormal bone metabolism. Altogether, our findings suggested that LL-37 exerted a protective role in regulating bone loss and abnormal bone metabolism in rats with osteoporosis by activating the Wnt/β-catenin pathway.
After menopause, when estrogen levels decrease, there is room for the activity of anthropogenic substances with estrogenic properties - endocrine disruptors (EDs) - that can interfere with bone remodeling and changes in calcium-phosphate metabolism. Selected unconjugated EDs of the bisphenol group - BPA, BPS, BPF, BPAF, and the paraben family - methyl-, ethyl-, propyl-, butyl-, and benzyl-parabens - were measured by high performance liquid chromatography-tandem mass spectrometry in the plasma of 24 postmenopausal women. Parameters of calcium-phosphate metabolism and bone mineral density were assessed. Osteoporosis was classified in 14 women, and 10 women were put into the control group. The impact of EDs on calcium-phosphate metabolism was evaluated by multiple linear regressions. In women with osteoporosis, concentrations of BPA ranged from the lower limit of quantification (LLOQ) - 104 pg/ml and methyl paraben (MP) from LLOQ - 1120 pg/ml. The alternative bisphenols BPS, BPF and BPAF were all under the LLOQ. Except for MP, no further parabens were detected in the majority of samples. The multiple linear regression model found a positive association of BPA (β=0.07, p<0.05) on calcium (Ca) concentrations. Furthermore, MP (β=-0.232, p<0.05) was negatively associated with C-terminal telopeptide. These preliminary results suggest that these EDs may have effects on calcium-phosphate metabolism., J. Vitku, L. Kolatorova, L. Franekova, J. Blahos, M. Simkova, M. Duskova, T. Skodova, L. Starka., and Obsahuje bibliografii
Osteoporosis is a systemic disease of the skeleton, characterized by reduction of bone mass and concurrent deterioration of bone structure. Consequently, bones are more fragile, and there is increased risk of fractures. The potential for acquisition of maximum bone mass is influenced by a number of factors. Among those are heredity, sex, nutrition, endocrine factors, mechanical influences and some risk factors. The best documented nutrient for metabolism of bone is calcium. Major role in the pathogenesis of osteoporosis have some micro and macro nutrients, prebiotics, alcohol, alternative diets, starvation and anorexia. Meta analysis of 29 randomized trials showed that supplementation with calcium and vitamin D3 reduces risk of bone fractures by 24 % and significantly reduces loss of bone mass. Osteoporosis has multi factor etiology. Osteoporosis is one of diseases which are influenced by nutrition and life style. It is preventable by means of adequate nutrition and sufficient physical activity., M. Stránský, L. Ryšavá., and Obsahuje seznam literatury
Osteoporosis in chronic diseases is very frequent and pathogenetically varied. It complicates the course of the underlying disease by the occurrence of fractures, which aggravate the quality of life and increase the mortality of patients from the underlying disease. The secondary deterioration of bone quality in chronic diseases, such as diabetes of type 1 and type 2 and/or other endocrine and metabolic disorders, as well as inflammatory diseases, including rheumatoid arthritis - are mostly associated with structural changes to collagen, altered bone turnover, increased cortical porosity and damage to the trabecular and cortical microarchitecture. Mechanisms of development of osteoporosis in some inborn or acquired disorders are discussed., I. Zofkova, P. Nemcikova., and Obsahuje bibliografii
a1_Osteoporosis is a serious disease characterized by high morbidity and mortality due to atraumatic fractures. In the pathogenesis of osteoporosis, except environment and internal factors, such as hormonal imbalance and genetic background, are also in play. In this study candidate genes for osteoporosis were classified according to metabolic or hormonal pathways, which regulate bone mineral density and bone quality (estrogen,RANKL/RANK/OPG axis, mevalonate, the canonical circuit and genes regulating the vitamin D system). COL1A1 and/or COL1A2 genes, which encode formation of the procollagen 1 molecule, were also studied. Mutations in these genes are well-known causes of the inborn disease‘ osteogenesis imperfecta’. In addition to this, polymorphisms in COL1A1 and/or COL1A2 have been found to be associated with parameters of bone quality in adult subjects. The authors discuss the perspectives for the practical utilization of pharmacogenetics (identification of single candidate genes using PCR) and pharmacogenomics (using genome wide association studies (GWAS) to choose optimal treatment for osteoporosis). Potential predictors of antiresorptive therapy efficacy include the following well established genes: ER, FDPS, Cyp19A1, VDR, Col1A1, and Col1A2, as well as the gene for the canonical (Wnt) pathway. Unfortunately, the positive outcomes seen in most association studies have not been confirmed b y other researchers. The controversial results could be explained by the use of different methodological approaches in individual studies (different sample size, homogeneity of investigated groups, ethnic differences, or linkage disequilibrium between genes). The key pitfall of association studies is the low variability (7-10 %) of bone phenotypes associated with the investigated genes., a2_Nevertheless, the identification of new genes and the verification of their association with bone density and/or quality (using both PCR and GWAS), remain a great challenge in the optimal prevention and treatment of osteoporosis., I. Zofkova, P. Nemcikova, M. Kuklik., and Obsahuje bibliografii