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See detailWhat is the current statut of chondroitin sulfate and glucosamine in the treatment of knee osteoarthritis?
Henrotin, Yves ULg; Marty, Marc; Mobasheri, Ali

in Maturitas (2014), 78

Chondroitin sulfate and glucosamine sulfate exert beneficial effects on the metabolism of in vitro models of cells derived from synovial joints: chondrocytes, synoviocytes and cells from subchondral bone ... [more ▼]

Chondroitin sulfate and glucosamine sulfate exert beneficial effects on the metabolism of in vitro models of cells derived from synovial joints: chondrocytes, synoviocytes and cells from subchondral bone, all of which are involved in osteoarthritis (OA). They increase type II collagen and proteoglycan synthesis in human articular chondrocytes and are able to reduce the production of some pro-inflammatory mediators and proteases, to reduce the cellular death process, and improve the anabolic/catabolic balance of the extracellular cartilage matrix (ECM). Clinical trials have reported a beneficial effect of chondroitin sulfate and glucosamine sulfate on pain and function. The structure-modifying effects of these compounds have been reported and analyzed in recent meta-analyses. The results for knee OA demonstrate a small but significant reduction in the rate of joint space narrowing. Chondroitin sulfate and glucosamine sulphate are recommended by several guidelines from international societies for the management of knee and hip OA, while others do not recommend these products or recommend only under condition. This comprehensive review clarifies the role of these compounds in the therapeutic arsenal for patients with knee OA [less ▲]

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See detailThe role of dietary protein and vitamin D in maintaining musculoskeletal health in postmenopausal women : A consensus statement from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)
Rizzoli, R; Stevenson, JC; Bauer, JM et al

in Maturitas (2014), 79

From 50 years of age, postmenopausal women are at an increased risk of developing sarcopenia and osteoporosis as a result of deterioration of musculoskeletal health. Both disorders increase the risk of ... [more ▼]

From 50 years of age, postmenopausal women are at an increased risk of developing sarcopenia and osteoporosis as a result of deterioration of musculoskeletal health. Both disorders increase the risk of falls and fractures. The risk of developing sarcopenia and osteoporosis may be attenuated through healthy lifestyle changes, which include adequate dietary protein, calcium and vitamin D intakes, and regular physical activity/exercise, besides hormone replacement therapy when appropriate. Protein intake and physical activity are the main anabolic stimuli for muscle protein synthesis. Exercise training leads to increased muscle mass and strength, and the combination of optimal protein intake and exercise produces a greater degree of muscle protein accretion than either intervention alone. Similarly, adequate dietary protein intake and resistance exercise are important contributors to the maintenance of bone strength. Vitamin D helps to maintain muscle mass and strength as well as bone health. These findings suggest that healthy lifestyle measures in women aged >50 years are essential to allow healthy ageing. The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommends optimal dietary protein intake of 1.0–1.2 g/kg body weight/d with at least 20–25 g of high-quality protein at each main meal, with adequate vitamin D intake at 800 IU/d to maintain serum 25-hydroxyvitamin D levels >50 nmol/L as well as calcium intake of 1000 mg/d, alongside regular physical activity/exercise 3–5 times/week combined with protein intake in close proximity to exercise, in postmenopausal women for prevention of age-related deterioration of musculoskeletal health. [less ▲]

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See detailAdvances in hormone replacement therapy with drospirenone, a unique progestogen with aldosterone receptor antagonism
Palacios, S.; Foidart, Jean-Michel ULg; Genazzani, A. R.

in Maturitas (2006), 55(4), 297-307

Unlike other currently available progestogens, drospirenone (DRSP) has a pharmacological profile, which closely mimics that of endogenous progesterone, most notably potent anti-aldosterone and anti ... [more ▼]

