Genetic factors play an important role in the pathogenesis of osteoporosis, and recent studies have shown that a polymorphic Sp1 binding site in collagen type I alpha1 (COLIA1) gene is associated with bone mass and vertebral fractures in women from the U.K. Information on the predictive value of the COLIA1 Sp1 polymorphism in other populations is limited, however, and no studies have yet been performed in osteoporotic males. In view of this, we analyzed COLIA1 genotypes in relation to bone density and biochemical markers of bone turnover and the presence of osteoporotic fractures in a case-control study of Danish men and women. COLIA1 genotype was determined by polymerase chain reaction analysis of genomic DNA extracted from peripheral blood samples and related to bone mass, biochemical markers of bone turnover, and the presence of fracture in a study of 375 osteoporotic vertebral fracture patients and normal controls. There was no significant effect of COLIA1 genotype on bone mass or biochemical markers when data from the control group (n = 195) and fracture group (n = 180) were analyzed separately. However, the genotype distribution was significantly different in the fracture cases compared with age-matched controls (chi2 = 16.48, n = 249,p = 0.0003) due mainly to over-representation of the ss genotype in the fracture patients (14.3% vs. 1.4%), equivalent to an odds ratio for vertebral fracture of 11.83 (95% confidence interval 2.64-52.97) in those with the ss genotype. Similar differences in genotype distribution between osteoporotic patients and controls were observed in both men (chi2 = 11.52, n = 95, p = 0.0032, OR = 2.04) and women (chi2 = 6.90, n = 154, p = 0.032, OR = 1.37). In keeping with the above, logistic regression analysis showed that the ss genotype was an independent predictor of osteoporotic fracture (p = 0.028). This study confirms that the COLIA1 Sp1 polymorphism is significantly associated with osteoporotic vertebral fractures. The association is seen in both men and women, and the effect on fracture risk appears to be partly independent of bone mineral density. Our results raise the possibility that genotyping at the Sp1 site could be of clinical value in identifying individuals at risk of osteoporotic fractures in both genders.
Three hundred and seventy-four general practitioners (GPs) in Denmark filled in a questionnaire on attitudes to include information on gender and diet in the strategy for prevention of coronary heart disease, cancer, osteoporosis, and overweight/underweight. Risk factors for disease in general were ranked as follows: smoking, alcohol, stress, diet, physical exercise, heredity and hygiene. The patients' lack of motivation, insufficient time for each patient, and inadequate knowledge about nutrition were stated as barriers to dietary counselling. The GPs stated that the gender of the patient was important only to the counselling on osteoporosis. Lack of time and insufficient knowledge were perceived as barriers for including gender specific issues in prevention. It is concluded that GPs consider dietary counselling important but lack time and knowledge. The results point at a need for better pre- and postgraduate training in nutrition, and for a better reimbursement system for time spent on prevention.
OBJECTIVES: Sunlight exposure of the skin is known to be the most important source of vitamin D. The aims of this study were: (i) to estimate vitamin D status amongst sunlight-deprived individuals (veiled Arab women, veiled ethnic Danish Moslem women and Danish controls); and (ii) through food intake analysis to estimate the oral intake of vitamin D necessary to keep a normal vitamin D status in sunlight-deprived individuals. DESIGN: Cross-sectional study amongst randomly selected Moslem women of Arab origin living in Denmark. Age-matched Danish women were included as controls. To control for racial differences, a group of veiled ethnic Danish Moslem women (all Caucasians) was included. SETTING: Primary Health Care Centre, City Vest and Department of Endocrinology and Metabolism C, University Hospital of Aarhus, Aarhus Amtssygehus, Aarhus, Denmark. SUBJECTS: Sixty-nine Arab women (60 veiled, nine non-veiled) and 44 age-matched Danish controls were randomly selected amongst patients contacting the primary health care centre for reasons other than vitamin D deficiency. Ten ethnic Danish Moslem women were included through a direct contact with their community. MAIN OUTCOME MEASURES: Serum levels of 25-hydroxyvitamin D were used as estimates of vitamin D status. Intact parathyroid hormone (PTH) was used to control for secondary hyperparathyroidism. Alkaline phosphatase and bone-specific alkaline phosphatase were used as markers for osteomalacic bone involvement. Oral intake of vitamin D and calcium were estimated through a historical food intake interview performed by a trained clinical dietician. RESULTS: Veiled Arab women displayed extremely low values of 25-hydroxyvitamin D: 7.1 +/- 1.1 nmol L-1, compared with 17.5 +/- 2. 3 (P
Vertebral deformities are prevalent in chronic obstructive pulmonary disease (COPD) patients and may cause excessive loss of height. As height is used for calculating reference values for pulmonary function tests, larger than normal height reduction could cause overestimation of lung function. In this cross-sectional study of 465 COPD patients and 462 controls, we explored how often lung function is misinterpreted due to height reduction in COPD patients, and whether the number or severity of vertebral deformities correlate with height reduction. Measured height was compared to recalled tallest height (RTH) and height calculated from arm span (ASH) to assess height reduction. Vertebral deformities were assessed from radiographs and pulmonary function was assessed using standard formulae. Height reduction was frequent in both the study and control groups, and increased with the number and severity of vertebral deformities. When using current measured height, lung function was overestimated in a significant proportion of COPD patients at relatively modest height reductions. The effects were smallest for forced expiratory volume in 1 s and forced vital capacity, and most pronounced for total lung capacity and residual volume. Therefore, we propose that in COPD patients with excessive height reduction, one might use RTH or ASH in calculating predicted values. Furthermore, such patients should be evaluated for co-existing vertebral deformities and osteoporosis.
