Giovanni Carlo Isaia

Bone Mineral Density at Diagnosis of Celiac Disease and after 1 Year of Gluten-Free Diet

Atypical or silent celiac disease may go undiagnosed for many years and can frequently lead to loss of bone mineral density, with evolution to osteopenia or osteoporosis. The prevalence of the latter conditions, in case of new diagnosis of celiac disease, has been evaluated in many studies but, due to the variability of epidemiologic data and patient features, the results are contradictory. The aim of this study was to evaluate bone mineral density by dual-energy X-ray absorptiometry in 175 consecutive celiac patients at time of diagnosis (169 per-protocol, 23 males, 146 females; average age 38.9 years). Dual-energy X-ray absorptiometry was repeated after 1 year of gluten-free diet in those with T-score value <−1 at diagnosis. Stratification of patients according to sex and age showed a higher prevalence of low bone mineral density in men older than 30 years and in women of all ages. A 1-year gluten-free diet led to a significant improvement in lumbar spine and femoral neck mean T-score value. We propose that dual-energy X-ray absorptiometry should be performed at diagnosis of celiac disease in all women and in male aged >30 years, taking into account each risk factor in single patients.

Quantitative heel ultrasound in a population-based study in Italy and its relationship with fracture history: the ESOPO study

We assessed the clinical usefulness of quantitative ultrasound (QUS) in defining the prevalence rates of osteoporosis and osteopenia and their association with fractures of the forearm, vertebrae, and hip. The ESOPO study was conducted in 2001 and assessed a random sample of 11,011 women and 4,981 men, in 83 centers spread all over Italy. A large array of risk factors was investigated, and self-reported history of fractures was collected in a questionnaire. After the patient had undergone interview and a brief physical examination, QUS of the heel was performed, using the Achilles apparatus (GE-Lunar, Madison, USA). The prevalence rate of osteoporosis in women 40–79 years old was approximately 18.5%, while the rate of osteopenia was about 44.7%; in men 60–79 years of age the rates were 10% and 36%, respectively. A strong association with fractures was found for osteoporosis and osteopenia in both men and women, independently of all traditional risk factors, including age. These results confirm the suitability of US measurements as a tool for detecting individuals at risk of fractures.

Role of iron metabolism and oxidative damage in postmenopausal bone loss

It has been suggested that iron-deficient rats have lower bone mass than iron-replete animals, but a clear association between bone and iron repletion has not been demonstrated in humans. A growing body of evidences also suggests a relation between lipid oxidation and bone metabolism and between iron metabolism and LDL oxidation. Iron availability to cells also depends on haptoglobin (Hp) phenotypes. Hp has also important antioxidant properties according to its phenotype, hence we evaluate whether Hp phenotype could influence bone density, iron metabolism and lipid oxidation. This cross-sectional study enrolled 455 postmenopausal women affected by osteoporosis (260) or not (195). Bone mineral density, markers of bone and iron metabolism, levels of oxidized LDL (oxLDL) and Hp phenotype were measured in all the subjects. Hp 1.1 and 2.2 frequency was higher and Hp 2.1 was lower in the patients with fragility fractures (80) compared with the controls. We therefore evaluate different Hp phenotypes as risk or protective factors against fragility fracture: Hp 2.1 is a protective factor against fracture while 1.1 is an important and 2.2 a moderate risk factor for fragility fractures. Lower serum iron was associated with elevated transferrin in patients with Hp 1.1; moreover patients had relative iron deficiency compared with the controls and fractured patients had higher level of oxLDL. We found that both iron metabolism and oxLDL varies according to Hp phenotypes and are predictive of bone density. Our data indicate that Hp 2.1 is a protective factor for fragility fractures, depending on its role on iron metabolism and its antioxidant properties.

