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Determinants of peak bone mass: clinical and genetic analyses in a young female Canadian cohort.

https://arctichealth.org/en/permalink/ahliterature202198
Source
J Bone Miner Res. 1999 Apr;14(4):633-43
Publication Type
Article
Date
Apr-1999
Author
L A Rubin
G A Hawker
V D Peltekova
L J Fielding
R. Ridout
D E Cole
Author Affiliation
Division of Rheumatology, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada.
Source
J Bone Miner Res. 1999 Apr;14(4):633-43
Date
Apr-1999
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Bone Density - genetics - physiology
Canada
Cohort Studies
Female
Genotype
Haplotypes
Hip
Humans
Multivariate Analysis
Osteoporosis - etiology - genetics - physiopathology
Receptors, Calcitriol - genetics
Risk factors
Spine
Abstract
Peak bone mass has been shown to be a significant predictor of risk for osteoporosis. Previous studies have demonstrated that skeletal mass accumulation is under strong genetic control, and efforts have been made to identify candidate loci. Determinants of peak bone mass also include diet, physical activity, hormonal status, and other clinical factors. The overall contribution of these factors, genetic and nongenetic, and their interaction in determining peak bone density status have not been delineated. Six hundred and seventy-seven healthy unrelated Caucasian women ages 18-35 years were assessed. A detailed, standardized interview was conducted to evaluate lifestyle factors, menstrual and reproductive history, medical conditions, medication use, and family history of osteoporosis. Bone mineral density (BMD) was measured at the lumbar spine (L2-L4) and the femoral neck (hip) using dual-energy X-ray absorptiometry. Genotyping of the vitamin D receptor (VDR) locus at three polymorphic sites (BsmI, ApaI, and TaqI) was performed. In bivariate analyses, BMD at the lumbar spine and hip was positively correlated with weight, height, body mass index (BMI), and level of physical activity, both now and during adolescence, but negatively correlated with a family history of osteoporosis. Hip, but not spine BMD, correlated positively with dietary intake of calcium, and negatively with amenorrhea of more than 3 months, with caffeine intake, and with age. Spine, but not hip BMD, correlated positively with age and with number of pregnancies. VDR haplotype demonstrated significant associations with BMD at the hip, level of physical activity currently, and BMI. In multivariate analysis, independent predictors of greater BMD (at the hip or spine) were: age (younger for the hip, older for the spine), greater body weight, greater height (hip only), higher level of physical activity now and during adolescence, no family history of osteoporosis, and VDR genotype (hip only). Weight, age, level of physical activity, and family history are independent predictors of peak BMD. Of these factors, weight accounts for over half the explained variability in BMD. VDR alleles are significant independent predictors of peak femoral neck, but not lumbar spine BMD, even after adjusting for family history of osteoporosis, weight, age, and exercise. However, the overall contribution of this genetic determinant is modest. Taken together, these factors explained approximately 17% and 21% of the variability in peak spine and hip BMD, respectively, in our cohort. Future research should be aimed at further evaluation of genetic determinants of BMD. Most importantly, understanding the critical interactive nature between genes and the environment will facilitate development of targeted strategies directed at modifying lifestyle factors as well as earlier intervention in the most susceptible individuals.
PubMed ID
10234586 View in PubMed
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A poly adenosine repeat in the human vitamin D receptor gene is associated with bone mineral density in young Swedish women.

https://arctichealth.org/en/permalink/ahliterature18216
Source
Calcif Tissue Int. 2003 Nov;73(5):455-62
Publication Type
Article
Date
Nov-2003
Author
E. Grundberg
H. Brändström
E L Ribom
O. Ljunggren
A. Kindmark
H. Mallmin
Author Affiliation
Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden. Elin.Grundberg@medsci.uu.se
Source
Calcif Tissue Int. 2003 Nov;73(5):455-62
Date
Nov-2003
Language
English
Publication Type
Article
Keywords
Adenosine - genetics
Adult
Body Composition - physiology
Bone Density - genetics
Calcaneus - ultrasonography
Cohort Studies
DNA Mutational Analysis
Densitometry, X-Ray
Deoxyribonucleases, Type II Site-Specific - genetics
Female
Genotype
Humans
Linkage (Genetics)
Microsatellite Repeats - genetics
Polymers
Polymorphism, Single Nucleotide - genetics
Premenopause
Receptors, Calcitriol - genetics
Research Support, Non-U.S. Gov't
Sweden
Abstract
Peak bone mass (PBM) and subsequent bone loss are important risk factors for development of osteoporosis later in life, and twin studies have reported strong genetic influence on PBM. The genetic factor influencing PBM is polygenetic, and many genes most likely exert relatively small effects on bone mass. The poly adenosine (A) microsatellite in the 3' untranslated region (UTR) of the VDR gene has been associated with both prostate and breast cancer risk but little is known about the effect of bone mineral density (BMD). In this report the poly A microsatellite and the linked BsmI SNP have been investigated in a population-based cohort of 343 Swedish women, aged 20-39. BMD was measured by dual x-ray absorptiometry at the spine, proximal femur, total body and heel and by quantitative ultrasound at the heel. Correlations were found between VDR genotypes and BMD at lumbar spine L2-L4, (ss versus LL, P = 0.03 and BB versus bb, P = 0.02, respectively), with a similar pattern concerning total hip (ss versus LL, P = 0.12 and BB versus bb, P = 0.16 respectively). After corrections for age, height, fat and lean mass, the VDR BsmI genotype was still associated to BMD at the lumbar spine (BB versus bb, P = 0.03). The polymorphisms were in linkage disequilibrium (Chi-square = 566, P
PubMed ID
12958689 View in PubMed
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Vitamin D and estrogen receptor-alpha genotype and indices of bone mass and bone turnover in Danish girls.

