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Biomedical subjects

Paul Lips

Publications and source records attributed to Paul Lips.

At least 19 recordsLinked to original sources
PubMed2007

Vitamin D receptor gene haplotype is associated with body height and bone size.

CONTEXT: Adult stature is a complex genetic trait. The vitamin D endocrine system has pleiotropic effects on several physiological processes, especially on skeletal metabolism. We recently identified promoter and 3'-untranslated region (UTR) haplotype alleles that influence vitamin D receptor (VDR) mRNA expression. OBJECTIVE: We studied whether VDR gene variants contribute to the genetic variation in height. DESIGN AND SUBJECTS: We studied VDR haplotype alleles and body height in two independent populations (n=7187). In a meta-analysis (n=14,157 from 27 studies and our current data), we evaluated the effect of the Bsm I polymorphism. RESULTS: Haplotypes of the linkage disequilibrium block 3 and block 5 were associated with body height differences with evidence for additive effects in the Rotterdam Study (P=0.00002) and the Longitudinal Aging Study Amsterdam study (P=0.001). Height differences between the extreme genotypes were 1.4 and 2.7 cm, respectively. The relationship was independent of age, gender, presence of vertebral fractures, and age-related height loss. In the Rotterdam population, we found the combined genotype to be associated with decreased vertebral area (P=0.03) and femoral narrow neck width (P=0.002). In the meta-analysis, subjects with the "BB" genotype were 0.6 cm (95% confidence interval, 0.2-1.1 cm) taller than those with the "bb" genotype (P=0.006). CONCLUSION: VDR gene variants are associated with differences in body height as evidenced by our study and by a meta-analysis. It remains for further studies to confirm whether the underlying mechanism of the association involves lower VDR expression in cells important for determining bone size.

Analysis of Variance↗
PubMed2007

Effect of mechanical loading on insulin-like growth factor-I gene expression in rat tibia.

Mechanical loading plays an essential role in maintaining skeletal integrity. Mechanical stimulation leads to increased bone formation. However, the cellular and molecular mechanisms that are involved in the translation of mechanical stimuli into bone formation, are not completely understood. Growth factors and osteocytes, which act as mechanosensors, play a key role during the bone formation after mechanical stimulation. The aim of this study was to characterize the role of IGF-I in the translation of mechanical stimuli into bone formation locally in rat tibiae. Fifteen female Wistar rats were randomly assigned to three groups (n = 5): load, sham-loaded, and control. The four-point bending model of Forwood and Turner was used to induce a single period of mechanical loading on the tibia shaft. The effects of mechanical loading on IGF-I mRNA expression were determined with non-radioactive in situ hybridization on decalcified tibiae sections, 6 h after the loading session. Endogenous IGF-I mRNA was expressed in trabecular and cortical osteoblasts, some trabecular and sub-endocortical osteocytes, intracortical endothelial cells of blood vessels, and periosteum. Megakaryocytes, macrophages, and myeloid cells also expressed IGF-I mRNA. In the growth plate, IGF-I mRNA was located in proliferative and hypertrophic chondrocytes. Mechanical loading did not affect the IGF-I mRNA expression in osteoblasts, bone marrow cells, and chondrocytes, but the osteocytes at the endosteal side of the shaft showed a twofold increase of IGF-I mRNA expression. The proportion of IGF-I mRNA positive osteocytes in loaded tibiae was 29.3 +/- 12.9% (mean +/- s.d.; n = 5), whereas sham-loaded and contra-lateral control tibiae exhibited 16.7 +/- 4.4% (n = 5) and 14.7 +/- 4.2% (n = 10) respectively (P < 0.05). Lamellar bone formation after a single mechanical loading session was observed at the endosteal side of the shaft. In conclusion, a single loading session results in a twofold up-regulation of IGF-I mRNA synthesis in osteocytes which are present in multiple layers extending into the cortical bone of mechanically stimulated tibia shaft 6 h after loading. This supports the hypothesis that IGF-I, which is located in osteocytes, is involved in the translation of mechanical stimuli into bone formation.

Animals↗
PubMed2006

The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis.

BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear. OBJECTIVE: To evaluate the relation between VDR polymorphisms, BMD, and fractures. DESIGN: Prospective multicenter large-scale association study. SETTING: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams. PARTICIPANTS: 26,242 participants (18,405 women). MEASUREMENTS: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures. RESULTS: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model). LIMITATIONS: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis. CONCLUSIONS: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures.

