Intravenous contrast injection significantly affects bone mineral density measured on CT.

OBJECTIVE: The objective is to evaluate the effect of intravenous contrast media on bone mineral density (BMD) assessment by comparing unenhanced and contrast-enhanced computed tomography (CT) examinations performed for other indications. METHODS: One hundred and fifty-two patients (99 without and 53 with malignant neoplasm) who underwent both unenhanced and two contrast-enhanced (arterial and portal venous phase) abdominal CT examinations in a single session between June 2011 and July 2013 were included. BMD was evaluated on the three examinations as CT-attenuation values in Hounsfield Units (HU) in the first lumbar vertebra (L1). RESULTS: CT-attenuation values were significantly higher in both contrast-enhanced phases, compared to the unenhanced phase (p < 0.01). In patients without malignancies, mean ± standard deviation (SD) HU-values increased from 128.8 ± 48.6 HU for the unenhanced phase to 142.3 ± 47.2 HU for the arterial phase and 147.0 ± 47.4 HU for the portal phase (p < 0.01). In patients with malignancies, HU-values increased from 112.1 ± 38.1 HU to 126.2 ± 38.4 HU and 130.1 ± 37.3 HU (p < 0.02), respectively. With different thresholds to define osteoporosis, measurements in the arterial and portal phase resulted in 7-25% false negatives. CONCLUSIONS: Our study showed that intravenous contrast injection substantially affects BMD-assessment on CT and taking this into account may improve routine assessment of low BMD in nonquantitative CT. KEY POINTS: • Routine CT may gain a role in bone attenuation measurements for osteoporosis • Contrast media injection has substantial influence on CT-derived bone density • Contrast-enhanced CT leads to underestimation of osteoporosis compared to unenhanced CT • Adjusting for contrast injection phase may improve CT screening protocols for osteoporosis.

Mild chronic kidney disease is associated with cognitive function in patients presenting at a memory clinic.

OBJECTIVE: In dialysis-dependent and severe chronic kidney disease (CKD) patients, cognitive impairment is found in 16-29%. In community-dwelling population without dementia mixed results have been observed. We investigated the relationship between renal function and cognition in patients from a memory clinic. METHODS: We performed a cross-sectional study of consecutive patients from a memory clinic between 2005 and 2009. Renal function was estimated with the Modification of Diet in Renal Diseases (MDRD) and Cockcroft-Gault (CG) formulas, and categorized into ordinal groups: reference ≥ 60 ml/min/1.73 m(2), mild CKD 45-59 ml/min/1.73 m(2) and moderate CKD <45 ml/min/1.73 m(2). Cognitive function was dichotomized (Mini-Mental State Examination (MMSE) ≥ 24 vs. <24). We performed multiple logistic regression analyses with adjustment for potential confounders. RESULTS: The cohort comprised 581 patients (mean age 77 ± 10 years). With the MDRD, there were 74 (12%) cases with moderate CKD and 108 (18%) with mild CKD. With the CG, these prevalences were 144 (30%) and 130 (27%). In mild CKD patients, a significant relationship was found between cognitive function and CKD according to the MDRD-formula [adjusted OR 2.10; 95%CI 1.09-4.05]. In moderate CKD patients, no significant adjusted associations were found. In patients without dementia, significant adjusted associations were found between CKD and MMSE (MDRD: mild CKD [OR 5.09; 95%CI 1.17-22.14] and moderate CKD [OR 5.03; 95%CI 1.10-22.98]; CG: mild CKD [OR 6.16; 95%CI 1.17-32.50] and moderate CKD [OR 5.60; 95%CI 1.01-30.91]). CONCLUSION: This study showed a significant association between mild CKD and impaired cognitive function in patients from a memory clinic, especially in patients without dementia.

Vitamin D and muscle function: is there a threshold in the relation?

