Combining bone resorption markers and heel quantitative ultrasound to discriminate between fracture cases and control

Rapport de synthèse : L'ostéoporose est reconnue comme un problème majeur de santé publique. Comme il existe actuellement des traitements préventifs efficaces pour minimiser le risque de fracture, il est essentiel de développer des nouvelles stratégies de détection des femmes à risque de fracture. Les marqueurs spécifiques du remodelage osseux dosés dans les urines ainsi que les ultrasons quantitatifs du talon ont été étudiés comme outils cliniques pour prédire le risque fracturaire chez les femmes âgées. Il n'existe cependant que très peu de donnée sur la combinaison de ces deux outils pour améliorer la prédiction du risque de fracture. Cette étude cas-contrôle, réalisée chez 368 femmes âgées de 76 ans en moyenne d'une cohorte suisse de femmes ambulatoires, évalue la capacité discriminative entre 195 femmes avec fracture non-vertébrale à bas traumatisme et 173 femmes sans fractures - de deux marqueurs urinaires de la résorption osseuse, les pyridinolines et les deoxypyridinolines, ainsi que deux ultrasons quantitatifs du talon, le Achilles+ (GE-Lunar, Madison, USA) et le Sahara (Hologic, Waltham, USA). Les 195 patientes avec une fracture ont été choisies identiques aux 173 contrôles concernant Page, l'indice de masse corporel, le centre médical et la durée de suivi jusqu'à la fracture. Cette étude montre que les marqueurs urinaires de la résorption osseuse ont une capacité environ identique aux ultrasons quantitatifs du talon pour discriminer entre les patientes avec fracture non-vertébrale à bas traumatisme et les contrôles. La combinaison des deux tests n'est cependant pas plus performante qu'un seul test. Les résultats de cette étude peuvent aider à concevoir les futures stratégies de détection du risque fracturaire chez les femmes âgées, qui intègrent notamment des facteurs de risque cliniques, radiologiques et biochimiques. Abstract : Summary : This nested case-control analysis of a Swiss ambulatory cohort of elderly women assessed the discriminatory power of urinary markers of bone resorption and heel quantitative ultrasound for non-vertebral fractures. The tests all discriminated between cases and controls, but combining the two strategies yielded no additional relevant information. Introduction : Data are limited regarding the combination of bone resorption markers and heel quantitative bone ultrasound (QUS) in the detection of women at risk for fracture. Methods In a nested case-control analysis, we studied 368 women (mean age 76.213.2 years), 195 with low-trauma non-vertebral fractures and 173 without, matched for age, BMI, medical center, and follow-up duration, from a prospective study designed to predict fractures. Urinary total pyridinolines (PYD) and deoxypyridinolines (DPD) were measured by high performance liquid chromatography. All women underwent bone evaluations using Achilles+ and Sahara heel QUS. Results : Areas under the receiver operating-characteristic curve (AUC) for discriminative models of the fracture group, with 95% confidence intervals, were 0.62 (0.560.68) and 0.59 (0.53-0.65) for PYD and DPD, and 0.64 (0.58-0.69) and 0.65 (0.59-0.71) for Achilles+ and Sahara QUS, respectively. The combination of resorption markers and QUS added no significant discriminatory information to either measurement alone with an AUC of 0.66 (0.600.71) for Achilles+ with PYD and 0.68 (0.62-0.73) for Sahara with PYD. Conclusions : Urinary bone resorption markers and QUS are equally discriminatory between non-vertebral fracture patients and controls. However, the combination of bone resorption markers and QUS is not better than either test used alone.

TBS (trabecular bone score) and diabetes-related fracture risk.