Adult↗
PubMed2006

Vitamin D status in relation to one-year risk of recurrent falling in older men and women.

BACKGROUND: Falls frequently occur in the elderly and are a major cause of morbidity and mortality. OBJECTIVE: The objective of the study was to prospectively investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and risk of recurrent falling in older men and women. DESIGN: This was a prospective cohort study. SETTING: An age- and sex-stratified random sample of the Dutch older population was determined. SUBJECTS: Subjects included 1231 men and women (aged 65 yr and older) participating in the Longitudinal Aging Study Amsterdam. MEASUREMENTS: Baseline serum 25(OH)D was determined by a competitive protein binding assay. During 1 yr, falls were prospectively recorded by means of a fall calendar. RESULTS: Low 25(OH)D (<10 ng/ml) was associated with an increased risk of falling. After adjustment for age, sex, education level, region, season, physical activity, smoking, and alcohol intake, the odds ratios (95% confidence interval) were 1.78 (1.06-2.99) for subjects who experienced two falls or more as compared with those who did not fall or fell once and 2.23 (1.17-4.25) for subjects who fell three or more times as compared with those who fell two times or less. There was a statistically significant effect modification by age, and stratified analyses (<75 and > or = 75 yr) showed that the associations were particularly strong in the younger age group; the odds ratios (95% confidence interval) were 5.21 (2.03-13.40) for two falls or more and 4.96 (1.52-16.23) for three falls or more. CONCLUSIONS: Poor vitamin D status is independently associated with an increased risk of falling in the elderly, particularly in those aged 65-75 yr.

Accidental Falls↗
PubMed2006

Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study.

BACKGROUND: Osteoporosis and fracture risk are considered to be under genetic control. Extensive work is being performed to identify the exact genetic variants that determine this risk. Previous work has suggested that a G/T polymorphism affecting an Sp1 binding site in the COLIA1 gene is a genetic marker for low bone mineral density (BMD) and osteoporotic fracture, but there have been no very-large-scale studies of COLIA1 alleles in relation to these phenotypes. METHODS AND FINDINGS: Here we evaluated the role of COLIA1 Sp1 alleles as a predictor of BMD and fracture in a multicenter study involving 20,786 individuals from several European countries. At the femoral neck, the average (95% confidence interval [CI]) BMD values were 25 mg/cm2 (CI, 16 to 34 mg/cm2) lower in TT homozygotes than the other genotype groups (p < 0.001), and a similar difference was observed at the lumbar spine; 21 mg/cm2 (CI, 1 to 42 mg/cm2), (p = 0.039). These associations were unaltered after adjustment for potential confounding factors. There was no association with fracture overall (odds ratio [OR] = 1.01 [CI, 0.95 to 1.08]) in either unadjusted or adjusted analyses, but there was a non-significant trend for association with vertebral fracture and a nominally significant association with incident vertebral fractures in females (OR = 1.33 [CI, 1.00 to 1.77]) that was independent of BMD, and unaltered in adjusted analyses. CONCLUSIONS: Allowing for the inevitable heterogeneity between participating teams, this study-which to our knowledge is the largest ever performed in the field of osteoporosis genetics for a single gene-demonstrates that the COLIA1 Sp1 polymorphism is associated with reduced BMD and could predispose to incident vertebral fractures in women, independent of BMD. The associations we observed were modest however, demonstrating the importance of conducting studies that are adequately powered to detect and quantify the effects of common genetic variants on complex diseases.

Adult↗
PubMed2006

High prevalence of vitamin D deficiency in pregnant non-Western women in The Hague, Netherlands.