Bone mass and metabolism in thalassemic children and adolescents treated with different iron-chelating drugs

We evaluated bone mineral density (BMD) and bone turnover in 22 homozygous prepubertal beta-thalassemic patients treated with desferrioxamine. Ten patients underwent treatment with desferrioxamine for the whole study period, while 12 patients stopped desferrioxamine and were then treated with deferiprone (L1). Lumbar and femoral BMD and bone metabolism markers were examined at baseline and after 1 and 3 years of follow up. All patients were prepubertal at baseline and they all became pubertal over the 3 years of follow up. At baseline, the mean lumbar Z score value was −2.048 SD ± 0.75; the Z score was less than −2 SD in 13 children, within −1 and −2 SD in 6, and within 0 and −1 SD in only 3 subjects. A significant BMD increase (P ≪ 0.0001) was observed at both the lumbar (+8.466%/year) and the femoral level (average of +3.46%/year at neck and +5.83%/year at the intertrochanteric region) after 3 years, without any significant difference being shown between patients treated with desferrioxamine and those treated with L1. The mean Z score SD values increased to −1.957 ± 0.975 at 1 year (not significantly different from baseline) and to −1.864 ± 1.221 at 3 year follow up (P ≪ 0.05 vs baseline); an increase in bone turnover was also observed. These findings show that low BMD, a hallmark of beta-thalassemia, improves significantly when puberty begins; this increase involves different skeletal sites, regardless of pharmacological treatment with different iron-chelating drugs.

Malnutrition in an elderly demented population living at home

Malnutrition is a frequent complication for elderly demented patients even if they live at their own home with the assistance of a caregiver. The present study evaluates nutritional characteristics of a population of 130 non-institutionalized demented patients. The results show that the mini nutritional assessment (MNA) total score is inversely related with the neuro-psychiatric inventory (NPI) score and that the level of cognitive impairment is related with the nutritional status: patients with mild cognitive impairment (MCI) showed a mean MNA score higher than patients affected by Alzheimers disease (AD) or vascular dementia (VaD). Moreover, patients depressed, with hallucinations or with behavioral disturbs are more exposed to underfeeding than only cognitively impaired subjects. In conclusion, an appropriated evaluation of nutritional status could prevent and treat nutrition-related problems even in the elderly demented patients living at home.

Body fat and C-reactive protein levels in healthy non-obese men

BACKGROUND AND AIM The relationships between C-reactive protein (CRP) levels, adipose tissue and metabolic alterations have not been clearly established in healthy non-obese subjects. We investigated the relationships between body fat, CRP levels and metabolic variables in healthy, non-obese sons of patients affected by metabolic syndrome (MS). METHODS AND RESULTS Age, CRP and interleukin 6 (IL-6) levels, anthropometric measures (body mass index, BMI; waist circumference and waist-to-hip ratio, WHR), total and regional fat content (as determined by means of dual X-ray absorptiometry, DXA), total and LDL cholesterol, and the metabolic variables related to MS (HDL-cholesterol, triglyceride, glucose and insulin levels; the fasting insulin resistance index, FIRI; blood pressure) were evaluated in 85 healthy non-obese sons of MS patients. Linear and multiple regression analyses were used to evaluate the relationships between body fat, metabolic variables and CRP levels, and to investigate whether the association between body fat content and metabolic variables persists after adjustment for CRP levels. Body fat was associated with all of the investigated variables. CRP levels were associated with total and regional body fat, the anthropometric index of weight, age, and with some metabolic alterations (HDL-cholesterol and triglyceride levels, systolic blood pressure, and fasting insulin and LDL-cholesterol levels). The associations between total body fat and the metabolic variables did not change after adjustment for CRP levels. Total body fat was the best predictor of CRP levels (p<0.0001). CONCLUSIONS In healthy, non-obese sons of MS patients, total body fat is the best predictor of CRP levels, and remains closely associated with metabolic abnormalities after adjustment for CRP levels. These findings strongly support the hypothesis that body fat is the main determinant of metabolic abnormalities and a low inflammatory state, at least in healthy subjects.

