Misdiagnosis of vertebral fractures on local radiographic readings of the multicentre POINT (Prevalence of Osteoporosis in INTernal medicine) study.

BACKGROUND: Osteoporotic vertebral fractures (VFs) are often misdiagnosed because asymptomatic and occurring in the absence of specific trauma. Further, diagnostic assessment of VFs may be suboptimal. AIM OF THE STUDY: To assess the misdiagnosis of vertebral fractures on local radiographic readings in the cohort of patients enrolled in the POINT study. METHODS: We enrolled hospitalised patients, admitted for any cause to the Internal Medicine Units of 37 hospitals participating to the cross-sectional previously published POINT study. The assessment of VFs was performed both by local radiologists and by two expert skeletal radiologists, by using semiquantitative method (SQ). To better evaluate mild vertebral deformities, the two central radiologists also used the algorithm-based qualitative assessment (ABQ). RESULTS: The radiographs of 661 patients (401 females; mean age 75.8±8.0) were evaluated. The inter-reader percent agreement between two central expert radiologists per-vertebra assessment was excellent (99.78%; k=0.984; 95% CI, 0.977-0.991). Central reading identified 318/661 (48.1%) patients with at least one VF. Local and central readings agreed in 502/661 (75.9%) patients, resulting in a fair reproducibility (k=0.52; 95% confidence interval 0.44-0.59). Diagnostic performance parameters of local readings were: sensitivity 76.1%; specificity 75.8%; PPV 74.46%; NPV 77.38%). By examining 9254 vertebrae, central and local readers diagnosed 665 (7.2%) and 562 (6.1%) VFs respectively. Misdiagnosis (102 false positives and 205 false negatives) mainly occurred for mild VFs. Local readings identified correctly 460 out 665 VFs diagnosed by central readings, resulting in sensitivity of 69.2% and PPV of 81.8%. CONCLUSIONS: Following a standardized protocol of acquisition techniques and of interpretation criteria, an excellent agreement between local and central readings for moderate and severe vertebral fractures resulted. However a significant amount of mild vertebral fractures, that are the most of VFs, were misdiagnosed by local radiologists. In order to improve VFs assessment, the radiologists should be trained and sensitized in relation to the relevant clinical significance of osteoporotic VFs identification.

Relationship between vitamin D and body fat distribution evaluated by DXA in postmenopausal women.

OBJECTIVE: The aim of this study was to explore the relationship between 25-hydroxyvitamin D (25[OH]D) serum concentrations and body fat distribution in a sample of postmenopausal women. METHODS: We enrolled sixty-two postmenopausal women; 25(OH)D serum concentrations, serum intact parathyroid hormone, blood analyses, and anthropometric measurements were carried out. Body fat composition was evaluated by dual-energy X-ray absorptiometry. Insulin resistance was estimated by homeostatic model assessment of insulin resistance (HOMA-IR) calculation. RESULTS: Low levels of vitamin D (<30 ng/mL) were found in 77.4% of the population studied. There was a correlation (P < 0.0001) between 25(OH)D and waist circumference (r = -0.543), android fat to gynoid fat (A/G) ratio (r = -0.554), high-density lipoprotein cholesterol (r = 0.498), and HOMA-IR (r = -0.520). A/G fat ratio (B = -34.90; 95% confidence interval [-55.30, -14.1]; P = 0.019), HOMA-IR (B = -3.17; 95% confidence interval [-5.99, -0.351]; P = 0.028), and high-density lipoprotein cholesterol (B = 0.361; 95% confidence interval [0.033, 0.698]; P = 0.032), were found to be independent predictors of lower 25(OH)D by multilogistic regression analysis. Except for waist circumference, both these results were maintained when correlations were adjusted for age, onset of menopause, serum intact parathyroid hormone, and medications, and when body mass index was added as covariate. CONCLUSIONS: Vitamin D deficiency and insufficiency are common conditions. A/G ratio appeared to be associated with 25(OH)D concentrations and it is well-known that the android disposition of body fat is more closely associated with the onset of metabolic syndrome. Longitudinal studies are needed to better characterize the direction and the causal links of this association.

High prevalence of fragility vertebral fractures in patients hospitalised in Internal Medicine Units. Results of the POINT (Prevalence of Osteoporosis in INTernal medicine) study.

