Estrogens, bone loss and preservation

Christiansen, Claus; Lindsay, Robert

doi:10.1007/bf01880410

Cited by 124 publications

(47 citation statements)

References 73 publications

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“…It probably involves decreased bone turnover and improved equilibrium between bone formation and resorption by inhibition of osteoclastic activity [17][18][19], but may also be at least partially due to enhanced balance [20] and conservation of calcium [21]. A lack of protective effect among HRT users with high body weight could have several different explanations.…”

Section: Discussionmentioning

confidence: 94%

Variation in the Efficacy of Hormone Replacement Therapy in the Prevention of Hip Fracture

Michaëlsson

Baron

Johnell³

et al. 1998

Osteoporosis International

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Use of postmenopausal hormone replacement therapy (HRT) has been associated with a reduced risk of osteoporotic fractures. However, it is uncertain whether this risk reduction is modified by other risk factors for hip fracture. In a population-based case-control study in Sweden, we investigated the association between HRT and hip fracture risk within categories of age, body measures and lifestyle factors in postmenopausal women, 50-81 years of age. Mailed questionnaires and telephone interviews were used to collect data. Of those eligible, 1328 incident cases with hip fracture (82.5%) and 3312 randomly selected controls (81.6%) answered the questionnaire. Ever use of HRT in women less than 75 years old was associated with an odds ratio (OR) of 0.66 (95% confidence interval: 95% CI 0.50-0.87) for hip fracture compared with OR 0.40 (95% CI 0.21-0.77) in women 75 years or older. We found a significant interaction between HRT and both weight and physical activity (p < 0.05). The protective effect of HRT was particularly pronounced in lean women: compared with never HRT users, ever users weighing under 60 kg had an OR of 0.44 (95% CI 0.30-0.66) whereas women weighing more than 70 kg had an OR of 0.91 (95% CI 0.53-1.56). Women with low recent leisure physical activity (less than 1 h/week) similarly benefited more from HRT for hip fracture prevention than women with a higher degree of recreational physical activity. The observed interactions with weight and physical activity suggest that HRT has the best protective effect against hip fracture among high-risk women.

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Section: Discussionmentioning

confidence: 94%

Variation in the Efficacy of Hormone Replacement Therapy in the Prevention of Hip Fracture

Michaëlsson

Baron

Johnell³

et al. 1998

Osteoporosis International

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“…10) Estrogen deficiency that occurs at menopause plays a major role in the development of osteoporosis in elderly women. 11) Therefore estrogen replacement therapy (ERT) has been widely used for the prevention of postmenopausal osteoporosis. However, ERT also shows undesirable side effects including increased incidence of breast cancer and heart disease.…”

Section: Discussionmentioning

confidence: 99%

Effects of Metabolites of the Lignans Enterolactone and Enterodiol on Osteoblastic Differentiation of MG-63 Cells