Unlike other currently available progestogens, drospirenone (DRSP) has a pharmacological profile, which closely mimics that of endogenous progesterone, most notably potent anti-aldosterone and anti-androgenic effects. Consequently, DRSP, when combined with 17 beta-estradiol (E2) as hormone replacement therapy (HRT), offsets E2-related water and sodium retention by blocking the mineralocorticoid receptor. This review evaluates the potential benefits offered by DRSP as the progestin component of HRT with respect to its anti-aldosterone activity, which translates into positive effects on body weight and blood pressure in clinical trials of continuous, combined E2/DRSP in post-menopausal women. In a 1-year, large-scale, randomised, controlled trial, E2 1 mg/DRSP 2 mg significantly decreased mean body weight by 1.2 kg versus baseline (P < 0.001), whereas patients receiving E2 1 mg gained weight. E2 1 mg/DRSP 2 mg also significantly lowered mean systolic blood pressure (SBP) by 9.0 mmHg from baseline (P < 0.05) versus 3.7 mmHg in the E2 1 mg group (P = 0.220) in a sub-group of hypertensive women. In addition, E2/DRSP was not associated with hyperkalaemia (potassium >= 5.5 meq/L) irrespective of concomitant use of ACE inhibitors, angiotensin II receptor antagonists or non-steroidal anti-inflammatory drugs, and co-morbid diabetes mellitus. In summary, as well as effectively treating climacteric symptoms, DRSP 2 mg combined with E2 I mg has shown positive effects on body weight and blood pressure in clinical trials, most likely due to DRSP's anti-aldosterone properties. This combination may therefore offer an alternative therapeutic option with additional benefits beyond current HRT agents for symptomatic post-menopausal women. (c) 2006 Elsevier Ireland Ltd. All rights reserved. [less ▲]

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See detailNew evidence regarding hormone replacement therapies is urgently required. Transdermal postmenopausal hormone therapy differs from oral hormone therapy in risks and benefits
Modena, M. G.; Sismondi, P.; Mueck, A. O. et al

in Maturitas (2005), 52(1), 1-10

Controversies about the safety of different postmenopausal hormone therapies (HTs) started 30 years ago and reached a peak in 2003 after the publication of the results from the Women Health Initiative ... [more ▼]

Controversies about the safety of different postmenopausal hormone therapies (HTs) started 30 years ago and reached a peak in 2003 after the publication of the results from the Women Health Initiative (WHI) trial and the Million Women Study (MWS) [Writing group for the women's health initiative investigations. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA 2002;288:321–33; Million women study collaborators. Breast cancer and hormone-replacement therapy in the million women study. Lancet 2003;362:419–27]. The single HT formulation used in the WHI trial for non hysterectomized women—an association of oral conjugated equine estrogens (CEE–0.625 mg/day) and a synthetic progestin, medroxyprogesterone acetate (MPA–2.5 mg/day)—increases the risks of venous thromboembolism, cardiovascular disease, stroke and breast cancer. The MWS, an observational study, showed an increased breast cancer risk in users of estrogens combined with either medroxyprogesterone acetate (MPA), norethisterone, or norgestrel. It is unclear and questionable to what extent these results might be extrapolated to other HRT regimens, that differ in their doses, compositions and administration routes, and that were not assessed in the WHI trial and the MWS. Significant results were achieved with the publication of the WHI estrogen-only arm study [Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701–1712] in which hormone therapy was reserved to women who had carried out hysterectomy. What emerged from this study will allow us to have some important argument to develop. [less ▲]

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See detailInterest of biochemical markers of bone turnover for long-term prediction of new vertebral fracture in postmenopausal osteoporotic women
Bruyère, Olivier ULg; Collette, Julien ULg; Delmas, Pierre et al

in Maturitas (2003), 44(4), 259-265

Objective: To analyse the interest of baseline levels and short-term (3-months) changes in serum osteocalcin (BGP), serum bone-specific alkaline phosphatase (BALP) and urinary C-telopeptide of type I ... [more ▼]

