25-hydroxyvitamin-d-2 and Hip-Fractures

The aim of this review is to summarize current knowledge on the relation between vitamin D and muscle function. Molecular mechanisms of vitamin D action on muscle tissue have been known for many years and include genomic and non-genomic effects. Genomic effects are initiated by binding of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) to its nuclear receptor, which results in changes in gene transcription of messenger RNA and subsequent protein synthesis. Non-genomic effects of vitamin D are rapid and mediated through a membrane-bound vitamin D receptor (VDR). Genetic variations in the VDR and the importance of VDR polymorphisms in the development of osteoporosis are still a matter of controversy and debate. Most recently, VDR polymorphisms have been described to affect muscle function. The skin has an enormous capacity for vitamin D production and supplies the body with 80-100% of its requirements of vitamin D. Age, latitude, time of day, season of the year and pigmentation can dramatically affect the production of vitamin D in the skin. Hypovitaminosis D is a common feature in elderly people living in northern latitudes and skin coverage has been established as an important factor leading to vitamin D deficiency. A serum 25-hydroxyvitamin D level below 50 nmol/l has been associated with increased body sway and a level below 30 nmol/l with decreased muscle strength. Changes in gait, difficulties in rising from a chair, inability to ascend stairs and diffuse muscle pain are the main clinical symptoms in osteomalacic myopathy. Calcium and vitamin D supplements together might improve neuromuscular function in elderly persons who are deficient in calcium and vitamin D. Thus 800 IU of cholecalciferol in combination with mg of elemental calcium reduces hip fractures and other non-vertebral fractures and should generally be recommended in individuals who are deficient in calcium and vitamin D. Given the strong interdependency of vitamin D deficiency, low serum calcium and high levels of parathyroid hormone, however, it is difficult to identify exact mechanisms of action.

Topics: 25-Hydroxyvitamin D 2; Aged; Blood Pressure; Calcium; Female; Hip Fractures; Humans; Male; Muscle Weakness; Muscle, Skeletal; Muscle, Smooth, Vascular; Parathyroid Hormone; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

Norway has the highest hip fracture rates worldwide and a relatively high vitamin A intake. Increased fracture risk at high intakes and serum concentrations of retinol (s-retinol) have been observed in epidemiologic studies.. We aimed to study the association between s-retinol and hip fracture and whether high s-retinol may counteract a preventive effect of vitamin D.. We conducted the largest prospective analysis of serum retinol and hip fracture to date in 21,774 men and women aged 65-79 y (mean age: 72 y) who attended 4 community-based health studies during 1994-2001. Incident hip fractures occurring up to 10.7 y after baseline were retrieved from electronic hospital discharge registers. Retinol determined by high-pressure liquid chromatography with ultraviolet detection in stored serum was available in 1154 incident hip fracture cases with valid body mass index (BMI) data and in a subcohort defined as a sex-stratified random sample (n = 1418). Cox proportional hazards regression weighted according to the stratified case-cohort design was performed.. There was a modest increased risk of hip fracture in the lowest compared with the middle quintile of s-retinol (HR: 1.41; 95% CI: 1.09, 1.82) adjusted for sex and study center. The association was attenuated after adjustment for BMI and serum concentrations of α-tocopherol (HR: 1.16; 95% CI: 0.88, 1.51). We found no increased risk in the upper compared with the middle quintile. No significant interaction between serum concentrations of 25-hydroxyvitamin D and s-retinol on hip fracture was observed (P = 0.68).. We found no evidence of an adverse effect of high serum retinol on hip fracture or any interaction between retinol and 25-hydroxyvitamin D. If anything, there tended to be an increased risk at low retinol concentrations, which was attenuated after control for confounders. We propose that cod liver oil, a commonly used food supplement in Norway, should not be discouraged as a natural source of vitamin D for fracture prevention.

