Etidronate for Prevention of Ectopic Mineralization in Patients With Pseudoxanthoma Elasticum.

BACKGROUND: In pseudoxanthoma elasticum (PXE), low pyrophosphate levels may cause ectopic mineralization, leading to skin changes, visual impairment, and peripheral arterial disease. OBJECTIVES: The authors hypothesized that etidronate, a pyrophosphate analog, might reduce ectopic mineralization in PXE. METHODS: In the Treatment of Ectopic Mineralization in Pseudoxanthoma Elasticum trial, adults with PXE and leg arterial calcifications (n = 74) were randomly assigned to etidronate or placebo (cyclical 20 mg/kg for 2 weeks every 12 weeks). The primary outcome was ectopic mineralization, quantified with 18fluoride positron emission tomography scans as femoral arterial wall target-to-background ratios (TBRfemoral). Secondary outcomes were computed tomography arterial calcification and ophthalmological changes. Safety outcomes were bone density, serum calcium, and phosphate. RESULTS: During 12 months of follow-up, the TBRfemoral increased 6% (interquartile range [IQR]: -12% to 25%) in the etidronate group and 7% (IQR: -9% to 32%) in the placebo group (p = 0.465). Arterial calcification decreased 4% (IQR: -11% to 7%) in the etidronate group and increased 8% (IQR: -1% to 20%) in the placebo group (p = 0.001). Etidronate treatment was associated with significantly fewer subretinal neovascularization events (1 vs. 9, p = 0.007). Bone density decreased 4% ± 12% in the etidronate group and 6% ± 9% in the placebo group (p = 0.374). Hypocalcemia (<2.20 mmol/l) occurred in 3 versus 1 patient (8.1% vs. 2.7%, p = 0.304). Eighteen patients (48.6%) treated with etidronate, compared with 0 patients treated with placebo (p < 0.001), experienced hyperphosphatemia (>1.5 mmol/l) and recovered spontaneously. CONCLUSIONS: In patients with PXE, etidronate reduced arterial calcification and subretinal neovascularization events but did not lower femoral 18fluoride sodium positron emission tomography activity compared with placebo, without important safety issues. (Treatment of Ectopic Mineralization in Pseudoxanthoma elasticum; NTR5180).

Accuracy of bone mineral density quantification using dual-layer spectral detector CT: a phantom study.

OBJECTIVES: To investigate the accuracy of bone mineral density (BMD) quantification using dual-layer spectral detector CT (SDCT) at various scan protocols. METHODS: Two validated anthropomorphic phantoms containing inserts of 50-200 mg/cm3 calcium hydroxyapatite (HA) were scanned using a 64-slice SDCT scanner at various acquisition protocols (120 and 140 kVp, and 50, 100 and 200 mAs). Regions of interest (ROIs) were placed in each insert and mean attenuation profiles at monochromatic energy levels (90-200 keV) were constructed. These profiles were fitted to attenuation profiles of pure HA and water to calculate HA concentrations. For comparison, one phantom was scanned using dual energy X-ray absorptiometry (DXA). RESULTS: At both 120 and 140 kVp, excellent correlations (R = 0.97, P < 0.001) were found between true and measured HA concentrations. Mean error for all measurements at 120 kVp was -5.6 ± 5.7 mg/cm3 (-3.6 ± 3.2%) and at 140 kVp -2.4 ± 3.7 mg/cm3 (-0.8 ± 2.8%). Mean measurement errors were smaller than 6% for all acquisition protocols. Strong linear correlations (R2 ≥ 0.970, P < 0.001) with DXA were found. CONCLUSIONS: SDCT allows for accurate BMD quantification and potentially opens up the possibility for osteoporosis evaluation and opportunistic screening in patients undergoing SDCT for other clinical indications. However, patient studies are needed to extend and translate our findings. KEY POINTS: • Dual-layer spectral detector CT allows for accurate bone mineral density quantification. • BMD measurements on SDCT are strongly linearly correlated to DXA. • SDCT, acquired for several indications, may allow for evaluation of osteoporosis. • This potentially opens up the possibility for opportunistic osteoporosis screening.