BACKGROUND: Vitamin D deficiency is common in dark-skinned persons living in northern countries. Vitamin D deficiency during pregnancy may have serious consequences for both mother and child. OBJECTIVE: The objective was to ascertain the prevalence of vitamin D deficiency in pregnant women of several ethnic backgrounds who were living in The Hague, a large city in the Netherlands. DESIGN: Midwives whose practice was visited by a large number of non-Western immigrants added the assessment of serum 25-hydroxyvitamin D [25(OH)D] to the standard blood test given to women who visited the practice during week 12 of pregnancy. Subsequently, the Municipal Health Service collected additional data from the midwives' files (June 2002 through March 2004): background variables, use of tobacco or alcohol or drugs, and infectious diseases. The women were grouped ethnically as Western, Turkish, Moroccan, and other non-Western. RESULTS: The vitamin D concentrations of 358 women were found in the midwives' files. Of these women, 29% were Western, 22% were Turkish, and 19% were Moroccan. Mean serum 25(OH)D concentrations in Turkish (15.2 +/- 12.1 nmol/L), Moroccan (20.1 +/- 13.5 nmol/L), and other non-Western women (26.3 +/- 25.9 nmol/L) were significantly (P </= 0.001) lower than those in Western women (52.7 +/- 21.6 nmol/L). Serum 25(OH)D was below the detection limit in 22% of the Turkish women. The differences between ethnic groups were not confounded by other determinants such as age, socioeconomic status, or parity. CONCLUSIONS: The prevalence of vitamin D deficiency in pregnant non-Western women in the Netherlands is very high, and screening should be recommended.

Adolescent↗
PubMed2006

Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission.

BACKGROUND: The prevalence of vitamin D deficiency in nursing home patients is high. OBJECTIVE: We aimed to ascertain whether lower serum 25-hydroxyvitamin D [25(OH)D] concentrations increase the risk of future nursing home admission and early death. DESIGN: We included 1260 independent, community-dwelling persons aged > or =65 y who were participating in the Longitudinal Aging Study Amsterdam (1995-1996). Study outcomes were time to nursing home admission during 6 y of follow-up and time to death until 1 April 2003. RESULTS: Vitamin D deficiency [25(OH)D < 25 nmol/L] and insufficiency [25(OH)D = 25-49.9 nmol/L] were present in 127 (10.1%) and 462 (36.7%) subjects, respectively. During follow-up, 138 subjects (11.0%) were admitted to nursing homes, and 380 subjects (30.2%) died. The risk of nursing home admission for participants with 25(OH)D deficiency was 53 cases per 1000 person-years higher than that for those with high 25(OH)D (> or =75 nmol/L) concentrations (58 compared with 5 cases). After adjustment for potential confounders, the hazard ratio (95% CI) of nursing home admission was 3.48 (1.39, 8.75) for vitamin D-deficient, 2.77 (1.17, 6.55) for vitamin D-insufficient, and 1.92 (0.79, 4.66) for vitamin D-borderline persons as compared with persons with high 25(OH)D (P for trend = 0.002). The results remained after additional adjustment for frailty indicators. Lower 25(OH)D was associated with higher mortality risk, but this association was not significant after adjustment for frailty indicators. CONCLUSION: Lower serum 25(OH)D concentrations in older persons are associated with a greater risk of future nursing home admission and may be associated with mortality.

Aged↗
PubMed2006

Alendronate with and without cholecalciferol for osteoporosis: results of a 15-week randomized controlled trial.

OBJECTIVE: Many osteoporosis patients have low 25-hydroxyvitamin D (25OHD) and do not take recommended vitamin D amounts. A single tablet containing both cholecalciferol (vitamin D3) and alendronate would improve vitamin D status concurrently, with a drug shown to reduce fracture risk. This study assessed the efficacy, safety, and tolerability of a once-weekly tablet containing alendronate 70 mg and cholecalciferol 70 microg (2800 IU) (ALN + D) versus alendronate 70 mg alone (ALN). METHODS: This 15-week, randomized, double-blind, multi-center, active-controlled study was conducted during a season when 25OHD levels are declining, and patients were required to avoid sunlight and vitamin D supplements for the duration of the study. Men (n = 35) and postmenopausal women (n = 682) with osteoporosis and 25OHD >or= 9 ng/mL were randomized to ALN + D (n = 360) or ALN (n = 357). MAIN OUTCOME MEASURES: Serum 25OHD, parathyroid hormone, bone-specific alkaline phosphatase (BSAP), and urinary N-telopeptide collagen cross-links (NTX). RESULTS: Serum 25OHD declined from 22.2 to 18.6 ng/mL with ALN (adjusted mean change = -3.4; 95% confidence interval [CI]: -4.0 to -2.8), and increased from 22.1 to 23.1 ng/mL with ALN + D (adjusted mean change = 1.2; 95% CI: 0.6 to 1.8). At 15 weeks, adjusted mean 25OHD was 26% higher (p < 0.001, ALN + D versus ALN), the adjusted relative risk (RR) of 25OHD < 15 ng/mL (primary endpoint) was reduced by 64% (incidence 11% vs. 32%; RR = 0.36; 95% CI: 0.27 to 0.48 [p < 0.001]), and the RR of 25OHD < 9 ng/mL (a secondary endpoint) was reduced by 91% (1% vs. 13%; RR = 0.09; 95% CI: 0.03 to 0.23 [p < 0.001]). Antiresorptive efficacy was unaltered, as measured by reduction in bone turnover (BSAP and NTX). CONCLUSION: In osteoporosis patients who avoided sunlight and vitamin D supplements, this once-weekly tablet containing alendronate and cholecalciferol provided equivalent antiresorptive efficacy, reduced the risk of low serum 25OHD, improved vitamin D status over 15 weeks, and was not associated with hypercalcemia, hypercalciuria or other adverse findings, versus alendronate alone.