OBJECTIVES: First, to determine the association between serum 25 hydroxyvitamin D (25OHD) concentration and muscle mass, strength, and performance. Second, to explore if there is a threshold in the association. DESIGN: Cross-sectional, single-center study. SETTING: The central part of the Netherlands (52° Northern latitude). PARTICIPANTS: A total of 802 independently living men and postmenopausal women 40 to 80 years of age. MEASUREMENTS: Health-related and lifestyle factors, including physical activity, 25OHD concentration, lean mass, handgrip strength, knee extension strength, and physical performance were determined. RESULTS: Overall, higher 25OHD level was significantly associated with higher lean mass (22.6 g per nmol/L, 95% CI 7.3-37.9), handgrip strength (0.020 kg per nmol/L, 95% CI 0.001-0.038), and physical performance (0.006 points per nmol/L, 95% CI 0.001-0.012), after adjustment for various confounders. This association was most pronounced below a 25OHD level of 60 nmol/L, with lean mass increase 79.6 g per nmol/L (95% CI 40.8-118.4, P < .01), handgrip strength 0.09 kg per nmol/L (95% CI 0.045-0.141, P < .01), and physical performance 0.02 points per nmol/L (95% CI 0.005-0.032, P < .01), and these significant associations attenuated to null above this threshold. CONCLUSION: In middle-aged men and (postmenopausal) women, a higher 25OHD level was significantly associated with higher lean mass, muscle strength, and performance. These associations were most pronounced below 60 nmol/L and absent above 60 nmol/L, indicating a ceiling effect.

Parkinson's disease and osteoporosis.

BACKGROUND: patients with Parkinson's disease (PD) have a high risk of sustaining osteoporotic fractures as a result of falls and reduced bone mass. OBJECTIVE: to summarise the underlying pathophysiological mechanisms of bone loss in PD by reviewing the available literature. METHODS: a Medline search was performed for articles published between January 1975 and January 2011, using the keywords 'bone mineral density', 'bone loss', 'bone metabolism', 'osteoporosis', 'osteopenia', 'Parkinson's disease' and 'Parkinsonism'. RESULTS: PD patients have a lower bone mineral density (BMD) than age-matched controls. Bone loss in PD is multifactorial, resulting from immobility, decreased muscle strength, and low body weight. Vitamin D deficiency is also important, not only because it reduces BMD, but also because cell function in the substantia nigra depends on vitamin D. Lastly, hyperhomocysteinaemia, an independent risk factor for osteoporosis, is common in PD, due to levodopa use, as well as vitamin B12 and folic acid deficiency. A few studies have demonstrated that treatment with bisphosphonates, vitamin D and calcium can increase BMD and reduce fractures in PD patients. CONCLUSION: bone loss in PD is multifactorial. It is clinically important because of the concomitant risk of fractures. Screening for osteoporosis should be considered more often, and therapeutic interventions should be initiated.

The association of chronic kidney disease with brain lesions on MRI or CT: a systematic review.

BACKGROUND AND PURPOSE: This review reports on the association between chronic kidney disease (CKD) established with glomerular filtration rate (GFR) and brain lesions established with MRI or CT. METHODS: Literature was searched combining synonyms of kidney function, brain lesions and terms for the definitions thereof, and MRI or CT. This resulted in 1507 articles, of which 20 were finally included. RESULTS: Cross-sectional studies found an association between GFR and white matter lesions (WML) with 7 out of 11 associations significant (odds ratios (OR) GFR, continuous variable: 0.84-0.89 per 10 ml/min/1.73 m(2)). Most significant results were found in studies including subjects from the general population. GFR was associated with silent cerebral infarcts (SCI) with 9 out of 12 associations significant (OR GFR, continuous variable: 0.96-0.99 per ml/min/1.73 m(2)). Brain atrophy was reported significant 4 out of 5 associations (OR GFR, continuous variable: 0.64 per 10 ml/min/1.73 m(2)). Additionally, 2 follow up studies were included. One established that serum creatinine at baseline is a significant predictor of the presence of SCI; the other that the presence of SCI at baseline is a significant predictor of a decrease in GFR. CONCLUSION: The results from this review show that CKD is associated with brain lesions. These brain lesions include WML, SCI and brain atrophy. This finding is of clinical importance because these brain lesions are predictive of stroke, cognitive decline and dementia. Additional follow up studies should be performed to better understand the causative pathway and to establish whether screening and preventive programs are beneficial.

Raloxifene and tibolone in elderly women: a randomized, double-blind, double-dummy, placebo-controlled trial.

