Wnt receptors, bone mass, and fractures: gene-wide association analysis of LRP5 and LRP6 polymorphisms with replication

ObjectiveGenes explaining the susceptibility to osteoporosis have not been fully elucidated. Our objective was to explore the association of polymorphisms capturing common variations of the lipoprotein receptor-related protein (LRP) 5 and 6 genes, encoding two Wnt receptors, with femoral neck bone mineral density (BMD) and osteoporotic fractures of the spine and the hip.DesignCross-sectional, case–control, and replication genetic association study.MethodsThirty-nine tagging and functional single nucleotide polymorphisms (SNPs) were analyzed in a group of 1043 postmenopausal women and 394 women with hip fractures. The results were replicated in a different group of 342 women.ResultsThree SNPs of the LRP6 gene were associated with BMD (nominal uncorrected P values <0.05) in the discovery cohort. One showed a significant association after multiple test correction; two of them were also associated in the replication cohort, with a combined standardized mean difference of 0.51 (P=0.009) and 0.47 (P<0.003) across rs11054704 and rs2302685 genotypes. In the discovery cohort, several LRP5 SNPs were associated with vertebral fractures (odds ratio (OR) 0.67; P=0.01), with hip fractures (unadjusted ORs between 0.59 and 1.21; P=0.005–0.033, but not significant after multiple test adjustment or age adjustment), and with height and the projected femoral neck area, but not with BMD. Transcripts of LRP5 and LRP6 were similarly abundant in bone samples.ConclusionsIn this study, we found common polymorphisms of LRP5 associated with osteoporotic fractures, and polymorphisms of the LRP6 gene associated with BMD, thus suggesting them as likely candidates to contribute to the explaination of the hereditary influence on osteoporosis.

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Genetic Variants in Smoking-Related Genes in Two Smoking Cessation Programs: A Cross-Sectional Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18126597 ◽

2021 ◽

Vol 18 (12) ◽

pp. 6597

Author(s):

Gloria Pérez-Rubio ◽

Luis Alberto López-Flores ◽

Ana Paula Cupertino ◽

Francisco Cartujano-Barrera ◽

Luz Myriam Reynales-Shigematsu ◽

...

Keyword(s):

Smoking Cessation ◽

Cross Sectional Study ◽

Nucleotide Polymorphisms ◽

Sectional Study ◽

Cross Sectional ◽

Single Nucleotide ◽

Genotype Frequencies ◽

Quitting Smoking ◽

Genes Encoding ◽

Genomic Regions

Previous studies have identified variants in genes encoding proteins associated with the degree of addiction, smoking onset, and cessation. We aimed to describe thirty-one single nucleotide polymorphisms (SNPs) in seven candidate genomic regions spanning six genes associated with tobacco-smoking in a cross-sectional study from two different interventions for quitting smoking: (1) thirty-eight smokers were recruited via multimedia to participate in e-Decídete! program (e-Dec) and (2) ninety-four attended an institutional smoking cessation program on-site. SNPs genotyping was done by real-time PCR using TaqMan probes. The analysis of alleles and genotypes was carried out using the EpiInfo v7. on-site subjects had more years smoking and tobacco index than e-Dec smokers (p < 0.05, both); in CYP2A6 we found differences in the rs28399433 (p < 0.01), the e-Dec group had a higher frequency of TT genotype (0.78 vs. 0.35), and TG genotype frequency was higher in the on-site group (0.63 vs. 0.18), same as GG genotype (0.03 vs. 0.02). Moreover, three SNPs in NRXN1, two in CHRNA3, and two in CHRNA5 had differences in genotype frequencies (p < 0.01). Cigarettes per day were different (p < 0.05) in the metabolizer classification by CYP2A6 alleles. In conclusion, subjects attending a mobile smoking cessation intervention smoked fewer cigarettes per day, by fewer years, and by fewer cumulative pack-years. There were differences in the genotype frequencies of SNPs in genes related to nicotine metabolism and nicotine dependence. Slow metabolizers smoked more cigarettes per day than intermediate and normal metabolizers.

