Relationship of Estrogen Receptor Genotypes to Bone Mineral Density and to Rates of Bone Loss in Men

Although it is well established that estrogen deficiencycauses osteoporosis among the postmenopausalwomen, the involvement of estrogen receptor (ER) in itspathogenesis still remains uncertain. In the presentstudy, we have generated rats harboring a dominantnegative ERa, which inhibits the actions of not only ERabut also recently identified ERb. Contrary to our expectation,the bone mineral density (BMD) of the resultingtransgenic female rats was maintained at the same levelwith that of the wild-type littermates when sham-operated.In addition, ovariectomy-induced bone loss wasobserved almost equally in both groups. Strikingly, however,the BMD of the transgenic female rats, after ovariectomized,remained decreased even if 17b-estradiol(E2) was administrated, whereas, in contrast, the decreaseof littermate BMD was completely prevented byE2. Moreover, bone histomorphometrical analysis ofovariectomized transgenic rats revealed that the higherrates of bone turnover still remained after treatmentwith E2. These results demonstrate that the preventionfrom the ovariectomy-induced bone loss by estrogen ismediated by ER pathways and that the maintenanceof BMD before ovariectomy might be compensatedby other mechanisms distinct from ERa and ERbpathways.

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No major effect of estrogen receptor gene polymorphisms on bone mineral density or bone loss in postmenopausal danish women

Bone ◽

10.1016/s8756-3282(99)00261-6 ◽

2000 ◽

Vol 26 (2) ◽

pp. 111-116 ◽

Cited By ~ 44

Author(s):

Y.Z Bagger ◽

H.L Jørgensen ◽

A.-M Heegaard ◽

L Bayer ◽

L Hansen ◽

...

Keyword(s):

Bone Mineral Density ◽

Estrogen Receptor ◽

Bone Loss ◽

Bone Mineral ◽

Gene Polymorphisms ◽

Receptor Gene ◽

Major Effect ◽

Estrogen Receptor Gene ◽

Mineral Density ◽

Receptor Gene Polymorphisms

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Effect of Endocrine Therapies on Bone in Breast Cancer Patients

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-1679 ◽

2011 ◽

Vol 96 (2) ◽

pp. 308-319 ◽

Cited By ~ 43

Author(s):

R. J. Santen

Keyword(s):

Breast Cancer ◽

Bone Mineral Density ◽

Estrogen Receptor ◽

Bone Density ◽

Bone Loss ◽

Bone Formation ◽

Postmenopausal Women ◽

Bone Mineral ◽

Mineral Density ◽

Markers Of Bone Formation

abstract Context: Two common strategies are used to treat estrogen receptor-positive breast cancer in women: tamoxifen to inhibit estrogen action, and aromatase inhibitors (AIs) to block estrogen biosynthesis. Recent data suggest that AIs are more effective than tamoxifen in the adjuvant and advanced disease settings and are now being more commonly used. Tamoxifen, as a selective estrogen receptor modulator, exerts estrogenic effects to preserve bone, whereas the AIs profoundly lower estrogen levels and cause bone loss. Recent comparative studies of these agents provide extensive data on fracture rates, bone mineral density, and markers of bone formation and resorption. Objective: The aim of the study was to review the mechanistic effects of estrogen on bone and clinical data regarding bone density, bone turnover markers, and fracture rates in women with breast cancer taking tamoxifen or AIs. Evidence Acquisition and Synthesis: Data presented reflect a review of the literature and data integration from the perspective of the author's knowledge of the field. Results: Tamoxifen increases bone density and reduces fractures in postmenopausal women with breast cancer, whereas AIs increase rate of fracture, accelerate loss of bone mineral density, and enhance levels of markers of bone formation and resorption. Bisphosphonates and denosumab counteract the effects of the AIs on bone. Guidelines for management of AI-induced bone loss are available from several sources, but a simple algorithm guides decision making most effectively. Conclusions: Endocrine therapy for postmenopausal women with breast cancer exerts substantial effects on bone, and guidelines are available to assist in the management of bone-related problems.

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P129 Predictors of low bone mineral density in rheumatoid arthritis

Rheumatology ◽

10.1093/rheumatology/keab247.124 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Malika A Swar ◽