CONTEXT: Type 2 diabetes is associated with increased fracture risk but paradoxically greater bone mineral density (BMD). Trabecular bone score (TBS) is derived from the texture of the spine dual x-ray absorptiometry (DXA) image and is related to bone microarchitecture and fracture risk, providing information independent of BMD. OBJECTIVE: This study evaluated the ability of lumbar spine TBS to account for increased fracture risk in diabetes. DESIGN AND SETTING: We performed a retrospective cohort study using BMD results from a large clinical registry for the province of Manitoba, Canada. Patients: We included 29,407 women 50 years old and older with baseline DXA examinations, among whom 2356 had diagnosed diabetes. MAIN OUTCOME MEASURES: Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Health service records were assessed for incident nontraumatic major osteoporotic fractures (mean follow-up 4.7 years). RESULTS: Diabetes was associated with higher BMD at all sites but lower lumbar spine TBS in unadjusted and adjusted models (all P < .001). The adjusted odds ratio (aOR) for a measurement in the lowest vs the highest tertile was less than 1 for BMD (all P < .001) but was increased for lumbar spine TBS [aOR 2.61, 95% confidence interval (CI) 2.30-2.97]. Major osteoporotic fractures were identified in 175 women (7.4%) with and 1493 (5.5%) without diabetes (P < .001). Lumbar spine TBS was a BMD-independent predictor of fracture and predicted fractures in those with diabetes (adjusted hazard ratio 1.27, 95% CI 1.10-1.46) and without diabetes (hazard ratio 1.31, 95% CI 1.24-1.38). The effect of diabetes on fracture was reduced when lumbar spine TBS was added to a prediction model but was paradoxically increased from adding BMD measurements. CONCLUSIONS: Lumbar spine TBS predicts osteoporotic fractures in those with diabetes, and captures a larger portion of the diabetes-associated fracture risk than BMD.

Staphylococcal biofilm formation on the surface of three different calcium phosphate bone grafts: a qualitative and quantitative in vivo analysis.

Differences in physico-chemical characteristics of bone grafts to fill bone defects have been demonstrated to influence in vitro bacterial biofilm formation. Aim of the study was to investigate in vivo staphylococcal biofilm formation on different calcium phosphate bone substitutes. A foreign-body guinea-pig infection model was used. Teflon cages prefilled with β-tricalcium phosphate, calcium-deficient hydroxyapatite, or dicalcium phosphate (DCP) scaffold were implanted subcutaneously. Scaffolds were infected with 2 × 10(3) colony-forming unit of Staphylococcus aureus (two strains) or S. epidermidis and explanted after 3, 24 or 72 h of biofilm formation. Quantitative and qualitative biofilm analysis was performed by sonication followed by viable counts, and microcalorimetry, respectively. Independently of the material, S. aureus formed increasing amounts of biofilm on the surface of all scaffolds over time as determined by both methods. For S. epidermidis, the biofilm amount decreased over time, and no biofilm was detected by microcalorimetry on the DCP scaffolds after 72 h of infection. However, when using a higher S. epidermidis inoculum, increasing amounts of biofilm were formed on all scaffolds as determined by microcalorimetry. No significant variation in staphylococcal in vivo biofilm formation was observed between the different materials tested. This study highlights the importance of in vivo studies, in addition to in vitro studies, when investigating biofilm formation of bone grafts.

Extra microchromosome mosaicism in amniotic cells confirmed in fetal tissues.

Mosaicism for an extra microchromosome was discovered in amniotic cell cultures of a 39-year-old woman. Using G, Q, C bands and silver staining, it was concluded that the extra chromosome was bisatellited. Parents' karyotype was normal. Parents elected for termination of the pregnancy. The presence of the extra microchromosome was confirmed in various tissues of the aborted fetus. The literature on the subject is briefly reviewed.

Nouvelles thérapies pour les maladies osseuses de l'enfant [New therapies for children affected by bone diseases].

Considerable progress has been achieved in recent years in treating children affected by bone diseases. Advances in the understanding of the molecular pathophysiology of genetic bone diseases have led to the development of enzyme replacement therapies for various lysosomal storage diseases, following the breakthrough initiated in treating Gaucher disease. Clinical studies are underway with tailored molecules correcting bone fragility and alleviating chronic bone pain and other manifestations of hypophosphatasia, or promoting growth of long bones in achondroplasia patients. We further report our very encouraging experience with intravenous bisphosphonate treatment in children suffering from secondary osteopenia and the high prevalence of calcium and vitamin D deficits in these severely disabled children.

