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The MTHFR c.677C>T polymorphism has been shown to have significant effects on skeletal health in middle-aged to elderly women and men. Despite an accumulating amount of data on MTHFR genetics and the association between homocysteine levels and fracture, it remains unknown if MTHFR c.677C>T genotype affects bone mineral accretion in youth or bone loss in adulthood. The purpose of this cross-sectional study was to examine the effects of this common allelic polymorphism on peak bone mass and bone turnover. We performed MTHFR genotyping in 780 healthy Danish men, aged 20 to 29 years, participating in the Odense Androgen Study. BMD at the spine, hip and whole-body was measured using a Hologic QDR-4500 densitometer. Genotype frequencies were compatible with Hardy-Weinberg equilibrium. Spine BMD was significantly associated with genotype, with a decrease in BMD of 0.20 SD for each copy of the T-allele. Effects were independent of age, BMI, smoking and serum levels of vitamin D and IGF-I. Associations with BMD of the hip and whole body were short of statistical significance. MTHFR genotype showed no association with the bone turnover markers 1-CTP, bone specific alkaline phosphatase or osteocalcin. In conclusion, significant skeletal effects of this common polymorphism were present at the lumbar spine in men at the age of 25 years.

The polymorphisms of the estrogen receptor (ER) gene defined by the restriction enodonucleases PvuII and XbaI have recently been reported to be associated with bone mineral density (BMD) in postmenopausal women. To investigate the possible relation of the PvuII and XbaI restriction fragment-length polymorphisms of the ER gene with BMD in Danish postmenopausal women, two studies were undertaken: 1) a cross-sectional study of 499 postmenopausal women, where the ER genotypes and alleles were related to BMD of the hip, spine, and lower forearm; and 2) a longitudinal study of 101 postmenopausal women followed up for 18 years. In the latter study, late postmenopausal bone loss in the hip and spine was determined over a period of 6 years in women (mean age of 63 to 69 years), and long-term postmenopausal bone loss in the lower forearm was determined over a period of 18 years in women (mean age of 51 to 69 years). Genotyping was performed through the restriction cleavage of polymerase chain reaction-amplified genomic DNA with the two restriction enzymes, PvuII and XbaI. Restriction fragment-length polymorphisms were represented as P or p (PvuII) and X or x (XbaI), with the lower case letters signifying the presence of the restriction site. The frequencies of the ER genotypes were similar to previously published genotype frequencies in Caucasian and Asian populations. No significant effect of the ER genotypes or alleles on BMD was found at any site, nor was there a relation between ER genotypes and the rate of bone loss either in the hip and spine over 6 years, or in the lower forearm over 18 years. In conclusion, we could not demonstrate any major effect of the ER gene polymorphisms on BMD or rate of bone loss in healthy postmenopausal Danish women.

Quantitative ultrasound (QUS) bone measurement is a promising, relatively new technique for the diagnosis of osteoporosis. Contrary to the more established method of bone densitometry (measurement of bone mineral density, BMD, e.g., using dual X-ray absorptiometry, DEXA), QUS does not employ ionizing radiation. It has, however, been a problem to achieve sufficient reproducibility of the QUS measurements. The aim of this study is to evaluate the possible advantages of measuring broadband ultrasound attenuation (BUA) at a region of interest (ROI) instead of at a fixed position, in terms of in vivo precision and correlation to hip bone mineral density. BUA was measured in 27 premenopausal women, 28 postmenopausal women, an 22 men on the DTU-one. Using high resolution images, a ROI is defined in the posterior part of the os calcis as an area with a local minimum of attenuation and a fixed position within the os calcis is defined relative to the water bath. All BUA measurements were performed twice. BMD at the hip was measured on the QDR-2000. The mean BUA values were significantly different between pre- and postmenopausal women, p = 0.0001 for both the ROI (BUAROI) and the fixed position (BUAFIX). The ROI was found in all subjects and was readily reproducible. The precision at the ROI: 1.20 CV% (95% CI: 1.01-1.29 CV%) was significantly better than at the fixed position: 3.87 CV% (95% CI: 3.23-4.48 CV%). BUAROI (r = 0.64) correlated significantly better than BUAFIX (r = 0.35) with HIP BMD. In conclusion, the use of an imaging technique enables BUA measurements to be performed at a ROI. The precision of BUA at the ROI is significantly better than at the fixed position. BUA measured at the ROI correlates better with HIP BMD than BUA measured at the fixed position.