Aged↗
PubMed2006

The effects of the aromatase inhibitor anastrozole on bone metabolism and cardiovascular risk indices in ovariectomized, androgen-treated female-to-male transsexuals.

OBJECTIVE: Cases of men with estrogen resistance and aromatase deficiency have highlighted the effects of estrogens on bone metabolism, the cardiovascular system and biochemical variables of the metabolic syndrome. In eugonadal men, administration of an aromatase inhibitor induces a substantial elevation of LH and testosterone due to the decreased negative-feedback signal of estrogen and may thwart the interpretation of results. As there is no gonad for LH to act on, no increase of serum testosterone concentration will be seen in female-to-male transssexuals. The aim of this study was to investigate the effects of estrogen deprivation on bone metabolism and vascular parameters without the interference of counter-regulatory effects as seen in eugonadal men. DESIGN: Thirty ovariectomized female-to-male transsexuals participated in this double-blind, randomized trial. During 3 months, subjects received the aromatase inhibitor anastrozole 1 mg/day (n = 16) or a placebo (n = 14) in addition to parenteral testosterone esters (Sustanon 250 every 2 weeks). RESULTS: Serum 17beta-estradiol (E(2)) concentration fell significantly from 134.0 +/- 78.8 to 77.7 +/- 130.6 pmol/l compared with placebo (P < 0.01). LH and FSH levels rose without the rise of testosterone levels observed in eugonadal men. Within the placebo group, E(2) remained at baseline levels. Of the endpoint variables measured (bone metabolism and vascular parameters) no significant changes were observed compared with placebo, or within the anastrozole-treated group. CONCLUSIONS: These results may indicate that the negative effects of estrogen deprivation in men only become manifest when the concentration falls below the levels induced by our intervention with anastrozole (77 pmol/l). This assumption is supported by the observation in the anastrozole group that, although effects of the reduction of serum E(2) on vascular parameters could not be demonstrated in subjects as a group, there was a correlation between individual serum E(2) and several vascular parameters.

Anastrozole↗
PubMed2005

Effect of long-term growth hormone treatment on bone mass and bone metabolism in growth hormone-deficient men.

UNLABELLED: Long-term GH treatment in GH-deficient men resulted in a continuous increase in bone turnover as shown by histomorphometry. BMD continuously increased in all regions of interest, but more in the regions with predominantly cortical bone. INTRODUCTION: Adults with growth hormone (GH) deficiency have reduced rates of bone turnover and subnormal BMD. GH treatment is effective in enhancing bone turnover as shown by biochemical markers and bone histomorphometric studies. However, it is uncertain whether long-term treatment will result in higher bone mass. In this study, we present BMD and histomorphometric data on 5 years of GH treatment in GH-deficient men. MATERIALS AND METHODS: Thirty-eight adult men with childhood onset GH deficiency (20-35 years) were included in the study. Twenty-six of these had multiple pituitary hormone deficiencies and were on stable conventional hormone replacement. BMC (total body) and BMD (lumbar spine and hip) were measured before and after 1, 2, 3, 4, and 5 years of treatment. BMD in various regions of the total body was calculated by computer software (head, trunk, arms, and legs). Transiliac bone biopsies were obtained before and after 1 and 5 years of GH treatment. RESULTS: Total body BMC increased 18% after 5 years of treatment. This increase was observed in all regions of interest: head, 13.7%; trunk, 27.8%; arms, 24.4%; legs, 13.8%. BMD also increased in all separately measured regions: lumbar spine, 9%; femoral neck, 11%; femoral trochanter, 16%. Lumbar spine area significantly increased (p=0.0002). Histomorphometric data showed increased osteoid surface (p<0.02), osteoid volume (p<0.01), and activation frequency (p<0.006), but trabecular bone volume did not increase significantly. Qualitative assessment of the cortical bone showed endosteal and periosteal bone formation. CONCLUSIONS: In conclusion, GH considerably increases BMC after long-term treatment. The combination of BMD and histomorphometric data suggests that GH has a greater effect on cortical than on trabecular bone.