BACKGROUND: Osteoporotic vertebral fractures (VFs) often go unrecognised in both healthy individuals and in pathological conditions. Few data exist on VFs in patients hospitalised in Internal Medicine Units (IMUs), who often suffer from multiple concomitant chronic disorders. AIM OF THE STUDY: This multicentre cross-sectional study was aimed at assessing the prevalence of VFs in an unselected population of patients referring to IMUs. Correlations between VFs and the main coexisting diseases were also investigated. METHODS: Information on demographic, clinical and laboratory findings, and on the presence of known risk factors for osteoporosis was recorded. The Genant's semi-quantitative method was used to evaluate, in a central reading centre, the presence and severity of VFs in the thoracic and lumbar spine. RESULTS: A cohort of 995 patients was evaluated. At least one VF of any grade was found in 47.5% of patients, with similar prevalence between females (48.1%) and males (46.7%). Older age, chronic obstructive pulmonary disease, and previous diagnosis of osteoporosis showed a significant association with VFs in multivariable analysis. However, 79.7% of the VFs were observed in patients without previous diagnosis of osteoporosis. Moreover, a VF of grade 2 or greater was found in 20.8% of patients. CONCLUSIONS: Fragility VFs is a very frequent finding in patients hospitalised in IMUs. Consequently, more attention should be devoted in this clinical setting to this comorbidity, which is known to be an additional factor for mortality and, when localised in the thoracic part of the spine, may negatively influence a concomitant respiratory insufficiency.

Lack of clinical predictors for low mineral density in children with celiac disease.

OBJECTIVES: Metabolic bone disease remains a significant and common complication of celiac disease (CD). Several studies have demonstrated low bone mineral density (BMD) at the time of CD diagnosis in both children and adults. Low BMD in children and adolescents is defined as an areal BMD <2 SD below the age-adjusted mean value (z score <-2 SD). The aim of the study was to evaluate the BMD in a pediatric population with CD at diagnosis and to correlate z score value, anti-tissue transglutaminase type 2 antibody (anti-tTG2) titer, symptoms, and Marsh-Oberhuber (MO) grading. METHODS: We enrolled 99 patients with celiac disease (male 35, female 64) ages 4 to 15 years at the diagnosis. All of the patients had positive test results for anti-tTG2 antibodies and histological lesions graded according to MO classification, and underwent lumbar dual-energy x-ray absorptiometry. BMD was estimated by z score. RESULTS: Low BMD (z score ≤-2 SD) was found in 13 (13.13%) patients; 22 (22.22%) patients with CD showed -2 < z score ≤ -1; -1 < z score < 0 was found in 41 (41.41%) patients. z score ≥ 0 was detected only in 23 (23.23%) patients with CD. Mean BMD value in patients with CD is z score -0.68. No correlations were found between z score value and anti-tTG2 titer (Spearman ρ 0.13), between z score value and MO degree (Spearman ρ -0.17), and between z score and symptoms (Spearman ρ-0.10). CONCLUSIONS: BMD of patients with CD at diagnosis does not seem to correlate with MO degree, anti-tTG2 titer, and symptoms. At the moment, we do not have clinical predictors for low mineral density in children with CD.

Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate.

BACKGROUND: Long-term complications of cystic fibrosis include osteoporosis and fragility fractures, but few data are available about effective treatment strategies, especially in young patients. We investigated treatment of low bone mineral density in children, adolescents, and young adults with cystic fibrosis. METHODS: We did a multicentre trial in two phases. We enrolled patients aged 5-30 years with cystic fibrosis and low bone mineral density, from ten cystic fibrosis regional centres in Italy. The first phase was an open-label, 12-month observational study of the effect of adequate calcium intake plus calcifediol. The second phase was a 12-month, double-blind, randomised, placebo-controlled, parallel group study of the efficacy and safety of oral alendronate in patients whose bone mineral apparent density had not increased by 5% or more by the end of the observational phase. Patients were randomly assigned to either alendronate or placebo. Both patients and investigators were masked to treatment assignment. We used dual x-ray absorptiometry at baseline and every 6 months thereafter, corrected for body size, to assess lumbar spine bone mineral apparent density. We assessed bone turnover markers and other laboratory parameters every 3-6 months. The primary endpoint was mean increase of lumbar spine bone mineral apparent density, assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01812551. FINDINGS: We screened 540 patients and enrolled 171 (mean age 13·8 years, SD 5·9, range 5-30). In the observational phase, treatment with calcium and calcifediol increased bone mineral apparent density by 5% or more in 43 patients (25%). 128 patients entered the randomised phase. Bone mineral apparent density increased by 16·3% in the alendronate group (n=65) versus 3·1% in the placebo group (n=63; p=0·0010). 19 of 57 young people (33·3%) receiving alendronate attained a normal-for-age bone mineral apparent density Z score. In the observational phase, five patients had moderate episodes of hypercalciuria, which resolved after short interruption of calcifediol treatment. During the randomised phase, one patient taking alendronate had mild fever versus none in the placebo group; treatment groups did not differ significantly for other adverse events. INTERPRETATION: Correct calcium intake plus calcifediol can improve bone mineral density in some young patients with cystic fibrosis. In those who do not respond to calcium and calcifediol alone, alendronate can safely and effectively increase bone mineral density. FUNDING: Telethon Foundation (Italy).

