Prediction of insufficient serum vitamin D status in older women: a validated model.

We developed an externally validated simple prediction model to predict serum 25(OH)D levels < 30, < 40, < 50 and 60 nmol/L in older women with risk factors for fractures. The benefit of the model reduces when a higher 25(OH)D threshold is chosen. INTRODUCTION: Vitamin D deficiency is associated with increased fracture risk in older persons. General supplementation of all older women with vitamin D could cause medicalization and costs. We developed a clinical model to identify insufficient serum 25-hydroxyvitamin D (25(OH)D) status in older women at risk for fractures. METHODS: In a sample of 2689 women ≥ 65 years selected from general practices, with at least one risk factor for fractures, a questionnaire was administered and serum 25(OH)D was measured. Multivariable logistic regression models with backward selection were developed to select predictors for insufficient serum 25(OH)D status, using separate thresholds 30, 40, 50 and 60 nmol/L. Internal and external model validations were performed. RESULTS: Predictors in the models were as follows: age, BMI, vitamin D supplementation, multivitamin supplementation, calcium supplementation, daily use of margarine, fatty fish ≥ 2×/week, ≥ 1 hours/day outdoors in summer, season of blood sampling, the use of a walking aid and smoking. The AUC was 0.77 for the model using a 30 nmol/L threshold and decreased in the models with higher thresholds to 0.72 for 60 nmol/L. We demonstrate that the model can help to distinguish patients with or without insufficient serum 25(OH)D levels at thresholds of 30 and 40 nmol/L, but not when a threshold of 50 nmol/L is demanded. CONCLUSIONS: This externally validated model can predict the presence of vitamin D insufficiency in women at risk for fractures. The potential clinical benefit of this tool is highly dependent of the chosen 25(OH)D threshold and decreases when a higher threshold is used.

Low vitamin D status is associated with more depressive symptoms in Dutch older adults.

PURPOSE: The existence of vitamin D receptors in the brain points to a possible role of vitamin D in brain function. We examined the association of vitamin D status and vitamin D-related genetic make-up with depressive symptoms amongst 2839 Dutch older adults aged ≥65 years. METHODS: 25-Hydroxyvitamin D (25(OH)D) was measured, and five 'vitamin D-related genes' were selected. Depressive symptoms were measured with the 15-point Geriatric Depression Scale. Results were expressed as the relative risk of the score of depressive symptoms by quartiles of 25(OH)D concentration or number of affected alleles, using the lowest quartile or minor allele group as reference. RESULTS: A clear cross-sectional and prospective association between serum 25(OH)D and depressive symptom score was observed. Fully adjusted models indicated a 22 % (RR 0.78, 95 % CI 0.68-0.89), 21 % (RR 0.79, 95 % CI 0.68-0.90), and 18 % (RR 0.82, 95 % CI 0.71-0.95) lower score of depressive symptoms in people in the second, third, and fourth 25(OH)D quartiles, when compared to people in the first quartile (P for trend <0.0001). After 2 years of daily 15 µg vitamin D supplementation, similar associations were observed. 25(OH)D concentrations did not significantly interact with the selected genes. CONCLUSION: Low serum 25(OH)D was associated with higher depressive symptom scores. No interactions between 25(OH)D concentrations and vitamin D genetic make-up were observed. In view of the probability of reverse causation, we propose that the association should be further examined in prospective studies as well as in randomized controlled trials.

The association between vitamin D status and parameters for bone density and quality is modified by body mass index.