Adult↗
PubMed2005

Adiposity in relation to vitamin D status and parathyroid hormone levels: a population-based study in older men and women.

OBJECTIVE: In small case-control studies, obesity was associated with worse vitamin D status. Our aim was to assess the association of adiposity (anthropometric measures as well as dual energy x-ray absorptiometry) with serum 25-hydroxyvitamin D (25-OH-D) and serum PTH levels in a large population-based study including older men and women. METHODS: Subjects were participants of the Longitudinal Aging Study Amsterdam and were aged 65 yr and older. In 453 participants, serum 25-OH-D and PTH were determined, and body mass index, waist circumference, waist to hip ratio, sum of skin folds, and total body fat percentage by dual energy x-ray absorptiometry were measured. RESULTS: After adjustment for potential confounders, higher body mass index, waist circumference, and sum of skin folds were statistically significantly associated with lower 25-OH-D (standardized beta values were -0.136, -0.137, and -0.140, respectively; all P < 0.05) and with higher PTH (0.166, 0.113, and 0.114, respectively; all P < 0.05). Total body fat percentage was more strongly associated with 25-OH-D and PTH (-0.261 and 0.287, respectively; both P < 0.001) compared with anthropometric measures. Total body fat percentage remained associated with 25-OH-D after adjustment for PTH, and with PTH after adjustment for 25-OH-D. CONCLUSION: Precisely measured total body fat is inversely associated with 25-OH-D levels and is positively associated with PTH levels. The associations were weaker if anthropometric measures were used, indicating a specific role of adipose tissue. Regardless of the possible underlying mechanisms, it may be relevant to take adiposity into account when assessing vitamin D requirements.

Adipose Tissue↗
PubMed2005

Estimates of optimal vitamin D status.

Vitamin D has captured attention as an important determinant of bone health, but there is no common definition of optimal vitamin D status. Herein, we address the question: What is the optimal circulating level of 25-hydroxyvitamin D [25(OH)D] for the skeleton? The opinions of the authors on the minimum level of serum 25(OH)D that is optimal for fracture prevention varied between 50 and 80 nmol/l. However, for five of the six authors, the minimum desirable 25(OH)D concentration clusters between 70 and 80 nmol/l. The authors recognize that the average older man and woman will need intakes of at least 20 to 25 mcg (800 to 1,000 IU) per day of vitamin D(3 )to reach a serum 25(OH)D level of 75 nmol/l. Based on the available evidence, we believe that if older men and women maintain serum levels of 25(OH)D that are higher than the consensus median threshold of 75 nmol/l, they will be at lower risk of fracture.

Adult↗
PubMed2005

Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people.