Objective: To analyse the interest of baseline levels and short-term (3-months) changes in serum osteocalcin (BGP), serum bone-specific alkaline phosphatase (BALP) and urinary C-telopeptide of type I collagen/creatinine ratio (U-TX) to predict 3-years changes in bone mineral density (BMD) and spinal deformity index (SDI) in postmenopausal osteoporotic women. Methods: Data were derived from a cohort of 603 osteoporotic women corresponding to the placebo arm of a 3-years prospective, double-blind study. Results: Baseline values of BALP, BGP and U-CTX were negatively and significantly correlated with baseline spinal BMD. Significant correlations were also observed between the changes in BMD observed after 36 months at the spine and baseline BALP (r = 0.20, P = 0.0001), BGP (r = 0.09, P = 0.05) and U-CTX (r = -0.11, P = 0.02). At 3 years, 71 women (15.9%) showed an increase in their SDI, corresponding to the occurrence of at least one new vertebral deformity. Baseline values of the four bone turnover markers (BTM) were not significantly related to the occurrence of new vertebral deformities. However, when considering the changes in the BTM observed after 3-months of follow-up, BGP (P = 0.003) and U-CTX (P = 0.047) were identified as significant predictors of an increase of SDI. The associated odds ratios (95% confidence interval (CI)) were 10.922 (2.218-53.78) for unit changes of log BGP and 1.369 (1.003-1.867) for unit changes of log U-CTX. The relative risk (RR) (IC 95%) of having a new vertebral fracture over 36 months was 0.31 (0.15-0.65) when being in the lowest quartile of 3-months changes in BGP as compared with the highest. Conclusion: We conclude that two sequential measurements of BGP and U-CTX performed at 3-months intervals could be of interest to identify postmenopausal osteoporotic women with the highest risk to present new vertebral deformities. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. [less ▲]

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See detailComparative effect of hormone replacement therapy on bone mass density and skin tensile properties
Pierard, Gérald ULg; Vanderplaetsen, S.; Pierard-Franchimont, Claudine ULg

in Maturitas (2001), 40(3), 221-227

Objectives: connective tissues constitutive of skin and bones are affected during the climacteric. Hormone replacement therapy (HRT) can help mitigate their atrophy. The aim of this study was to compare ... [more ▼]

Objectives: connective tissues constitutive of skin and bones are affected during the climacteric. Hormone replacement therapy (HRT) can help mitigate their atrophy. The aim of this study was to compare the HRT effect on the skin tensile properties and bone mass density. Methods: a total of 120 postmenopausal women (60 untreated, 60 receiving HRT) were enrolled in the study. Skin tensile properties were assessed on the volar forearm using a computerized suction device. A 500 mbar suction was applied through a 4-mm diameter hollow probe. Two operating modes were applied using a steep and a progressive Suction, respectively. BMD was measured on the hip, femoral neck and lumbar spine using dual X-ray absorptiometry. Results: in both groups of women skin elasticity was correlated with BMD. HRT significantly reduced the climacteric-associated decline in skin elasticity. A trend in better preserved BMD was also found in these women without, however, reaching significance. Conclusions: it is concluded that measures of the skin tensile properties can be sensitive enough to disclose HRT efficacy upon connective tissue atrophy. Any decrease in skin elasticity during the climacteric should prompt to perform a BMD assessment. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. [less ▲]

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See detailGenetics of menopause-associated diseases.
Massart, François ULg; REGINSTER, Jean-Yves ULg; Brandi, M L

in Maturitas (2001), 40(2), 103-16

Menopause is the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. It is estimated that perhaps 50 million women worldwide will go into menopause annually ... [more ▼]

Menopause is the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. It is estimated that perhaps 50 million women worldwide will go into menopause annually. Atherosclerotic cardiovascular disease, osteoporotic fractures and Alzheimer's dementia are common chronic disorders after menopause, representing major health problems in most developed countries. Apart from being influenced by environmental factors, these chronic disorders recognize a strong genetic component, and there are now considerable clinic evidences that these disorders are related to low hormonal milieu of postmenopausal women. Here, we review up-to-date available data suggesting that genetic variation may contribute to higher susceptibility to four sporadic chronic syndromes such as osteoporosis (OP), osteoarthritis (OA), Alzheimer's disease (AD) and coronary artery disease (CAD). For these four syndromes candidate genes that today appear as major loci in genetic susceptibility encode for proteins specific of a given system, as the vitamin D receptor (VDR) gene for the skeleton and, therefore, OP or angiotensin converting enzyme (ACE) for the cardiovascular system and, therefore, CAD. The investigation of gene polymorphisms in various pathological conditions typical of postmenopause offer an explanation not only of their genetic inheritance but also of their co-segregation in given individuals. In this view, it may be possible to identify a common set of genes whose variants contribute to a common genetic background for these different disorders. Ideal candidates appear genes of the estrogen response cascade [i.e. estrogen receptor (ERs), enzymes involved in estrogen metabolism or co-activators and co-inhibitors]. All together this information may represent the basis both for future recognition of individuals at risk and for the pharmacogenetic driving of drug responsiveness. [less ▲]

