S. Gonnelli

Validation of a food frequency questionnaire for nutritional calcium intake assessment in Italian women

Objective: To evaluate a food frequency questionnaire assessing calcium intake in women.Design: Estimates of calcium intake from the food frequency questionnaire were compared with those from 14 day records from 206 Caucasian women aged 25–75u2005y in Siena, Italy.Subjects: Subjects were randomly recruited from the residents list of the city of Siena, Italy. Of the 250 initially recruited, 39 did not meet the inclusion criteria or failed to complete the diet record and five outliers were excluded before the statistical analysis on the basis that their diet record was unlikely to represent habitual intake.Results: Mean dietary calcium intakes were 829±255 (s.d.) mg/day from the questionnaire and 818±260 (s.d.) mg/day from the diet record. The mean difference in intake by the two methods (−11.3±116.4u2005mg/day) did not differ significantly from zero. Specificity in classifying women consuming less than 800u2005mg/day calcium was 86.6%, and sensibility in classifying women consuming more than 800u2005mg/day calcium was 89.4%.Conclusions: The food frequency questionnaire could be used in epidemiological studies to assess calcium intake in young to elderly women. The specificity in identifying low calcium intake subjects makes it useful also as an educational tool in diet counselling and for prescribing calcium supplementation.Sponsorship: None.

Vitamin D receptor genotypes and intestinal calcium absorption in postmenopausal women

Abstract. Several studies have shown that bone mass and bone turnover are genetically determined. This genetic component is thought to be mediated in part by polymorphisms at the vitamin D receptor (VDR) locus, even though the underlying molecular mechanisms are still unknown. To evaluate a possible site of differential action of the VDR gene alleles we examined their correlation with intestinal calcium absorption in 120 Caucasian postmenopausal women (aged 61 ± 0.6 years). VDR gene polymorphisms for Apa I, Bsm I, and Taq I restriction endonucleases were assessed by Southern blotting analysis. The most common genotypes observed in our population were AaBbTt (37%), AABBtt (20%), aabbTT (15%), AabbTT (15%), and AABbTt (9%). Although there was some evidence of 13% higher lumbar BMD values in aabbTT genotype with respect to AABBtt genotype, this difference of approximately 0.1 g/cm2 did not reach statistical significance, possibly because of the limited number of observations. On the contrary, no relationship was found between genotypes and femoral neck BMD values. Intestinal calcium absorption was significantly lower in BB and tt genotypes than, in bb and TT genotypes, respectively, and in AABBtt genotype than in either aabbTT or AaBbTt genotypes (P= 0.0015 ANOVA). No significant differences in intact PTH, alkaline phosphatase, 25OHD3, and 1,25(OH)2D3 were found among subjects with different VDR genotypes. These results are consistent with a possible role of VDR alleles on intestinal calcium absorption.

Vertebral fractures in patients with chronic obstructive pulmonary disease: the EOLO Study

SummaryThis study aimed to evaluate the prevalence of vertebral fractures to investigate the determinants of vertebral fracture risk in patients with COPD. The risk of vertebral fractures is strictly related to the severity of the disease. The use of glucocorticoids and the presence of low values of quantitative ultrasound (QUS) may represent additional risk factors.IntroductionChronic obstructive pulmonary disease (COPD) appears to be associated with osteoporosis. Our study aimed to evaluate the prevalence of vertebral fractures and to investigate the main determinants of vertebral fracture risk in patients with COPD.MethodsIn 3,030 ambulatory COPD patients (1,778 men and 1,262 women) aged 50xa0years or over, we evaluated: COPD severity, presence of vertebral fractures on lateral chest X-ray and bone status by using a quantitative ultrasound device.ResultsIn men there was a strong association between COPD severity and fractures (pu2009<u20090.001), conversely in women the association between COPD severity and fractures was at limit (pu2009=u20090.049). In men, but not in women, glucocorticoid treatment was significantly associated with vertebral fractures. The patients with high or moderate risk of osteoporosis presented an increased risk of vertebral fracture (OR 2.71; 95% CI 2.04–3.60 and OR 1.54; 95% CI 1.26–1.88, respectively). Logistic regression analysis showed that COPD severity and glucocorticoid treatment, both inhaled and oral, were associated with increased risk of vertebral fractures.ConclusionIn COPD patients the risk of vertebral fractures is strictly related to the severity of the disease. The use of glucocorticoids and reduced QUS at calcaneous may represent additional risk factors.