UNLABELLED: Hyperhomocysteinemia may contribute to the development of osteoporosis. The relationship of Hcy and vitamin B12 with bone turnover markers, BUA, and fracture incidence was studied in 1267 subjects of the Longitudinal Aging Study Amsterdam. High Hcy and low vitamin B12 concentrations were significantly associated with low BUA, high markers of bone turnover, and increased fracture risk. INTRODUCTION: Hyperhomocysteinemia may contribute to the development of osteoporosis. Vitamin B12 is closely correlated to homocysteine (Hcy). The main objective of our study was to examine the association of Hcy and vitamin B12 status and the combined effect of these two with broadband ultrasound attenuation (BUA), bone turnover markers, and fracture. MATERIALS AND METHODS: Subjects were 615 men and 652 women with a mean age of 76 +/- 6.6 (SD) years of the Longitudinal Aging Study Amsterdam (LASA). At baseline (1995/1996), blood samples were taken after an overnight fast for dairy products. Plasma Hcy was measured with IMx, serum vitamin B12 with competitive immunoassay (IA) luminescence, serum osteocalcin (OC) with immunoradiometric assay (IRMA), and urinary excretion of deoxypyridinoline (DPD) with competitive IA and corrected for creatinine (Cr) concentration. CVs were 4%, 5%, 8%, and 5%, respectively. BUA was assessed in the heel bone twice in both the right and left calcaneus. Mean BUA value was calculated from these four measurements. CV was 3.4%. After baseline measurements in 1995, a 3-year prospective follow-up of fractures was carried out until 1998/1999. Subjects were grouped by using two different approaches on the basis of their vitamin B12 concentration, normal versus low (<200 pM) or lowest quartile (Q1) versus normal quartiles (Q2-Q4), and Hcy concentration, normal versus high (>15 microM) or highest quartile (Q4) versus normal quartiles (Q1-Q3). Analysis of covariance was performed to calculate mean values of BUA, OC, and DPD/Cr(urine) based on the specified categories of Hcy and vitamin B12 and adjusted for several confounders (potential confounders were age, sex, body weight, body height, current smoking [yes/no], mobility, cognition). The relative risk (RR) of any fracture was assessed with Cox regression analysis. Quartiles were used when Hcy and vitamin B12 were separately studied in their relationship with fracture incidence. RESULTS: Fourteen percent of the men and 9% of the women had high Hcy (>15 microM) and low vitamin B12 (<200 pM) concentrations. Women with vitamin B12 levels <200 pM and Hcy concentrations >15 microM had lower BUA, higher DPD/Cr, and higher OC concentrations than their counterparts. In men, no differences were found between the different Hcy and vitamin B12 categories in adjusted means of BUA, OC, or DPD/Cr(urine). Twenty-eight men and 43 women sustained a fracture during the 3-year follow-up period. The adjusted RR for fractures (95% CI) for men with high Hcy and/or low vitamin B12 concentrations was 3.8 (1.2-11.6) compared with men with normal Hcy and vitamin B12 concentrations. Women with high Hcy and/or low vitamin B12 concentrations had an adjusted RR for fractures of 2.8 (1.3-5.7). CONCLUSIONS: High Hcy and low vitamin B12 concentrations were significantly associated with low BUA, high markers of bone turnover, and increased fracture risk.

Aged↗
PubMed2005

The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women.

OBJECTIVE: The objective of this study was to examine whether low levels of oestradiol and testosterone are associated with impaired mobility, low muscle strength and the incidence of falls in a population-based sample of older men and women. DESIGN: Cross-sectional population-based study, based on data of the Longitudinal Ageing Study Amsterdam (LASA), including 623 men and 663 women, aged 65-88 years. MEASUREMENTS: Serum levels of oestradiol, testosterone, albumin and sex hormone-binding globulin (SHBG) were measured. Physical performance, functional limitations and muscle strength were assessed, and a follow-up on falls was performed prospectively within 3 years. RESULTS: After adjustment for age, level of education, alcohol use, physical activity, chronic disease and body mass index (BMI), men in the highest quartile of the oestradiol/SHBG ratio had significantly higher physical performance scores than men in the lowest quartile (beta = 0.103). Serum levels of total testosterone were positively associated with muscle strength (beta = 0.085). Calculated bioavailable testosterone levels were positively associated with physical performance and muscle strength (beta = 0.128 and 0.109 respectively). No associations of oestradiol levels with mobility were seen in women. Levels of oestradiol and testosterone were not associated with falls. CONCLUSIONS: It can be concluded that low levels of sex hormones were associated with impaired mobility and low muscle strength in men, but not in women. Levels of sex hormones were not associated with the incidence of falls neither in men, nor in women.

Accidental Falls↗
PubMed2005

Effects of 10 years of growth hormone (GH) replacement therapy in adult GH-deficient men.