Marwan Bukhari

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Bone Mineral Density ◽

Family History ◽

Bone Loss ◽

Femoral Neck ◽

Bone Mineral ◽

Fragility Fracture ◽

Mineral Density ◽

History Of

Abstract Background/Aims Osteoporosis (OP) is an extra-articular manifestation of rheumatoid arthritis (RA) that leads to increased fracture susceptibility due to a variety of reasons including immobility and cytokine driven bone loss. Bone loss in other populations has well documented risk factors. It is unknown whether bone loss in RA predominantly affects the femoral neck or the spine. This study aimed to identify independent predictors of low bone mineral density (BMD) in patients RA at the lumbar spine and the femoral neck. Methods This was a retrospective observational cohort study using patients with Rheumatoid arthritis attending for a regional dual X-ray absorptiometry (DEXA) scan at the Royal Lancaster Infirmary between 2004 and 2014. BMD in L1-L4 in the spine and in the femoral neck were recorded. The risk factors investigated were steroid use, family history of osteoporosis, smoking, alcohol abuse, BMI, gender, previous fragility fracture, number of FRAX(tm) risk factors and age. Univariate and Multivariate regression analysis models were fitted to explore bone loss at these sites using BMD in g/cm2 as a dependant variable. . Results 1,527 patients were included in the analysis, 1,207 (79%) were female. Mean age was 64.34 years (SD11.6). mean BMI was 27.32kg/cm2 (SD 5.570) 858 (56.2%) had some steroid exposure . 169(11.1%) had family history of osteoporosis. fragility fracture history found in 406 (26.6%). 621 (40.7%) were current or ex smokers . There was a median of 3 OP risk factors (IQR 1,3) The performance of the models is shown in table one below. Different risk factors appeared to influence the BMD at different sites and the cumulative risk factors influenced BMD in the spine. None of the traditional risk factors predicted poor bone loss well in this cohort. P129 Table 1:result of the regression modelsCharacteristicB femoral neck95% CIpB spine95%CIpAge at scan-0.004-0.005,-0.003<0.01-0.0005-0.002,0.00050.292Sex-0.094-0.113,-0.075<0.01-0.101-0.129,-0.072<0.01BMI (mg/m2)0.0080.008,0.0101<0.010.01130.019,0.013<0.01Fragility fracture-0.024-0.055,0.0060.12-0.0138-0.060,0.0320.559Smoking0.007-0.022,0.0350.650.0286-0.015,0.0720.20Alcohol0.011-0.033,0.0 5560.620.0544-0.013,0.1120.11Family history of OP0.012-0.021,0.0450.470.0158-0.034,0.0650.53Number of risk factors-0.015-0.039,0.0080.21-0.039-0.075,-0.0030.03steroids0.004-0.023,0.0320.030.027-0.015,0.0690.21 Conclusion This study has shown that predictors of low BMD in the spine and hip are different and less influential than expected in this cohort with RA . As the FRAX(tm) tool only uses the femoral neck, this might underestimate the fracture risk in this population. Further work looking at individual areas is ongoing. Disclosure M.A. Swar: None. M. Bukhari: None.

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SAT0477 A TWO-YEAR LONGITUDINAL STUDY COMPLETION, LONGITUNEAL STUDY, THE DIFFERENCE IN BONE LOSS IN PATIENTS WITH EROSIVE AND NON-EROSIVE HAND OSTEOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4790 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1195.2-1195

Author(s):

K. Pavelka ◽

L. Šenolt ◽

O. Sleglova ◽

J. Baloun ◽

O. Růžičková

Keyword(s):

Bone Mineral Density ◽

Longitudinal Study ◽

Lumbar Spine ◽

Bone Loss ◽

Bone Mineral ◽

Hand Osteoarthritis ◽

Mineral Density ◽

Erosive Disease ◽

Femur Neck ◽

American College Of Rheumatology

Background:Hand osteoarthritis (OA) and its more severe subset erosive hand OA are common causes of pain and morbidity. Some metabolic factors were suggested to be implicated in erosive disease. Few studies investigated differences in systemic bone loss between erosive and non-erosive hand OA.Objectives:To compare the change of bone mineral density (BMD) between patients with erosive and non-erosive hand OA in a two-year longitudinal study.Methods:Consecutive patients with symptomatic HOA fulfilling the American College of Rheumatology (ACR) criteria were included in this study. Erosive hand OA was defined by at least one erosive interphalangeal joint. All patients underwent clinical assessments of joint swelling and radiographs of both hands. DEXA examination of lumbar spine, total femur and femur neck was performed at the baseline and after two years.Results:Altogether, 141patients (15 male) with symptomatic nodal HOA were included in this study and followed between April 2012 and January 2019. Out of these patients, 80 had erosive disease after two years. The disease duration (p<0.01) was significantly higher in patients with erosive compared with non-erosive disease at baseline.Osteoporosis (T-score <-2.5 SD) was diagnosed in 12.5% (9/72) of patients with erosive hand OA and in 8.06% (5/57) of patients with non-erosive hand OA at baseline. BMD was significantly lowered in patients with erosive compared with non-erosive disease at baseline (lumbar spine: 1.05g/cm2 vs. 1.13 g/cm2, p<0.05, total femur: 0.90 g/cm2 vs. 0.97 g/cm2, p<0.01 and femur neck: 0.86 g/cm2 vs. 0.91, p<0.05). T-scores of lumbar spine (-0.96 vs. -0.41 SD, p<0.05), total femur (-0.69 vs. -0.33 SD, p<0.05) and femur neck (-1.14 vs. -0.88 SD, p<0.05) were also significantly lowered in patients with erosive compared with non-erosive disease.Two years, the BMD remained also significantly lowered in patients with erosive compared with non-erosive disease (lumbar spine: 1.05g/cm2 vs. 1.14 g/cm2, p<0.05, total femur: 0.92 g/cm2 vs. 0.97 g/cm2, p<0.05 and femur neck: 0.86 g/cm2 vs. 0.91, p<0.05), which was in agreement with the finding for T-scores of lumbar spine (-1.05 vs. -0.39 SD, p<0.05), total femur (-0.74 vs. -0.34 SD, p<0.01) and femur neck (-1.07 vs. -0.72 SD, p<0.01).Conclusion:These results suggest that patients with erosive hand OA are at higher risk for the development of general bone loss. Over two years patients with erosive disease had significant lower bone mineral density at all measured sites.References:[1]This work was supported by the project AZV no. 18-00542 and MHCR No. 023728.Acknowledgments:Project AZV no. 18-00542 and MHCR No. 023728Disclosure of Interests:Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Ladislav Šenolt: None declared, Olga Sleglova: None declared, Jiří Baloun: None declared, Olga Růžičková: None declared

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