Carlina V. Albanese

Phalangeal Osteosonogrammetry Study: Age‐Related Changes, Diagnostic Sensitivity, and Discrimination Power

Phalangeal osteosonogrammetry was introduced as a method for bone tissue investigation in 1992. It is based on the measure of the velocity of ultrasound (amplitude‐dependent speed of sound [AD‐SoS]) and on the interpretation of the characteristics of the ultrasound signal. In this study we have collected a database of 10,115 subjects to evaluate the performance of AD‐SoS and to develop a parameter that is able to quantify the signal characteristics: ultrasound bone profile index (UBPI). The database only includes females of which 4.5% had documented vertebral osteoporotic fractures, 16% lumbar spine dual X‐ray absorptiometry (DXA), and 6% hip DXA. The analysis of the ultrasound signal has shown that with aging the UBPI, first wave amplitude (FWA), and signal dynamics (SDy) follow a trend that is different from the one observed for AD‐SoS; that is, there is no increase during childhood. In the whole population, the risk of fracture per SD decrease for AD‐SOS was odds ratio (OR) 1.71 (CI, 1.58‐1.84). The AD‐SoS in fractured subjects was significantly lower than in a group of age‐matched nonfractured subjects (p < 0.0001). In a small cohort of hip‐fractured patients UBPI proved to be lower than in a control age‐matched group (p < 0.0001). When the World Health Organization (WHO) working group criteria were applied to this population to identify the T score value for osteoporosis, for AD‐SoS we found a T score of −3.2 and for UBPI we found a T score of −3.14. Sixty‐six percent of vertebral fractures were below the AD‐SoS −3.2 T score and 62% were below UBPI −3.14. We observed the highest incidence of fractures (63.6%) among subjects with AD‐SoS who had both DXA T score values below the threshold. We conclude from this study that ultrasound investigation at the hand phalanges is a valid methodology for osteoporosis assessment. It has been possible to quantify signal changes by means of UBPI, a parameter that will improve the possibility of investigating bone structure.

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.

Inflammation is the main determinant of low bone mineral density in pediatric inflammatory bowel disease

Aims: To assess bone mineral density (BMD) in children with Crohns disease (CD) and ulcerative colitis (UC) and to investigate the role of inflammation and steroids on BMD. Methods: Lumbar spine areal BMD was measured by DXA, and volumetric BMD was then estimated (BMAD); inflammatory cytokines (TNF‐&agr;, IL‐6, IL‐10, and IL‐12) were dosed in peripheral blood; and cumulative and daily doses of steroids were calculated. Therapy with infliximab (IFX) was considered for CD patients. Results: Fifty‐six patients with IBD (35 CD, 21 UC) were studied. An inverse correlation was found between BMAD and IL‐6 in patients with UC (r = −0.65); no correlation was found between BMAD and serum levels of TNF‐&agr;, IL‐10, and IL‐12 in all patients. Disease activity indexes use inversely correlated with BMAD (r = −0.62 in patients with CD and r = −0.64 in patients with UC). Cumulative dose of corticosteroids and duration of therapy did not correlate with BMAD. The 10 patients with CD who were treated with IFX had higher BMAD (−1 ± 0.8) than those never treated with IFX (−1.8 ± 0.8). Mean Pediatric Crohns Disease Activity Index and body mass index in patients with CD (R2 = 0.48) and IL‐6 level in patients with UC (R2 = 0.43) were found to be independent and significant predictors of BMAD. Conclusions: In children with IBD, inflammation is an important determinant of bone loss, as shown by the correlation of BMAD with serum IL‐6 and with disease activity indexes as well as by the beneficial effect of IFX on bone density. Corticosteroids seem to be a less important variable in pediatric IBD‐related BMD reduction than previously believed.

Periprosthetic DXA after total hip arthroplasty with short vs. ultra-short custom-made femoral stems

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.

Sarcopenia in liver cirrhosis: the role of computed tomography scan for the assessment of muscle mass compared with dual-energy X-ray absorptiometry and anthropometry.

Background Sarcopenia evaluated by computed tomography (CT) scan at the lumbar site has been identified as a risk factor for morbidity and mortality in cirrhosis. Aim The aim of this study was to compare the measurement of muscle mass through CT scan, considered the gold standard, with other reliable techniques to evaluate the rate of agreement between different available methods for the assessment of muscle mass in cirrhosis. The correlation between measurements of muscle mass and of muscle strength was also investigated. Patients and methods Adult patients eligible for liver transplantation were studied. Lumbar skeletal muscle cross-sectional area was measured by CT and muscle depletion was defined using previously published cut-offs. Mid-arm muscle circumference was calculated following anthropometric measures. The Fat-Free Mass Index and the Appendicular Skeletal Muscle Index were calculated using dual-energy X-ray absorptiometry. Muscle strength was evaluated using the Hand Grip test. Results Fifty-nine patients with cirrhosis were included. Sarcopenia was diagnosed in 76% of the patients according to CT evaluation. A significant reduction in Fat-Free Mass Index and Appendicular Skeletal Muscle Index was observed in 42–52% of the patients, whereas 52% showed a mid-arm muscle circumference less than 10th percentile. Skeletal muscle mass evaluation through CT was only weakly correlated with dual-energy X-ray absorptiometry and anthropometry evaluation. No correlation was observed between CT measurement of muscle mass and Hand Grip test. Conclusion CT scan can identify the highest percentage of sarcopenia in cirrhosis and no other techniques are actually available as a replacement. Future efforts should focus on approaches for assessing both skeletal muscle mass and function to provide a better evaluation of sarcopenia in cirrhotic patients.