Ultrasound parameters in osteoporotic patients treated with salmon calcitonin: A longitudinal study

Speed of sound (SOS) and broadband ultrasound attenuation (BUA) of ultrasound (US) in bone have been proposed as alternatives to radiation-based methods for the quantitative assessment of osteoporosis. However, the usefulness of US in monitoring response to treatment in osteoporotic patients has yet to be defined. To compare US with bone mineral density (BMD), we studied 112 osteoporotic women (age range 50–64 years). Seventy-eight of them were treated with salmon calcitonin nasal spray (CT; 200 IU/day, 1 month on and 1 month off) and calcium (500 mg/day); 34 patients were given only calcium. One hundred and four women complied with treatment throughout the 2-year study period. At baseline and after 1 and 2 years we measured BMD at lumbar spine by dual-energy X-ray absorptiometry (DXA), and SOS, BUA and Stiffness index, by an Achilles ultrasound unit. Moreover, biochemical markers of bone turnover (alkaline phosphatase, osteocalcin and hydroxyproline) were also measured at baseline and after 6, 12 and 24 months. In the calcitonin-treated group at the end of the study period BMD had increased by 1.99%, SOS by 0.20%, BUA by 0.88% and Stiffness by 2.12%. By contrast in the calcium-treated group all parameters had decreased (BMD, −2.66%; SOS, −0.55%; BUA, −3.30%; Stiffness, −6.0%) by the end of the study period. The differences between groups were significant for BMD, SOS and Stiffness. At baseline a significant, but weak correlation was found between BMD and US parameters. The correlation coefficients between percentage changes at the end of the study period, in BMD and in SOS, BUA and Stiffness, were all significant (p<0.001), being 0.41, 0.53 and 0.57 respectively. In conclusion, ultrasound measurements carried out in conjunction with BMD measurements will yield a more comprehensive assessment of skeletal status and may be helpful in monitoring the response to treatment in osteoporotic patients.

The Usefulness of Bone Turnover in Predicting the Response to Transdermal Estrogen Therapy in Postmenopausal Osteoporosis

Transdermal estrogen therapy is now an accepted form of treatment for postmenopausal osteoporosis. Ninety postmenopausal osteoporotic women were randomized to receive either transdermal estrogen (0.05 mg/day 17β‐estradiol) and calcium (n = 45) or calcium alone (n = 45). The study period was 2 years. Bone mineral density (BMD) at the lumbar spine (by dual‐energy X‐ray absorptiometry [DXA]) and markers of bone turnover (alkaline phosphatase, osteocalcin, hydroxyproline, pyridinoline cross‐links) were assessed at baseline and after 1 and 2 years. In the estrogen‐treated group, BMD showed a significant increase (p < 0.001) both after 1 and 2 years, with a reduction in biochemical markers. To investigate the effectiveness of estrogen treatment of postmenopausal osteoporosis in relation to bone turnover, we also divided the patients on the basis of bone turnover, as assessed by measurement of whole body retention (WBR) of99mTc‐methylene diphosphonate. WBR revealed that 26 patients had high bone turnover (HT) and 55 had low bone turnover (LT). The response to estrogen was greater in the HT patients than in the LT patients; in fact BMD increased by 5.7 and 6.6% in HT patients and by 2.6 and 2.7% in LT patients after 1 and 2 years, respectively. In conclusion, the present study demonstrates that, while the BMD decreases in the patients treated with calcium alone, 2‐year treatment with transdermal estrogen increases axial BMD and that the response to estrogen treatment is influenced by bone turnover. Therefore, the evaluation of bone turnover may be useful to identify those postmenopausal osteoporotic women who may especially benefit from treatment with estrogen.

Ultrasonographic assessment of bone in normal Italian males and females

Recently ultrasound techniques have been proposed to evaluate skeletal status. Speed of sound and attenuation through the bone are the ultrasound properties currently used to assess bone strength and fragility. The speed of sound in m s-1 (SOS), broadband ultrasound attenuation in dB MHz-1 (BUA) and stiffness (S) in 134 healthy females (age range 10-90 years) and in 100 healthy males (age range 10-93 years) was measured using the Achilles scanner (Lunar Corp., Madison, WI, USA). A polynomial function was applied to the observed data to evaluate a pattern of age-related BUA, SOS and S changes. Peak values of SOS, BUA and S were reached in both sexes at the age of 30 years. Average decreases of 12.9% in BUA, 4.9% in SOS and 28.9% in S were found in men aged between 30 and 90 years. In women average decreases of 17.2% in BUA, 4.2% in SOS and 31.9% in S were discovered in those aged between 30 and 90 years. The analysis of SOS, BUA and S changes between pre- and post-menopausal women revealed a significant decrease of these parameters with years since menopause. These data indicate an age-related decrease of ultrasound signals in both sexes. Furthermore, this technique is able to detect, in females, menopause related changes due to oestrogen failure. In contrast, in males, the age-related loss of ultrasound signals appears to be more linear.