The association of vitamin D status with bone mineral density (BMD) and Quantitative Ultrasound measurements (QUS) has been inconsistent in previous studies, probably caused by moderating effects. This study explored (1) the association of vitamin D status with QUS and BMD, and (2) whether these associations were modified by body mass index (BMI), age, gender, or physical activity. Two-independent cohorts of the Longitudinal Aging Study Amsterdam (LASA-I, 1995/1996, aged ≥65; LASA-II, 2008/2009, aged 61-71) and baseline measurement of the B-vitamins for the prevention of osteoporotic fractures (B-PROOF) study (2008-2011, aged 65+) were used. QUS measurements [broadband ultrasound attenuation (BUA) and speed of sound (SOS)] were performed at the calcaneus in all three cohorts (N = 1,235, N = 365, N = 1319); BMD was measured by Dual X-ray absorptiometry (DXA) in B-PROOF (N = 1,162 and 1,192 for specific sites) and LASA-I (N = 492 and 503). The associations of vitamin D status with BUA and BMD were modified by BMI. Only in persons with low-to-normal BMI (<25 kg/m(2)) and serum 25(OH)D <25 nmol/L was associated with lower BUA as compared to the reference group (≥50 nmol/L) in LASA-I and B-PROOF. Furthermore, in LASA-I, these individuals had lower BMD at the hip and lumbar spine. In LASA-II, no associations with BUA were observed. Vitamin D status was not associated with SOS, and these associations were not modified by the effect modifiers tested. The association between vitamin D status and BUA and BMD was modified by BMI in the older-aged cohorts: there was only an association in individuals with BMI <25 kg/m(2).

Vitamin D status is associated with physical performance: the results of three independent cohorts.

UNLABELLED: This study, on the association between vitamin D status and physical performance and its decline, shows that vitamin D status is associated with physical performance in several older age groups. However, vitamin D status does not predict a decline in physical performance in individuals aged 55-65 years. INTRODUCTION: Previous research in the Longitudinal Aging Study Amsterdam (LASA) showed an association of vitamin D status with physical performance and its decline in persons aged 65 years and older. The current study aims to determine these associations in younger individuals and to replicate previous research of LASA. METHODS: Data from three independent cohorts were used: two cohorts of LASA (LASA-II with measurements in 2002 (n = 707) and 2009 (n = 491), LASA-I-2009 (n = 355)) and the baseline measurement of the B-Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) study (n = 2,813). Participants performed three tests (walking test, chair stands, and tandem stand; range total score 0-12), except in LASA-II-2002 (only walking and chair stands tests; range total score 0-8). Multiple linear and logistic regression were used to assess whether vitamin D status was associated with total physical performance and its decline, respectively. RESULTS: The mean age of the participants was 60.0 (SD 3.0), 65.9 (2.9), 78.4 (5.3), and 74.4 (6.8) years for LASA-II-2002, LASA-II-2009, LASA-I-2009, and B-PROOF, respectively. Vitamin D status was not predictive of a clinical decline in total physical performance score in the LASA-II-2002 cohort (aged 55-65 years). After adjustment for confounding, participants with serum 25(OH)D < 50 nmol/L scored 0.8 (95 % confidence interval 0.4-1.2), 0.9 (0.3-1.5), 1.5 (0.8-2.3), and 0.6 (0.3-0.9) points lower on total physical performance than participants with serum 25(OH)D ≥ 75 nmol/L. CONCLUSION: Our study confirmed that serum 25(OH)D is associated with physical performance. However, vitamin D status did not predict a clinical decline in physical performance in individuals aged 55-65 years.

Associations of vitamin D status and vitamin D-related polymorphisms with sex hormones in older men.