Alterations of bone microarchitecture in young patients with inflammatory bowel diseases are associated with fracture risk during growth

Aims: Inflammatory bowel diseases (IBD) appearing during childhood and adolescence compromise peak bone mass acquisition and increase fracture risk. The structural determinants of bone fragility in IBD however remain unknown. Methods: We investigated volumetric bone mineral density (vBMD), trabecular and cortical bone microstructure at distal radius and tibia by high-resolution pQCT (XtremeCT, Scanco, Switzerland), aBMD at distal radius, hip and spine and vertebral fracture assessment (VFA) by DXA in 107 young patients (mean age 22.8 yrs, range 12.2-33.7 yrs; 62 females and 45 males) with Crohn's disease (n=75), ulcerative colitis (n=25), undetermined colitis (n=2), and no definitive diagnosis (n=5), and in 389 healthy young individuals. Results: Mean disease duration was 6.1 yrs, 89/107 IBD patients received corticosteroids, 83 other immunomodulators, and 59 vitamin D. Clinical fractures were reported by 38 patients (mean age at 1st fracture, 12.6 yrs), the vast majority of the forearm, arm or hand; 5 had vertebral crush fractures (Grade 1 or 2) and 11 had multiple fractures. As compared to healthy controls (matched 2:1 for age, sex, height and fracture history), the 102 patients with established IBD had similar weight but significantly lower aBMD at all sites, lower trabecular (Tb) BV/TV and number, and greater Tb separation and inhomogeneous Tb distribution (1/SD TbN) at both distal radius and tibia, lower tibia cortical thickness (CTh), but no differences in cortical vBMD nor bone perimeter. Among IBD's, aBMD was not associated with fractures (by logistic regression adjusted for age, age square, sex, height, weight and protein intake). However, radius and tibia Tb BV/TV, thickness and SD 1/TbN, as well as radius Tb separation and perimeter, were significantly associated with fracture risk (fully adjusted as above), whereas cortical vBMD and CTh were not. After adjustment for aBMD at radius, respectively at femur neck, radius SD 1/TbN and tibia BV/TV, TbTh and perimeter remained independently associated with fracture risk. Conclusions: Young subjects with IBD have low bone mass and poor bone microarchitecture compared to healthy controls. Alterations of bone microarchitecture, particularly in the trabecular bone compartment, are specifically associated with increased fracture risk during growth.

Trabecular bone score is associated with volumetric bone density and microarchitecture as assessed by central QCT and HRpQCT in Chinese American and white women.

Although high-resolution peripheral quantitative computed tomography (HRpQCT) and central quantitative computed tomography (QCT) studies have shown bone structural differences between Chinese American (CH) and white (WH) women, these techniques are not readily available in the clinical setting. The trabecular bone score (TBS) estimates trabecular microarchitecture from dual-energy X-ray absorptiometry spine images. We assessed TBS in CH and WH women and investigated whether TBS is associated with QCT and HRpQCT indices. Areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry, lumbar spine (LS) TBS, QCT of the LS and hip, and HRpQCT of the radius and tibia were performed in 71 pre- (37 WH and 34 CH) and 44 postmenopausal (21 WH and 23 CH) women. TBS did not differ by race in either pre- or postmenopausal women. In the entire cohort, TBS positively correlated with LS trabecular volumetric bone mineral density (vBMD) (r = 0.664), femoral neck integral (r = 0.651), trabecular (r = 0.641) and cortical vBMD (r = 0.346), and cortical thickness (C/I; r = 0.540) by QCT (p < 0.001 for all). TBS also correlated with integral (r = 0.643), trabecular (r = 0.574) and cortical vBMD (r = 0.491), and C/I (r = 0.541) at the total hip (p < 0.001 for all). The combination of TBS and LS aBMD predicted more of the variance in QCT measures than aBMD alone. TBS was associated with all HRpQCT indices (r = 0.20-0.52) except radial cortical thickness and tibial trabecular thickness. Significant associations between TBS and measures of HRpQCT and QCT in WH and CH pre- and postmenopausal women demonstrated here suggest that TBS may be a useful adjunct to aBMD for assessing bone quality.

