Genetic and Environmental Correlations Between Bone Formation and Bone Mineral Density: A Twin Study

Harris, Mark; Nguyen, Tuan V.; Howard, G.; Kelly, Paul; Eisman, John A.

doi:10.1016/s8756-3282(97)00252-4

Cited by 115 publications

(85 citation statements)

References 19 publications

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“…The cross sectional area (CSA, mm 2 ), volumetric bone mineral density (vBMD, mg/cm 3 ), and polar moment of inertia (g*mm) were analyzed using a validated software (BonAlyse 1.3, BonAlyse OY, Jyväskylä, Finland). On the basis of the vBMD calibration of the scan system used, 169 mg/cm 3 and 280 mg/cm 3 were used as thresholds for the outer border of radius and tibia, respectively, and 100 mg/cm 3 for the inner border of the tibia. We also used a high threshold of 711 mg/cm 3 to specifically locate the cortical bone in the tibial shaft.…”

Section: Methodsmentioning

confidence: 99%

The COMT val158met Polymorphism Is Associated with Early Pubertal Development, Height and Cortical Bone Mass in Girls

et al. 2005

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Estrogens are involved in accretion of bone mass during puberty. Catechol-O-Methyltransferase (COMT) is involved in the degradation of estrogens. In this cross-sectional study we investigated associations between the COMT val158met polymorphism, which results in a 60 -75% difference in enzyme activity between the val (high activity ϭ H) and the met (low activity ϭ L) variant, and skeletal phenotypes in 246 healthy pre/early pubertal girls. Girls with COMT LL were 5.4 cm taller than COMT HH girls. Dual x-ray absorptiometry showed higher values of bone mineral content (BMC), and larger areas of total body, femur and spine in COMT LL . Cortical BMC, measured by peripheral quantitative computerized tomography in the tibia, was 9.8% higher in COMT LL compared with COMT HH . This was due to a larger cortical cross sectional area while the cortical volumetric bone mineral density was not associated with COMT genotype. COMT LL girls had higher serum levels of free estradiol and insulin like growth factor. Regression models indicated that COMT genotype exerted effects on skeletal growth mainly via a regulation of free estradiol, resulting in an affected pubertal development (Tanner staging). We propose that the COMT LL genotype results in higher free estradiol levels and earlier pubertal development, leading to an increased skeletal growth in pre/early pubertal girls. Peak bone mineral density (BMD) is an important determinant of the risk of developing osteoporosis later in life (1,2). It is generally well accepted that about 70% of the variation in peak BMD is due to genetic differences (3,4). Several different hormones, growth factors and nutritional factors are involved in the regulation of the accretion of bone mass (5,6). During childhood, thyroid hormones and the GH/IGF-axis are the principal hormones controlling growth (7-9). The following pubertal growth period is crucial for bone accretion, with past

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Section: Methodsmentioning

confidence: 99%

The COMT val158met Polymorphism Is Associated with Early Pubertal Development, Height and Cortical Bone Mass in Girls

et al. 2005

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“…Family-based studies have also yielded strong heritability estimates for BMD (Gueguen et al 1995), with effects that are maximal in young adults and persist even after adjusting for lifestyle factors that are known to regulate BMD (Krall & Dawson-Hughes 1993). Other determinants of osteoporotic fracture risk also have a heritable component, including: femoral neck geometry and hip axis length (Arden et al 1996, Flicker et al 1996, Slemenda et al 1996, ultrasound properties of bone (Arden et al 1996), biochemical markers of bone turnover (Morrison et al 1992, Tokita et al 1994, Garnero et al 1996, Harris et al 1998, body mass index (Carmichael & McGue 1995, Kaprio et al 1995, Arden & Spector 1997, muscle strength (Arden & Spector 1997), age at menarche (Kaprio et al 1995) and age at menopause (Snieder et al 1998). The data are conflicting with regard to the influence of genetic factors on bone loss; Christian et al (1989) found no evidence for a genetic effect on bone loss at the wrist in ageing male twins, whereas Kelly et al (1993) concluded that there were strong genetic effects on axial bone loss in female twins.…”