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See detailDepressive vulnerability is not an independent risk factor for osteoporosis in postmenopausal women.
Reginster, Jean-Yves ULg; Deroisy, Rita ULg; Paul, I. et al

in Maturitas (1999), 33(2), 133-7

Major depression has been repeatedly but not consistently reported to be associated with low bone mineral density (BMD) and to an increased risk for fracture in women. We have investigated, in healthy ... [more ▼]

Major depression has been repeatedly but not consistently reported to be associated with low bone mineral density (BMD) and to an increased risk for fracture in women. We have investigated, in healthy postmenopausal women, whether depressive symptomatology, assessed by the General Health Questionnaire (GHQ), was associated to a significant decrease in BMD, hence supporting the hypothesis of an independent pathogenetic link between the two disorders. We investigated 121 postmenopausal women, aged 48-77 years, spontaneously attending a screening visit for osteoporosis in an outpatient facility. BMD of the spine and the non-dominant hip (total and neck areas) were measured by Dual Energy X-Ray absorptiometry. All subjects completed to the 'General Health Questionnaire' translated and validated in French. No significant correlations were observed between the GHQ score and BMD of the spine (P = 0.54), the total hip area (P = 0.65), or the femoral neck area (P = 0.65). No differences in terms of spinal or femoral BMD were observed between women with GHQ score < 5 or > or = 5. When comparing values of BMD between women within the upper and the lower quartiles for GHQ score, no difference was observed for spine (P = 0.69), total hip (P = 0.80), or femoral neck (P = 0.93). Similarly, GHQ scores were not significantly different when comparing women in the upper and lower quartiles of BMD distribution at the spine or the hip. In conclusion, notwithstanding the clinical pattern of postmenopausal osteoporosis can lead to depression and, on the other hand, hormonal and behavioral disturbances reported in depression might be enhancing factors for accelerated bone loss, our present results do not support the hypothesis that otherwise healthy postmenopausal women with increased depressive complaints are also more prone to exhibit osteoporotic fractures. [less ▲]

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See detailPlasma Estradiol Concentrations and Pharmacokinetics Following Transdermal Application of Menorest 50 or Systen (Evorel) 50
Reginster, Jean-Yves ULg; Albert, Adelin ULg; Deroisy, Rita ULg et al

in Maturitas (1997), 27(2), 179-86

OBJECTIVES: In order to compare the pharmacokinetics of two transdermal estrogen replacement therapy (ERT) systems designed to release 50 micrograms 17 beta-estradiol/day, two studies were performed in ... [more ▼]

OBJECTIVES: In order to compare the pharmacokinetics of two transdermal estrogen replacement therapy (ERT) systems designed to release 50 micrograms 17 beta-estradiol/day, two studies were performed in healthy postmenopausal volunteers. METHODS: Both studies had a cross-over design and incorporated a 1-week wash-out period between treatments. In the first study, Menorest 50 and Systen 50 (Evorel 50) were compared over four days of application in 30 women. In the second, 13 women wore each of the two systems for a total of 12 days each (three patches each for 4 days), and comparison was made during the third patch period (steady state, between days 8 and 12). Plasma 17 beta-estradiol levels were assayed using specific direct radioimmunoassays, and pharmacokinetic parameters were calculated by standard methods. All the samples of the first study were re-analysed using a different radioimmunoassay and the results of both assays were compared. RESULTS: In both studies, plasma 17 beta-estradiol levels rose at a comparable rate and reached similar peak levels with each of the two formulations. Levels then remained relatively constant throughout both evaluation periods with Menorest 50, but began to decline after 12 hours in the first study and after 30 h under steady state conditions in the second study with Systen 50. The difference between the two products was statistically significant in both studies. Analysis of pharmacokinetic parameters confirmed the greater bioavailability of Menorest 50. In addition, 17 beta-estradiol levels remained within the suggested therapeutic ranges for relief of acute symptoms and protection against osteoporosis for longer periods of time with Menorest 50 than with Systen 50. CONCLUSION: Since the acute efficacy, long-term protective effects, side effects and risks associated with ERT may depend on critical threshold plasma levels, much attention should be paid to the pharmacokinetic profiles of different formulations. The comparison of these two different radioimmunoassays demonstrates the comparability of their results. [less ▲]