Periprosthetic DXA after total hip arthroplasty with short vs. ultra-short custom-made femoral stems: 37 patients followed for 3 years.

BACKGROUND AND PURPOSE: Dual-energy X-ray absorptiometry (DXA) analysis of the 7 periprosthetic Gruen zones is the most commonly used protocol to evaluate bone remodeling after the implantation of conventional femoral stems. We assessed the value of DXA after cementless primary total hip arthroplasty (THA) by comparing the effect of progressive shortening of the stem of two femoral implants on periprosthetic bone remodeling using a specifically developed protocol of analysis with 5 periprosthetic regions of interest (ROIs). PATIENTS AND METHODS: Bone mineral density (BMD) was evaluated in 37 patients in the plateau stage, 3 years after THA. Two femoral implants featuring conceptually new designs and surgical technique were tested: types 1 and 2, characterized by extremely short stem and virtual absence of distal stem, respectively. RESULTS: We found that progressive shortening of the femoral stem produces more proximal loading, which effectively preserves metaphyseal bone stock and increases periprosthetic BMD in the medial ROIs over time. In the type 2 group, higher absolute BMD values were observed in medial ROIs 4 and 5. No differences were found in ROIs 1, 2, and 3. INTERPRETATION: This study shows the flexibility of DXA in adapting the protocol of periprosthetic analysis to the specific requirements of new implant designs, and it shows its high sensitivity in evaluation of the biological response of bone to changes in implant shape.

Performance of five phalangeal QUS parameters in the evaluation of gonadal-status, age and vertebral fracture risk compared with DXA.

The aim of this cross-sectional study was to study the value of five different quantified ultrasound (QUS) parameters-amplitude-dependent speed of sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), fast-wave amplitude (FWA), bone transmission time (BTT) and signal dynamic (SDY)-measured at the phalanges of the hand in discriminating women with vertebral fracture and their relationship with some determinants of bone mass, in particular age and gonadal status compared with lumbar spine and hip dual-energy x-ray absorptiometry (DXA). We included 791 women aged 35-84 y, divided into pre-menopause, early menopause and late postmenopause groups on the basis of gonadal status and years since menopause (YSM). The presence of vertebral fracture was evaluated radiographically. All QUS parameters were very sensitive to changes in early postmenopause, with a doubled decrease in early postmenopausal with respect to late postmenopause. In particular AD-SoS and BTT decreases were markedly high in the early postmenopause group. In the late menopause group, similar decreases were observed for AD-SoS, UBPI and hip bone mineral density (BMD). In the multiple logistic model, DXA and QUS significantly discriminate women with and without fractures (p < 0.0001); odds ratio (OR) was higher at lumbar spine BMD (OR 4.01), FWA (OR 3.88), AD-SoS (OR 3.81) and total hip BMD (OR 3.77). Even adjusting the logistic model for age, height, weight, lumbar spine and total hip BMD, all QUS parameters remained significantly predictive of vertebral fracture. AD-SoS showed the best performances both in terms of OR and ROC analysis. QUS parameters show a different behavior in evaluating the effect on bone mass of the time since menopause; AD-SoS and BTT showed a high sensitivity to first changes in bone tissue after menopause. After correction for potential confounders, AD-SoS showed the same ability of lumbar spine BMD in discriminating women with or without vertebral fractures and in the prediction of fracture risk.

Clinical applications of body composition measurements using DXA.

Dual-energy X-ray absorptiometry (DXA) scanning was primarily developed for the diagnosis of osteoporosis and was initially applied to studies of the clinically important sites of the lumbar spine, femoral neck, and forearm. The rapid adoption of DXA has led to the development of different, competing generations of equipment. Improvements have been achieved through advances in X-ray generation and detection technology, modification of data acquisition protocols, and implementation of more sophisticated image analysis algorithms. As a result, DXA has been extended to allow the study of the total skeleton and its regional parts, as well as soft-tissue composition measurement. The three major components of the body: fat mass, lean mass, and bone mineral mass, can now be easily measured using a single whole body DXA scan with high precision and low scanning time. The comprehensive view of body composition provided by DXA makes it an attractive technique for a variety of clinical applications such as the prevention of cardiovascular and metabolic diseases, clinical management of different chronic diseases, and monitoring of the impact of treatment regimens on body tissues. In this article we review the contribution DXA has made to the understanding of body composition in clinical studies in adults.