The aims of this study were to investigate myopathy in relation to vitamin D status, and to study the muscular effects of vitamin D treatment on vitamin D-deficient individuals. Further, hypovitaminosis D myopathy was investigated in relation to alkaline phosphatase (ALP), the most commonly used marker for hypovitaminosis D osteopathy. Eight patients with osteomalacia had an isokinetic dynamometer test of all major muscle groups before and after 3 months of vitamin D treatment. The most pronounced improvements in muscle power were seen in the weight-bearing antigravity muscles of the lower limbs. A cross-sectional study was performed among 55 vitamin D-deficient veiled Arab women living in Denmark and 22 Danish controls. An isometric dynamometer model was used for determination of quadriceps muscle power. Both maximal voluntary contraction (MVC) and electrically stimulated values (single twitch, maximal production rate (MPR), and maximal relaxation rate (MRR)) were determined. The women underwent high-dose vitamin D treatment and were retested after 3 and 6 months. Prior to vitamin D treatment all parameters of muscle function in the group of vitamin D-deficient Arab women were significantly reduced compared with Danish controls. MVC: 259.4 +/- 11.0 N (Newton) versus 392.6 +/- 11. 4 N (P
General practitioners (GPs) in Denmark (n = 374) answered a questionnaire on attitudes toward including information on diet and sex in the prevention of coronary artery disease, cancers, osteoporosis, and weight problems. Risk factors for disease were ranked as follows: smoking, alcohol, stress, diet, physical exercise, heredity, and hygiene. Patients' lack of motivation, insufficient time for each patient, and inadequate knowledge about nutrition were listed by GPs as barriers to dietary counseling. GPs stated that the sex of the patient was important only for counseling on osteoporosis. Lack of time and insufficient knowledge were perceived as barriers to including sex-specific issues in prevention. One-half of the GPs were questioned about the issue of prevention on the basis of female case stories and the other half on the basis of male case stories with identical wording. Responses to the case stories indicated that GPs would give dietary guidance and recommend loss of weight to slightly overweight male patients to a much greater degree than to overweight female patients for prevention of coronary artery disease, give dietary counseling and recommend loss of weight and exercise to female patients more than to male patients for prevention of cancers, recommend a supplement of calcium and vitamin D for prevention of osteoporosis to female patients, and recommend weight gain and discuss psychosocial issues more with underweight female patients than with underweight male patients. Female GPs included measures of prevention such as dietary counseling, exercise prescription, dietary supplement prescription, and discussion of psychosocial issues to a greater extent than did male GPs.
We tested whether cortical porosity of the proximal femur measured using StrAx1.0 software provides additional information to areal bone mineral density (aBMD) or Fracture Risk Assessment Tool (FRAX) in differentiating women with and without fracture. Porosity was associated with fracture independent of aBMD and FRAX and identified additional women with fractures than by osteoporosis or FRAX thresholds.
Neither aBMD nor the FRAX captures cortical porosity, a major determinant of bone strength. We therefore tested whether combining porosity with aBMD or FRAX improves identification of women with fractures.
We quantified femoral neck (FN) aBMD using dual-energy X-ray absorptiometry, FRAX score, and femoral subtrochanteric cortical porosity using StrAx1.0 software in 211 postmenopausal women aged 54-94 years with nonvertebral fractures and 232 controls in Tromsø, Norway. Odds ratios (ORs) were calculated using logistic regression analysis.