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Bone mineral density predictors in long-standing type 1 and type 2 diabetes mellitus

BMC Endocrine Disorders ◽

10.1186/s12902-021-00815-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Stefana Catalina Bilha ◽

Letitia Leustean ◽

Cristina Preda ◽

Dumitru D. Branisteanu ◽

Laura Mihalache ◽

...

Keyword(s):

Diabetes Mellitus ◽

Bone Mineral Density ◽

Lumbar Spine ◽

Femoral Neck ◽

Bone Mineral ◽

Mineral Density ◽

Cross Sectional ◽

The Impact

Abstract Background Despite the increased fracture risk, bone mineral density (BMD) is variable in type 1 (T1D) and type 2 (T2D) diabetes mellitus. We aimed at comparing independent BMD predictors in T1D, T2D and control subjects, respectively. Methods Cross-sectional case-control study enrolling 30 T1D, 39 T2D and 69 age, sex and body mass index (BMI) – matched controls that underwent clinical examination, dual-energy X-ray absorptiometry (BMD at the lumbar spine and femoral neck) and serum determination of HbA1c and parameters of calcium and phosphate metabolism. Results T2D patients had similar BMD compared to T1D individuals (after adjusting for age, BMI and disease duration) and to matched controls, respectively. In multiple regression analysis, diabetes duration – but not HbA1c- negatively predicted femoral neck BMD in T1D (β= -0.39, p = 0.014), while BMI was a positive predictor for lumbar spine (β = 0.46, p = 0.006) and femoral neck BMD (β = 0.44, p = 0.007) in T2D, besides gender influence. Age negatively predicted BMD in controls, but not in patients with diabetes. Conclusions Long-standing diabetes and female gender particularly increase the risk for low bone mass in T1D. An increased body weight partially hinders BMD loss in T2D. The impact of age appears to be surpassed by that of other bone regulating factors in both T1D and T2D patients.

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BMD status of Postmenopausal Women in relation with BMI: A study with 93 cases

Bangladesh Journal of Nuclear Medicine ◽

10.3329/bjnm.v17i2.28200 ◽

2016 ◽

Vol 17 (2) ◽

pp. 138-141

Author(s):

Samira Sharmin ◽

Mabubul Haque ◽

Syedur Rahman Miah ◽

Md Mahbub Ur Rahman ◽

Jasmine Ara Haque ◽

...

Keyword(s):

Lumbar Spine ◽

Femoral Neck ◽

Postmenopausal Women ◽

Lumbar Vertebrae ◽

The Body ◽

Mineral Density ◽

Cross Sectional ◽

T Score ◽

Minimal Trauma ◽

The Mean

Objectives: Low bone mass is a common disorder in elderly population which predisposes to fracture with minimal trauma. This study was performed to find out the association between the Body Mass Index (BMI) and Bone Mineral Density (BMD) in postmenopausal women.Materials and Methods: This cross sectional study was carried out at Institute of Nuclear Medicine and Allied Sciences Comilla and Mitford, Dhaka over a period of 12 months from January 2013 to December 2013. A total 93 postmenopausal women were enrolled for this study. All postmenopausal women underwent a BMD scan of femoral neck and lumbar vertebrae using a Dual Energy X-ray Absorptiometry (DEXA). Participants were categorized into three groups according to their age and BMI. BMD were expressed base on T-score according to WHO criteria. The relation among BMI, age and BMD were assessed.Results: The results of this study showed that the mean age of the study group was 57.13±7.49 years with range of 46 to 75 years. The most postmenopausal women were in age group 55-65years. The mean BMI of the study subjects were 24.18±5.08 kg/m2 with a range of 15.62 to 36.20 kg/m2. Among 93 subjects osteopenia was greater at lumbar spine (45.2%) with T-score mean±SD-1.83±0.33 and osteoporosis at femoral neck (51.6%) with T-score mean ±SD-3.36±-0.67. Pearsons correlation coefficient test showed inverse relationship between age and BMD both lumbar spine (r = -0.301, p = 0.003) and femoral neck (r = -0.303, p=0.003) whereas the positive relation between BMI and BMD both at lumbar spine (r=0.338, p=0.001) and femoral neck (r =0.343, p=0.001). These showed that with advancing age, BMD decreases and the risk of osteoporosis increases and with increasing BMI, BMD increases and risk of osteoporosis decreases.Conclusion: The findings of this study portrait that aging and low BMI are risk factors associated with bone loss. So preventive measure should be taken for high risk post menopausal women.Bangladesh J. Nuclear Med. 17(2): 138-141, July 2014

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Association between renal function and bone mineral density in healthy postmenopausal Chinese women

BMC Endocrine Disorders ◽

10.1186/s12902-019-0476-y ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Shuang Li ◽

Junkun Zhan ◽

Yanjiao Wang ◽

Yi Wang ◽

Jieyu He ◽

...

