Healthy Postmenopausal Subjects Research Articles

Expression of circulating Mir-139-5p is associated with Postmenopausal Osteoporosis in Indian women

Background: Osteoporosis in post-menopausal women is known to progress periodically and is highly associated with inflammation. MicroRNAs regulate inflammatory process, which may therefore control bone metabolism. Deregulation of miRNAs associated with inflammation may lead to development and progression of osteoporosis. We selected four miRNAs known to be involved in inflammation to test their association with post-menopausal osteoporosis. Methods: We quantified four circulating miRNAs, hsa-miR-139-5p, hsa-miR-342-3p, hsa-miR-146a and hsa-miR-24-3p in plasma samples of 25 post-menopausal osteoporosis and 25 post-menopausal healthy subjects. Related biochemical tests were done using Cobas e411 and ELISA. Results: Upon quantification of circulating miRNAs, we observed that hsa-miR-139-5p was expressed higher in post-menopausal osteoporotic samples (p=0.01). The expression of hsa-miR-24-3p was seen lower in osteoporotic samples though not highly significant (p=0.2). Conclusion: Differential expression of hsa-miR-139-5p and hsa-miR-24-3p was seen in osteoporosis subjects. These miRNA could be significantly involved in development and progression of osteoporosis. Further studies are required to highlight miRNAs’ involvement in regulating bone metabolism, which could be manipulated to use them as marker or therapeutic strategies to alleviate osteoporosis.

Circulating levels of omentin-1 in patients with breast cancer

Aims of the Study : It seems adipocytokines play an important role in association between obesity and breast cancer. Omentin-1 is a novel discovered plasma adipocytokine produced mainly in visceral adipose tissue. The aim of present study was to estimate. Circulating levels of omentin-1 in postmenopausal breast cancer patients as compare to healthy postmenopausal subjects . Materials and Methods: This study consisted of 30 postmenopausal women with newly diagnosed breast cancer and 30 healthy postmenopausal subjects aged 45 to 70 years. Serum levels of omentin-1 were measured by enzyme-linked immunosorbent assay. Results: The mean age of the case group was 54.0±8.3 years, and the control group was 50.3±3.2 years. The mean serum levels of omentin-1 in the case group were 73.0±29.7 ng/mL and in the control group were 108.9±65.4 ng/mL. The mean serum omentin-1 levels were found to be significantly lower in breast cancer patients (P=0.009). We also demonstrated the negative correlation of Omentin-1 with BMI in both groups (p=0.005), however we did not find any association between age and serum omentin-1 levels (P=NS) Conclusion : Our studied showed that Omentin-1 level was significantly reduced in the breast cancer patients as compare to healthy controls. Decreased omentin-1 levels may contribute to the development of cancer, however determination of its role and mechanisms needs more investigations. To sum up, our data suggest that omentin-1 can be used as a marker for early detection of breast cancer in postmenopausal women.

Circulating levels of omentin-1 in patients with breast cancer

Background: It seems adipocytokines play an important role in breast cancer. Omentin-1 is a novel discovered plasma adipocytokine produced mainly in visceral adipose tissue. The aim of present study was to estimate. Circulating levels of omentin-1 in postmenopausal breast cancer patients as compare to healthy postmenopausal subjects. Materials and Methods: This study consisted of 30 postmenopausal women with newly diagnosed breast cancer and 30 healthy postmenopausal subjects aged 45 to 70 years. Serum levels of omentin-1 were measured by enzyme-linked immunosorbent assay. Results: The mean age of the case group was 54.3±8.3 years, and the control group was 50.3±3.2 years. The mean serum levels of omentin-1 in the case group were 73.1±29.7 ng/mL and in the control group were 108.8±65.4 ng/mL. The mean serum omentin-1 levels were found to be significantly lower in breast cancer patients (P=0.009). We also demonstrated the negative correlation of Omentin-1 with BMI in both groups (p=0.005), however, we did not find any association between age and serum omentin-1 levels (P=NS). Conclusion: Our studied showed that Omentin-1 level was significantly reduced in the breast cancer patients as compare to healthy controls. Decreased omentin-1 levels may contribute to the development of cancer, however determination of its role and mechanisms needs more investigations. To sum up, our data suggest that omentin-1 can be used as a marker for early detection of breast cancer in postmenopausal women. K e y w o r ds: Breast cancer, omentin, serum

Consumption of onion juice modulates oxidative stress and attenuates the risk of bone disorders in middle-aged and post-menopausal healthy subjects.