Hypothalamic–pituitary–adrenal axis function and cytokine production in multiple sclerosis with or without interferon‐β treatment

Objectives –Pro‐inflammatory cytokines mediate brain damage in multiple sclerosis (MS); they can also influence the hypothalamic–pituitary–adrenal (HPA) axis function. We evaluated the possible abnormalities of HPA axis function in relapsing‐remitting MS (RR‐MS). Material and methods –IFN‐γ, TNF‐α and IL‐6 production by ex‐vivo lymphocytes from 10 normal volunteers and 10 RR‐MS patients before and during IFN‐β therapy was assessed; pituitary‐adrenal function was evaluated by means of CRH and ACTH stimulation tests. Results–In untreated patients the production of IFN‐γ, TNF‐α, IL‐6 was increased, and was significantly decreased by IFN‐β. Neither basal, nor stimulated ACTH, cortisol, DHEA, DHEAs, 17‐α‐OH‐progesterone levels differed between controls and RR‐MS patients, both before and during treatment. Moreover, no correlation was found between endocrine and immune parameters. Conclusion–In MS the HPA axis function seems normal and not influenced by IFN‐β treatment. This result is discussed in relation to the increased production of pro‐inflammatory cytokines found in this disease.

Prevalence of and factors associated with prolonged length of stay in older hospitalized medical patients.

To characterize elderly medical patients and identify factors associated with prolonged length of stay.

Insulin resistance in HIV-infected patients: relationship with pro-inflammatory cytokines released by peripheral leukocytes

OBJECTIVES Abnormalities of insulin sensitivity are increasingly reported in HIV infection. Considering that cytokines (particularly TNF-alpha and IL-1beta) can induce insulin resistance in infections, we investigated the relationship between insulin sensitivity and cytokine release from peripheral blood mononuclear cells (PBMCs) in HIV-infected patients. METHODS Fourteen HIV-positive patients treated with dual-NRTI (nucleosidic reverse transcriptase inhibitors) regimens, and fourteen healthy controls were studied. Insulin resistance was assessed by homeostatic model for insulin resistance (HOMA-IR). Cytokine production by PBMCs ex vivo was measured. RESULTS Plasma glucose levels did not differ in HIV patients and in controls. Insulin concentrations and HOMA-IR were significantly higher in HIV-infected patients than in controls (respectively, 11.4+/-4.3 vs. 7.86+/-1.1mIU, P=0.005; 2.27+/-0.91 vs. 1.6+/-0.2, P=0.025). A significant positive linear correlation was observed between HOMA-IR and TNF-alpha concentrations in the supernatants of unstimulated PBMC cultures in HIV patients (r=0.771;P=0.001), but not in controls. CONCLUSIONS Our results are in accordance with previous findings showing that insulin resistance may indeed be present in PI-naive HIV patients, and suggest that either TNF-alpha, or other mediators released in parallel with this cytokine may induce a state of insulin resistance, unrelated to highly active antiviral treatments, in poorly controlled HIV disease.

The use of raloxifene in osteoporosis treatment.

Introduction: Osteoporosis is a common disease characterized by the occurrence of fragility fractures. Major osteoporotic fractures are associated with decreased quality of life and high costs. Areas covered: This review summarizes clinical data on raloxifene (RLX), a second generation selective estrogen-receptor modulator (SERM), currently approved for the treatment of postmenopausal osteoporosis. RLX has estrogen effects on bone and lipid profile, whereas it has anti-estrogen effects on uterus and breast cells. Its main side effects are hot flushes and venous thromboembolism. Literature searches were conducted to retrieve articles reporting RLX clinical trial data. For comparison of safety and efficacy, post-marketing studies on RLX were included. Expert opinion: RLX is effective in reducing vertebral fracture risk in osteoporotic women, it is safe and its ability to prevent breast cancer has to be considered in the analyses of cost/effect and of the ideal candidate to this treatment. RLX has to be avoided in patients with previous history of venous thromboembolism.