Keyword(s):

Bone Mineral Density ◽

Renal Function ◽

Femoral Neck ◽

Bone Mineral ◽

Chinese Women ◽

Mineral Density ◽

Cross Sectional ◽

Total Hip ◽

The Relationship ◽

Osteoporosis Risk

Abstract Background The relationship between renal function and bone mineral density (BMD) is controversial. The aim of this study was to determine the relationship of renal function with BMD and osteoporosis risk in healthy postmenopausal Chinese women. Methods A cross-sectional study was conducted in 776 healthy postmenopausal Chinese women. Dual-energy X-ray absorptiometry was used to measure BMDs. Clinical, demographic, and biochemical data were obtained at the time of image acquisition. Estimated glomerular filtration rate (eGFR) was calculated using a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Results Women with eGFR levels of at least 90 ml/min/1.73m2 had a lower prevalence of osteoporosis compared with women with decreased eGFR levels (60 ml/min/1.73 m2 ≤ eGFR < 90.0 ml/min/1.73 m2). BMDs at femoral neck and total hip were significantly lower in the lower eGFR class than the higher class (0.717 ± 0.106 vs 0.744 ± 0.125 g/cm2, P < 0.01; 0.796 ± 0.116 vs 0.823 ± 0.129 g/cm2, P < 0.01, respectively). eGFR was positively correlated with BMDs at femoral neck and total hip in unadjusted analysis (P < 0.05). After controlling for age, menopausal duration and body mass index (BMI), decreased eGFR was not associated with osteoporosis risk. Conclusions After adjustments for age, menopausal duration and BMI, the decline in renal function was not independently associated with osteoporosis risk in healthy postmenopausal Chinese women.

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Relation between intima-media thickness and bone mineral density in postmenopausal women: a cross-sectional study

Sao Paulo Medical Journal ◽

10.1590/s1516-31802011000300004 ◽

2011 ◽

Vol 129 (3) ◽

pp. 139-145 ◽

Cited By ~ 9

Author(s):

Daniela Fodor ◽

Cosmina Bondor ◽

Adriana Albu ◽

Laura Muntean ◽

Siao-pin Simon ◽

...

Keyword(s):

Lumbar Spine ◽

Femoral Neck ◽

Postmenopausal Women ◽

Atherosclerotic Plaque ◽

Vertebral Fractures ◽

Mineral Density ◽

Cross Sectional ◽

T Score ◽

Osteoporotic Vertebral Fractures ◽

The Relationship

CONTEXT AND OBJECTIVES: Controversy exists regarding the relationship between atherosclerosis and osteoporosis. The aim of this study was to determine the relationship between intima-media thickness (IMT) of the common carotid artery (CCA), presence of calcified atherosclerotic plaques and bone mineral density (BMD) evaluated by dual energy X-ray absorptiometry (DXA), in postmenopausal women. DESIGN AND SETTING: Cross-sectional study at Second Internal Medicine Clinic, Cluj-Napoca, Romania. METHODS: We studied the IMT (left and right CCA and mean IMT) and T-score (lumbar spine L2-L4, femoral neck and total hip) in 100 postmenopausal women (mean age 64.5 years). The presence of calcified atherosclerotic plaque and osteoporotic vertebral fractures was also noted. RESULTS: IMT in the left and right CCA and mean IMT were significantly associated with T-score measured for the lumbar spine L2-L4, femoral neck and total hip, with lower T-score, in the osteoporotic group than in the normal and osteopenic groups (P < 0.05). IMT had a significantly negative correlation with the lumbar spine T-score and femoral neck T-score; and mean IMT with lowest T-score. Mean IMT (P < 0.001), high blood pressure (P = 0.005) and osteoporotic vertebral fractures (P = 0.048) showed statistical significance regarding the likelihood of developing atherosclerotic plaque. CONCLUSIONS: In women referred for routine osteoporosis screening, the relationship between CCA, atherosclerosis and osteoporosis can be demonstrated using either cortical or trabecular BMD. Vertebral fractures may be considered to be a likelihood factor for atherosclerotic plaque development.