Osteoporosis is a chronic inflammatory condition that is characterized by the loss of bone mineral density (BMD). The current study was undertaken to evaluate the impact of onion juice intake on the bone mineral density (BMD) and bone loss in corroboration with antioxidant effects in human (in vivo) as well as inhibitory effects on the differentiation of osteoclasts in the cell line (in vitro). For in vitro studies, the RAW 264.7 (osteoclast progenitor) cells were used to examine the anti-osteoclastogenic effect of onion. In the case of in vivo studies, twenty-four subjects were divided into two groups and advised to intake 100 mL of onion juice or placebo for 8 weeks. Anthropometric measurements and blood samples were collected at the initial, 2(nd), 6(th), 8(th) and 10(th) week. The result of in vitro studies indicated that onion extract would effectively inhibit the osteoclastogenesis and its differentiation. Significant changes in the levels of alkaline phosphatase (ALP), free radicals, total antioxidant capacity (TEAC) and various antioxidants were observed in onion administered subjects. The BMD of three postmenopausal women was also found to be mildly improved on supplementation with onion juice. Onion juice consumption showed a positive modulatory effect on the bone loss and BMD by improving antioxidant activities and thus can be recommended for treating various bone-related disorders, especially osteoporosis.

SAT0460 Low Bone Mass in Patients with Systemic Sclerosis: Relationships with Dickkopf-1 Levels and 25-Hydroxyvitamin D Status

BackgroundPatients (pts) affected by systemic sclerosis (SSc) show increased risk of bone loss as a result of the chronic inflammatory state, physical inactivity, gut malabsorption or malnutrition, decrease activation of...

AB0362 B-Cell Activating Factor of the Tumor Necrosis Factor Family (BAFF) in Postmenopausal Rheumatoid Arthritis Patients with Low Bone Mass: A Possible Protective Role of Hydroxychloroquine

BackgroundThe increasing role of B-cells in the pathogenesis and management of RA, the common occurrence of postmenopausal osteoporosis with RA and the suggested responsibility of BAFF in autoantibodies production with...

Prospective evaluation of free radicals and antioxidant activity following 6-month risedronate treatment in patients with postmenopausal osteoporosis

In addition to the well-described implications of estrogen deficiency in postmenopausal osteoporosis (PMO), free radicals are also effective on bone metabolism. The antioxidant vitamins C and E play an important role in the production of collagen, mesenchymal cell differentiation into osteoblasts, and bone mineralization. Therefore, the incidence of osteoporosis and the risk of fractures were decreased with vitamin C and E. It was proposed that free oxygen radicals are responsible for biological aging, atherosclerosis, carcinogenesis, and osteoclastic activity via their negative effects on the cell and DNA. In this study, we aimed to investigate and compare the levels of free radicals and serum antioxidant activity in patients with PMO and healthy subjects before and after six-month treatment with risedronate, which is an inhibitor of bone resorption. Twenty-three postmenopausal patients aged between 52-83 (mean [± standard deviation] 67.6 ± 8.17) with T scores below -2.5 in femur neck or L1-L4, and 23 postmenopausal healthy subjects were enrolled into the study. Patients who had received any medications within the last 6 months that could alter bone metabolism were excluded. Serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were analyzed in both groups. The patients with PMO were commenced on 5 mg of risedronate, 1,200 mg of calcium, and 800 IU of vitamin D daily. The patients were reevaluated at the end of the sixth month. MDA and SOD levels were similar in patients with PMO when compared to the healthy group before the treatment, while the GPx levels were lower in patients with PMO (P = 0.014). GPx (P = 0.028) and MDA (P = 0.04) levels were increased in patients with PMO after the treatment. In contrast, SOD levels were decreased when compared to the initial levels (P = 0.006). There may be an insufficiency in different steps of the enzymatic antioxidant systems in patients with PMO without treatment. We observed an increment in lipid peroxidation levels and GPx levels with risedronate. We think that the decrement in SOD levels may be related with the utilized antioxidants due to the increased free radicals and the compensatory increment in the other steps of the antioxidant system.

