A 1-year prospective study of the effect of infliximab on bone metabolism in inflammatory bowel disease patients.

OBJECTIVES: Infliximab (IFX) treatment has shown potentially beneficial effects on bone metabolism in inflammatory bowel disease (IBD) patients. We aimed to prospectively evaluate the impact of IFX treatment on bone metabolism in antitumour necrosis factor (TNF)-α-naive IBD patients using established bone metabolism markers and an in-vitro osteoblast model. MATERIALS AND METHODS: A total of 37 anti-TNFα-naive IBD patients and 20 healthy controls were included. All measurements were performed at baseline and repeated in IBD patients following IFX therapy. Bone mineral density was measured by dual-energy X-ray absorptiometry. Parathyroid hormone, vitamin D, osteoprotegerin, soluble receptor activator of nuclear factor B ligand and proinflammatory and anti-inflammatory cytokines were measured. Bone formation was measured using osteocalcin (OC) and procollagen type 1N propeptide, and bone resorption was measured using serum type 1 collage c-telopeptide. The effect of control and IBD patient sera on human osteoblast viability and differentiation was analysed. RESULTS: OC level was higher in controls than IBD patients (P=0.018). After IFX, OC and procollagen type 1N propeptide increased significantly (P=0.002 and 0.011) and (P<0.001 and P=0.016) at weeks 6 and 30 after treatment, respectively. There was a nonsignificant decrease in serum type 1 collage c-telopeptide. After IFX therapy, proinflammatory cytokines TNF-α, interleukin-6 and interleukin-13 decreased significantly (P=0.016, week 54; P=0.005, week 6 and P=0.025, week 6), respectively. Sera from IBD patients before IFX showed increased osteoblast viability compared with the controls (P=0.003 to P<0.005), but induced reduced osteoblast differentiation. After IFX, viability reduced to control levels, but osteoblast differentiation increased (P=0.041). CONCLUSION: IFX treatment induced beneficial effects on bone metabolism. Osteoblast culture results suggest that IBD patients may have increased osteoblast viability, but reduced differentiation, which has implications for bone strength.

Adalimumab Therapy Has a Beneficial Effect on Bone Metabolism in Patients with Crohn's Disease.

BACKGROUND: Infliximab has been shown to have beneficial effects on bone metabolism in patients with Crohn's disease (CD) although as yet the exact mechanisms have not been fully elucidated. AIM: To evaluate the impact of adalimumab therapy on bone metabolism using a combined in vivo and in vitro model. METHODS: Parathyroid hormone, vitamin D, bone formation markers, bone resorption marker, pro-inflammatory cytokines, anti-inflammatory cytokines, osteoprotegerin, and sRANKL were measured in control patients and pre- and post-treatment with adalimumab in CD patients. The effect of control patients' and pre- and post-treatment CD patients' sera on human osteoblasts (hFOB 1.19) in vitro cell viability and differentiation was also analyzed. RESULTS: There was a significant increase in bone formation markers osteocalcin (P < 0.05) and procollagen type 1 N-terminal propeptide (P < 0.01) at 1 and 3 months post-treatment. Moreover, there was a sustained but not significant fall in serum CTx, a bone resorption marker. No significant change was seen over time with other parameters measured. Serum from CD patients pre-treated with adalimumab showed increased osteoblast viability compared with that of post-treated patients at 6 months (P = 0.002) and controls. However, post-adalimumab treatment sera at 6 months appeared to increase osteoblast differentiation (P = 0.001), which is likely to be important in new bone formation. CONCLUSIONS: This first study evaluating the role of adalimumab as a possible bone protector in Crohn's disease patients has shown that similar to infliximab, adalimumab has complex and potentially beneficial effects on bone metabolism.

The relationship between the apolipoprotein E e4 allele and hippocampal magnetic resonance imaging volume in community-dwelling individuals with mild Alzheimer's disease.

BACKGROUND: The degree of hippocampal magnetic resonance imaging (MRI) volume loss in Alzheimer's disease (AD) is commonly accepted as a marker of disease severity, yet remains expensive, unavailable, or not tolerated by many patients. AIM: To examine whether the presence of one or more apolipoprotein E (ApoE) e4 alleles is associated with smaller hippocampal MRI volumes in a population of early AD patients. METHODS: A total of 88 consecutive patients attending a community-based memory disorders clinic who had both mild dementia on the Clinical Dementia Rating scale and Diagnostic and Statistical Manual of Mental Disorders criteria for probable AD were recruited. We examined the relationship between ApoE e4 allele load and hippocampal atrophy on MRI volumes. RESULTS: There was no association between the ApoE e4 load and hippocampal volume in this cohort. CONCLUSION: This study suggests that the presence of one or more ApoE e4 alleles cannot be used to estimate pathological disease load in early AD.

Anxiety and behavioural disturbance as markers of prodromal Alzheimer's disease in patients with mild cognitive impairment.

BACKGROUND: Depression and anxiety have been reported to be independently predictive of conversion to Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI). Anxiety symptoms have been less well studied and findings in this regard have been inconsistent. The objectives of this study are to determine which symptoms among a range of neuropsychiatric symptoms known to commonly occur in patients with MCI are predictive of later conversion to AD. We also wish to determine whether these symptoms track existing measures of declining cognitive and functional status or may be considered distinct and sensitive biomarkers of evolving Alzheimer's pathology. METHODS: One hundred and sixty-one patients with MCI were identified from consecutive referrals to a memory clinic. Univariate, multivariate and cox regression analyses were conducted. RESULTS: Seventy-six per cent of all patients had at least one neuropsychiatric symptom at baseline of which anxiety (52%), affective disturbance (37%) and aggression (32%) were the most common. Increasing symptom frequency was observed with increasing clinical severity. Anticipatory anxiety and activity disturbances were significantly associated with earlier conversion to AD although this association did not remain significant following adjustment for cognitive status at baseline. CONCLUSION: Neuropsychiatric symptoms and anxiety symptoms in particular are common in patients with MCI. In this sample anxiety for upcoming events and purposeless activity frequently co-occurred and were significant clinical predictors of earlier conversion to AD. However, these findings were not independent of cognitive status at baseline and therefore may be markers of severity rather than independent predictors of disease progression.

Vascular biomarkers of cognitive performance in a community-based elderly population: the Dublin Healthy Ageing study.

BACKGROUND: population studies suggest that cardiovascular risk factors may be associated with cognitive impairment. Epidemiological studies evaluating individual markers of vascular disease as risk factors for cognitive dysfunction have yielded inconsistent results. Homocysteine has emerged as a marker consistently associated with poorer outcomes. Existing studies have largely examined individual vascular risks in isolation and have tended to ignore patient psychological status. OBJECTIVE: to investigate the association between markers of vascular disease and cognition in a community-dwelling non-demented elderly population while adjusting for vascular and non-vascular confounds. DESIGN: cross-sectional community based assessment. PARTICIPANTS: 466 subjects with mean age 75.45 (s.d., 6.06) years. 208 (44.6%) were male. RESULTS: higher levels of homocysteine were consistently associated with poorer performance in tests assessing visual memory and verbal recall. No other vascular biomarker was found to be associated with cognitive performance. Factors such as alcohol use, tea intake, life satisfaction, hypertension and smoking were positively correlated with global cognitive performance. Negative correlations existed between cognitive performance and depression, past history of stroke, intake of fruit and use of psychotropic medication. CONCLUSIONS: homocysteine was the only vascular biomarker associated with poorer function in a number of domains on neuropsychological testing, independent of vascular and non-vascular confounds. Other psychosocial factors may need to be taken into account as potential confounds in future studies investigating cognition.