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Adequacy of androgen replacement influences bone density response to testosterone in androgen-deficient men

Acta Endocrinologica ◽

10.1530/eje.1.01920 ◽

2005 ◽

Vol 152 (6) ◽

pp. 881-886 ◽

Cited By ~ 40

Author(s):

Ashraf Aminorroaya ◽

Sharyn Kelleher ◽

Ann J Conway ◽

Lam P Ly ◽

David J Handelsman

Keyword(s):

Osteoporotic Fractures ◽

Testosterone Replacement ◽

Longitudinal Assessment ◽

Mineral Density ◽

Cross Sectional ◽

X Ray ◽

Dexa Scan ◽

Density Response ◽

Sectional Analysis ◽

Design And Methods

Objective: Androgen deficiency (AD) leads to bone loss and contributes to osteoporotic fractures in men. Although low bone mineral density (BMD) in AD men is improved by testosterone replacement, the responses vary between individuals but the determinants of this variability are not well defined. Design and methods: Retrospective review of dual energy X-ray absorptiometry (DEXA) of the lumbar spine and proximal femur in men with established AD requiring regular androgen replacement therapy (ART). After a DEXA scan all men were treated with testosterone implants (800 mg, ~6 month intervals). Patients were classified as having a congenital, childhood, or post-pubertal onset, as well as according to the adequacy of treatment prior to their first DEXA scan as untreated, partially treated or well treated. Results: Men with AD requiring regular ART (n = 169, aged 46.3±1.1 years, range 22–84 years) underwent a DEXA scan prior to being treated with testosterone implants (800 mg, ~6 month intervals). In cross-sectional analysis at the time of the first DEXA scan untreated men (n = 24) had significantly reduced age-adjusted BMD at all four sites (L1–L4, femoral neck, Ward’s triangle and trochanter). Well-treated men (n = 77) had significantly better age-adjusted BMD at all four sites compared with those who were partially treated (n = 66) or untreated (n = 24) with their age-adjusted BMD being normalized. In a longitudinal assessment of men (n = 60) who had two or more serial DEXA scans, at the second DEXA scan after a median of 3 years, men who were previously partially treated (n = 19) or untreated (n = 11) had proportionately greater improvements in BMD, significantly for Ward’s triangle (P = 0.025) and the trochanter (P = 0.044) compared with men (n = 30) previously well treated. Conclusions: The present study demonstrates a positive relationship between adequacy of testosterone replacement and BMD in men with overt organic AD. Additionally, the BMD of well-treated AD men approximates that of age-matched non-AD controls. The greatest BMD gains are made by those who have been either untreated or partially treated, and optimal treatment over time (median 3 years) normalizes BMD to the level expected for healthy men of the same age.

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352 The Effect of Epidural Steroid Injections on Bone Mineral Density and Vertebral Fracture Risk: A Systematic Review and Critical Appraisal of Current Literature

Neurosurgery ◽

10.1093/neuros/nyx417.352 ◽

2017 ◽

Vol 64 (CN_suppl_1) ◽

pp. 280-280

Author(s):

Panagiotis Kerezoudis ◽

Lorenzo Rinaldo ◽

Mohammed Ali Alvi ◽

Sandy Goncalves ◽

Christine Hunt ◽

...