OBJECTIVE: Evidence regarding relationships of serum 25-hydroxyvitamin D (25(OH)D) with sex hormones and gonadotropin concentrations remains inconsistent. Polymorphisms in vitamin D-related genes may underly these relationships. Our aim was to examine the relationship of vitamin D status and polymorphisms in vitamin D-related genes with sex hormone and gonadotropin levels. DESIGN AND MEASUREMENTS: We analysed data from the Longitudinal Aging Study Amsterdam, an ongoing population-based cohort study of older Dutch individuals (65-89 years). We included data of men with measurements of serum 25-hydroxyvitamin D (25(OH)D) (n=643) and determination of vitamin D-related gene polymorphisms (n=459). 25(OH)D concentrations were classified into four categories: <25, 25-50, 50-75 and >75nmol/L. Outcome measures were total testosterone, calculated bioavailable and free fraction testosterone, SHBG, estradiol, LH and FSH concentrations. Hypogonadism was defined as a total testosterone level <8.0nmol/L. RESULTS: Serum 25(OH)D was positively associated with total and bioavailable testosterone levels. After adjustments for confounders, men with serum 25(OH)D less than 25 (n=56), 25-50 (n=199) and 50-75nmol/L (n=240) had lower total testosterone levels compared to men with serum 25(OH)D higher than 75nmol/L (n=148) (ß (95% confidence interval): -2.1 (-3.7 to -0.4nmol/L), -0.8 (-1.9 to 0.4nmol/L) and -1.4 (-2.4 to -0.3nmol/L), respectively). For bioavailable testosterone the association was significant only for men with serum 25(OH)D less than 25nmol/L (-0.8 (-1.4 to -0.1nmol/L)) compared to men with serum 25(OH)D >75nmol/L. Serum 25(OH)D was not related to SHBG, estradiol or gonadotropin levels. Hypogonadism (n=29) was not associated with lower serum 25(OH)D. No significant differences were found in hormone levels between the different genotypes of the vitamin D-related gene polymorphisms. Also, the polymorphisms did not modify the relationships of serum 25(OH)D with sex hormones or gonadotropins. CONCLUSION: Vitamin D status is positively associated with testosterone levels. No association was found between vitamin D-related gene polymorphisms and hormone levels.

Gender-Specific Associations of Serum Insulin-Like Growth Factor-1 With Bone Health and Fractures in Older Persons.

CONTEXT: IGF-1 plays a role in bone metabolism. Although IGF-1 and bone mass both decrease with advancing age, their relationship in older individuals remains to be elucidated. OBJECTIVE: The objective was to investigate associations of serum IGF-1 cross-sectionally with quantitative ultrasound and bone mineral density (BMD), and longitudinally with 3-year change in BMD and 10-year fracture risk in older individuals. DESIGN, SETTING, AND PATIENTS: The study included 627 men and 656 women aged ≥ 65 years from the Longitudinal Aging Study Amsterdam, an ongoing, population-based cohort study. MAIN OUTCOME MEASURES: Main outcome measures included baseline serum IGF-1 concentration; baseline quantitative ultrasound of the heel, including broadband ultrasound attenuation and speed of sound; BMD measured at several body sites at baseline and after 3 years; and prospective fracture incidence over 10 years. Associations were adjusted for relevant confounders. RESULTS: Women, but not men, in the lowest quintile of IGF-1 concentration had lower broadband ultrasound attenuation (B = -4.53; P = .03) and a greater 3-year decrease in total hip BMD (B = -0.02; P = .05), than women in the highest quintile of IGF-1. Moreover, compared to women in the highest quintile of IGF-1, women in the combined lowest four quintiles of IGF-1 had an increased 10-year fracture risk (hazard ratio = 1.98; P = .05). CONCLUSIONS: Associations of lower IGF-1 with lower BUA, greater 3-year decrease in BMD, and increased 10-year fracture risk were only observed in women, not in men. These results support previous findings of gender differences in the relationship between IGF-1 and bone in older individuals.

Thresholds for Serum 25(OH)D Concentrations With Respect to Different Outcomes.

