Harald J. J. Verhaar

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.

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.

Functional-task exercise versus resistance strength exercise to improve daily function in older women: A randomized, controlled trial

Objectives: To determine whether a functional‐task exercise program and a resistance exercise program have different effects on the ability of community‐living older people to perform daily tasks.

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.

Differences in gait parameters at a preferred walking speed in healthy subjects due to age, height and body weight

The objective of our cross-sectional study was to investigate the changes associated with age and gender in walking speed, stride length and cadence of healthy women and men over the adult age range, and establish the effects of anthropometric indices such as height and body weight. We examined 118 women and 121 men (age range, 19–90 years). Subjects walked at their preferred speed over a 12-meter walkway crossing two Kistler force plates: cadence was calculated from heel strike times recorded from the Kistler force plates; walking speed was measured using an infrared reflecting system; and stride length was calculated from the walking speed and cadence. Older healthy subjects had lower values for walking speed and stride length than younger subjects. While there is little difference in the percentage reduction between women and men over the adult age range, the absolute values for walking speed are lower in women than men at all ages. In women, the percentage of explained variance for decline in walking speed was 30%, and for decline in stride length 40%. If body weight was also taken into account, the percentage of explained variance for walking speed was 37%, and for stride length 59%. A similar calculation for men yields 34% for decline in walking speed, and 42% for decline in stride length. Cadence was not associated with age, height and body weight. The standard errors for the estimates of walking speed in both women and men, respectively, are reduced by 8% and 3% using the multiple regression technique. The corresponding standard errors for stride length were reduced by, respectively, 19% and 13% if height in either sexes, or height and body weight in women, were taken into account. In conclusion, preferred walking speed and stride length decline with age in healthy people. Lower values found in old healthy subjects partly contributed to the difference in height and body weight between old and young subjects. Cadence was not correlated with age, height and body weight.

Stimulatory effects of estrogen and progesterone on proliferation and differentiation of normal human osteoblast-like cells in vitro

Here we report that osteoblast-like cells derived from female and male adult human trabecular bone are able to directly respond to 17 beta-estradiol (E2) and progesterone (P). In short-term (1 day) cultures using serum-free and phenol red-free medium, both steroid hormones were found to stimulate DNA synthesis and growth of the human osteoblast-like cells. P was more potent in stimulating osteoblast growth compared to E2. On the other hand, E2 showed a stronger differentiation-inducing effect as determined by analysis of the number of cells displaying cytochemical alkaline phosphatase (AP) activity, a marker for the mature osteoblast phenotype. Combination of E2 and P resulted in a further increase in DNA synthesis, but did not further affect the number of cells expressing AP activity. In conclusion, female sex steroids may be involved in regulating bone mass in human adults via a direct anabolic action on the bone forming cells.

The association between vitamin D and cognition: A systematic review

Vitamin D insufficiency and deficiency are a major health care problem. The association between vitamin D levels and cognitive function is still under debate. We conducted a systematic review to assess the association between levels of vitamin D and cognition. Therefore, the databases of Embase and Pubmed were searched through June 2012 for observational studies relating vitamin D levels to cognition. Our initial search yielded 2182 articles. After applying exclusion criteria, there were 28 studies eligible for inclusion: 25 cross-sectional and 6 prospective studies (3 studies show cross-sectional as well as prospective data). The main finding of the 25 cross-sectional studies was a statistically significant worse outcome on one or more cognitive function tests or a higher frequency of dementia with lower vitamin D levels or intake in 18 out of 25 (72%) studies, whereas 7 (28%) studies failed to show an association. Four out of 6 (66.7%) prospective studies showed a higher risk of cognitive decline after a follow-up period of 4-7 years in participants with lower vitamin D levels at baseline. In conclusion, this review supports the hypothesis that hypovitaminosis D is associated with worse outcome on one or more cognitive function tests or a higher frequency of dementia in cross-sectional as well as prospective studies. Further studies should focus on the role of vitamin D supplementation in the prevention of cognitive decline in participants with low vitamin D levels.