OBJECTIVE: GH-deficient adults have changes in body composition, bone mineral density (BMD) and lipid profile that can be altered by GH substitution. However, long-term data on GH substitution (up to 10 years of follow-up) are limited. DESIGN: The effects of 10 years of GH replacement therapy on BMD, body composition, bone parameters, serum lipids and glucose metabolism were studied. PATIENTS: Twenty-three childhood-onset GH-deficient men (mean age at baseline 28.6 years) were studied during 10 years of GH substitution therapy. A group of 19 age-matched healthy men served as a control group for BMD measurements at baseline and after 10 years. RESULTS: BMD of the lumbar spine increased during the 10 years of GH therapy. Bone markers and BMD in the hip increased during the first 5 years of GH therapy, but were not different from baseline after 10 years. BMD changes over time in the lumbar spine and femoral neck were significantly different in the patients compared to the controls. After 10 years the difference between the groups had decreased, but BMD was still higher in the controls than in the patients. Lipid profile had improved after 10 years of GH therapy, but body mass index (BMI), waist-hip ratio (WHR), fasting glucose and glycosylated haemoglobin (HbA1c) had increased compared to baseline. CONCLUSIONS: This long-term follow-up study found that 10 years of GH substitution in GH-deficient men causes sustained improvements in BMD in the lumbar spine and lipid profile but not in body composition.

Absorptiometry, Photon↗
PubMed2005

Endocrine and inflammatory markers as predictors of frailty.

OBJECTIVE: To examine the association of serum concentrations of 25-hydroxyvitamin D [25(OH)D], interleukin-6 (IL-6), C-reactive protein (CRP) and IGF-1 with prevalent and incident frailty. DESIGN: The Longitudinal Aging Study Amsterdam (LASA), a prospective cohort study with 3-yearly measurement cycles. Setting General population-based sample. PARTICIPANTS: The respondents were men and women aged 65 and over, who participated at T1 (1995/1996, N = 1720) and T2 (1998/1999, N = 1509). Blood samples were obtained at T1 (N = 1271). Measurements The presence of frailty at T1 and 3-year incidence of frailty. Frailty is defined as the presence of three out of nine frailty indicators. RESULTS: At T1, 242 (19.0%) of all respondents were frail. Those who were frail at T1 had higher CRP and lower 25(OH)D levels. Serum 25(OH)D remained associated with frailty after adjustment for potential confounders with an odd ratios (OR) of 2.60 [95% confidence interval (95% CI) 1.60-4.21] for 25(OH)D < 25 nmol/l and 1.72 (95% CI 1.19-2.47) for 25(OH)D 25-50 nmol/l vs. high levels of 25(OH)D. Of the nonfrail at T1, 125 respondents (14.1%) became frail at T2. After adjustment, moderately elevated CRP levels (3-10 microg/ml) (OR 1.69, 95% CI 1.09-2.63) and low 25(OH)D (OR 2.04, 95% CI 1.01-4.13) were associated with incident frailty. No consistent associations were observed for IL-6 and IGF-1. CONCLUSION: Low 25(OH)D levels were strongly associated with prevalent and incident frailty; moderately elevated levels of CRP were associated with incident frailty.

Aged↗
PubMed2005

Late-life anemia is associated with increased risk of recurrent falls.

OBJECTIVES: To examine whether anemia is associated with a higher incidence of recurrent falls. DESIGN: Prospective cohort study. SETTING: Community-dwelling sample in The Netherlands. PARTICIPANTS: Three hundred ninety-four participants aged 65 to 88 from the Longitudinal Aging Study Amsterdam. MEASUREMENTS: Anemia was defined according to World Health Organization criteria as a hemoglobin concentration less than 12 g/dL in women and less than 13 g/dL in men. Falls were prospectively determined using fall calendars that participants filled out weekly for 3 years. Recurrent fallers were identified as those who fell at least two times within 6 months during the 3-year follow-up. RESULTS: Of the 394 persons, 11.9% (18 women and 29 men) had anemia. The incidence of recurrent falls was 38.3% of anemic persons versus 19.6% of nonanemic persons (P=.004). After adjustment for sex, age, body mass index, and diseases, anemia was significantly associated with a 1.91 times greater risk for recurrent falls (95% confidence interval=1.09-3.36). Poor physical function (indicated by muscle strength, physical performance, and limitations) partly mediated the association between anemia and incidence of recurrent falls. CONCLUSION: Late-life anemia is common and associated with twice the risk of recurrent falls. Muscle weakness and poor physical performance appear to partly mediate this association.

Accidental Falls↗