OBJECTIVES: The authors' first aim was to study the effects of raloxifene and tibolone on body mass density, handgrip strength, and other secondary frailty components. The secondary aim was to compare the effects of raloxifene and tibolone and their safety in older women. DESIGN/SETTING/PARTICIPANTS: A randomized, double-blind, double- dummy, placebo-controlled trial conducted in an academic hospital in the Netherlands among 318 community living women aged >70 were randomized; 290 received the allocated intervention: 97 placebo, 101 raloxifene, and 92 tibolone. INTERVENTIONS: Randomization was made to raloxifene 60 mg, tibolone 1.25 mg, or placebo. Assessments were performed at baseline and after 3, 6, 12, and 24 months. The study was conducted from July 2003 to January 2008. The tibolone group stopped earlier in February 2006, because of results of the Long-Term Intervention on Fractures with Tibolone study, suggesting an increased risk of cerebrovascular accident. MEASUREMENTS: Primary endpoints were body mass density and handgrip strength. Secondary endpoints were muscle power and strength, mobility measures, body composition, verbal memory, mental processing speed, anxiety, mood, and quality of life. RESULTS: Tibolone and raloxifene had similar body mass density-effect sizes (d = .24-.47), and had no effect on handgrip muscle strength. For the 15 words test the effect on direct recall of concrete and abstract words (d = .40 and d =.27, respectively) and on delayed recall of concrete words (d = .77) were significantly higher in the raloxifene group compared to placebo and to tibolone. In the raloxifene group the health status (EuroQol VAS (0-100) was improved 2.4 points [95% CI 0.5-4.2; P = .012] over 24 months. CONCLUSION: In women >70 years old, raloxifene and tibolone significantly and similarly increased body mass density but not muscle strength. Raloxifene had also positive effects on verbal memory and health status. New research with selective estrogen receptor modulators like raloxifene might be promising on frailty endpoints in elderly women. TRIAL REGISTRATION NUMBER: Nederlands Trial Register: 1232.

Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial.

BACKGROUND: Percutaneous vertebroplasty is increasingly used for treatment of pain in patients with osteoporotic vertebral compression fractures, but the efficacy, cost-effectiveness, and safety of the procedure remain uncertain. We aimed to clarify whether vertebroplasty has additional value compared with optimum pain treatment in patients with acute vertebral fractures. METHODS: Patients were recruited to this open-label prospective randomised trial from the radiology departments of six hospitals in the Netherlands and Belgium. Patients were aged 50 years or older, had vertebral compression fractures on spine radiograph (minimum 15% height loss; level of fracture at Th5 or lower; bone oedema on MRI), with back pain for 6 weeks or less, and a visual analogue scale (VAS) score of 5 or more. Patients were randomly allocated to percutaneous vertebroplasty or conservative treatment by computer-generated randomisation codes with a block size of six. Masking was not possible for participants, physicians, and outcome assessors. The primary outcome was pain relief at 1 month and 1 year as measured by VAS score. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00232466. FINDINGS: Between Oct 1, 2005, and June 30, 2008, we identified 431 patients who were eligible for randomisation. 229 (53%) patients had spontaneous pain relief during assessment, and 202 patients with persistent pain were randomly allocated to treatment (101 vertebroplasty, 101 conservative treatment). Vertebroplasty resulted in greater pain relief than did conservative treatment; difference in mean VAS score between baseline and 1 month was -5·2 (95% CI -5·88 to -4·72) after vertebroplasty and -2·7 (-3·22 to -1·98) after conservative treatment, and between baseline and 1 year was -5·7 (-6·22 to -4·98) after vertebroplasty and -3·7 (-4·35 to -3·05) after conservative treatment. The difference between groups in reduction of mean VAS score from baseline was 2·6 (95% CI 1·74-3·37, p<0·0001) at 1 month and 2·0 (1·13-2·80, p<0·0001) at 1 year. No serious complications or adverse events were reported. INTERPRETATION: In a subgroup of patients with acute osteoporotic vertebral compression fractures and persistent pain, percutaneous vertebroplasty is effective and safe. Pain relief after vertebroplasty is immediate, is sustained for at least a year, and is significantly greater than that achieved with conservative treatment, at an acceptable cost. FUNDING: ZonMw; COOK Medical.

Clinical course of pain in acute osteoporotic vertebral compression fractures.