Topics: 25-Hydroxyvitamin D 2; Aged; Calcifediol; Case-Control Studies; Cod Liver Oil; Cohort Studies; Dietary Supplements; Elder Nutritional Physiological Phenomena; Female; Follow-Up Studies; Hip Fractures; Humans; Incidence; Male; Norway; Nutrition Surveys; Nutritional Status; Osteoporotic Fractures; Proportional Hazards Models; Prospective Studies; Registries; Risk Factors; Vitamin A

The primary aim of the study was to explore the potential relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and Mini Nutritional Assessment (MNA) score, a surrogate for protein energy undernutrition, in elderly (≥65 years old) subjects with and without a hip fracture. A secondary aim of the study was to provide estimates of the MNA discriminatory performance in the detection of subjects with low levels of 25(OH)D (<20 ng/ml). The study population consisted of 101 patients with a hip fracture, recruited from a single urban Hospital in Athens, Greece, and 85 community dwelling subjects with no history of hip fracture. Serum 25(OH)D was measured, nutritional status was determined by the MNA questionnaire in all subjects, and linear correlation between variables was investigated. Receiver operator characteristic (ROC) curve analysis was performed and discriminatory performance was further assessed by calculating positive and negative likelihood ratios (LR). MNA scores were significantly correlated with 25(OH)D levels (rho=0.685, p<0.001) and this finding was robust in both groups and unaffected by gender. ROC curve analysis demonstrated an area under the curve (AUC) of 0.860 [standard error (SE): 0.026, 95% confidence interval (CI): 0.810-0.910], which provided a significantly better estimation of 25(OH)D status than simple guess (p<0.001). The lowest cutoff value in MNA score, providing a sensitivity over 90% was 25.25, which was associated with a sensitivity of 90.9% and a specificity of 53.6%. The same analysis revealed acceptable results only within hip fracture patients. MNA score might be a satisfactory surrogate marker for 25(OH)D levels with which it is linearly correlated. However, it appears that its discriminatory performance, as a diagnostic tool for 25(OH)D insufficiency, is rather suboptimal.

Topics: 25-Hydroxyvitamin D 2; Aged; Aged, 80 and over; Biomarkers; Calcifediol; Cohort Studies; Cross-Sectional Studies; Female; Geriatric Assessment; Greece; Hip Fractures; Humans; Male; Nutrition Assessment; Nutritional Status; Osteoporosis; Osteoporotic Fractures; Protein-Energy Malnutrition; Sensitivity and Specificity; Vitamin D Deficiency

Hormone levels were compared over a 1-year period between elderly women who had sustained a hip fracture and women of similar age and functional ability. Our study suggests progressive hormonal changes that may contribute to severe bone loss during the year following hip fracture.. Alterations in hormones affecting the musculoskeletal system may increase risk of hip fracture or poor post-fracture recovery in postmenopausal women. Most studies lack appropriate reference groups, and thus cannot assess the extent to which these alterations are attributable to hip fracture.. Women aged ≥65 years hospitalized for an acute hip fracture (Baltimore Hip Studies, BHS-3; n = 162) were age-matched to 324 women enrolled in the Women's Health and Aging Study I, a Baltimore-based cohort with similar functional status to the pre-fracture status of BHS-3 women. Both studies enrolled participants from 1992 to 1995. Insulin-like growth hormone-1 (IGF-1), parathyroid hormone (PTH), 1,25 dihydroxyvitamin D [1,25(OH)2D], and osteocalcin were evaluated at baseline and 2, 6, and 12 months post-fracture, and at baseline and 12 months in the comparison group. Between-group differences in trajectories of each hormone were examined.. Baseline mean IGF-1 levels were significantly lower in hip fracture patients than the comparison group (75.0 vs. 110.5 μg/dL; p < 0.001). Levels increased by 2 months post-fracture, but remained significantly lower than those in the comparison group throughout the 12-month follow-up (p < 0.01). Levels of PTH and osteocalcin were similar between groups at baseline, but rose during the year post-fracture to significantly differ from the comparison women (p < 0.001). 1,25(OH)2D levels did not differ between the hip fracture and comparison women at any time.. Older women who have sustained a hip fracture have progressive changes in hormonal milieu that exceed those of women of similar health status during the year following fracture.

