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.     

Strategy for urinary protein analysis

SUMMARY: Recent studies have highlighted the intrinsic toxicity of filtered proteins and their contribution to deterioration of renal function. In-depth analysis of proteinuria may assess the degree of glomerular and/or tubular involvement and help in the prognostication of an individual patient. One should consider not only the quantity but also the quality of the urinary protein. Apart from quantitating the total urinary protein, assessment of the quality of the protein may be achieved by performing sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) for an overview assessment follow by automated nephelometry or simple radial immunodiffusion measurement of specific proteins for calculating the selectivity index and detecting tubular dysfunction.     

Functional radiographic examination of the cervical spine in patients with post-traumatic headache

The segmental extension-flexion motion of the cervical spine and the overall C1-C7 motion were measured on functional X-rays in 19 patients with post-traumatic headache and 19 age- and sex-matched controls. The extension-flexion C1-C7 motion was reduced in patients with post-traumatic headache due to reduced motion in three segments: C2-C3, C5-C6 (p less than 0.05), and C6-C7 (p less than 0.01). In both groups a negative correlation between the C1-C7 motion and age was found, but the regression coefficients were different. Only in the control group could a negative correlation between segmental motion and age be demonstrated. In the patients with post-traumatic headache a statistically significant negative correlation between the log (pain index) and the age-corrected C1-C7 motion was found (p less than 0.04). On the segmental level a negative correlation between the log (pain index) and the age-corrected C1-C2 and C5-C6 motion could be demonstrated (p less than 0.05). Regarding C6-C7 there was a tendency to negative correlation. Furthermore, a negative correlation between the frequency of associated symptoms (dizziness, visual disturbances and ear symptoms) and the age-corrected C5-C6 motion was found. Consequently the decrement of motion primarily affected C2-C3, C5-C6, and C6-C7, whereas the analysis of correlation with pain index indicated C1-C2 and C5-C6 (C6-C7) as the most important segments involved.     

A randomized trial of laypersons' perception of the benefit of osteoporosis therapy: number needed to treat versus postponement of hip fracture

BACKGROUND: Information on the benefits of therapeutic interventions can be ex-pressed in various ways, including relative risk reduction, absolute risk reduction,and number needed to treat (NNT). An alternative to such risk-based measures is postponement of an adverse outcome (eg, hip fracture in the case of osteoporosis). OBJECTIVE: The goal of this study was to examine whether laypersons' perception of the benefit of an osteoporosis therapy differs when it is presented in terms of the NNT to avoid 1 hip fracture compared with the duration of postponement of hip fracture. METHODS: This was a cross-sectional, randomized, controlled trial. Face-to-face interviews of a representative sample of the Danish population were conducted in respondents' homes. Respondents were randomized to receive information about the benefits of a hypothetical osteoporosis intervention either in terms of different magnitudes of NNT (10, 50, 100, or 400) or different durations of postponement of hip fracture (1 month, 6 months, 1 year, or 4 years). Participants were subsequently asked if they would consent to the intervention. RESULTS: A total of 1728 individuals were contacted at home and asked if they would take part in a face-to-face interview; 967 (56%) were successfully interviewed. The age (mean age, 44.5 years; range, 20-74 years) and sex distribution (51% male, 50% female) of the sample was similar to that of the general Danish population. Based on NNTs of 10, 50, 100, and 400, the proportions of respondents who said they would consent to the intervention were a respective 65%,61%, 63%, and 57%. Increasing NNT was not significantly associated with a lower proportion of consent (test for trend chi-square(1)= 0.75; P = NS). Forty-three percent of respondents indicated that the concept of NNT was difficult to understand, and 38% interpreted NNT in a way that was probably incorrect. In terms of postponement of hip fracture by 1 month, 6 months, 1 year, and 4 years, the proportions who said they would consent to the intervention were a respective 25%, 40%, 39%, and 53%. Increasing postponement of hip fracture was significantly associated with higher proportions of consent (test for trend chi-square(1)= 20.09;P < 0.001). Logistic regression analysis found that consenting to therapy was inversely associated with age (NNT: OR, 0.83; 95% CI, 0.72-0.96; postponement of fracture: OR, 0.84; 95% CI, 0.73-0.98) and with the magnitude of benefit presented in terms of postponement of fracture. No other variables were significantly associated with consent to therapy. CONCLUSIONS: When laypersons were presented with brief information about the benefit of a hypothetical osteoporosis intervention and were then offered this therapy, their choices were sensitive to the magnitude of treatment benefit when it was presented in terms of postponement of hip fracture but not in terms of NNT. These findings suggest that it may be easier for laypersons to understand a potential treatment benefit in terms of postponement of fracture rather than NNT.     