Analysis of Skeletal Status by Quantitative Ultrasonometry in a Cohort of Postmenopausal Women with High Blood Cholesterol Without Documented Osteoporosis

Osteoporosis and atherosclerosis are leading causes of mortality and morbidity in the Western world. A link between osteoporosis and atherosclerosis was proposed by epidemiologic and laboratory data. In the present study, we investigated skeletal status in postmenopausal women with hypercholesterolemia using quantitative ultrasonometry (QUS). Six hundred healthy postmenopausal subjects were enrolled within a 2-mo period by primary care physicians. Information on lifestyle and calcium intake was collected for each enrolled subject. Subjects (n = 256) were divided into two groups according to lipid profile: normal (n = 180) with serum cholesterol <200 mg/dL and hypercholesterolemic (n = 76) with serum cholesterol ≥200 mg/dL. Hypercholesterolemic subjects were further stratified into two groups, one receiving dietary treatment (n = 34) and the other receiving statin treatment (n = 42). We found a statistically significant reduction in amplitude dependent speed of sound (AD-SoS) in hypercholesterolemic subjects compared with subjects with normal cholesterol ( p = 0.006). Calcium intake behaved similarly to AD-SoS ( p = 0.0001). No statistical significant difference in AD-SoS were observed between the group on diet treatment versus the group on statin ( p = 0.52). Calcium intake was lower in patients on statins treatment compared with subjects on diet treatment only ( p < 0.0001). Our data suggest that hypercholesterolemia per se is a risk factor for impaired skeletal status. Our data also call attention to the risk of a poor calcium intake in patient receiving diet to lower plasma cholesterol. Moreover, our data suggest that statins per se may exert a protective effect on bone independently from calcium intake. (E-mail: francedt@igea.it)

Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: A key mechanism in osteoporosis

Compelling evidences suggest that increased production of osteoclastogenic cytokines by activated T cells plays a relevant role in the bone loss induced by estrogen deficiency in the mouse. However, little information is available on the role of T cells in post-menopausal bone loss in humans. To investigate this issue we have assessed the production of cytokines involved in osteoclastogenesis (RANKL, TNFα and OPG), in vitro osteoclast (OC) formation in pre and post-menopausal women, the latter with or without osteoporosis. We evaluated also OC precursors in peripheral blood and the ability of peripheral blood mononuclear cells to produce TNFα in both basal and stimulated condition by flow cytometry in these subjects.Our data demonstrate that estrogen deficiency enhances the production of the pro-osteoclastogenetic cytokines TNFα and RANKL and increases the number of circulating OC precursors. Furthermore, we show that T cells and monocytes from women with osteoporosis exhibit a higher production of TNFα than those from the other two groups.Our findings suggest that estrogen deficiency stimulates OC formation both by increasing the production of TNFα and RANKL and increasing the number of OC precursors. Women with post-menopausal osteoporosis have a higher T cell activity than healthy post-menopausal subjects; T cells thus contribute to the bone loss induced by estrogen deficiency in humans as they do in the mouse.

Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women

Females are disproportionately affected by constipation, which is often aggravated during pregnancy. Bowel function also changes during the luteal phase of the menstrual cycle. The aim was to compare the effects of acute administration of female sex steroids on gastric emptying, small bowel transit and colonic transit in healthy postmenopausal subjects. A second aim was to determine whether withdrawal of the hormones was associated with a change in transit. Forty-nine postmenopausal females were randomized to receive for 7 days 400 mg day(-1) micronized progesterone, 0.2 mg day(-1) oestradiol, combination of the two, or placebo. Treatment groups were balanced on age. Participants underwent whole gut transit measurement by scintigraphy using a 99m-labeled technetium-egg meal and 111-labeled indium-charcoal via a delayed-release capsule. Transit measurement was repeated after withdrawal of the study medications. The primary endpoints were ascending colon (AC) emptying half-life time (t1/2) and colonic geometric centre (GC) at 24 h. Secondary analysis variables were GC at 4 and 48 h, gastric emptying t1/2 and colonic filling at 6 h. There was a significant overall effect of progesterone on colonic transit with shorter AC emptying t1/2 and significantly greater colonic GC at 48 h. No transit endpoints were altered by oestradiol or combined hormonal treatment relative to placebo. Oestradiol and progesterone resulted in looser stool consistency. Withdrawal of the hormone supplement was not associated with significant alteration in transit. Micronized progesterone does not retard colonic transit in postmenopausal females.

The effects of degree of hepatic or renal impairment on the pharmacokinetics of exemestane in postmenopausal women.

Two studies were conducted to compare the pharmacokinetics and tolerability of exemestane in postmenopausal subjects with various degrees of impairment of hepatic or renal function with those in healthy postmenopausal subjects. All subjects were postmenopausal females. In study 1, nine subjects had normal hepatic function (Child-Pugh grade A), and nine had moderately (grade B) and eight severely (grade C) impaired hepatic function. In study 2, six subjects had normal renal function, and six moderately (creatinine clearance, CrCL, 30-60 ml/min per 1.73 m(2)) and seven severely (CrCL <29 ml/min per 1.73 m(2)) impaired renal function. Each subject took a single oral dose of 25 mg exemestane. Samples of plasma (to 168 h after dosing) and urine (to 72 h in study 1, or 96 h in study 2) were taken for pharmacokinetic analysis. Safety and tolerability were assessed by monitoring vital signs, laboratory safety tests, ECG and adverse events. Exposure to exemestane was increased two- to threefold in patients with hepatic impairment. Thus, the geometric mean AUC(0- infinity ) values were 41.71 (90% CI 32.2 to 54.0), 99.02 (76.5 to 128.2) and 118.59 ng.h/ml (90.2 to 156.0) in healthy subjects, and in patients with moderate and severe hepatic impairment, respectively ( P<0.01). C(max) also increased twofold. Compared with healthy subjects, patients with hepatic impairment had lower apparent oral clearance and apparent volume of distribution of exemestane. Renal impairment was also associated with two- to threefold increases in AUC(0- infinity ): 34.64 (90% CI 23.9 to 50.2), 94.10 (64.9 to 136.4) and 65.52 ng.h/ml (46.5 to 92.4) in healthy subjects, and in patients with moderate and severe hepatic impairment, respectively ( P<0.05). C(max) did not change significantly. Apparent oral clearance was directly correlated with CrCL ( r(2)=0.43). Exemestane was tolerated well, with no safety concerns. Oral clearance of exemestane was reduced in the presence of significant hepatic or renal disease. However, in view of the relatively large safety margin and the mild nature of the side effects of exemestane, the therapeutic implications of these changes in pharmacokinetics are considered minor and of no clinical significance.

