Association of a common allelic polymorphism (C677T) in the methylene tetrahydrofolate reductase gene with a reduced risk of osteoporotic fractures. A case control study in Danish postmenopausal women.

Twin studies indicate a substantial genetic component in the development of osteoporosis. One of the latest studied candidate genes is the one coding for methylene tetrahydrofolate reductase (MTHFR) (C677T) in which a point mutation gives rise to a thermolabile variant of MTHFR. The aim of this study was to investigate the influence of this mutation on peripheral measures of bone density and on the odds ratios (OR) for hip and lower forearm fracture in a case control study of Danish postmenopausal women. A total of 74 women with lower forearm fracture, 41 women with hip fracture, and 207 age-matched controls were included. All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel as well as bone mineral density (BMD) measured by dual X-ray absorptiometry at the distal forearm. The MTHFR (C677T) genotypes were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Only 2 of 21 individuals with the TT genotype had sustained a fracture as opposed to 46 of 142 with the CT genotype and 67 of 159 with the CC genotype (P = 0.007). Using logistic regression, the following odds ratios were found when comparing the individuals homozygotic for the C-allele with those homozygotic for the T-allele: lower forearm fracture OR = 3.93 (1.25; 12.40, P = 0.02), hip fracture OR = 6.99 (l.35; 36.92, P = 0.02) and the fractures combined OR = 4.33 (1.73; 10.81, P = 0.002). In this study, the MTHFR (C677T) genotypes were not significantly associated with BMD at the lower forearm or with ultrasound parameters measured at the calcaneus. However, a significant increase in the odds ratio of fracture was found for the wild-type C-allele.

Odds ratios for hip- and lower forearm fracture using peripheral bone densitometry; a case-control study of postmenopausal women.

BACKGROUND: Dual-energy X-ray absorptiometry (DXA) measured at the lumbar spine and particularly at the hip remain the gold-standard for diagnosing osteoporosis. However, devices for assessing the peripheral skeleton present several advantages in terms of lower price and portability. A major concern when using peripheral densitometry is the poor correlation with the central measurements. The main aim of this study is, therefore, to assess the possibility of expressing ultrasound measurements at the heel and bone mineral density (BMD) measured at the distal forearm as fracture odds ratios rather than an absolute measure of bone mass. METHODS: A total of 76 women with lower forearm fracture, 47 women with hip fracture and 231 age-matched women (controls) were included. All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel using the DTU-one ultrasound scanner as well as BMD measured by dual X-ray absorptiometry on the DTX-200 at the distal forearm. RESULTS: BUA, SOS and BMD at the distal forearm were all significantly lower in fracture patients compared with their respective control groups. The odds ratio for lower forearm fracture was 3.1 (95% CI: 1.8; 5.2) for heel-BUA (T-score cutoff: -2.3), 4.1 (2.3; 7.4) for heel-SOS (-2.1) and 2.2 (1.3; 3.7) for lower forearm BMD (-2.7). The odds ratio for hip fracture was 3.4 (1.5-7.7) for heel-BUA (-2.7), 3.6 (1.6; 8.1) for heel-SOS (-2.6) and 3.2 (1.4; 7.4) for lower forearm BMD (-2.9). CONCLUSION: Peripheral densitometry can discriminate between hip- and lower forearm fracture patients and age-matched controls. Significantly elevated odds ratios for incurring these fractures can be calculated using device- and site specific t-score cutoff values. The results from this case-control study need to be confirmed by prospective cohort studies.