The issues of the pathogenesis of postmenopausal osteoporosis

In examining the theory of the development of postmenopausal osteoporosis (PO) should be clear ambiguity and the capacity of this concept.

Software is currently being considered as a variety of metabolic osteopathy, developing on the background of cessation of ovarian-menstrual cycle naturally or after surgery and is characterized by reduced bone mass, a violation of their mikroarhitektoniki with a consequent increase in fragility and risk of fractures of bones [6].

Histomorphological features of software include the following mechanisms:

∙ Rapid loss of integrity of the spongy substance in connection with increased activity of osteoclasts that are morphologically manifested destruction preexisting bone substance;

∙ slow thinning of the cortical layer and a decrease in cancellous bone mass due to decreased activity of osteoblasts.

Studied the mechanisms of bone loss in software include:

∙ excessive bone resorption;

∙ reduction of remodeling due to inhibition of osteoblast function.

Discussed at the present time the hypothesis of the pathogenesis of postmenopausal osteoporosis based on the following pathogenetic mechanisms:

∙ Reduce interstinalnoy calcium absorption, leading to activation of the parathyroid glands and increased bone resorption.

∙ deficiency of secretion of calcitonin, which stimulates the synthesis of calcitriol in the kidney and, consequently, reduced calcium absorption.

∙ eating habits, leading to insufficient intake of Ca and P (deficiency in the diet, excessive consumption of drinks vysokogazirovannyh, etc.);

∙ gipoestrogenemiya [1.11].

The existing hypotheses on the effect of estrogens in bone remodeling software are subject to constant revision. The hypothesis proposed by Eriksen et al., The leading role of estrogen deficiency in the genesis of accelerated osteoporosis in postmenopausal women are currently reviewed. Gipoestrogenemiya may cause a greater severity of osteoporosis in women compared with men, but can not be a leading factor in the development of software [10].

But we can not ignore the numerous facts confirming the effect of estrogen on bone. Based on these consider the following mechanisms of action of estrogens:

∙ direct local effect on osteoblasts and osteoclasts;

∙ Local indirect effect mediated by bone monocytes, macrophages, and emissions of cytokines and growth factors;

∙ a system of indirect action, mediated by calcitonin.

In the appointment of estrogen, a decrease in the number of points of bone resorption, the most pronounced in the cancellous bone [14].

It is possible that estrogen reduces the sensitivity to external stimuli of osteoclast bone resorption, for example, by reducing the sensitivity of parathyroid hormone and receptor number of osteoclasts to PTH [14] and possibly to 1,25 - (OH) D ₃ [11]. As shown in Anderson, osteoclasts contain highly specific receptors for estrogen, but it is unclear what effect estrogen is mediated by these receptors [2]. It is established that estrogens block the lysosomal activity of osteoclasts man. Showed the presence of estrogen receptors in internatsinalizovannyh osteoclasts at concentrations equal to or greater than the osteoblasts [10]. In ═ vitro 17b-estradiol acts directly on osteoblasts, increasing the level of mRNA expression a1-chain of procollagen I tipaS [9]. Despite the existence of receptors for estradiol in osteoblast surface, as shown by experiments in vitro and in vivo (animal and human), the introduction of estradiol does not stimulate the proliferation of these cells [10].

Substantial doubt about the significance of the contribution subject to the direct action of estrogens. It is shown that the total number of estrogen receptors of osteoclasts and osteoblasts is significantly lower compared to other estrogen-dependent tissues. This suggests a significant influence of other mechanisms of action of estrogens [1].

Among the indirect local factors have the most significant influence cytokines. It is shown that bone monocytes and macrophages release IL-1 and tumor necrosis factor, which increases the stimulatory effect on osteoblast maturation of osteoclasts from bone marrow progenitor cells [10]. In addition, these same cytokines stimulate the release of IL-6, M-CSF, GM-CSF, also responsible for the maturation of osteoclasts. Under the action of estrogen production of IL-6 is blocked in osteoclasts, bone marrow and stromal cells. Blood monocytes, releasing increased amounts of IL-6 in postmenopausal women, estrogen therapy inhibited by appointment or progesterone [11]. In response to estrogen by osteoblasts may release transforming growth factor (TGF)-b, which is an inhibitor of osteoclasts [3].

Systemic indirect effect of estrogen may be mediated by calcitonin. In in vitro experiments showed that 17b-estradiol is able to stimulate the thyroid C-cells, increasing the release of calcitonin. Perhaps this explains the observed effect of calcitonin in some studies with reduced calcitonin menopause [2]. The greatest recognition in explaining the mechanisms of postmenopausal osteoporosis hypothesis on greater exposure to bone resorption under the influence of PTH in the absence of estradiol. So, it was shown that with age, PTH content increases, especially in postmenopausal women [2,7].

The study of the mechanism of action of estrogen on bone require further study, however, shown that they inhibit the action of stimulants of bone resorption such as parathyroid hormone [7,9].