Section: What Is the Evidence For A Genetic Contribution To Osteoporomentioning

confidence: 99%

Role of genetic factors in the pathogenesis of osteoporosis

Stewart¹,

Ralston²

2000

Journal of Endocrinology

195

125

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Osteoporosis is a common disease with a strong genetic component characterised by low bone mass, microarchitectural deterioration of bone tissue and an increased risk of fracture. Twin and family studies have shown that genetic factors play an important role in regulating bone mineral density and other determinants of osteoporotic fracture risk, such as ultrasound properties of bone, skeletal geometry and bone turnover. Osteoporosis is a polygenic disorder, determined by the effects of several genes, each with relatively modest effects on bone mass and other determinants of fracture risk. It is only on rare occasions that osteoporosis occurs as the result of mutations in a single gene. Linkage studies in man and experimental animals have defined multiple loci which regulate bone mass but the genes responsible for these effects remain to be defined. Population-based studies and case-control studies have similarly identified polymorphisms in several candidate genes that have been associated with bone mass or osteoporotic fracture, including the vitamin D receptor, oestrogen receptor and collagen type I I gene. The individual contribution of these genes to the pathogenesis of osteoporosis is small however, reflected by the fact that the relationship between individual candidate genes and osteoporosis has been inconsistent in different studies. An important aim of future work will be to define how the genes which regulate bone mass, bone turnover and other aspects of bone metabolism interact with each other and with environmental variables to cause osteoporosis in individual patients. If that aim can be achieved then there is every prospect that preventative therapy could be targeted to those at greatest risk of the osteoporosis, before fractures have occurred.

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“…Several twin and family studies suggest that heritability strongly contributes to BMD [5][6][7] and osteoporotic fracture risk [8][9][10]. Genetic factors also play a role in expression of biochemical markers of bone turnover, skeletal geometry and ultrasound properties of bone [11][12][13][14]. These observations led to interest in finding genes that predispose individuals in the general population to osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Farnesyl diphosphate synthase: A novel genotype association with bone mineral density in elderly women

et al. 2007

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Mini-Abstract-Farnesyl diphosphate synthase (FDPS) is the molecular target of nitrogencontaining bisphosphonates. We analyzed the association between a SNP in the FDPS gene with bone mineral density (BMD) in post-menopausal Caucasian women. The SNP was associated with decreased BMD after adjusting for age and BMI. Genetic variation in FDPS may contribute to BMD in this population.Objective-We evaluated the association between a single nucleotide polymorphism in the farnesyl diphosphate synthase gene (FDPS), BMD and bone turnover markers.Methods-283 community-dwelling Caucasian women aged 65 or older were screened from the greater Boston area. A validated FDPS SNP (rs2297480, A/C) was genotyped and evaluated for effect on bone mineral density (spine, hip, forearm) and bone turnover markers (urine N-telopeptide crosslinked collagen type 1, osteocalcin and bone-specific alkaline phosphatase).Results-BMD was lower at all sites measured in women with the C/C or C/A genotypes. Statistically significant differences (p<0.05) were found at the PA spine, trochanter, distal radius, and proximal ulna after adjustment for age and BMI. No significant differences were found in bone turnover markers.Conclusion-These findings suggest that a single nucleotide polymorphism in the FDPS gene (rs2297480) may be a genetic marker for lower BMD in postmenopausal Caucasian women.

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Genetic and Environmental Correlations Between Bone Formation and Bone Mineral Density: A Twin Study

Cited by 115 publications

References 19 publications

The COMT val158met Polymorphism Is Associated with Early Pubertal Development, Height and Cortical Bone Mass in Girls

The COMT val158met Polymorphism Is Associated with Early Pubertal Development, Height and Cortical Bone Mass in Girls

Role of genetic factors in the pathogenesis of osteoporosis

Farnesyl diphosphate synthase: A novel genotype association with bone mineral density in elderly women

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