Feng

Shi

2008

Biological & Pharmaceutical Bulletin

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The role of estrogens and estrogen-like molecules in regulating bone cell activities is central to understanding the etiology and treatment of postmenopausal osteoporosis. 1,2) In the past few years, natural estrogen-like molecules, the phytoestrogens, have attracted attention for their potential roles in osteoporosis prevention and treatment. 3) In contrast to the isoflavone-type phytoestrogens such as genistein, lignan-type phytoestrogens have rarely been studied, although they are widely distributed in the plant kingdom. Cereals, grains, berries, and garlic are good dietary sources of lignans. Recently, lignans have received considerable attention for their potential role in the prevention of osteoporosis.4) Lignans are metabolized into the more biologically active mammalian lignans enterodiol and enterolactone by microbiota in the colon. 5)Osteoblasts play a crucial role in bone formation through proliferation and differentiation. Osteoblast differentiation, an important process for its function, confers marked rigidity and strength on bone while still maintaining some degree of elasticity. Thus stimulation of osteoblast differentiation has been suggested to be an important therapeutic approach for the prevention and treatment of bone disease such as osteoporosis.6,7) While the isoflavone genistein 8) and arylnaphthalene-type lignans 9) have been shown to increase the differentiation of osteoblast-like cells, the effect of enterolignans, enterodiol and enterolactone, are unknown. Therefore we carried out the present research to determine whether enterodiol and enterolactone ( Fig. 1) have stimulatory effects on osteoblast differentiation. MATERIALS AND METHODSCell Culture MG-63 cells (purchased from the American Type Culture Collection), a human osteoblast-like cell line, were used to assess the cellular responses to enterolignans. Cells were cultured in 25 cm 2 flasks in Dulbeco's modified Eagle's medium (DMEM, Gibco) containing 10% heatinactivated fetal bovine serum, L-glutamine 2 mM, penicillin 100 U/ml, and streptomycin 100 mg/ml. Cultures were maintained at 37°C in a humidified atmosphere containing 5% CO 2 . When digested, the cells were washed with phosphatebuffered saline (PBS, Gibco), detached with trypsin-EDTA solution (0.25% trypsin, Gibco) at 37°C for 5 min, centrifuged, and resuspended for further cell tests.Cytotoxicity Assay Following incubation of cells with enterolactone and enterodiol (purchased from Sigma) for specified times in 96-well plates, 20 ml of PBS containing 5 mg/ml of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT, Sigma) was added to each well. Plates were incubated at 37°C for 4 h, then the medium was replaced with 150 ml of dimethyl sulphoxide (DMSO, Sigma). After 10-min incubation, absorbance in control and treated wells was measured in a plate reader at 490 nm.Alkaline Phosphotase Test Alkaline phosphotase (ALP) activity was measured colorimetrically using disodium phenyl phosphate as the substrate. The enzyme ALP expressed by the cells hydrolyzed the su...

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“…(7,8) It is well known, however, that estrogen replacement therapy causes various adverse side effects and often fear of cancer may preclude the use of estrogen. A class of related compounds called SERMs bind directly to the estrogen receptors and provide similar bone protective effects.…”

mentioning

confidence: 99%

Selective Modification of Bone Quality by PTH, Pamidronate, or Raloxifene

Brennan

Rizzoli

Ammann

2009

Journal of Bone and Mineral Research

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Bone strength, a determinant of resistance to fracture, depends on BMD, geometry, microarchitecture, bone turnover rates, and properties of the bone at the material level. Despite comparable antifracture efficacy, anti-catabolics and bone anabolic agents are likely to modify the various determinants of bone strength in very different ways. Eight weeks after ovariectomy (OVX), 8-mo-old osteoporotic rats received pamidronate (APD; 0.6 mg/kg, 5 days/mo, SC), raloxifene (3 mg/kg, 5/7 days, tube feeding), PTH(1-34) (10 mg/kg, 5/7 days, SC), or vehicle for 16 wk, and we measured vertebral BMD, maximal load, stiffness and energy, microarchitecture, and material properties by nanoindentation, which allows the calculation of the elastic modulus, tissue hardness, and working energy. Markers of bone turnover, plasma osteocalcin, and urinary deoxypyridinoline (Dpd) were also determined. PTH induced greater maximal load than APD or raloxifene, as well as greater absorbed energy, BMD, and increased bone turnover markers. PTH markedly increased trabecular bone volume and connectivity to values higher than sham. Animals treated with APD had BV/TV values significantly higher than OVX but lower than sham, whereas raloxifene had no effect. Tissue hardness was identical in PTH-treated and OVX untreated controls. In contrast, APD reversed the decline in strength to levels not significantly different to sham, reduced bone turnover, and increased hardness. Raloxifene markedly increased material level cortical hardness and elastic modulus. These results show the different mechanisms by which anti-catabolics and bone anabolics reduce fracture risk. PTH influences microarchitecture, whereas bisphosphonates alter material-level bone properties, with probable opposite effects on remodeling space. Raloxifene primarily improved the material stiffness at the cortical level.

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Estrogens, bone loss and preservation

Abstract: Estrogens ProgestinsEstrogens can be defined as compounds that are able to produce vaginal cornification or uterotrophic effects in oophorectomized rats or mice [1]. Estrogens are divided into four main groups:

Cited by 124 publications

References 73 publications

Variation in the Efficacy of Hormone Replacement Therapy in the Prevention of Hip Fracture

Variation in the Efficacy of Hormone Replacement Therapy in the Prevention of Hip Fracture

Effects of Metabolites of the Lignans Enterolactone and Enterodiol on Osteoblastic Differentiation of MG-63 Cells

Selective Modification of Bone Quality by PTH, Pamidronate, or Raloxifene

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