The use of ultrasound in the assessment of bone status

The assessment of skeletal status has wide clinical applications, especially in the management of osteoporosis. Osteoporosis, once thought of as an unpreventable and untreatable aging process, has revealed many of its secrets over the last decade, and the advent of successful drug therapy has changed our perception of the disease. Non-invasive techniques play a fundamental role in the diagnosis of osteoporosis and in the assessment of the efficacy of drug treatments. The primary technique used in osteoporosis is dual X-ray absorptiometry (DXA), that has been established as a reliable means of measuring bone density. Quantitative ultrasound (QUS), because of the relative portability of the equipment, ease of use, lack of ionizing radiation and low cost, has great potential for widespread use. Five devices for QUS assessment have recently been approved by the Food and Drug Administration and many more applications are in progress. QUS is a relatively new technology, at least in its application to bone fragility. Nevertheless, QUS has demonstrated that it is able to detect bone fragility as well as DXA. However, diagnosis of osteoporosis by QUS remains contentious, but the problems are due more to the limitations of the present T-scores rather than to the technique. A better option for QUS would be to report results in terms of remaining lifetime fracture risk, keeping in mind that a risk estimate needs not only the QUS or DXA measurement, but also the specific data, such as age, weight, gender, hormonal status and fracture history of the patient.

Usefulness of Bone Quantitative Ultrasound in Management of Osteoporosis in Men

In order to evaluate the usefulness of QUS at the phalanx in the diagnosis of osteoporosis and in the prediction of fracture risk in males. The study consisted of 182 subjects (age 61.2 +/- 9.4 yr), of which 22 had had a previous nontraumatic bone fracture. In all subjects, bone mineral density (BMD) at the lumbar spine and femur was measured by DXA. Moreover, in the same subjects, QUS parameters, the amplitude-dependent speed of sound (AD-SOS), and the parameters characterizing the graphic trace (fast-wave amplitude, signal dynamic, and bone transmission time [BTT]) were assessed at the phalanxes using the DBM Sonic 1200 (IGEA). According to World Health Organization (WHO) criteria, all the patients were divided into two groups: 62 osteoporotic subjects and 120 nonosteoporotic subjects. All QUS parameters were significantly lower in osteoporotic than in nonosteoporotic patients. Receiver operating characteristic (ROC) analysis showed a moderate ability of AD-SOS, BTT, and ultrasound bone profile index (UBPI) in distinguishing between healthy and osteoporotic men. Among osteoporotic patients, BMD values were lower in patients with fracture than in those without fracture. AD-SOS and BTT were significantly reduced in men with fracture. Furthermore, in a regression analysis, only BTT and DXA parameters were predictive of fracture. Moreover, performing a multivariate regression analysis BTT entered before BMD at the lumbar spine and at Wards triangle. In conclusion, our data show that QUS parameters are reduced in osteoporotic males; however, only BTT was comparable to DXA parameters in the prediction of fracture risk in men.

Unusual clinical features and early brain MRI lesions in a family with cerebral autosomal dominant arteriopathy

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described inherited disorder. The pathologic gene maps on chromosome 19. The clinical spectrum of the disease consists of recurrent strokes, migraine, transient ischemic attacks, mood changes, and dementia. We report a genetically assessed CADASIL family with atypical clinical presentations of epileptic seizures. In two asymptomatic family members there were early brain abnormalities on MRI. Our report expands the clinical spectrum of CADASIL and suggests that it is possibly an undiagnosed disorder.

Undiagnosed vertebral fractures influence quality of life in postmenopausal women with reduced ultrasound parameters.

BackgroundOsteoporosis, a multifactorial systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to increased bone fragility, is a worldwide public health problem. Vertebral fractures affect approximately 20% of postmenopausal women and are a hallmark of osteoporosis, but they may pass unnoticed, although they may lead to long-term immobility and disability.Questions/purposesThe aims of the present study were (1) to determine the prevalence and the severity of vertebral fractures in a large cohort of Italian women aged 60 years or older with reduced values of quantitative ultrasound parameters; and (2) to assess whether vertebral fractures and other variables may be associated with health-related quality of life.MethodsA total of 2450 women without back pain aged 60 years or older, after the completion of the Quality of Life Questionnaire of the European Foundation for Osteoporosis QUALEFFO, underwent quantitative ultrasound evaluation of the calcaneus; in those with a stiffness t-score of ≤ −2 (n = 1194), radiographic evaluation of the thoracic and lumbar spine was carried out and then quantitative morphometry was performed by dedicated software (MorphoXpress). The radiographic analysis was carried out on 885 women who presented films of adequate quality. Multivariate regression was used to adjust for confounding variables.ResultsOf those who underwent radiographic analysis, 681 had no vertebral fractures, and 204 women (23.1%) had one or more previously undiagnosed vertebral fractures. The prevalence of previously undiagnosed vertebral fractures increased with advancing age with more than 30% of women older than 75 years having at least one fracture. Older age, body mass index, and severe vertebral fractures were independently associated with a worse total QUALEFFO score.ConclusionsWe found that approximately one in four women showed evidence of undiagnosed vertebral fractures, and there was a strong age effect trend. Moreover, the severity grade of vertebral fractures, more than the number of fractures, was associated with a worsening of health-related quality of life as assessed by QUALEFFO. These findings confirm the clinical relevance of an early diagnosis of vertebral fractures and seem to support the usefulness of quantitative ultrasound measurements in the stratification of postmenopausal women at increased fracture risk.Level of EvidenceLevel III, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.