PURPOSE: The authors prospectively determined the natural course of pain in patients with conservatively treated acute osteoporotic vertebral compression fractures (VCF). In addition, the type of conservative therapy that these patients received was assessed. MATERIALS AND METHODS: Patients older than 50 years, referred for spine radiography for acute back pain, were asked to complete a baseline clinical questionnaire. Patients with an acute VCF were followed up at 6 and 23 months with a questionnaire that included a Visual Analog Score (VAS) and type of pain medication and other conservative treatment. Significant pain relief was defined as a decrease in VAS of 50% or more. RESULTS: Forty-nine patients (mean age, 78 years; range, 51-95) with acute VCF were followed up for almost 2 years. Significant pain relief was noted in 22 of 35 patients (63%) at 6 months and in 25 of 36 (69%) at 23 months. In patients with persisting pain at 23 months (mean VAS 6.4), some decrease in VAS was apparent at 6 months but not in the 6-23 months interval. No predictors for significant pain relief could be identified. Patients with significant pain relief used less pain medication and had less physical therapy. CONCLUSIONS: In most patients with an acute VCF, pain decreases significantly with conservative therapy, predominantly in the first 6 months. However, almost 2 years after an acute VCF, a third of patients still had severe pain necessitating pain medication and physical therapy in the majority. No predictors for transition from acute to chronic pain could be identified.

PTH analogues and osteoporotic fractures.

IMPORTANCE OF THE FIELD: At present there are two parathyroid hormone (PTH) analogues (PTH 1 - 34 and PTH 1 - 84) registered for the treatment of established osteoporosis in postmenopausal women (PTH 1 - 34 and PTH 1 - 84) and in men (PTH 1 - 34 only) who are at increased risk of having a fracture. AREAS COVERED IN THIS REVIEW: The efficacy and safety of PTH 1 - 34 and PTH 1 - 84 in the management of osteoporosis is evaluated by reviewing published literature and presentations from scientific meetings through to 2010. WHAT THE READER WILL GAIN: This review focuses on data on fracture risk reduction and safety endpoints of PTH analogues. The adverse reactions reported most are nausea, pain in the extremities, headache and dizziness. TAKE HOME MESSAGE: Exogenous PTH analogues, given as daily subcutaneous injections, stimulate bone formation, increase bone mass and bone strength, and improve calcium balance. In postmenopausal women with osteoporosis, PTH analogues reduced the risk of vertebral (PTH 1 - 34 and PTH 1 - 84) and non-vertebral fractures (only PTH 1 - 34). In men and women with glucocorticosteroid-induced osteoporosis, PTH 1 - 34 reduced the risk of vertebral fractures. In general, PTH analogues are well tolerated with an acceptable safety profile: they can be used for the prevention and treatment of fractures in postmenopausal women with severe, established osteoporosis.

Effects of probiotics on acquisition and spread of multiresistant enterococci.

Ampicillin-resistant Enterococcus faecium (ARE) and vancomycin-resistant E. faecium (VRE) are important nosocomial pathogens. We quantified effects of probiotics and antibiotics on intestinal acquisition of ARE colonization in patients hospitalized in two non-intensive care unit (non-ICU) wards with high ARE prevalence. In a prospective cohort study with crossover design, all patients with a length of stay of >48 h were offered a multispecies probiotic product twice daily until discharge (4.5 months, intervention period) or not (4.5 months, control period). Perianal ARE carriage was determined <48 h after admission, twice weekly, and <48 h before discharge. The first isolates were genotyped by multiple-locus variable-number tandem repeat analysis (MLVA). Risk factors for acquisition were determined by Cox proportional hazards modeling, with special emphasis on ecological postantibiotic effects and delays between actual acquisition and culture positivity. Of 530 patients included, 94 (18%) were ARE colonized on admission. Of the remaining 436 noncolonized patients, 92 acquired ARE colonization: 28 (25%) of 110 probiotic users and 64 (20%) of 326 control patients (chi(2) test, P = 0.325). In all, 661 ARE strains were isolated from 186 patients, of which 186 were genotyped. In both wards, two MLVA types (MTs; MT1 and MT159) were responsible for >80% of acquisitions. Both MTs were genetically different from the probiotic E. faecium strain. Antibiotics to which ARE is resistant (hazard ratio [HR], 7.73 [95% confidence interval (CI), 4.52 to 13.22]), an ecological postantibiotic effect (HR, 7.11 [95% CI, 3.10 to 16.30]), and age (HR, 1.01 [95% CI, 0.99 to 1.02]) were associated with ARE acquisition. The HR of probiotics was 1.43 (95% CI, 0.88 to 2.34). In a setting with high selective antibiotic pressure, probiotics failed to prevent acquisition of multiresistant enterococci.

Muscle strength and mobility in vitamin D-insufficient female geriatric patients: a randomized controlled trial on vitamin D and calcium supplementation.

