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Bo Abrahamsen

Publications and source records attributed to Bo Abrahamsen.

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Increased RANKL/OPG mRNA ratio in iliac bone biopsies from women with hip fractures.

RANKL (receptor activator of NF-kappaB) is a potent physiological inducer of osteoclastogenesis. Its actions are blocked by the decoy receptor osteoprotegerin (OPG), and treatment with OPG blocks bone resorption in postmenopausal women. Both positive and negative associations between serum OPG and bone mineral density (BMD) have been reported in the literature. We hypothesized that decreased OPG production relative to RANKL within bone itself could lead to increased risk of osteoporotic fracture. We included ten women with hip fracture (age 76.3 +/- 8.0 years, N.S, : hip BMD 0.686 +/- 1.3 g/cm2, P < 0.05) and 24 women with osteoarthrosis of the hip (age 72.8 +/- 7.2 years, hip BMD 0.832 +/- 1.1 g/cm(2)). Transiliac biopsies were obtained at the time of surgery. Total RNA was extracted from biopsies and reverse-transcribed. Real-time quantification of mRNA was performed with a SYBR Green I real time PCR assay, calculating relative gene expression with normalization of results for beta actin mRNA. Actin normalized mRNA levels for OPG and interleukin (IL)-6 were significantly lower in fracture patients, with a significantly higher RANKL/OPG ratio in patients with fractures. There was no significant difference in tumor necrosis factor (TNF), IL-1, IL-1ra, or IL-7 expression. IL-6 mRNA levels were lower in fracture patients (P < 0.05). The effect of increased RANKL/OPG ratio (Z = 2.08, P < 0.05) on fracture risk was additive to that of hip BMD T score (Z = -1.95, P < 0.05) when assessed using logistic regression. Elderly women with hip fractures exhibit an increased RANKL/OPG mRNA content of iliac bone. This is associated with increased fracture susceptibility, which is not in itself explained by low BMD.

Absorptiometry, Photon↗

[Osteodensitometry].

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Absorptiometry, Photon↗

A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study.

A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) has recently been associated with bone mineral density (BMD) in postmenopausal Japanese women. It is not known whether this effect is also present in European populations and whether it is caused by lower peak bone mass or accelerated postmenopausal bone loss. MTHFR genotyping was done in 1748 healthy postmenopausal Danish women participating in a prospective study of risk factors for osteoporosis. At the time of enrollment, 3-24 months after last menstrual period, the less prevalent genotype (TT, 8.7% of the population) was associated with significantly lower BMD at the femoral neck (ANOVA, p < 0.05), total hip (p < 0.01), and spine (p < 0.05 adjusted for lifestyle covariates, p = 0.06 without adjustment). The mean difference was between 0.1 and 0.3 SD, depending on measurement site. MTHFR genotype added significantly to prediction of BMD by weight and age. Fracture incidence was increased more than 2-fold in subjects with the TT genotype (risk ratio [RR], 2.6; 95% CI 1.2-5.6). This remained significant when the Cox analysis was controlled for BMD (RR, 2.4; 95% CI 1.1-5.2). No differences in serum osteocalcin, bone-specific alkaline phosphatase, and 25-OH-vitamin D were found between genotypes. The response to hormone replacement therapy (HRT) did not differ, but the association of the TT genotype with reduced BMD was maintained at the total hip after 5 years of HRT. The MTHFR TT genotype is associated with low BMD and increased fracture incidence in early postmenopausal women.

Alleles↗

Standardization of BMD T-Scores in the first five years after the menopause: do femoral neck-equivalent and older normative range T-Scores improve diagnostic agreement?

Calculating T-scores using an older reference population reduces inconsistency between measurement sites when osteoporosis is diagnosed in the elderly. The present analysis in a younger, early postmenopausal cohort examined 5-yr consistency of normalization by local and femoral neck-equivalent T-scores. NHANES (femur) and Hologic (spine and forearm) references were applied to baseline, 1-, 2-, 3-, and 5-yr scans in 925 untreated women in a national cohort study, and alternative local and neck-equivalent scores calculated. The baseline prevalence of osteopenia/osteoporosis was 35.5%/4.1% (spine), 31.0%/1.2% (neck), 31.3%/1.2% (total hip), and 37.2%/2.5% (forearm). It increased to 54.6%/7% by combining sites. The prevalences at 5-yr were 57.2%/12.4% (spine), 51.9%/5.0% (neck), 46.6%/3.7% (total hip), 52.5%/7.4% (forearm), and 77.3%/17.8% (any). A T-score cut-off at the lowest of four sites of -1.65 for osteopenia and -3.37 for osteoporosis was equivalent in patient numbers to T<-1 and T<-2.5 at the femoral neck. The proportion of inconsistently classified subjects decreased from 48% to 42% (p<0.05) with neck-equivalent scores. No improvement remained after 5 yr. Kappa scores did not improve by the use of local or femoral neck scores. In conclusion, adjusted thresholds cannot remove the anatomic discrepancy between T-scores. To overcome this problem, risk-based diagnostic cut-offs must therefore be calculated separately for each measurement site and fracture localization.

Absorptiometry, Photon↗

Effect of long-term hormone replacement therapy on plasma homocysteine in postmenopausal women: a randomized controlled study.

OBJECTIVE: The purpose of this study was to investigate the long-term effect of hormone replacement therapy on total homocysteine and to study whether there was any difference in effect between opposed and unopposed hormone replacement therapy or whether the methylenetetrahydrofolate reductase C677T polymorphism was associated with the effect of hormone replacement therapy on total homocysteine. STUDY DESIGN: Two hundred nine healthy postmenopausal women were randomized to hormone replacement therapy (n = 103) or no substitution (n = 106) 5 to 7 years earlier. RESULTS: Women who received hormone replacement therapy had significantly lower total homocysteine concentrations than women in the control group; median total homocysteine values were 8.6 micromol/L and 9.7 micromol/L, respectively, in a per-protocol analysis (P =.02). The effect was comparable in all methylenetetrahydrofolate reductase genotypes, and no difference between unopposed and opposed hormone replacement therapy could be demonstrated. Similar results were obtained when an intention-to-treat analysis was performed. CONCLUSION: Long-term hormone replacement therapy results in lower total homocysteine concentrations in all methylenetetrahydrofolate reductase genotypes without demonstrable difference in effect between unopposed and opposed hormone replacement therapy.

Estradiol↗