CONTEXT: Vitamin D is essential for bone health. In addition, vitamin D has recently been proposed to play a role in the pathophysiology of many chronic diseases. Despite the large number of studies published on vitamin D, the threshold for a sufficient serum 25-hydroxyvitamin D [25(OH)D] concentration is still debated and may differ according to outcomes and subgroups. OBJECTIVE: The objective of the study was to estimate the thresholds for serum 25(OH)D concentration with respect to the different outcomes and for different subgroups. DESIGN, SETTING, AND PARTICIPANTS: Observational data from the Longitudinal Aging Study Amsterdam, an ongoing population-based Dutch cohort study [n = 1164, mean (SD) age 75.2 (6.5) y], were used. MAIN OUTCOME MEASURES: Falling, fractures, hypertension, cardiovascular disease, blood pressure, PTH, grip strength, physical performance, functional limitations, body mass index (BMI), and mortality were measured. To determine thresholds, spline curves were used. Visual inspection and the statistical best fit of the spline regression models were used together to estimate the best estimate of the thresholds. RESULTS: Thresholds for serum 25(OH)D concentrations in the whole sample ranged from 46 nmol/L (PTH) to 68 nmol/L (hypertension). On average, women, the oldest old (≥ 75 y), and individuals with a high BMI (>25 kg/m(2)) had lower thresholds compared with men, the youngest old (65-75 y), and individuals with a low to normal BMI (<25 kg/m(2)). CONCLUSION: The results indicate that thresholds for serum 25(OH)D may vary according to different outcomes and subgroups. This study does not support the high thresholds (>75 nmol/L) as advised by some experts, and the higher requirements in women, older persons, and those with high BMI.

Serum insulin-like growth factor 1 and late-life depression: a population-based study.

OBJECTIVE: Serum insulin-like growth factor 1 (IGF-1) concentration decreases, while the prevalence of depressive symptoms increases with advancing age. Although basic research indicates a link between low IGF-1 concentration and depression, this has scarcely been investigated in humans. This study investigates whether lower IGF-1 concentrations are associated with prevalent and incident late-life depression over a 3-year period. METHODS: The study included 1188 participants, aged ≥ 65 years, from the Longitudinal Aging Study Amsterdam (LASA), an ongoing, population-based cohort study. Depression was assessed at baseline and after three years using the Center for Epidemiological Studies-Depression Scale (CES-D) and the Diagnostic Interview Schedule (DIS), and categorized into minor depression and major depression (MDD). Serum IGF-1 concentration was determined at baseline. Associations were adjusted for relevant confounders. RESULTS: Serum IGF-1 concentrations were within the normal range (mean 13.9 nmol/l, standard deviation 5.3 nmol/l). At baseline, in men, as compared to high concentrations, mid concentrations decreased the probability of prevalent minor depression (odds ratio [OR] = 0.35, 95% confidence interval [CI] = 0.15-0.82). In women, as compared to high concentrations, low concentrations tended to increase the probability of prevalent MDD (OR = 2.66, 95% CI = 0.89-7.89). At three-year follow-up, in men, no significant prospective associations were detected. In women, as compared to high concentrations, mid concentrations decreased the probability of incident minor depression (OR = 0.43, 95% CI = 0.19-0.95). CONCLUSIONS: Several associations, which differed across the genders, were observed between IGF-1 and depression. Cross-sectional findings were not supported by longitudinal findings, which suggest that IGF-1 may not play an important predictive role in the development of depression in older persons over time. However, a more acute role of IGF-1 in current depression, as indicated by the cross-sectional results, may be possible. Further studies are needed to elucidate the complex relation between IGF-1 and late-life depression.

BMI and Body Fat Mass Is Inversely Associated with Vitamin D Levels in Older Individuals.

OBJECTIVE: To assess the association between obesity (measured by Body Mass Index (BMI) and fat percentage) and serum 25(OH)D levels in older persons. DESIGN: Cross-sectional analysis of data from 'the B-PROOF study' (B-vitamins for the Prevention Of Osteoporotic Fractures). PARTICIPANTS: 2842 participants aged 65 years and older. MEASUREMENTS: BMI and fat percentage, measured by Dual Energy X-ray, and serum 25(OH)D levels. RESULTS: Mean age was 74 years (6.5 SD), with 50% women. Mean serum 25(OH)D levels were 55.8 nmol/L (25 SD). BMI and total body fat percentage were significant inversely associated with serum 25(OH)D levels after adjustment for confouders (ß-0.93; 95% CI [-1.15; -0.71], p<0.001 and ß-0.84; 95% CI [-1.04; -0.64], p<0.001). This association was most prominent in individuals with a BMI in the 'overweight' and 'obesity' range (ß -1.25 and -0.96 respectively) and fat percentage in the last two upper quartiles (ß-1.86 and -1.37 respectively). CONCLUSION: In this study, higher BMI and higher body fat percentage were significantly associated with lower serum 25(OH)D levels in older persons. This association was particularly present in individuals with overweight, and higher fat percentages, suggesting that these persons are at increased risk of vitamin D insufficiency.