Keyword(s):

Vertebral Fracture ◽

Femoral Neck ◽

Osteoporotic Fractures ◽

Mineral Density ◽

Steroid Injections ◽

Epidural Steroid Injections ◽

Vertebral Fracture Risk ◽

Patients At Risk ◽

One Year ◽

Epidural Steroid

Abstract INTRODUCTION Epidural steroid injections (ESIs) are a common treatment for the management of patients with radicular back pain. It is also known that the long-term enteral administration of exogenous steroids disrupts bone health and skeletal micro-architecture METHODS A systematic and critical review of recent literature was conducted in accordance with PRISMA guidelines. RESULTS >A total of 8 studies were included in the analysis (6 retrospective, 2 prospective). A total of 7233 patients with a mean age ranging between 49 and 74 years and an average follow-up between 6 and 60 months were studied. Steroids that were used included triamcinolone, dexamethasone, and methylprednisolone (MP), with a mean number of injections ranging from 1 to 14.7 and average cumulative dose in MP equivalents between 80 and 8130 mg. A single ESI was shown to decrease BMD as measured at the femoral neck by 1.8%, and increase the risk of vertebral fracture by 21%. Significant reductions in BMD were associated with a cumulative MP dose of 200 mg over a one year period and 400 mg over three years, but not in doses of less than 200 mg of MP equivalents for postmenopausal women and at least 3 g for healthy men. The risk of osteopenia and osteoporosis was lower in patients that were receiving anti-osteoporotic medication during the treatment course. CONCLUSION ESIs can decrease BMD, both locally (lumbar spine) and systemically (femoral neck) and increase the risk of vertebral fracture. Therefore, ESIs should be recommended with caution, especially in patients at risk for osteoporotic fractures, such as women of postmenopausal age. Anti-osteoporotic medication might be considered prior to ESI.

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Potential role of FRAX analysis in postmenopausal women with osteopenia

Open Medicine ◽

10.2478/s11536-011-0002-8 ◽

2011 ◽

Vol 6 (2) ◽

pp. 185-189

Author(s):

Aleksandar Dimić ◽

Stojanovic Sonja ◽

Nedovic Jovan ◽

Stankovic Aleksandra ◽

Stamenkovic Bojana ◽

...

Keyword(s):

Hip Fracture ◽

High Risk ◽

Postmenopausal Women ◽

Hip Fractures ◽

Potential Role ◽

Osteoporotic Fractures ◽

Significant Negative Correlation ◽

Mineral Density ◽

Fracture Development

AbstractEarly diagnosis of osteoporosis and estimation of subjects that are at high risk for fracture, is neccesary for osteoporosis treatment. Dual-energy X-ray absorptometry (DXA) is a modern method for bone mineral density (BMD) evaluation. However, along BMD, clinical risk factors may significantly influence fracture development. Therefore, FRAX algorithm was designed for the assessment of a ten-year risk for serious osteoporotic fractures (SOF), as well as hip fractures. In the current study, we tried to evaluate the possible lumbal spine and hip BMD influence on ten year risk for SOF and hip fractures and potential role of FRAX in predicting the therapy in postmenopausal women with osteopenia. We performed the study on 385 postmenopausal women. According to the DXA measurements, at the lumbal (L) spine (L1–L4) and hip (femor neck), patients were then classified as normal, osteopenic, or osteoporotic. BMD evaluation included the L spine and the hip (subgroup 1), and only on the L spine (subgroup 2). By filling up the FRAX questionnaire, a ten-year risk for SOF fracture and hip fracture was calculated. BMD evaluation, in complete patient’s group and in subgroup 1, resulted in the highest number of osteoporosis (61.04%, 48.08%, retrospectively), while ospeopenia was a main finding in subgroup 2. In the subgroup 1, a high risk for SOF and hip fracture was detected in 16.45% and with high risk for hip fracture in 11.38% subjects. In subgroup 2, only high risk for hip fracture was observed in 3.16% subjects, indicating the active medicament treatment. Simultaneously, correlation of BMD results with FRAX values for SOF and hip fracture, showed significant negative correlation (p<0.001). Obtained results showed significant role of femur neck BMD evaluation in predicting the future factors, which may, together with FRAX analysis, improve the therapy approach in postmenopausal women with ospeopenia.

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Pharmacogenomic effects of β-blocker use on femoral neck bone mineral density

Journal of the Endocrine Society ◽

10.1210/jendso/bvab092 ◽

2021 ◽

Author(s):

Kathleen T Nevola ◽

Archana Nagarajan ◽

Alexandra C Hinton ◽

Katerina Trajanoska ◽

Melissa M Formosa ◽

...