Percutaneous Vertebroplasty and Pulmonary Cement Embolism: Results from VERTOS II

BACKGROUND AND PURPOSE: The reported incidence of PCE during PV varies, depending on the sensitivity of diagnostic tests used. To assess the true incidence of PCE, we performed native chest CT during follow-up in a large proportion of patients from the VERTOS II trial. MATERIALS AND METHODS: VERTOS II is a prospective multicenter randomized controlled trial comparing PV with conservative therapy in 202 patients. After a mean follow-up of 22 months (median, 21 months; range, 6–42 months), 54 of 78 patients (69%) with 80 vertebrae treated with PV underwent native chest CT to detect possible PCE. The presence, location, number, and size of PCE were recorded. In addition, the presence of pulmonary parenchymal changes adjacent to PCE was noted. Possible risk factors for PCE, such as age, sex, number of treated vertebrae, cement volume per vertebra, and presence and location of perivertebral cement leakage, were evaluated. RESULTS: PCE was detected in 14 of 54 patients (26% 95% CI, 16%–39%). All patients were asymptomatic. Cement emboli were small and randomly distributed in peripheral small vessels. There were no reactive pulmonary changes. Cement leakage in the azygos vein was the only risk factor for the occurrence of PCE (OR, 43; 95% CI, 5–396). CONCLUSIONS: Small and clinically silent PCE occurred in a quarter of patients treated with PV. Cement leakage into the azygos vein was the only risk factor. With time, these small cement emboli remained inert, without inflammatory pulmonary response. Standard postprocedural CT or chest radiographs are not necessary.

Age-sensitive cognitive function, growth hormone and insulin-like growth factor 1 plasma levels in healthy older men.

Circulating levels of growth hormone (GH) change during the process of aging. Decline of cognitive functioning with aging is also well established. In this study, we investigated whether insulin-like growth factor 1 (IGF-1) and the GH response to a challenge of GH-releasing hormone and GH-releasing peptide 6 were associated with age-sensitive cognitive functions, but not with functions that do not decline with aging, in 17 healthy male subjects aged between 66 and 76 years. In addition, relations with anthropometric measures were examined. Neuropsychological performance was scored on tests of variables not sensitive to aging (general knowledge, vocabulary, basic visual perception and reading ability), and of variables sensitive to aging (visuoconstructive ability, perceptual motor and mental processing speed, and verbal long-term memory). After correcting for education, the serum GH response was significantly associated with two age-sensitive cognitive tests (measures of mental processing speed), but with none of the tests not sensitive to aging. However, the direction of the association was opposite to the relation between IGF-1 and these cognitive tests: higher levels of GH response were associated with poorer cognitive performance, whereas higher levels of IGF-1 were associated with better performance. GH response, but not IGF-1, was inversely correlated with body mass index. The results are in accordance with previous research suggesting a disruption of the relation between IGF-1 and GH secretion in older age.

Frequency and Outcome of Pulmonary Polymethylmethacrylate Embolism during Percutaneous Vertebroplasty

BACKGROUND AND PURPOSE: During percutaneous polymethylmethacrylate (PMMA) vertebroplasty (PV), PMMA cement may migrate into the venous system and subsequently be transported to the pulmonary arteries. Frequency, outcome, and imaging findings of PMMA pulmonary embolism are poorly understood. We retrospectively assessed the frequency and outcome of PMMA embolism during PV in a large patient cohort and evaluated the relationship of the volume of injected PMMA to the occurrence of pulmonary PMMA embolism. MATERIALS AND METHODS: Between 2001 and 2007, 532 osteoporotic compression fractures in 299 consecutive patients were treated with PV. PMMA embolism was defined as venous PMMA migration toward the lungs visible on biplane fluoroscopy during PV. CT was performed immediately and 1 year after PMMA migration. RESULTS: Venous PMMA migration occurred during 11 PVs in 11 patients (2.1%, 95% confidence interval, 1.1–3.7%). CT in 8 patients demonstrated small peripheral pulmonary PMMA emboli. All 11 patients remained asymptomatic during 1-year follow-up. Repeat CT scanning after 1 year in 6 patients demonstrated unchanged pulmonary PMMA deposits without late reactive changes. Mean injected cement volume in patients with and without PMMA embolism was not different (3.6 ± 1.06 mL versus 3.3 ± 1.16 mL, P = .43). Similar comparison for thoracic and thoracolumbar vertebrae yielded P values of .07 and .9. CONCLUSION: Pulmonary PMMA embolism during PV is an infrequent complication without permanent clinical sequelae. After 1 year, no pulmonary reaction was seen on CT. No definite relationship of PMMA emboli with injected cement volume could be established.