Investigation of hypoglycemic,hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark in diabetic rats

Objective

To investigate the hypoglycemic, hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark (AETPB) in streptozotocin (STZ)-induced diabetic rats.

Methods

Acute toxicity was studied in rats after the oral administration of AETPB to determine the dose to assess hypoglycemic activity. In rats, diabetes was induced by injection of STZ (60 mg/kg, i.p.) and diabetes was confirmed 72 h after induction, and then allowed for 14 days to stabilize blood glucose level. In diabetic rats, AETPB was orally given for 28 days and its effect on blood glucose and body weight was determined on a weekly basis. At the end of the experimental day, fasting blood sample was collected to estimate the haemoglobin (Hb), glycosylated haemoglobin (HbA1c), serum creatinine, urea, serum glutamate-pyruvate transaminase (SGPT), serum glutamate-oxaloacetate transaminase (SGOT) and insulin levels. The liver and kidney were collected to determine antioxidants levels in diabetic rats.

Results

Oral administration of AETPB did not exhibit toxicity and death at a dose of 2 000 mg/kg. AETPB treated diabetic rats significantly (P<0.001, P<0.01 and P<0.05) reduced elevated blood glucose, HbA1c, creatinine, urea, SGPT and SGOT levels when compared with diabetic control rats. The body weight, Hb, insulin and total protein levels were significantly (P<0.001, P<0.01 and P<0.05) increased in diabetic rats treated with AETPB compared to diabetic control rats. In diabetic rats, AETPB treatment significantly reversed abnormal status of antioxidants and lipid profile levels towards near normal levels compared to diabetic control rats.

Conclusions

Present study results confirm that AETPB possesses significant hypoglycemic, hypolipidemic and antioxidant activities in diabetic condition.     

Association study of common variants in the sFRP1 gene region and parameters of bone strength and body composition in two independent healthy Caucasian male cohorts

Bone mineral density (BMD) and bone strength are predictive parameters for the development of osteoporosis and related fracture later in life. Although it is well known that BMD and bone strength have a high heritability, not much of the variation is already explained. Mice models showed that sFRP1 has an influence on bone formation. Therefore this study aimed to investigate the effect of common genetic variation on BMD and bone strength in Caucasian men of different ages. Using HapMap we selected 13 tagSNPs which tag most common genetic variation in and around sFRP1 and we genotyped these SNPs in the young cohort of the Odense Androgen Study (OAS). The OAS includes a total of 1383 Danish men from two different age groups ([20-29 years]: N=783; [60-74 years]: N=600) and is well characterised. The subjects were phenotyped for BMD at several sites, and additionally for body composition and hip geometry parameters. Based on the results of the young cohort we selected three SNPs for further analysis in the complete OAS population. To conclude we tried to replicate the results of two SNPs in an independent population of 994 Belgian men. We found a strong association for rs9694405 with BMI as well in both cohorts separately as in the whole OAS population. Further we found rs4736965 associated with several hip geometry parameters in the same population. However we were not able to replicate those results in the Belgian population. At last we found in the OAS population age specific effects for rs10106678 with whole body BMD and waist to hip ratio.