Keyword(s):

Bone Mineral Density ◽

Single Nucleotide Polymorphisms ◽

Femoral Neck ◽

Bone Mineral ◽

Nucleotide Polymorphisms ◽

Rotterdam Study ◽

Mineral Density ◽

Single Nucleotide ◽

Β Blocker ◽

Using Data

Abstract Context Recent studies have shown that β-blocker (BB) users have a decreased risk of fracture and higher bone mineral density (BMD) compared to non-users, likely due to the suppression of adrenergic signaling in osteoblasts, leading to increased BMD. There is also variability in the effect size of BB use on BMD in humans, which may be due to pharmacogenomic effects. Objective To investigate potential single nucleotide polymorphisms (SNPs) associated with the effect of BB use on femoral neck BMD, we performed a cross-sectional analysis using clinical data, dual-energy X-ray absorptiometry, and genetic data from the Framingham Heart Study’s (FHS) Offspring Cohort. We then sought to validate our top four genetic findings using data from the Rotterdam Study, the BPROOF Study, the MOFS, and the Hertfordshire Cohort Study. Design We used sex-stratified linear mixed models to determine SNPs that had a significant interaction effect with BB use on femoral neck (FN) BMD across 11 gene regions. We also evaluated the association of our top single nucleotide polymorphisms (SNPs) from the FHS with microRNA (miRNA) expression in blood and identified potential miRNA-mediated mechanisms by which these SNPs may impact FN BMD. Results One polymorphism (rs11124190 in HDAC4) was validated in females using data from the Rotterdam Study, while another (rs12414657 in ADRB1) was validated in females using data from the MOFS. We performed an exploratory meta-analysis of all 5 studies for these polymorphisms, which further validated our findings. Conclusions This analysis provides a starting point for investigating the pharmacogenomic effects of BB use on BMD measures.

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Age-related changes in bone tissue in men

PAIN JOINTS SPINE ◽

10.22141/2224-1507.11.2.2021.236564 ◽

2021 ◽

Vol 11 (2) ◽

pp. 62-69

Author(s):

A.S. Musiienko ◽

N.V. Zaverukha

Keyword(s):

Lumbar Spine ◽

Femoral Neck ◽

Bone Tissue ◽

Clinical Signs ◽

Osteoporotic Fractures ◽

State Institution ◽

Mineral Density ◽

Healthy Men ◽

Age Related ◽

Age Related Changes

The purpose of the study was to establish age-related changes of male bone tissue. Materials and methods. The study was conducted by the Department of Clinical Physiology and Pathology of the Musculoskeletal System of the State Institution “D.F. Chebotarev Institute of Gerontology by the National Academy of Medical Sciences of Ukraine”. It involved 342 healthy men aged 20 to 89 years without osteoporosis and osteoporotic fractures or any pathology with a confirmed impact on bone tissue, as well as any somatic pathology in the sub- and decompensation. The following methods of examination were used: questionnaire, anthropometric measurements, clinical and instrumental examination. Bone mineral density (BMD) was measured by the dual-energy X-ray absorptiometry machine “Prodigy, GEНС Lunar” at the level of the entire skeleton, lumbar spine (L1-L4), proximal femur and femoral neck, distal and ultra-distal forearm bones. Results. We have detected a significant 14.8 % decrease of BMD at the level of femoral neck in the group of men aged 60–69 years, by 20 % in the group of men aged 70–79 years, and by 24.1 % in the group of men aged 80–89 years compared to the men aged 20–29 years; at the same time, at the lumbar spine there was registered a decrease of this parameter by 1.6 % in men aged 60–69 years, by 1.9 % in men of 70–79 years and by 0.8 % in men of 80–89 years, respectively. Among the examined practically healthy men, the bone tissue remained at the normal level relative to age in 67.8 %; osteopenia was detected in 27.8 %, and osteoporosis in 4.4 %. Conclusions. An age-associated BMD reduction was registered at various skeletal sites in the practically healthy men without any clinically significant factors affecting bone tissue metabolism. The most pronounced BMD loss was observed at the level of femoral neck. At the same time, 4.4 % of examined had osteoporosis without any clinical signs.

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