Bisphosphonates for cardiovascular risk reduction: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Bisphosphonates might be effective in reducing cardiovascular events due to their ability to reduce calcification in arterial walls. We aimed to investigate the effects of treatment with bisphosphonates on the prevention of atherosclerotic processes and cardiovascular disease. METHODS: Pubmed, Embase and the Cochrane Library were systematically reviewed by two independent investigators for randomized controlled studies published up to January 2016, in which the effect of bisphosphonates on arterial wall disease, cardiovascular events, cardiovascular mortality or all-cause mortality were reported. There was no restriction for the type of population used in the trials. Random-effects models were used to calculate the pooled estimates. RESULTS: 61 trials reporting the effects of bisphosphonates on the outcomes of interest were included. Bisphosphonates had beneficial effects on arterial wall disease regarding arterial calcification (pooled mean percentage difference of 2 trials -11.52 (95% CI -16.51 to -6.52, p < 0.01, I(2) 13%), but not on arterial stiffness (pooled mean percentage difference of 2 trials -2.82; 95% CI -10.71-5.07; p = 0.48, I(2) 59%). No effect of bisphosphonate treatment on cardiovascular events was found (pooled RR of 20 trials 1.03; 95% CI 0.91-1.17, I(2) 16%), while a lower risk for cardiovascular mortality was observed in patients treated with bisphosphonates (pooled RR of 10 trials 0.81; 95% CI 0.64-1.02; I(2) 0%) although not statistically significant. Patients treated with bisphosphonates had a reduced risk of all-cause mortality (pooled RR of 48 trials 0.90; 95% CI 0.84-0.98; I(2) 53%). CONCLUSIONS: In this systematic review and meta-analysis it is shown that bisphosphonates reduce arterial wall calcification but have no effect on arterial stiffness or on cardiovascular events. Bisphosphonates tend to reduce the risk of cardiovascular mortality and reduce all-cause mortality in various patient groups, including osteoporosis and cancer patients.

Opportunistic screening for osteoporosis on routine computed tomography? An external validation study.

OBJECTIVES: Opportunistic screening for osteoporosis using computed tomography (CT) examinations that happen to visualise the spine can be used to identify patients with osteoporosis. We sought to verify the diagnostic performance of vertebral Hounsfield unit (HU) measurements on routine CT examinations for diagnosing osteoporosis in a separate, external population. METHODS: Consecutive patients who underwent a CT examination of the chest or abdomen and had also received a dual-energy X-ray absorptiometry (DXA) test were retrospectively included. CTs were evaluated for vertebral fractures and vertebral attenuation (density) values were measured. Diagnostic performance measures and the area under the receiver operator characteristics curve (AUC) for diagnosing osteoporosis were calculated. RESULTS: Three hundred and two patients with a mean age of 57.9 years were included, of which 82 (27%) had osteoporosis according to DXA and 65 (22%) had vertebral fractures. The diagnostic performance for vertebral HU measurements was modest, with a maximal AUC of 0.74 (0.68 - 0.80). At that optimal threshold the sensitivity was 62% (51 - 72%) and the specificity was 79% (74 - 84%). CONCLUSIONS: We confirmed that simple trabecular vertebral density measurements on routine CT contain diagnostic information related to bone mineral density as measured by DXA, albeit with substantially lower diagnostic accuracy than previously reported. KEY POINTS: • We externally validated the value of vertebral trabecular bone attenuation for osteoporosis • These diagnostic performance measures were, however, substantially lower than previously reported • This information might be useful when considering the implementation of opportunistic osteoporosis screening.

Vertebral fractures on routine chest computed tomography: relation with arterial calcifications and future cardiovascular events.