BACKGROUND AND AIMS: Insufficient vitamin D status, commonly found in older people, has been associated with muscle weakness which, in old age, impairs mobility and is a risk factor for falling. In a randomized, double-blind placebo-controlled trial, we tested the hypothesis that vitamin D + calcium supplementation improves muscle strength and mobility, compared with calcium mono-therapy in vitamin D-insufficient female geriatric patients. METHODS: Seventy female geriatric patients >65 years of age with serum 25-hydroxyvitamin D3 (25OHD) concentrations between 20 and 50 nmol/L, visiting an outpatient geriatric department, were included. Participants received either cholecalciferol 400 IU/day + calcium 500 mg/day (D/Cal group) or a placebo + calcium 500 mg/day (Plac/Cal group) for 6 months. At baseline and 6 months, muscle strength, power and functional mobility were tested. RESULTS: At baseline, 25OHD was significantly (p<0.05) associated with knee extension strength (r=0.42), handgrip strength (r=0.28), leg extension power (r=0.34), Timed Get Up and Go (r=-0.31) and Modified Cooper test (r=0.44). At 6 months, a significant difference in 25OHD (77.2 vs 41.6 nmol/L, p<0.001) and 1,25OHD was found between the two groups. Significantly improving vitamin D status in the D/Cal group compared with the Plac/Cal group did not result in a significant difference in strength or functional mobility between the two groups. CONCLUSIONS: Daily 400 IU vitamin D + 500 mg calcium supplementation is not enough to significantly improve strength or mobility in vitamin D-insufficient female geriatric patients.

Raloxifene and body composition and muscle strength in postmenopausal women: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To compare the effects of raloxifene and placebo on body composition and muscle strength. DESIGN: Randomized, double-blind, placebo-controlled trial involving 198 healthy women aged 70 years or older conducted between July 2003 and January 2008 at the University Medical Centre, Utrecht, The Netherlands. METHODS: Participants were randomly assigned to receive raloxifene 60 mg or placebo daily for 12 months. Measurements were taken at baseline, 3, 6, and 12 months, and change from baseline was calculated. Main outcome measures were body composition (bioelectrical impedance analysis), muscle strength, and muscle power (maximum voluntary isometric knee extension strength, explosive leg extensor power, and handgrip strength). RESULTS: At 12 months, the body composition of women taking raloxifene was significantly different from that of women taking placebo: fat-free mass (FFM) had increased by a mean of 0.83 (2.4) kg in the raloxifene group versus 0.03 (1.5) kg in the placebo group (P=0.05), and total body water had increased by a mean of 0.6 (1.8) litres in the raloxifene group versus a decrease of 0.06 (1.1) litres in the placebo group (P=0.02). Muscle strength and power were not significantly different. CONCLUSION: Raloxifene significantly changed body composition (increased FFM; increased water content) compared with placebo in postmenopausal women.

Raloxifene improves verbal memory in late postmenopausal women: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The aim of this study was to examine the effects of raloxifene compared with those of placebo on verbal memory, mental processing speed, depression, anxiety, and quality of life. METHODS: A randomized, double-blind, placebo-controlled trial of 213 healthy women 70 years or older was conducted between July 2003 and January 2008 at the University Medical Centre Utrecht, the Netherlands. Participants were randomly assigned to receive raloxifene (60 mg) or placebo daily for 12 months. Measurements were taken at baseline and after 3, 6, and 12 months. The change in scores from baseline was calculated. The main outcome measures were direct and delayed verbal memory (Groningen 15 Words test), mental processing speed (Trails B test), mood/depression (Geriatric Depression Scale), anxiety (State-Trait Anxiety Inventory 1 and 2), and quality of life (Women's Health Questionnaire and EuroQol-5 dimensional questionnaire). RESULTS: Direct verbal memory improved significantly with raloxifene compared with placebo: the women receiving raloxifene repeated more words in the words A + B test than did the women receiving placebo (P = 0.025). At 12 months, the change from baseline was 16 words in the raloxifene group and 10 words in the placebo group. In the words A test, direct repetition was also significantly better among women receiving raloxifene than among women receiving placebo (P = 0.023), with the change from baseline in the number of words repeated being nine words in the raloxifene group and six words in the placebo group at 12 months. CONCLUSIONS: In postmenopausal women, raloxifene gave significantly improved verbal memory when compared with placebo.

Predicting osteoporosis in patients with a low-energy fracture.

