Determination of bone mineral density of the hip and spine in human pedigrees by genetic and life-style factors

Deng, Hong Wen; Chen, Wei Min; Conway, Theresa; Zhou, Yan; Davies, K. Michael; Stegman, Mary Ruth; Deng, Hong‐Wen; Recker, Robert R.

doi:10.1002/1098-2272(200009)19:2<160::aid-gepi4>3.0.co;2-h

Cited by 94 publications

(69 citation statements)

References 63 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Osteoporosis has long been known to have a genetic basis. Various twin (3)(4)(5) and family (19)(20)(21) studies have shown that genetic factors contribute to approximately 60% to 90% of BMD variance and other markers of osteoporosis, (22,23) which our cross-sectional estimates confirm. However, with regard to the longitudinal changes of BMD, the heritability estimates are much lower even in early postmenopausal women.…”

Section: Discussionmentioning

confidence: 99%

“…All of the previous studies evaluating heritability of bone mass or longitudinal bone loss have considered age as a simple covariate in their models. (3)(4)(5)(6)(7)(8)(9)(10)12,(19)(20)(21)(22)(23) The results of our study also show that age can be treated as a simple covariate for cross-sectional BMD measures because heritability estimates change little across a 40-year age span (all of them are generally between 70% and 90%). However, the age effect has to be considered for the longitudinal changes, as the model fits change completely with advanced aging.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of age on genetic influence on bone loss over 17 years in women: The Healthy Ageing Twin Study (HATS)

Moayyeri

Hammond

Hart

et al. 2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

The rate of bone loss varies across the aging period via multiple complex mechanisms. Therefore, the role of genetic factors on bone loss may also change similarly. In this study, we investigated the effect of age on the genetic component of bone loss in a large twin-based longitudinal study. During 17 years of follow-up in TwinsUK and Healthy Ageing Twin Study (HATS), 15,491 hip and lumbar spine dualenergy X-ray absorptiometry (DXA) scans were performed in 7056 twins. Out of these subjects, 2716 female twins aged >35 years with at least two scans separated for >4 years (mean follow-up 9.7 years) were included in this analysis. We used a mixed-effects randomcoefficients regression model to predict hip and spine bone mineral density (BMD) values for exact ages of 40, 45, 50, 55, 60, 65, 70, 75, and 80 years, with adjustment for baseline age, weight, height, and duration of hormone replacement therapy. We then estimated heritability of the changes in BMD measures between these age ranges. Heritability estimates for cross-sectional hip and spine BMD were high (ranging between 69% and 88%) at different ages. Heritability of change of BMD was lower and more variable, generally ranging from 0% to 40% for hip and 0% to 70% for spine; between age 40 and 45 years genetic factors explained 39.9% (95% confidence interval [CI], 25%-53%) of variance of BMD loss for total hip, 46.4% (95% CI, 32%-58%) for femoral neck, and 69.5% (95% CI, 59%-77%) for lumbar spine. These estimates decreased with increasing age, and there appeared to be no heritability of BMD changes after the age of 65 years. There was some evidence at the spine for shared genetic effects between cross-sectional and longitudinal BMD. Whereas genetic factors appear to have an important role in bone loss in early postmenopausal women, nongenetic mechanisms become more important determinants of bone loss with advanced age. ß

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of age on genetic influence on bone loss over 17 years in women: The Healthy Ageing Twin Study (HATS)

Moayyeri

Hammond

Hart

et al. 2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…The effect of nicotine on bone mineral density reduction is achieved through increased levels of estrogen metabolism in the liver, impaired circulation, reduced resorption of calcium and vitamin D, and a direct action on bone cells (Deng et al, 2000). In our study, this risk factor was present in seven subjects in the group with BMD ≤ -2.5 SD and in three women with normal BMD.…”

Section: Figurementioning

confidence: 99%

Impact of Vitamin D Deficiency on Fluctuation of Calcium and Parathyroid Hormone Levels in Postmenopausal Osteoporosis

Milivojac¹,

Rašeta²,

Aksentić³

et al. 2015

sgia

View full text Add to dashboard Cite

SUMMARYThe primary role of vitamin D is regulation of calcium, phosphorus and bone metabolism. Vitamin D status assessment is based on measuring of 25 (OH) D concentrations, and disorders of vitamin D status may be manifested as a vitamin D insufficiency, vitamin D deficiency and vitamin D hypervitaminosis. It is generally accepted that values above 75 nmol / L will suffice to prevent the occurrence of secondary hyperparathyroidism. Although vitamin D deficiency can be found at any age, it is most common in women with postmenopausal osteoporosis, and in older women. The aim of this study was to determine the vitamin D status, parathyroid hormone levels and calcium levels in women with newly diagnosed postmenopausal osteoporosis, and to compare the results with the same parameters observed and measured in women without osteoporosis, and to establish whether there is a connection between vitamin D levels and levels of other parameters. The study involved 85 postmenopausal women, all of which were screened for osteoporosis by measuring bone mineral density in the lumbar spine and hip region using DXA method. Of these, 50 women were found to have osteoporosis while 35 had regular DXA values. Our results showed a high incidence of vitamin D deficiency in postmenopausal women, with significantly higher vitamin D deficiency in women with osteoporosis. The values of parathyroid hormone were higher, and the values of ionized calcium were lower in women with osteoporosis, and there is a negative correlation between 25 (OH) D and parathyroid hormone. The most common risk factors for osteoporotic fracture in postmenopausal women were early menopause and previous fracture in adulthood. Reduced levels of vitamin D in women with postmenopausal osteoporosis leads to changes in calcium and parathyroid hormone metabolism