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See detailIncrease in Cytokine Production (Il-1 Beta, Il-6, Tnf-Alpha but Not Ifn-Gamma, Gm-Csf or Lif) by Stimulated Whole Blood Cells in Postmenopausal Osteoporosis
Zheng, S. X.; Vrindts-Gevaert, Yvonne; Lopez, Marie-Josée ULg et al

in Maturitas (1997), 26(1), 63-71

Postmenopausal osteoporosis is a progressive disorder characterized by a decreased bone mass and increased susceptibility to fractures. Several investigations have suggested that one of the mechanisms ... [more ▼]

Postmenopausal osteoporosis is a progressive disorder characterized by a decreased bone mass and increased susceptibility to fractures. Several investigations have suggested that one of the mechanisms through which estrogen prevents bone loss was a modulation on secretion or release of various cytokines that are known to influence bone remodeling, even if some recent data have challenged this hypothesis. However, in established osteoporosis, the possibility that enhanced cytokines activity may account for the progression of this disease remains unclear and controversial. We sought here to determine whether production of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, GM-CSF and LIF, after direct stimulation in whole blood, was different in healthy (n = 30) or osteoporotic postmenopausal women (n = 24) and whether lumbar bone density (1-BMD) correlated with the values of cytokine production observed in these conditions. A significant difference was observed between the osteoporotic and control subjects for IL-1 beta (p < 0.0001), IL-6 (p < 0.001) and TNF-alpha (p = 0.027) productions, the values being higher in the osteoporotic women. No significant differences between the groups were observed for IFN-gamma (p = 0.51), GM-CSF (p = 0.70) or LIF (p = 0.97). In the whole population, statistically significant negative correlations were observed between lumbar BMD and IL-1 beta (r = -0.46) (p < 0.0005), IL-6 (r = -0.50) (p < 0.0001) and TNF-alpha (r = -0.39) (p < 0.005) production while no such correlations were observed for IFN-gamma, GM-CSF or LIF. In conclusion, the study of cytokine production by immune cells cultured in autologous whole blood suggests that in women more than 10 years past the menopause and presenting a decrease in lumbar bone density corresponding to the new WHO definition of "osteoporosis', production of IL-1 beta, IL-6 and TNF-alpha is still increased compared to controls matched for age and ovarian function, while no differences are reported for IFN-gamma, GM-CSF or LIF production. [less ▲]

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See detailEfficacy of Sustained-Release Vaginal Oestriol in Alleviating Urogenital and Systemic Climacteric Complaints
Foidart, Jean-Michel ULg; Vervliet, J.; Buytaert, Ph

in Maturitas (1991), 13(2), 99-107

In a double-blind, placebo-controlled study, 109 patients suffering from local and vasomotor postmenopausal complaints were randomly assigned to treatment with either depot vaginal suppositories ... [more ▼]

In a double-blind, placebo-controlled study, 109 patients suffering from local and vasomotor postmenopausal complaints were randomly assigned to treatment with either depot vaginal suppositories containing 3.5 mg oestriol (E3) or a placebo. The treatment schedule comprised one vaginal suppository twice weekly for 3 weeks initially, followed by maintenance therapy with one vaginal suppository weekly for the 6-month study period. The effectiveness of the therapy was assessed on the basis of questionnaires (Kupperman index for vasomotor complaints and an original urogenital index for local complaints) and gynaecological examinations which included assessments of vaginal cytology, vaginal pH and Doderlein bacilli. To rule out induced endometrial proliferation, endometrial biopsies were performed in 50 women before and after the study. The vaginal depot (E3) formulation showed highly significant superiority over the placebo with respect to therapeutic effect on local urogenital complaints and alleviation of vasomotor complaints, including hot flushes. Analysis of the endometrial biopsies indicated that the monotherapy used caused no endometrial stimulation. Taking into account the minimal rate of adverse effects, the 3.5 mg E3 depot formulation studied represents a useful variant in the range of preparations available for the treatment of post-menopausal complaints. [less ▲]

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