Variation in the PTH Gene, Hip Fracture, and Femoral Neck Geometry in Elderly Women

Tenne, Max; McGuigan, Fiona; Ahlborg, Henrik; Gerdhem, Paul; Åkesson, Kristina

doi:10.1007/s00223-010-9351-6

Cited by 11 publications

(3 citation statements)

References 47 publications

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“…To minimize variability, all variables were analyzed by a single operator. The coefficient of variation for these measurements was between 0.6 and 3.7% [49].…”

Section: Methodsmentioning

confidence: 92%

Variation in the MC4R Gene Is Associated with Bone Phenotypes in Elderly Swedish Women

et al. 2014

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Osteoporosis is characterized by reduced bone mineral density (BMD) and increased fracture risk. Fat mass is a determinant of bone strength and both phenotypes have a strong genetic component. In this study, we examined the association between obesity associated polymorphisms (SNPs) with body composition, BMD, Ultrasound (QUS), fracture and biomarkers (Homocysteine (Hcy), folate, Vitamin D and Vitamin B12) for obesity and osteoporosis. Five common variants: rs17782313 and rs1770633 (melanocortin 4 receptor (MC4R); rs7566605 (insulin induced gene 2 (INSIG2); rs9939609 and rs1121980 (fat mass and obesity associated (FTO) were genotyped in 2 cohorts of Swedish women: PEAK-25 (age 25, n = 1061) and OPRA (age 75, n = 1044). Body mass index (BMI), total body fat and lean mass were strongly positively correlated with QUS and BMD in both cohorts (r2 = 0.2–0.6). MC4R rs17782313 was associated with QUS in the OPRA cohort and individuals with the minor C-allele had higher values compared to T-allele homozygotes (TT vs. CT vs. CC: BUA: 100 vs. 103 vs. 103; p = 0.002); (SOS: 1521 vs. 1526 vs. 1524; p = 0.008); (Stiffness index: 69 vs. 73 vs. 74; p = 0.0006) after adjustment for confounders. They also had low folate (18 vs. 17 vs. 16; p = 0.03) and vitamin D (93 vs. 91 vs. 90; p = 0.03) and high Hcy levels (13.7 vs 14.4 vs. 14.5; p = 0.06). Fracture incidence was lower among women with the C-allele, (52% vs. 58%; p = 0.067). Variation in MC4R was not associated with BMD or body composition in either OPRA or PEAK-25. SNPs close to FTO and INSIG2 were not associated with any bone phenotypes in either cohort and FTO SNPs were only associated with body composition in PEAK-25 (p≤0.001). Our results suggest that genetic variation close to MC4R is associated with quantitative ultrasound and risk of fracture.

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“…To minimize variability, all variables were analyzed by a single operator. The coefficient of variation for these measurements was between 0.6 and 3.7% [49].…”

Section: Methodsmentioning

confidence: 92%

Variation in the MC4R Gene Is Associated with Bone Phenotypes in Elderly Swedish Women

et al. 2014

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“…Tenne et al [30] investigated whether the SNPs within PTH play a role in femoral neck geometry and bone quality in 750 elderly women aged 75 years. They showed that carriers of haplotype 9 had lower values for hip geometry parameters suggestive of increased fracture risk: cross-sectional moment of inertia (p = 0.029), femoral neck width (p = 0.049), and section modulus (p = 0.06).…”

Section: Bone Mineral Densitymentioning

confidence: 99%

Parathyroid hormone and its receptor gene polymorphisms: implications in osteoporosis and in fracture healing

Noordin

Glowacki

2015

Rheumatol Int

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Parathyroid glands secrete parathyroid hormone (PTH) which plays multiple roles in calcium homeostasis and in bone remodeling. Secretion of PTH is regulated by extracellular calcium levels and other humoral factors including 1α,25(OH)2D3. PTH regulates gene expression and induces biological effects directly and indirectly. The human gene encoding PTH is located on chromosome 11. In this review, we study the diverse PTH along with its receptor gene polymorphisms and their association with osteoporosis and fracture healing. Genetic factors are associated with osteoporosis by influencing bone mineral density (BMD), bone turnover, calcium homeostasis, and susceptibility to osteoporotic fractures. Polymorphisms in genes encoding PTH may contribute to genetic regulation of BMD and thus susceptibility to fracture risk. PTH stimulates the proliferation of osteoprogenitor cells, production of alkaline phosphatise, and bone matrix proteins that contribute to hard callus formation and increases strength at the site of fractured bone. During remodeling, PTH promotes osteoclastogenesis restoring the original shape, structure, and mechanical strength of the bone. Some PTH polymorphisms have shown an association with fracture risk. Further research is needed to elucidate the relative importance of PTH genetics and the mechanisms of genetic contributions to gene-gene interactions in the pathogenesis of osteoporosis and in fracture healing.

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“…However, a recently published study by Leslie et al in the Manitoba cohort provides the first evidence that HAL is also predictive of incident hip fracture in both men and women, independent of BMD or FRAX [117]. Like HLA, NSA, and other hip geometry parameters including buckling ratio and section modulus have been found to predict hip fracture in postmenopausal Caucasian women [114, 118–121]. However, to date, it is not yet clear if this risk is independent of BMD.…”

Section: Introductionmentioning

confidence: 99%

Osteoporosis Imaging in the Geriatric Patient

et al. 2016

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Given the expected rapid growth of the geriatric world population (=individuals aged >65 years) to 1.3 billion by 2050, age-related diseases such as osteoporosis and its sequelae, osteoporotic fractures, are on the rise. Areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) is the current gold standard to diagnose osteoporosis, to assess osteoporotic fracture risk, and to monitor treatment-induced BMD changes. However, most fragility fractures occur in patients with normal or osteopenic aBMD, indicating that factors beyond BMD impact bone strength. Recent developments in DXA technology such as TBS, VFA, and hip geometry analysis are now available to assess some of these non-BMD parameters from the DXA image. This review will discuss the use of DXA and DXA-assisted technologies and their respective advantages and disadvantages. Special attention is given to if and how each method is indicated in the geriatric population, and the latest ISCD 2015 guidelines have been incorporated.

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Variation in the PTH Gene, Hip Fracture, and Femoral Neck Geometry in Elderly Women

Cited by 11 publications

References 47 publications

Variation in the MC4R Gene Is Associated with Bone Phenotypes in Elderly Swedish Women

Variation in the MC4R Gene Is Associated with Bone Phenotypes in Elderly Swedish Women

Parathyroid hormone and its receptor gene polymorphisms: implications in osteoporosis and in fracture healing

Osteoporosis Imaging in the Geriatric Patient

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