Women with fractures had lower FN aBMD, higher FRAX score, and higher cortical porosity than controls (all p?20 %, whereas porosity >80th percentile identified 61 women (29 %). Porosity identified 26 % additional women with fractures than identified by the osteoporosis threshold and 21 % additional women with fractures than by this FRAX threshold.
Cortical porosity is a risk factor for fracture independent of aBMD and FRAX and improves identification of women with fracture.
Three hundred and seventy-four general practitioners (GPs) in Denmark filled in a questionnaire on practices regarding prevention of coronary heart disease (CHD), cancer, osteoporosis, and overweight/underweight. Half of the GPs were questioned about the issue of prevention based upon female case stories and the other half on male case stories with identical wording. The GPs more often in relation to: Prevention of CHD gave dietary counselling and recommended weight loss to slightly overweight male than female patients. Prevention of cancers gave dietary counselling and recommended weight loss and increase of exercise to female than to male patients. Prevention of osteoporosis recommended a supplement of calcium and vitamin D to female than to male patients. Treatment of underweight recommended weight gain and discussion of psycho-social issues to underweight female than male patients. In conclusion, GPs distinguish between men and women in relation to prevention strategies in general practice. There is a need for well-described prevention and action strategies with relevant gender differentiation for use in general practice.
The current study aimed to assess a possible association between the bone turnover marker procollagen type 1 amino-terminal propeptide (P1NP) and future hip fractures in elderly Norwegian men and women and to elucidate the relation between P1NP, bone mineral density and 25-hydroxyvitamin D (25(OH)D). Men and women aged 71 to 77 from two population based health studies in Norway (1999-2001) were followed for a median period of 7.3 years with respect to hip fractures. The study was designed as a case-cohort study. P1NP and 25(OH)D were analysed in frozen serum samples obtained at baseline in hip fracture patients (n=340) and in randomly selected sex stratified sub-cohorts. Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) in a subset of participants. Cox proportional hazards regression with inverse probability weighting and robust variance was performed. No significant correlation between 25(OH)D and P1NP was found. A negative correlation between P1NP and BMD was observed in women (Rho=-0.36, p=0.001). A similar trend was observed in men. No association between quartiles of P1NP and rate of subsequent hip fractures was found. Spline analyses suggested a higher rate of hip fracture at P1NP levels above 60 µg/L in both men and women. A higher hip fracture rate, which was independent of BMD, was also indicated in women with very low levels of P1NP.
Serum parathyroid hormone (PTH) was associated with increased bone turnover markers and cortical porosity of the inner transitional zone at the proximal femur. These results suggest that PTH through increased intracortical bone turnover leads to trabecularisation of inner cortical bone in postmenopausal women.
Vitamin D deficiency leads to secondary hyperparathyroidism and increased risk for fractures, whereas its association with cortical porosity is less clear. We tested (i) whether serum 25-hydroxyvitamin D (25(OH)D) and PTH were associated with cortical porosity and (ii) whether the associations of 25(OH)D) and PTH with fracture risk are dependent on cortical porosity.
This case-control study included 211 postmenopausal women, 54-94 years old, with prevalent fractures and 232 controls from the Tromsø Study. Serum 25(OH)D, PTH, and bone turnover markers (procollagen type I N-terminal propeptide [PINP] and C-terminal cross-linking telopeptide of type I collagen [CTX]) were measured. Femoral subtrochanteric cortical and trabecular parameters were quantified using computed tomography, and femoral neck areal bone mineral density (FN aBMD) was quantified using dual-energy X-ray absorptiometry.
Compared with controls, fracture cases exhibited reduced serum 25(OH)D and increased PTH, PINP, and CTX, increased femoral subtrochanteric cortical porosity, and reduced cortical thickness and FN aBMD (all, p??0.10). PTH was associated with increased PINP, CTX, and cortical porosity of the inner transitional zone and reduced trabecular bone volume/tissue volume and FN aBMD (p ranging from 0.003 to 0.054). Decreasing 25(OH)D and increasing PTH were associated with increased odds for fractures, independent of age, height, weight, calcium supplementation, serum calcium, cortical porosity, and thickness.
These data suggest that serum PTH, not 25(OH)D, is associated with increased intracortical bone turnover resulting in trabecularisation of the inner cortical bone; nevertheless, decreasing 25(OH)D) and increasing PTH are associated with fracture risk, independent of cortical porosity and thickness.