The multicenter cross-sectional study was designed to develop a simple rule to predict the risk of osteoporosis in the patients with a low-energy fracture (LEF). Furthermore, we aimed to investigate the incidence of fall-related risk factors. We included 206 patients with age over 50 and an LEF at the emergency room. All patients underwent osteoporosis and fall risk assessment and dual-energy X-ray absorptiometry (DEXA) of both hips and the lumbar spine. The incidence of osteoporosis in our study population was 41% (84 cases of 206). Fifty-four percent of the patients reported at least one fall-related risk factor. Mobility problems occurred in 31% and osteoarthritis in 19%. The final osteoporosis prediction rule included age, positive family history, immobility, and low-body weight. The discrimination of the rule after correction for over-optimism was good (receiver operating curve (ROC)=ROC area=0.79). This simple rule may be helpful to select patients who need further osteoporosis assessment.

Medical treatment of osteoporosis in the elderly.

Fractures, mostly of the hip and pelvis, wrist, and sometimes of the vertebra, account for nearly half of emergency department treatments for elderly individuals seen because of a fall. Bone density measurements show that more than half of these patients have osteoporosis. The notion that it is too late to start treatment in a late stage of the disease forms a barrier to treatment. The aim of this article is to evaluate the effectiveness of therapeutic options for osteoporosis in the elderly, with a view to reducing the incidence of fractures. Although most studies of fracture reduction with medical treatment were not designed for the "geriatric" population, the average age of participants in most clinical trials was about 70 years. Nowadays, clinicians can choose from several effective treatments for the prevention of osteoporotic fractures in high-risk postmenopausal women. Data on the antifracture potential of calcium/vitamin D, raloxifene, bisphosphonates, strontium ralenate, and parathyroid hormone are now available. In all major studies patients also received calcium and vitamin D supplements. Bisphosphonates and strontium ranelate are good choices for first- or second-line treatment, while for the time being parathyroid hormone should only be used for the second-line treatment of osteoporosis in the elderly. The ease of use of bisphosphonates, with once weekly, once monthly, or intravenous administration, may be advantageous for elderly patients already taking multiple medications.

Efficacy of tibolone and raloxifene for the maintenance of skeletal muscle strength, bone mineral density, balance, body composition, cognitive function, mood/depression, anxiety and quality of life/well-being in late postmenopausal women >/= 70 years: study design of a randomized, double-blind, double-dummy, placebo-controlled, single-center trial.

BACKGROUND: Postmenopausal women are prone to develop functional disabilities as a result of reduction in muscle strength and muscle mass caused by diminished levels of female sex hormones. While hormone replacement therapy may counteract these changes, conventional hormone replacement therapy is associated with potential harmful effects, such as an increased risk of breast cancer, and its prescription is not recommended. For this reason newer alternative drugs, such as tibolone, a synthetic steroid with estrogenic, progestogenic and androgenic activity, and raloxifene, a selective estrogen receptor modulator, may be more appropriate. This trial investigates the effect of tibolone and raloxifene on muscle strength. METHODS: We recruited 318 elderly women in our single-center randomized, double-blind, double-dummy, placebo-controlled trial. Participants were randomized to tibolone 1.25 mg (Org OD 14, Organon NV, the Netherlands) plus placebo, raloxifene 60 mg (Evista(R), Eli Lilly, United States) plus placebo or two placebo tablets daily for 24 months.The primary aim is to determine if there is a difference between tibolone and placebo or if there is a difference between raloxifene and placebo. Primary endpoints are muscle strength and bone mineral density. The secondary endpoints are postural balance, body composition, cognitive function, anxiety, mood and quality of life. The secondary aim is to determine if there is a difference between tibolone and raloxifene. The measure of effect is the change from the baseline visit to the visits after 3 months, 6 months, 12 months, and 24 months. A follow-up measurement is planned at 30 months to determine whether any effects are sustained after cessation of the study. By December 2007 the blind will be broken and the data analyzed. TRIAL REGISTRATION NUMBER: NTR: 1232.

Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial.