RELATIONSHIP OF BONE TURNOVER PARAMETERS, ENDOGENOUS HORMONES AND VIT D DEFICIENCY TO HIP FRACTURE IN ELDERLY POSTMENOPAUSAL WOMEN

SUMMARYHip fracture is one of the severest consequences of osteoporosis affecting elderly women, but abnormalities of bone turnover responsible for bone loss have not been clearly defined. This study evaluated the relationship of bone turnover parameters to hip fracture in postmenopausal elderly women. We also investigated the effects of endogenous hormones and vitamin D deficiency on osteoporotic hip fracture. The subjects were 21 osteoporotic patients with hip fracture (study group) and 20 healthy postmenopausal women (control group). We measured osteocalcin levels, total and bone alkaline phosphatase (T‐ALP and B‐ALP), calcitonin, intact parathyroid hormone (iPTH), serum 25 hydroxyvitamin D (25OHD), urinary free deoxypyridinoline (D‐pyr) and cross‐linked N‐telopeptides of type 1 collagen (NTx) levels. Serum T‐ALP and B‐ALP levels in the study group were lower than those of the control group. The mean serum 25OHD levels in the study group were not significantly different from the control group, but in five cases the mean serum iPTH level was increased. The mean urinary NTx levels were significantly increased in the study group compared with the control group (p&lt;0.05). There was no significant increase in urinary free D‐pyr between the two groups. There was significant correlation between serum T‐ALP levels and B‐ALP levels and between serum iPTH levels and B‐ALP levels. The mean serum SHBG level in the study group was higher than in the control group (p&lt;0.05). These data suggest that postmenopausal hip fracture patients have biochemical evidence of decreased bone formation and increased bone resorption compared with postmenopausal healthy subjects. We suggest these abnormalities play a role in the decrease of bone mass and the consequent increase in bone fragility that characterises osteoporotic hip fracture.

Discrimination ability of pyridinoline crosslinks related markers for bone resorption in postmenopause and osteoporosis.

We investigated the discrimination ability of pyridinolines crosslinks related bone resorption markers. Amino-terminal pyridinolines crosslinked telopeptides (NTx) and carboxy-terminal pyridinolines crosslinked telopeptides (ICTP), pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured in 62 premenopausal (PRE), 30 early postmenopausal healthy subjects (POST) and 24 vertebral osteoporosis patients (VX). NTx, Pyr and Dpyr was significantly higher in POST than in PRE. ICTP was not changed in POST compared with PRE. NTx, ICTP, Pyr and Dpyr were significantly higher in VX than in PRE and POST. To evaluate discriminatory ability of four markers, we calculated t-scores, and generated receiver operating characteristic (ROC) curves. In POST, NTx, Pyr and Dpyr had a moderate t-score, 1.8, 1.4 and 1.3, respectively. The ICTP t-score was only −0.2. In VX compared with POST, ICTP, Pyr and Dpyr had a high t-score, 5.9, 7.9 and 7.5, respectively, but t-score of NTx was moderate, 3.6. The areas under ROC curves for NTx, ICTP, Pyr and Dpyr in POST were 75.8%, 33.8%, 78.1% and 79.5%, respectively. In VX compared with POST, those for NTx, ICTP, Pyr and Dpyr were 94.0%, 86.0%, 97.4% and 95.1%, respectively. In conclusion, NTx performed well in early postmenopausal status, but did not in osteoporosis. ICTP did not have discrimination power in postmenopause but performed well in osteoporosis. Pyr, Dpyr performed moderately well in postmenopause and performed well in osteoporosis.

Distal radius: in vivo assessment with quantitative MR imaging, peripheral quantitative CT, and dual X-ray absorptiometry.

To evaluate in vivo the relationship between magnetic resonance (MR) imaging relaxation time and bone mineral density (BMD) at the distal radius. The 1/T2* MR imaging relaxation rates and dual X-ray absorptiometry (DXA) measurements were evaluated in the trabecular bone of the distal 5 cm of the radius in 14 healthy premenopausal women and 11 healthy postmenopausal women and in 11 women with osteoporosis. Trabecular and total BMD were measured with peripheral quantitative computed tomography (CT). In healthy women, 1/T2* values and trabecular BMD at peripheral quantitative CT were significantly correlated but 1/T2* and total BMD were not. Statistically significant (P = .03) correlations between 1/T2* and DXA were found only in the most distal area covered with DXA. The 1/T2* values were more closely correlated with age and showed higher relative annual decreases (0.47%-0.81%) than peripheral quantitative CT (0.20%-0.59%) or DXA (0.10%-0.39%). Pre- and postmenopausal healthy subjects could be distinguished only with MR imaging, and postmenopausal healthy and osteoporotic subjects only with CT and DXA. MR imaging relaxation rates correlate well with trabecular BMD in vivo.