In addition to indirect mechanisms of action through gipoestrogenemii calcitonin, parathyroid hormone, 1,25 - (OH) D ₃ hypothesized direct effects of estrogen on bone via estrogen receptors of osteoblasts [11].

Numerous studies have shown prophylactic and therapeutic effects of estrogen and increase bone mineral saturation (IOCs) under their influence. At present it is generally accepted that the effect of estrogen on bone is dose-dependent manner and shows decreased bone resorption without stimulating bone formation. Isolated appointment of estrogen does not lead to the restoration of MNCs, and only slows down the rate of decline [14].

Reviewed the role of progesterone and testosterone in the development of software. It is shown that when there is insufficient secretion of progesterone, due to anovulation, luteal phase deficiency, amenorrhea may also develop osteoporosis [7]. Testosterone, an anabolic steroid as an active, plays a similar role. Thus, when a bilateral oophorectomy at any age rapidly develop osteoporosis, and this plays an important role of sex steroid deficiency - estrogen, progesterone and testosterone [1].

During the normal ovulatory cycle processes of bone turnover occur depending on the level of sex hormones in the different phases of the cycle. In the days of menstruation and the early phase of proliferation against low level of sex hormones in bone resorption processes predominate. In the middle of the second phase of the cycle, marking the peak of secretion of progesterone and estrogen second peak, dominated by the process of building bone.

Perhaps the violation of such processes is the basis for reduction of MNCs in women with impaired ovarian-menstrual cycle [2]. Progestins exert a protective effect on bone tissue as follows:

∙ directly - through specific receptors stimulate osteoblast kosteoobrazovanie

∙ indirectly - by blocking the receptors for glucocorticoids, and reducing their inhibitory effect on bone [1,7].

Value the importance of features of eating disorders and other risk factors for software requires a detailed study, but found that even a quantitative and / or qualitative features of the diet may lead to the development of software or to prevent it. Thus, a comparative study of MNC by X-ray absorptiometry and dvuhenergticheskoy calcium, phosphorus and magnesium in the diet for 3 days, 70 women and 124 healthy software postmenopausal woman cooks a duration of 5-7 years. None of the surveyed have not taken drugs and hormone replacement therapy did not receive prophylactic treatment. It is shown that in patients for consumption of these minerals was significantly lower even in comparison with the norms for healthy women of reproductive age. In both groups, intake of these minerals positively correlated with LSM [5].

Recently, the dependence of bone mineral density on body weight, or more precisely, the mass of adipose tissue (body fat mass) [2,4,12,13]. In 43 postmenopausal healthy women were conducted the following studies: oral glucose tolerance test, determination of body fat mass and bone density in relation to height (which can provide results regardless of body size) by dual-energy x-ray absorptiometry, and volyumometriya third lumbar vertebra. It was shown that circulating levels of insulin is positively correlated (r = 0.28-0.52) with the ratio of LSM / height and density of L _III, as well as with body fat mass (r = 0.38-0.56). The method of multiple regression analysis on the assumption that the body fat mass and insulin levels - independent variables, it is shown that the ratio of LSM / LSM growth in the determination of trochanteric correlated with body fat mass, and the determination of femoral neck - the level of insulin. Volumetric density of the L _III correlated only with insulin levels. The authors conclude that the severity of osteoporosis in postmenopausal women may also affect the status of carbohydrate metabolism [8.13].

Previously it was assumed the role of interleukin-6 in the development of software is not supported by recent studies. Thus, in a comparative study of Serum IL-6 and MNCs in 45 healthy women aged 25 to 74 years age was identified changes in the level of IL-6, however, a correlation between the MNC and IL-6, despite the fact that showed a significant increase in its levels with the onset of menopause [14].

Concluding the description of the existing hypotheses on the pathogenesis of now software, we should mention about the only literary communication, linking higher incidence of hip fractures in postmenopausal women not to the properties of bone and other skeletal structures. Thus, the study Burnett was installed a different distribution of receptors for estrogen and progestogen in the tissues of the round ligament of the hip among pre-and postmenopausal women. Thus, in postmenopausal women are virtually absent estrogen receptors and a small amount of progesterone receptors are found. In premenopausal observed an inverse relationship between steroid hormone receptors, and the absolute number of receptors is much higher. It is possible that changes in the mechanical properties of the round ligament leads to increased mobility of the femoral head, which, under certain conditions leads to a turning point in the most "weak" spot - the femoral neck [6].

According to the recommendations of the Russian Association of Osteoporosis (2005), the National Federation of the United States of osteoporosis (NOF, 2007) the first-line drug for the prevention and treatment is alendronate sodium. In clinical practice in the Republic of Belarus is widely used alendronate sodium - "Osteotab" manufacturing Pharmaceutical Company ╚Pharmacare Int. Co. ╩, Which is available as tablets of 10 mg and 70 mg. Published results of a prospective randomized clinical trials of Osteotaba in the treatment of software, which confirmed the efficacy of alendronate (Osteotab) at preferential rates increase in BMD of the proximal femur [15]. ═

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