CONTEXT: Serum testosterone levels decline significantly with aging. Testosterone supplementation to older men might beneficially affect the aging processes. OBJECTIVE: To investigate the effect of testosterone supplementation on functional mobility, cognitive function, bone mineral density, body composition, plasma lipids, quality of life, and safety parameters in older men with low normal testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled trial of 237 healthy men between the ages of 60 and 80 years with a testosterone level lower than 13.7 nmol/L conducted from January 2004 to April 2005 at a university medical center in the Netherlands. INTERVENTION: Participants were randomly assigned to receive 80 mg of testosterone undecenoate or a matching placebo twice daily for 6 months. MAIN OUTCOME MEASURES: Functional mobility (Stanford Health Assessment Questionnaire, timed get up and go test, isometric handgrip strength, isometric leg extensor strength), cognitive function (8 different cognitive instruments), bone mineral density of the hip and lumbar spine (dual-energy x-ray absorptiometry scanning), body composition (total body dual-energy x-ray absorptiometry and abdominal ultrasound of fat mass), metabolic risk factors (fasting plasma lipids, glucose, and insulin), quality of life (Short-Form Health 36 Survey and the Questions on Life Satisfaction Modules), and safety parameters (serum prostate-specific antigen level, ultrasonographic prostate volume, International Prostate Symptom score, serum levels of creatinine, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, hemoglobin, and hematocrit). RESULTS: A total of 207 men completed the study. During the study, lean body mass increased and fat mass decreased in the testosterone group compared with the placebo group but these factors were not accompanied by an increase of functional mobility or muscle strength. Cognitive function and bone mineral density did not change. Insulin sensitivity improved but high-density lipoprotein cholesterol decreased; by the end of the study, 47.8% in the testosterone group vs 35.5% in the placebo group had the metabolic syndrome (P = .07). Quality-of-life measures were no different except for one hormone-related quality-of-life measure that improved. No negative effects on prostate safety were detected. CONCLUSION: Testosterone supplementation during 6 months to older men with a low normal testosterone concentration did not affect functional status or cognition but increased lean body mass and had mixed metabolic effects. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN23688581.

Oral testosterone supplementation and chronic low-grade inflammation in elderly men: a 26-week randomized, placebo-controlled trial.

BACKGROUND: To determine the effect of oral testosterone supplementation on systemic low-grade inflammation measured by high-sensitive C-reactive protein (hs-CRP) in aging men with low testosterone levels. METHODS: Two hundred thirty-seven men aged 60 to 80 years with a testosterone level of <13.7 nmol/L (below the 50th percentile of the population distribution) were recruited into a double-blind randomized placebo-controlled trial. Participants were randomized to either 4 capsules of 40 mg testosterone undecanoate (Andriol Testocaps, NV Organon, Oss, The Netherlands) or placebo daily for 26 weeks. Serum levels of hs-CRP were measured at baseline and at 26 weeks using a near-infrared particle immunoassay of the Synchron LX System (Beckman Coulter, Fullteron, CA). RESULTS: The median baseline hs-CRP level was 1.95 mg/L (0.30-6.43) in the testosterone group compared with 1.90 mg/L (0.40-5.91) in the placebo group. After 26 weeks of testosterone supplementation therapy, the 2 intervention groups were not statistically significantly different (median hs-CRP 2.20 vs 2.00 mg/L, interquartile range 0.40-6.54 vs 0.50-5.70, P = .36). In subgroup analysis, neither baseline testosterone level, nor age, nor baseline CRP-level modified the effect of testosterone supplementation on CRP levels. CONCLUSION: Oral testosterone undecanoate supplementation, in dosage of 160 mg daily for 26 weeks, does not increase hs-CRP levels in elderly men.

Intensity, but not duration, of physical activities is related to cognitive function.

BACKGROUND: Physical activity is thought to facilitate cognitive performance and to slow down the rate of age-related cognitive decline. This study aimed to investigate the association between the time spent on physical activity as well as the average intensity of these activities and cognitive function. DESIGN: Cross-sectional analysis. METHODS: Our study population comprised of 1927 healthy men and women aged 45-70 years in the Netherlands, examined from 1995 until 2000. Physical activity was assessed with an extensive questionnaire, and cognitive function by a neuropsychological test battery. RESULTS: Multivariate linear regression analysis showed that intensity of weekly physical activities is significantly positively associated with processing speed, memory, mental flexibility and overall cognitive function. No significant associations were observed between the time spent weekly on physical activities and the various cognitive domains. At the same time, variation in activities was significantly positively associated with speed, memory, mental flexibility and overall cognitive function. CONCLUSIONS: Average intensity of weekly physical activities and variation in activities are positively and significantly associated with cognitive performance on processing speed, memory and mental flexibility as well as performance on overall cognitive function.