Calcitonin and postmenopausal bone loss

In order to establish the role of calcitonin (CT) in postmenopausal bone loss, we studied CT metabolism in 25 pre- and postmenopausal women. Postmenopausal women presented a highly significant reduction of CT basal levels compared to premenopausal females ( p < 0.01). Also, production rates of CT in osteoporotics were significantly lower than in either young premenopausal (18–25 years old), older premenopausal (35–40 years old), or postmenopausal healthy subjects. In a study in rabbits, we found that injection of CT, along with equimolar amounts of anti-SCT antibodies extracted from serum of pagetic patients, did not inhibit the hypocalcemic response to the hormone, thus demonstrating that resistance to CT treatment cannot be accounted for by antibody production. In a subsequent clinical study in patients with Paget's disease of bone, we found that 200 IU/day of salmon CT (SCT), given by nasal spray, improved both clinically and biochemically the activity of the disease, as demonstrated by 37 ± 4% decrease of serum alkaline phosphatase and 35 ± 5% fall of urinary excretion of hydroxyproline after six months of therapy. The effectiveness of CT as nasal spray was further tested in healthy women at an early stage of menopause. A 12-month course of intranasal SCT counteracted early postmenopausal bone loss, presumably by inhibiting bone resorption. In conclusion, intranasal CT seems to be a very attractive alternative to be considered for the prevention of postmenopausal osteoporosis.

Decreased plasma calcitonin response to a calcium clamp in primary hyperparathyroidism.

In order preoperatively to evaluate the calcium induced plasma calcitonin (CT) response in patients with mild primary hyperparathyroidism (PHPT), 7 postmenopausal (PM) females with PHPT and 14 PM healthy subjects underwent a 2 h calcium infusion. The infusions were performed by means of the 'calcium clamp' technique previously described by us in order to obtain an identical calcium stimulus in all subjects. Immunoreactive calcitonin (iCT) was determined by means of a sensitive RIA utilizing rabbit antibodies directed against the carboxy-terminal amino acid sequence of the CT molecule. All patients with PHPT had normal basal plasma iCT levels: 10 +/- 5 pg-eq/ml (mean +/- SD) as a group and not different from the control group: 13 +/- 5 pg-eq/ml. In the control group significantly increased plasma iCT was seen at 30, 60, 90 and 120 min in contrast to that of the PHPT group where a blunted response was observed. The results indicate a diminished CT reserve in these patients which may imply an impaired defence against the PTH mediated bone resorption seen in patients with PHPT.

Serum Growth Hormone, Serum Immunoreactive Insulin and Blood Glucose Response to Intravenous Tolbutamide in Postmenopausal Women with and without Natural Oestrogen Therapy

Abstract The response of serum growth hormone, serum immunoreactive insulin and blood glucose to intravenously administered tolbutamide was studied in twenty non‐obese and four obese healthy volunteer postmenopausal women with or without oestrogen therapy. Fasting blood glucose and the maximal fall in blood glucose during the test (44 % and 45 %) was normal in the non‐obese control and oestrogen groups, and the two groups did not differ significantly from each other. Even the four obese women, two on oestrogen therapy and two without, showed a normal blood glucose response to tolbutamide. Moreover the response of serum immunoreactive insulin to tolbutamide was normal in subjects both with and without oestrogen therapy and there were no significant differences between the two groups. The response of serum growth hormone to tolbutamide was small in both groups, but slightly more pronounced in the non‐obese women undergoing oestrogen therapy than in the controls. It is concluded that a postmenopausal period of five years leads to no impairment in carbohydrate metabolism in healthy women, and an oestrogen therapy for 3–7 years has no effects on glucose tolerance in healthy postmenopausal subjects.