Early Stage Primary Bone Lymphoma: A Retrospective, Multicenter Rare Cancer Network Study

Purpose/Objective(s): Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas, and 4-5% of all extranodal lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with stage I and II PBL.Materials/Methods: Between 1987 and 2008, 116 consecutive patients with PBL treated in 13 RCNinstitutions were included in this study. Inclusion criteriawere: age.17 yrs, PBLin stage I and II, andminimum6months follow-up. The median agewas 51 yrs (range: 17-93).Diagnosticwork-up included plain boneXray (74%of patients), scintigraphy (62%), CT-scan (65%),MRI (58%), PET (18%), and bone-marrow biopsy (84%).All patients had biopsy-proven confirmation of non-Hodgkin's lymphoma (NHL). The histopathological type was predominantly diffuse large B-cell lymphoma (78%) and follicular lymphoma (6%), according to theWHOclassification. One hundred patients had a high-grade, 7 intermediate and 9 low-gradeNHL. Ninety-three patients had anAnn-Arbor stage I, and 23 had a stage II. Seventy-seven patients underwent chemoradiotherapy (CXRT), 12 radiotherapy (RT) alone, 10 chemotherapy alone (CXT), 9 surgery followed by CXRT, 5 surgery followed by CXT, and 2 surgery followed by RT. One patient died before treatment.Median RT dosewas 40Gy (range: 4-60).Themedian number ofCXTcycleswas 6 (range, : 2-8).Median follow-upwas 41months (range: 6-242).Results: Following treatment, the overall response rate was 91% (CR 74%, PR 17%). Local recurrence was observed in 12 (10%) patients, and systemic recurrence in 17 (15%) patients. Causes of death included disease progression in 16, unrelated disease in 6, CXT-related toxicity in 1, and secondary cancer in 2 patients. The 5-yr overall survival (OS), disease-free survival (DFS), lymphoma- specific survival (LSS), and local control (LC) were 76%, 69%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for survival were: age\50 years (p = 0.008), IPI score #1 (p = 0.009), complete response (p\0.001), CXT (p = 0.008), number of CXT cycles $6 (p = 0.007), and RT dose . 40 Gy (p = 0.005). In multivariate analysis age, RT dose, complete response, and absence of B symptoms were independent factors influencing the outcome. There were 3 patients developing grade 3 or more (CTCAE.V3.0) toxicities.Conclusions: This large multicenter study, confirms the relatively good prognosis of early stage PBL, treated with combined CXRT. Local control was excellent, and systemic failure occurred infrequently. A sufficient dose of RT (. 40 Gy) and completeCXT regime (. 6 cycles) were associated with a better outcome. Combined modality appears to be the treatment of choice.Author Disclosure: L. Cai, None; M.C. Stauder, None; Y.J. Zhang, None; P. Poortmans, None; Y.X. Li, None; N. Constantinou, None; J. Thariat, None; S. Kadish, None; M. Ozsahin, None; R.O. Mirimanoff, None.

Relationship Between the Development of the Spinal Canal and the Etiopathogenesis of Lumbar Spinal Stenosis

