The Relationship Between Plasma AOPP And Osteoporosis In Postmenopausal Women

BackgroundsOsteoporosis(OP) is the most common metabolic bone disorder, characterised by decreased bone mass and altered bone micro-architecture, leading to excessive skeletal fragility. Osteoporosis is the most prevalent metabolic bone disease and a major clinical and public health problem. As the population gets older morbidity, mortality and financial cost attributed to osteoporosis are expected to rise. The disease may be classified as primary type 1, primary type 2, or secondary. The form of osteoporosis most common in women after menopause is referred to as primary type 1 or postmenopausal osteoporosis. Osteoporosis is a major public health threat which afflicts 55% of Americans aged 50 and above. Of these, approximately 80% are women. Therefore, managing on postmenopausal osteoporosis admits no delay.The most popular method of measuring BMD is dual energy x-ray absorptiometry (DEXA) which is considered the gold standard for the diagnosis of osteoporosis. Osteoporosis is diagnosed when the bone mineral density is less than or equal to 2.5 standard deviations below that of a young adult reference population. This is translated as a T-score. The World Health Organization has established the following diagnostic guidelines:T-score -1.0 or greater is "normal"; T-score between -1.0 and -2.5 is "low bone mass" (or "osteopenia"); T-score -2.5 or below is osteoporosis. Measurements of spine bone mineral density(BMD) is widely used in clinical. Free oxygen radicals or reactive oxygen species (ROS) include hydroxyl radicals (OH-), superoxide anion radical (O2-), hydrogen peroxide (H2O2) and lead to the specific oxidation of some enzymes, protein oxidation and degradation. Their effects are eliminated by enzymatic antioxidant mechanisms such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase. Oxidative stress is an imbalance between the free radicals and antioxidant mechanism in biological systems. Abnormally high levels of oxidants and/or low levels or activity of antioxidants can specifically impair the balance. i.e., Lipid peroxidation caused by attacking on polyunsaturated fatty acid can impair the biofilm's structure and function and cell surface receptors; to damage amina and thiol. of proteins induce protein denatuation,crosslinking and loss of enzyme activity; damaging DNA strand breaks and mutations.Free radicals can cause protein aggregation and cross-linked peptide strand breaks, the formation of protein and lipid-bound polymers induce the protein the loss of function. Free radicals attack on amino acid side-chain protein molecules, such as lysine, arginine, proline, threonine, can produce the corresponding protein carbonyl derivatives induced decrease of protein sulfhydryl levels in vivo. protein oxidized by hypochlorous acid (HOCl) in macrophage and oxidized glycosylated protein can produce advanced oxidation protein products (AOPP) and advanced glycation end products (AGE) which can be used as protein marker of oxidative damage. Unsaturated fatty acids attacked by free redicals on biofilm which induces cell deformability decreased and brittleness increased that affecting the ion channel function, increasing membrane permeability. Lipid peroxidation can also add new free radicals and lead to advanced lipid oxidation products such as malondialdehyde (malondialchehyche MDA),4-hydroxy-nonnenal, oxidized low-density lipoprotein (oxidized low density lipoprotein ox-LDL) and iso-prostaglandin. Free radicals can also be related to the base which impairs the DNA strand. i.e.,8-oxo-guanine oxidized by guanine, under the action of the repair enzymes to 8 hydroxy-deoxyguanosine form of excision. Oxygen free radicals can make the collagen fibers of collagen cross-linked, hyaluronic degradated and extracellular matrix demolish.Oxidative stress occurs when the levels of ROS are higher than the levels of antioxidants thus overwhelming the system. The negative role of free radicals is mainly due to its unpaired electrons in structure and it is highly reactive and able to quickly react with the surrounding, then its half-life is very short and difficult to measure. Therefore, oxidation products caused by cross-linked ROS and molecules (lipids, proteins, DNA) can be the markers of oxidative stress.Advanced oxidation protein products (AOPP) are proposed by Witko Sarsat in 1996, which are the dityrosinecontaining and cross-linking protein products. They are formed during oxidative stress by the reaction between proteins and chlorinated oxidants such as chloramines or hypochlorous acid (HOCl). Segmented neutrophils and monocytes can produce the respiratory burst in the appropriate stimulation, which can produce a large number of high activity reactive oxygen species (reactive oxygenspecies, ROS). Phagocytes generates chlorine dioxide under the effect of myeloperoxidase which can make hydrogen peroxide generated hypochlorite (one of the most lively chemical properties and toxic substances produced by phagocytic) in duration of ROS formation. Recently, increased levels of AOPP have been found in the patients with diabetes, uremia, coronary artery disease, chronic inflammatory bowel diseases, as well as obesity, implying that accumulation of AOPP may be relevant in a number of pathophysiologicconditions. AOPP as a new uremic toxins and inflammatory mediators can be used as a novel marker of oxidant-mediated protein damage.Malondialdehyde (MDA) is the principal and most studied product of polyunsaturated fatty acid peroxidation. The main source of MDA in biological samples is the peroxidation of polyunsaturated fatty acids with two or more methylene-interrupted double bonds. Excessive MDA with proteins, nucleic acids and other molecules to form lipofuscin deposition in the cell, and this is an important reason for the body cell senescence. At the same time, it can also react with phospholipid protein, changing cell membrane permeability, causing tissue damage. MDA is the products of lipid peroxidation, its content directly reflects the rate of lipid peroxidation. Therefore, it used as markers to determine the damage of free radicals, indirectly reflects the level of cell damage by free radicals.Objectives:We aimed to investigate plasma AOPPs and MDA levels in postmenopausal women with osteoporosis(OP) and in healthy controls; and to determine the relationship between AOPP, MDA and lumbar(L2-L4) BMD in this present study.Methods:49 postmenopausal women fulfilling OP diagnostic criteria of World Health Organization(WHO) and 39 postmenopausal healthy Women without OP were enrolled. Patients in the study population were selected among individuals that were not pre-diagnosed or pre-treated for OP. Patients with diseases known to be associated with increased oxidative stress, metabolic bone diseases, fracture history, which were smokers, alcohol users and taking antioxidant drug treatment, were excluded from the study. Dual Energy X-ray Absorptiometry(DEXA) results, body mass indices and demographic data were recorded. In order to investigate the presence of compression fractures,lumbar spine radiographs were performed. Plasma AOPP and malondialdehyde (MDA) levels were measured by spectrophotometer.Results:No differences in age and BMI were found between the two groups. The only notable exceptions which was discriminating for the attribution of the study subjects to either of the two groups, was the years since menopause. No compression deformities were encountered in the lumbar spine of all subjects. Plasma MDA(P<0.05) and AOPP(P<0.001) levels were significantly higher in patient group than those of in the control group. There was negative relationship between AOPP and BMD(r=-0.555, P<0.001) in all subjects but this phenomenon no exsists in patient group. There was no relationship between MDA and BMD.Conclusions AOPP may play an important role in postmenopausal osteoporosis and therefore it might be considered when pathogenesis of postmenopausal OP has been investigated.