Topics: 25-Hydroxyvitamin D 2; Aged; Aged, 80 and over; Case-Control Studies; Female; Follow-Up Studies; Hip Fractures; Hormones; Humans; Insulin-Like Growth Factor I; Osteocalcin; Osteoporotic Fractures; Parathyroid Hormone

Clinical demand for quick, cheap, precise and accurate 25-hydroxyvitamin D (25(OH)D) results has led to the development of a variety of assay methods. Lack of standardization of these methods has resulted in inter-method disagreement and challenged whether current assays recognize 25(OH)D2 and 25(OH)D3 equally.. We studied 172 patient samples from hip fracture cases using DiaSorin (DS) and IDS radioimmunoassays and the Nichols Advantage-automated protein binding assay (NA-CLPBA) in comparison to high-performance liquid chromatography (HPLC). 52 patient samples were analysed before and after three months treatment with 1000 IU of daily ergocalciferol (vitamin D2).. Linear regression analysis in pre-treatment samples demonstrated a positive Y-intercept for each immunoassay compared with HPLC, and a slope that varied from 0.64 (IDS) to 0.97 (DS, NA-CLPBA). Bland Altman analysis demonstrated that all the three assays had a proportional positive bias relative to HPLC at values from 20 to 50 nmol/L. Regression analysis of post-treatment samples demonstrated a slope that was not significantly different from zero for the IDS and NA-CLPBA and 0.2 for the DS method, with a positive intercept for all assays of between 8 and 22, indicating less than 50% of 25(OH)D2 measured by HPLC was detected.. These results demonstrate the need for assay-specific decision limits for 25(OH)D3 in order to define appropriate thresholds for treatment institution. Treatment with vitamin D2 may not be accurately monitored with any of the three commercial assays studied. Clinicians and biochemists who continue to use 25(OH)D assays need to be urgently informed of these issues.

Topics: 25-Hydroxyvitamin D 2; Calcifediol; Chromatography, High Pressure Liquid; Hip Fractures; Humans; Sensitivity and Specificity

Incidence of hip fracture among patients with Parkinson's disease (PD) is high, especially in elderly women. To determine effects of various factors on hip fracture risk, we prospectively studied fractures in a cohort of 115 elderly patients of both genders with PD (46 men, 69 women; mean age, 71.9 years) for 1 year. At baseline, we recorded body mass index (BMI), Hoehn and Yahr stage, and postmenopausal interval, and also measured bone mineral density (BMD) and serum concentrations of ionized calcium, intact parathyroid hormone (PTH), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP; a bone resorption marker), and 25-hydroxyvitamin (25-OHD). During the year hip fractures occurred in 18 patients (2 male and 16 female). We compared baseline variables between patients with and without hip fracture. PD patients with decreased BMI, lower BMD, and low concentrations of serum ionized calcium, and 25-OHD (mean 4.0 ng/ml) with compensatory hyperparathyroidsim had increased risk of hip fracture. Female PD patients with long postmenopausal intervals also had increased hip fracture risk. BMI, illness duration, postmenopausal intervals, Hoehn and Yahr stage, 25-OHD, PTH, calcium, and ICTP were determinants of BMD in patients with fracture. Elderly PD patients with low BMI, low BMD, and serum 25-OHD concentrations < or =5 ng/ml with secondary hyperparathyroidism have increased risk of hip fracture, as do female PD patients with long postmenopausal intervals.