Vitamin D status is associated with functional limitations and functional decline in older individuals.

CONTEXT: Vitamin D is known to influence muscle health. A reduction in muscle mass increases the risk of functional limitations among older individuals. OBJECTIVE: The aim of this study was to examine the relationship between vitamin D status and functional limitations. DESIGN, SETTING, AND PARTICIPANTS: Two independent cohorts of the Longitudinal Aging Study Amsterdam were used. Participants were aged 65 to 88 years (older cohort, n = 1237; baseline 1995) and 55 to 65 years (younger cohort, n = 725; baseline 2002). MAIN OUTCOME MEASURES: Questions on the ability and degree of difficulty to perform 6 functions of daily life were asked. RESULTS: Of the participants, 56% in the older cohort and 30% in the younger cohort had ≥1 limitation. Vitamin D deficiency (25-hydroxyvitamin D level of <20 ng/mL) compared with the value in the reference group (>30 ng/mL) was related to the presence of functional limitations at baseline (odds ratio [OR] = 1.7; 95% confidence interval [CI], 1.2-2.5 and OR = 2.2; 95% CI 1.3-3.7 for the older and younger cohorts, respectively). In the older cohort, vitamin D deficiency was associated with an increase in limitations at 3 years (OR = 2.0; 95% CI, 1.1-3.5), whereas vitamin D deficiency in the younger cohort was associated with an increase in limitations at 6 years (OR = 3.3; 95% CI, 1.1-10.1). Analyses were adjusted for confounders. CONCLUSION: Vitamin D status is associated with functional limitations cross-sectionally and longitudinally in individuals aged 55 to 65 years and those 65 years and older. The possible association of vitamin D with functional limitations is present after a shorter follow-up time in the oldest age group compared with the younger age group.

The impact of medication on vitamin D status in older individuals.

OBJECTIVE: Vitamin D deficiency and polypharmacy are common in the elderly. However, knowledge on the associations between the use of specific medicines and serum 25-hydroxyvitamin D (25(OH)D) is limited. The aim of this study was to (better) define the associations between the use of specific medicines and serum 25(OH)D. METHODS: Two different cohorts (1995/1996 and 2002/2003) from the Longitudinal Aging Study Amsterdam (LASA) were used for cross-sectional analyses. LASA is based on an age and sex-stratified random sample of the Dutch older population. Study participants were aged 65-88 years in the first cohort (n = 1301) and 55-65 years in the second cohort (n = 736). Serum 25(OH)D of users of several groups of medicines were compared with levels of non-users using multiple linear regression analysis. RESULTS: Of all participants, 75.4% (first cohort) and 61.1% (second cohort) were using at least one medicine. In both cohorts, the number of medicines was associated with lower serum 25(OH)D. In the first cohort, after adjustment for confounding, users of any kind of medicine, loop diuretics and inhaled corticosteroids (only men) had respectively 4.4 nmol/l (P<0.01), 4.7 nmol/l (P = 0.04) and 7.3 nmol/l (P = 0.02) lower serum 25(OH)D than non-users. In the second cohort, the use of oral antidiabetics, calcium-channel blockers and angiotensin-converting enzyme inhibitors was associated with respectively 7.4 nmol/l (P = 0.04), 7.7 nmol/l (P = 0.01) and 7.6 nmol/l (P<0.01) lower serum 25(OH)D. CONCLUSIONS: These data show that users of several medicines have lower serum 25(OH)D than non-users. Vitamin D supplementation may be considered in patients with chronic use of medicines.