INTRODUCTION: The presence of a pre-existing narrow spinal canal may have an important place in the ethiopathogenesis of lumbar spinal stenosis. By consequence the study of the development of the spinal canal is crucial. The first goal of this work is to do a comprehensive literature search and to give an essential view on the development of spinal canal and its depending factors studied until now. The second goal is to give some considerations and hypothesize new leads for clinically useful researches. MATERIALS AND METHODS: A bibliographical research was executed using different search engines: PubMed, Google Schoolar ©, Ovid ® and Web Of Science ©. Free sources and avaible from the University of Lausanne (UNIL) and Centre Hospitalier Universitaire Vaudois (CHUV) were used. At the end of the bibliographic researches 114 references were found, 85 were free access and just 41 were cited in this work. Most of the found references are in English or in French. RESULTS AND DISCUSSION: The spinal canal is principally limited by the vertebrae which have a mesodermal origin. The nervous (ectodermal) tissue significantly influences the growth of the canal. The most important structure participating in the spinal canal growth is the neurocentral synchondrosis in almost the entire vertebral column. The fusion of the half posterior arches seems to have less importance for the canal size. The growth is not homogeneous but, depends on the vertebral level. Timing, rate and growth potentials differ by regions. Especially in the case of the lumbar segment, there is a craniocaudal tendency which entails a greater post-natal catch-up growth for distal vertebrae. Trefoil-shape of the L5 canal is the consequence of a sagittal growth deficiency. The spinal canal shares some developmental characteristics with different structures and systems, especially with the central nervous system. It may be the consequence of the embryological origin. It is supposed that not all the related structures would be affected by a growth impairment because of the different catch-up potentials. Studies found that narrower spinal canals might be related with cardiovascular and gastrointestinal symptoms, lower thymic function, bone mineral content, dental hypoplasia and Harris' lines. Anthropometric correlations found at birth disappear during the pediatric age. All factors which can affect bone and nervous growth might be relevant. Genetic predispositions are the only factors that can never be changed but the real impact is to ascertain. During the antenatal period, all the elements determining a good supply of blood and oxygen may influence the vertebral canal development, for example smoking during pregnancy. Diet is a crucial factor having an impact on both antenatal and postnatal growth. Proteins intake is the only proved dietetic relationship found in the bibliographic research of this work. The mechanical effects due to locomotion changes are unknown. Socioeconomic situation has an impact on several influencing factors and it is difficult to study it owing to numerous bias. CONCLUSIONS: A correct growth of spinal canal is evidently relevant to prevent not-degenerative stenotic conditions. But a "congenital" narrower canal may aggravate degenerative stenosis. This concerns specific groups of patient. If the size of the canal is highly involved in the pathogenesis of common back pains, a hypothetical measure to prevent developmental impairments could have a not- negligible impact on the society. It would be interesting to study more about dietetic necessities for a good spinal canal development. Understanding the relationship between nervous tissues and vertebra it might be useful in identifying what is needed for the ideal development. Genetic importance and the post-natal influences of upright standing on the canal growth remain unsolved questions. All these tracks may have a double purpose: knowing if it is possible to decrease the incidence of narrower spinal canal and consequently finding possible preventive measures. The development of vertebral canal is a complex subject which ranges over a wide variety of fields. The knowledge of this subject is an indispensable tool to understand and hypothesize the influencing factors that might lead to stenotic conditions. Unfortunately, a lack of information makes difficult to have a complete and satisfactory interdisciplinary vision.

Expression and function of interleukin-7 in secondary and tertiary lymphoid organs.

Interleukin-7 (IL-7) is known since many years as stromal-cell derived cytokine that plays a key role for the adaptive immune system. It promotes lymphocyte development in the bone marrow and thymus as well as naive and memory T cell homeostasis in the periphery. More recently, IL-7 reporter mice and other approaches have led to the further characterization of the various stromal cell sources of IL-7 in secondary lymphoid organs (SLO) and other tissues. We will review these advances along with a discussion of the regulation of IL-7 and its receptor, and compare the biological effects IL-7 has on adaptive as well as innate immune cells in SLO. Finally, we will review the role of IL-7 in development of SLO and tertiary lymphoid tissues that frequently are associated with sites of chronic inflammation.

PPARβ/δ governs Wnt signaling and bone turnover.

Peroxisome proliferator-activated receptors (PPARs) act as metabolic sensors and central regulators of fat and glucose homeostasis. Furthermore, PPARγ has been implicated as major catabolic regulator of bone mass in mice and humans. However, a potential involvement of other PPAR subtypes in the regulation of bone homeostasis has remained elusive. Here we report a previously unrecognized role of PPARβ/δ as a key regulator of bone turnover and the crosstalk between osteoblasts and osteoclasts. In contrast to activation of PPARγ, activation of PPARβ/δ amplified Wnt-dependent and β-catenin-dependent signaling and gene expression in osteoblasts, resulting in increased expression of osteoprotegerin (OPG) and attenuation of osteoblast-mediated osteoclastogenesis. Accordingly, PPARβ/δ-deficient mice had lower Wnt signaling activity, lower serum concentrations of OPG, higher numbers of osteoclasts and osteopenia. Pharmacological activation of PPARβ/δ in a mouse model of postmenopausal osteoporosis led to normalization of the altered ratio of tumor necrosis factor superfamily, member 11 (RANKL, also called TNFSF11) to OPG, a rebalancing of bone turnover and the restoration of normal bone density. Our findings identify PPARβ/δ as a promising target for an alternative approach in the treatment of osteoporosis and related diseases.