Bone preservation with a conservative metaphyseal loading implant

Proximal load transfer and the absence of distal fixation of the stem are crucial to obtain the best behaviour of the femoral bone after total hip replacement. In this study, dual energy X-ray absorptiometry (DEXA) was employed to understand and compare the bone density changes and thus the re-distribution of mechanical forces in two different extra short stems. Two cohorts of ten patients were included in this retrospective study. Both implants are custom-made and present a well defined lateral flare. The first model is fully coated and presents a short stem (Group A), the second is an unstemmed metaphyseal implant with a polished tip (Group B). DEXA scans were obtained in all patients at the two-year follow-up. A higher BMD was detected in ROIs 1, 2, 4, 5 in Group B confirming a preservation of the proximal bone mass and thus indirectly a more proximal load transfer. The results obtained confirm the importance of the geometry of the implant on proximal bone density. Loading both medial and lateral proximal femoral flares and the complete absence of the diaphyseal portion of the stem provide the optimal bone remodelling of the femur after total hip replacement.

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).

Quantitative ultrasound of the phalanges and DXA of the lumbar spine and proximal femur in evaluating the risk of osteoporotic vertebral fracture in postmenopausal women

PurposeThis study was undertaken to compare the quantitative ultrasound (QUS) parameters of amplitudedependent speed of sound (AD-SoS) and ultrasound bone profile index (UBPI) of the phalanges with bone mineral density (BMD) of the lumbar spine and proximal hip using dual-energy X-ray absorptiometry (DXA) in discriminating women with vertebral fracture.Materials and methodsA total of 692 postmenopausal Caucasian women were included in the study. The presence of vertebral fracture was evaluated by radiography. AD-SoS and UBPI were measured at the phalangeal metaphysis using a DBM Sonic device. Multiple logistic regression analysis was performed to estimate the odds ratio (OR) for vertebral fractures. The ORs were also adjusted for the significant anthropometric variables of age, weight and height. Furthermore, for QUS parameters, the ORs were also adjusted for lumbar spine and total hip BMD.ResultsAll measurements obtained with DXA and QUS significantly discriminated between women with and without fractures (p<0.0001). However, the OR was higher for lumbar spine BMD (OR 4.01), AD-SoS (OR 3.81), total hip (OR 3.7) and femoral neck BMD (OR 3.62).ConclusionsThe QUS parameter AD-SoS showed diagnostic sensitivity equal to that of lumbar DXA in discriminating between women with and without osteoporotic vertebral fractures.RiassuntoObiettivoConfronto fra i parametri ultrasonografici quantitativi (QUS) amplitude dependent speed of sound (AD-SoS) e ultrasound bone profile index (UBPI) a livello delle falangi della mano con la densità minerale ossea (BMD) alla colonna lombare e al femore prossimale mediante tecnica dual energy X-ray absorptiometry (DXA) nel discriminare le fratture vertebrali.Materiali e metodiSono state incluse 692 donne in post-menopausa. La presenza di fratture vertebrali è stata documentata radiograficamente. AD-SoS e UBPI sono stati misurati alla metafisi delle falangi della mano utilizzando il DBM Sonic. L’analisi logistica è stata utilizzata per determinare il rischio relativo di frattura vertebrale (odds rario, OR). OR è stato altresì aggiustato per variabili antropometriche significative: età, peso e altezza. Inoltre per i parametri QUS, OR è stato aggiustato anche per la BMD lombare e femorale.RisultatiNel modello logistico DXA e QUS discriminano significativamente fra donne con e senza fratture vertebrali (p<0,0001). L’OR è risultato più alto per la BMD lombare (OR 4,01), AD-SoS (OR 3,81), femore totale (OR 3,7) e collo femorale (OR 3,62).ConclusioniIl parametro AD-SoS ha dimostrato una sensibilità diagnostica uguale a quella della scansione lombare DXA nel discriminare tra donne non fratturate e donne con fratture vertebrali da osteoporosi.

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 &rgr; 0.13), between z score value and MO degree (Spearman &rgr; −0.17), and between z score and symptoms (Spearman &rgr; −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.

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.