Topics: 25-Hydroxyvitamin D 2; Age Factors; Aged; Body Mass Index; Bone Density; Calcium; Cohort Studies; Collagen; Collagen Type I; Female; Hip Fractures; Humans; Male; Menopause; Parathyroid Hormone; Parkinson Disease; Peptides; Prospective Studies; Risk Factors

Secondary hyperparathyroidism may cause bone loss and structural deterioration of bone and may thus be a cause of fracture in the elderly. Vitamin D deficiency, renal impairment and medications are potential causes of hyperparathyroidism and may also directly predispose to fracture. We present the first findings of an ongoing study of hip fracture, vitamin D deficiency and hyperparathyroidism in a large Australian nursing home.. Descriptive prevalence study.. Two hundred and fifty-one nursing home residents were eligible for inclusion. Informed consent and successful venepuncture were obtained for 99. Residents were of median age 83 years with interquartile range (IR) 77-89 years.. 25-Hydroxyvitamin D (25OHD), intact parathyroid hormone (PTH), creatinine and biochemistry, demographic data and current medications.. Fifty-two per cent of 99 subjects had 25OHD below the reference range of 28-165 nmol/l and 96.5% were below the reference range mean. Those with low 25OHD had lower plasma calcium corrected for albumin than those with normal 25OHD (medians 2.34 vs 2.41 mmol/l, 95% confidence interval for the difference between medians (CI) -0.10 to -0.04 mmol/l, P = 0.0001) and higher PTH (medians 5.8 vs 3.9 pmol/l, CI 0.10-2.6 pmol/l, P = 0.0360). Twenty-eight per cent of 97 residents had PTH above the upper reference range limit of 6.5 pmol/l. Residents receiving frusemide had higher PTH than other residents (medians 6.95 vs 3.45 pmol/l, CI 1.9-4.2 pmol/l, P < 0.0001). In linear modelling, the most important predictor of the natural logarithm of PTH was daily frusemide dose, adjusted R2 (Ra2) = 31.8%, F = 39.3, P < 0.001. Creatinine and the reciprocal of 25OHD were other significant predictors with the final Ra2 = 39.4%, F = 17.7, P < 0.001.. Vitamin D deficiency is a common risk factor for secondary hyperparathyroidism in nursing home residents despite a climate in which vitamin D nutrition is thought to be ample. However, the daily frusemide dose is a more important predictor of PTH in this population.

Topics: 25-Hydroxyvitamin D 2; Aged; Aged, 80 and over; Australia; Calcium; Female; Furosemide; Hip Fractures; Homes for the Aged; Humans; Hyperparathyroidism, Secondary; Male; Middle Aged; Nursing Homes; Parathyroid Hormone; Risk Factors; Serum Albumin; Vitamin D Deficiency

In a previous study we observed lower serum concentrations of 25(OH)D, 24,25(OH)2D, and 1,25(OH)2D in patients with hip fracture than in aged control subjects. In order to evaluate the effect of trauma on vitamin D metabolite levels, we measured serum concentrations of vitamin D binding protein (DBP) in 118 patients with hip fracture and 71 aged control subjects. Serum DBP was lower in the patients than in the controls (mean +/- SD 315 +/- 60 vs 371 +/- 44 mg/l, P less than 0.001). Serum DBP correlated positively with serum total protein, albumin, alpha 2-globulin, and the vitamin D metabolite levels in the patients. When correcting for differences in serum DBP, serum 25(OH)D and 24,25(OH)2D still were significantly lower in patients than in controls, whereas serum 1,25(OH)2D was not. The free 1,25(OH)2D index (10(5) x molar ratio 1,25(OH)2D/DBP) was lower in patients than in controls, but the level of significance was marginal. This difference was not significant when patients and controls with impairment of renal function were excluded. It is concluded that the difference in serum 25(OH)D and 24,25(OH)2D between patients and controls is largely preexistent. However, the lower serum 1,25(OH)2D in the patients is mainly caused by the trauma. The free 1,25(OH)2D concentrations are almost similar in the two groups when renal function is normal.

Topics: 25-Hydroxyvitamin D 2; Aged; Alpha-Globulins; Calcifediol; Ergocalciferols; Femoral Neck Fractures; Hip Fractures; Humans; Hydroxycholecalciferols; Serum Albumin; Vitamin D; Vitamin D-Binding Protein