https://arctichealth.org/en/permalink/ahliterature81633
Source
J Bone Miner Metab. 2006;24(4):329-36
Publication Type
Article
Date
2006
Author
Cusack Siobhan
Mølgaard Christian
Michaelsen Kim F
Jakobsen Jette
Lamberg-Allardt Christel J E
Cashman Kevin D
Author Affiliation
Department of Food and Nutritional Sciences, University College, Cork, Ireland.
Source
J Bone Miner Metab. 2006;24(4):329-36
Date
2006
Language
English
Publication Type
Article
Keywords
Age Factors
Biological Markers
Bone Density - genetics
Bone Remodeling - genetics
Child
Denmark
Densitometry, X-Ray
Estrogen Receptor alpha - genetics
Female
Genotype
Humans
Receptors, Calcitriol - genetics
Abstract
Peak bone mass is a major determinant of osteoporosis risk in later life. It is under strong genetic control; however, little is known about the identity of the genes involved. In the present study, we investigated the relationship between polymorphisms in the genes encoding the vitamin D receptor (VDR) (FokI, TaqI) and estrogen receptor-alpha (ERalpha) (PvuII, XbaI), and bone mineral density (BMD), bone mineral content (BMC), and markers of bone turnover in 224 Danish girls aged 11-12 years. BMD and BMC were measured by dual-energy X-ray absorptiometry. Serum osteocalcin, 25(OH)D, and parathyroid hormone (PTH) were measured by ELISA assays and urinary pyridinium cross-links by HPLC. Physical activity, dietary calcium, and Tanner stage were assessed by questionnaire. In general, there were no significant differences in anthropometrical variables, physical activity, dietary calcium, serum 25(OH)D, or PTH among genotype groups. BMD or BMC of lumbar spine or whole body (adjusted for body and bone size and pubertal status) were not associated with VDR or ERalpha genotypes or the combination of these genotypes. This lack of association remained even after adjustment for dietary and environmental factors. VDR genotypes had no effect on bone turnover markers. XX and PP ERalpha genotypes were associated (P
PubMed ID
16816928 View in PubMed
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Vitamin D receptor gene BsmI-polymorphism in Finnish premenopausal and postmenopausal women: its association with bone mineral density, markers of bone turnover, and intestinal calcium absorption, with adjustment for lifestyle factors.

https://arctichealth.org/en/permalink/ahliterature187765
Source
J Bone Miner Metab. 2002;20(6):383-90
Publication Type
Article
Date
2002
Author
Marika Laaksonen
Merja Kärkkäinen
Terhi Outila
Tarja Vanninen
Carola Ray
Christel Lamberg-Allardt
Author Affiliation
Calcium Research Unit, Division of Nutrition, Department of Applied Chemistry and Microbiology, University of Helinski, Finland.
Source
J Bone Miner Metab. 2002;20(6):383-90
Date
2002
Language
English
Publication Type
Article
Keywords
Adult
Aged
Biological Markers
Bone Density - genetics
Bone and Bones - metabolism
Calcium - metabolism
Female
Finland
Humans
Intestinal Absorption
Life Style
Middle Aged
Osteoporosis, Postmenopausal
Polymorphism, Genetic
Postmenopause
Premenopause
Receptors, Calcitriol - genetics
Abstract
Bone mineral density (BMD) is regulated by genetic and environmental factors. Sixty percent to 80% of bone mass is suggested to be under polygenetic control, but the role of individual genes seems to be modest. Several studies have indicated that the vitamin D receptor ( VDR) gene has a role in the regulation of BMD and bone metabolism, but the results are very controversial. We studied the associations between BsmI-polymorphism of the VDR gene and BMD and bone metabolism in 24 premenopausal (aged 22-45 years) and 69 postmenopausal (aged 48-65 years) Finnish women. The BMD of the lumbar spine and femoral neck and bone turnover markers were measured, and the intestinal calcium absorption was investigated, using a method based on the absorption of non-radioactive strontium. The genotype distribution was 16%, BB; 34.5%, Bb; and 49.5%, bb, which differs from the genotype distribution found in other Caucasian populations, but is similar to earlier Finnish reports. The winter value of 25-hydroxyvitamin-D (25-OH-D) was highest for the BB genotype in both age groups (analysis of covariance [ANCOVA]; premenopausal women P = 0.5, postmenopausal women P = 0.03, and for the groups combined P = 0.02). Lumbar spine BMD and intestinal strontium absorption were highest for the BB genotype in both age groups, but these results were nonsignificant. The markers of bone metabolism did not differ significantly between the VDR genotypes. The BB genotype had the best vitamin D status, which could explain the differences in calcium absorption between the genotypes. However, the conclusions of our study are limited because of the small number of subjects.
PubMed ID
12434167 View in PubMed
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