show abstract

“…These factors generally affect BMD and obesity-related phenotype variation significantly . Generally, adjustment for significant covariates in genetic analyses can increase the genetic signal to noise ratio by decreasing the proportion of the residual phenotypic variation attributable to random environmental factors (Deng et al 2000). This can improve statistical power in our linkage and/or association analyses.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…Low bone mineral density (BMD) is an important risk factor for osteoporotic fractures, and osteoporosis is mainly characterized by low BMD. It is known that BMD variation is determined largely by genetic factors, with heritability estimates ranging from 0.5 to 0.9 (Dequeker et al 1987;Pocock et al 1987;Slemeda et al 1991;Gueguen et al 1995;Nguyen et al 1998;Deng et al 1999Deng et al , 2000. Interleukin-6 (IL6) is a pleiotropic cytokine that has important effects on osteoclast differentiation and function (Roodman 1992;Jilka et al 1992).…”

Section: Introductionmentioning

confidence: 99%

Linkage and association of the CA repeat polymorphism of the IL6 gene, obesity-related phenotypes, and bone mineral density (BMD) in two independent Caucasian populations

et al. 2003

Self Cite

View full text Add to dashboard Cite

Genetic factors play an important role in osteoporosis and obesity, two serious public health problems in the world. We investigated the relationships between obesity-related phenotypes, bone mineral density (BMD) and the CA repeat polymorphism of the IL6 gene in two large independent samples using the quantitative transmission disequilibrium test (QTDT). The first sample consisted of 1,816 individuals from 79 multigenerational pedigrees. Each pedigree was identified through a proband with BMD Z-scores £ )1.28 at the hip or spine. The second sample was a randomly ascertained set of 636 individuals from 157 nuclear families. Ten alleles containing 9-18 CA repeats were identified in our Caucasian populations. For body mass index (BMI), fat mass and percentage fat mass (PFM), highly significant (P<0.01) or significant (P<0.05) results were found for linkage in our sample of nuclear families and for association in the multigenerational pedigrees. We also observed weak evidence for linkage (P=0.069) with spine BMD and for association with hip BMD in the sample of multigenerational pedigrees. Our results suggest that genetic variation in or near the IL6 locus may be involved in the etiology of obesity and osteoporosis.Keywords Osteoporosis AE Obesity AE IL6 gene AE Association AE Linkage AE Transmission disequilibrium test IntroductionOsteoporosis is a major public health problem, particularly for women, who have a 40-50% lifetime risk of osteoporotic fractures (Melton et al. 1992). Low bone mineral density (BMD) is an important risk factor for osteoporotic fractures, and osteoporosis is mainly characterized by low BMD. It is known that BMD variation is determined largely by genetic factors, with heritability estimates ranging from 0.5 to 0.9 (Dequeker et al. 1987;Pocock et al. 1987;Slemeda et al. 1991;Gueguen et al. 1995;Nguyen et al. 1998;Deng et al. 1999Deng et al. , 2000. Interleukin-6 (IL6) is a pleiotropic cytokine that has important effects on osteoclast differentiation and function (Roodman 1992;Jilka et al. 1992). IL6 maps to chromosome 7p21. IL6 mRNA expression in bone is enhanced in 95% of patients with osteoporotic vertebral fractures compared with 50% of postmenopausal controls (Ralston 1994). Some have reported an association between polymorphisms of the IL6 gene and BMD (Murray et al. 1997;Tsukamoto et al. 1999;Ferrari et al. 2001;Ota et al. 2001). However, others have reported negative results (Takacs et al. 2000;Weerakulwattana et al. 2001). In addition, the IL6 gene locus showed weak linkage with BMD of the lumbar spine but not of the femoral neck in Caucasian families in UK (Duncan et al. 1999). Recently, we performed a whole genome screen in a sample of 53 pedigrees with 630 Caucasian subjects. Chromosome 7p22 showed some evidence of linkage to spine BMD with a multi-point LOD=1.93 (Deng et al. 2002b).

show abstract

Determination of bone mineral density of the hip and spine in human pedigrees by genetic and life-style factors

Cited by 94 publications

References 63 publications

Effects of age on genetic influence on bone loss over 17 years in women: The Healthy Ageing Twin Study (HATS)

Effects of age on genetic influence on bone loss over 17 years in women: The Healthy Ageing Twin Study (HATS)

Impact of Vitamin D Deficiency on Fluctuation of Calcium and Parathyroid Hormone Levels in Postmenopausal Osteoporosis

Linkage and association of the CA repeat polymorphism of the IL6 gene, obesity-related phenotypes, and bone mineral density (BMD) in two independent Caucasian populations

Contact Info

Product

Resources

About