Osteoporosis and cardiovascular disease often coexist. Vertebral fractures incidentally imaged in the course of routine care might be able to contribute to the prediction of cardiovascular events. Following a case-cohort design, 5,679 patients undergoing chest CT were followed for a median duration of 4.4 years. Cases were defined as patients who subsequently developed a cardiovascular event (n = 493). The presence and severity of vertebral fractures, as well as aortic, coronary and valvular calcifications on CT were investigated. Cases were more likely to be male (69 vs 60 %) and older (66 vs 61 years old). Prevalent vertebral fractures conferred an elevated risk of cardiovascular events after adjustment for age and gender [hazard ratio (HR) of 1.28, 95 % confidence interval (CI) 1.07 to 1.54]. This effect remained moderate after correction for cardiovascular calcifications (HR 1.20, CI 0.99-1.44). However, in terms of discrimination, vertebral fractures did not have substantial incremental prognostic value after correction (C-index was 0.683 vs 0.682 for models with and without vertebral fractures respectively). Prevalent vertebral fractures on routine clinical chest CT are related to future cardiovascular events but do not have additional prognostic value to models that already include age, gender and cardiovascular calcifications.

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.

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.

Prevalent vertebral fractures on chest CT: higher risk for future hip fracture.

Subclinical or undiagnosed vertebral fractures on routine chest computed tomography (CT) may be useful for detecting patients at increased risk of future hip fractures who might benefit from preventive interventions. We investigated whether prevalent vertebral fractures on routine chest CT are associated with future hip fractures. From a source population of 5679 patients ≥40 years old undergoing chest CT in one of three Dutch hospitals between 2002 and 2005, patients hospitalized for hip fractures (n = 149) during a median follow-up of 4.4 years were identified. Following a case-cohort design, a random sample of 576 patients was drawn from the source population and added to the cases. In this group, the presence and severity of vertebral fractures was determined using semiquantitative vertebral fracture assessment and multivariate case-cohort appropriate Cox modeling. We found that cases were older (69 versus 63 years) and more often female (48% versus 38%) than the source population. Compared with those with no fracture, patients with any vertebral fracture had triple the risk of future hip fracture (age- and gender-adjusted hazard ratio [HR] = 3.1, 95% confidence interval [CI] 2.1-4.7). This HR rose to 3.8 (CI 2.6-5.6) if mild fractures were discounted. Future fracture risk increased significantly with increasing severity of vertebral fracture status: from mild (HR = 2.4, CI 1.5-3.7) and moderate (HR = 4.8, CI 2.5-9.2) to severe (HR = 6.7, CI 2.9-15.5). The same was true for having higher cumulative fracture grades: 1 to 3 (HR = 2.7, CI 1.8-4.1), 4 to 6 (HR = 4.8, CI 2.2-10.5), or ≥7 (HR = 11.2, CI 3.7-34.6). In conclusion, prevalent vertebral fractures on routine clinical chest CT are associated with future hip fracture risk.

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.

Geriatric conditions in acutely hospitalized older patients: prevalence and one-year survival and functional decline.

BACKGROUND: To study the prevalence of eighteen geriatric conditions in older patients at admission, their reporting rate in discharge summaries and the impact of these conditions on mortality and functional decline one year after admission. METHOD: A prospective multicenter cohort study conducted between 2006 and 2008 in two tertiary university teaching hospitals and one regional teaching hospital in the Netherlands. Patients of 65 years and older, acutely admitted and hospitalized for at least 48 hours, were invited to participate. Eighteen geriatric conditions were assessed at hospital admission, and outcomes (mortality, functional decline) were assessed one year after admission. RESULTS: 639 patients were included, with a mean age of 78 years. IADL impairment (83%), polypharmacy (61%), mobility difficulty (59%), high levels of primary caregiver burden (53%), and malnutrition (52%) were most prevalent. Except for polypharmacy and cognitive impairment, the reporting rate of the geriatric conditions in discharge summaries was less than 50%. One year after admission, 35% had died and 33% suffered from functional decline. A high Charlson comorbidity index score, presence of malnutrition, high fall risk, presence of delirium and premorbid IADL impairment were associated with mortality and overall poor outcome (mortality or functional decline). Obesity lowered the risk for mortality. CONCLUSION: Geriatric conditions were highly prevalent and associated with poor health outcomes after admission. Early recognition of these conditions in acutely hospitalized older patients and improving the handover to the general practitioner could lead to better health outcomes and reduce the burden of hospital admission for older patients.

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.

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.

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.