Vitamin E, Vitamin A, and carotenoids in male common lizard tissues

Vitamin E, vitamin A, and carotenoids are essential micronutrients for animals because of their antioxidant and immunostimulant functions and their implications for growth, development, and reproduction. In contrast to mammals and birds, information about their occurrence and distribution is generally lacking in reptiles, constraining our understanding of the use of these micronutrients. Using high-performance liquid chromatography, we determined the concentrations of vitamin E, vitamin A, and carotenoids in plasma, storage sites (liver and abdominal fat bodies), and in the colored ventral skin of male Common Lizards, Lacerta vivipara. All tissues shared a similar micronutrient profile, except the liver, which also showed traces of vitamin A(1). The main vitamin E compound present was a-tocopherol followed by lower concentrations of gamma-(beta-)tocopherol. Vitamin A(2) was the main vitamin A compound and it showed the highest concentration in the liver, where vitamin A(2) esters and traces of vitamin A(1) were found. Lutein was the main carotenoid, and it formed esters in the liver and the ventral skin. Zeaxanthin and low concentrations of beta-carotene were also present. The liver was the main storage site for carotenoid and vitamin A, whereas hepatic vitamin E concentrations resembled those present in abdominal Fat bodies. Compared with abdominal fat bodies, the ventral skin contained lower concentrations of vitamin A and vitamin E, but similar concentrations of carotenoicls. These results suggest that important differences exist in micronutrient presence, concentration, and distribution among tissues of lizards and other taxa such as birds and mammals.

(Young Investigator Award) Trabecular Bone Score Helps Classifying Women At Risk Of Fracture Prospectively In The Ofely Study

Introduction: To determine the metabolic effect of teriparatide (TPTD) on bone, 99mTc-MDP skeletal plasma clearance was measured in postmenopausal women with osteoporosis treated with TPTD 20 μg/day. Methods: Ten postmenopausal women with osteoporosis had radionuclide bone scans at baseline, 3, and 18 months after starting TPTD 20 μg/day and after 6 months off therapy. Participants were injected with 600 MBq 99mTc- MDP and whole body bone scans acquired at 10 min, 1, 2, 3, and 4 h. Multiple blood samples were taken between 5 min and 4 h and free 99mTc-MDP measured using ultrafiltration. 99mTc-MDP plasma clearance (Kbone) was evaluated using the Patlak plot method. Regional differences in Kbone were studied by measuring the whole skeleton and subregions. Serum procollagen type I Nterminal propeptide (PINP), bone-specific alkaline phosphatase (BSAP), and urinary N-terminal telopeptide (NTX) were measured at each visit.Discussion: The median increase from baseline in whole skeleton Kbone was 22% (P=0.004) at 3 months and 34% (P= 0.002) at 18 months, decreasing to 0.7% after 6 months off therapy. In subregions, Kbone value increases were statistically significant at 3 months and in all subregions except the pelvis at 18 months. After 6 months off therapy, subregional Kbone values also returned toward baseline. Bone markers increases from baseline were statistically significant at 3 and 18 months (BSAP, 15% and 36%; PINP, 137% and 192%; NTX, 109% and 125%). After 6 months off therapy, PINP and NTX values had declined, though remained above baseline (BSAP, −3%; PINP, 43%; NTX, 56%). Increased Kbone values in the whole body and lower extremities were correlated with increases in most bone markers at 3 and 18 months. Increased skeletal uptake of 99mTc-MDP during treatment with TPTD is indicative of increased bone formation and is supported by increases in bone turnover markers.Conclusion: Changes in Kbone and skeletal uptake measured by radionuclide bone scans in patients taking TPTD are the result of metabolic activity of the drug. These data may provide physicians with useful insights when interpreting bone scan results in this population.

Spine Bone Texture Assessed by Trabecular Bone Score (TBS) to Evaluate Bone Health in Thalassemia Major.

Due to the increasing survival of thalassemic patients, osteopathy is a mounting clinical problem. Low bone mass alone cannot account for the high fracture risk described; impaired bone quality has been speculated but so far it cannot be demonstrated noninvasively. We studied bone quality in thalassemia major using trabecular bone score (TBS), a novel texture measurement extracted from spine dual-energy X-ray absorptiometry (DXA), proposed in postmenopausal and secondary osteoporosis as an indirect index of microarchitecture. TBS was evaluated in 124 adult thalassemics (age range 19-56 years), followed-up with optimal transfusional and therapeutical regimens, and in 65 non-thalassemic patients (22-52 years) undergoing DXA for different bone diseases. TBS was lower in thalassemic patients (1.04 ± 0.12 [range 0.80-1.30]) versus controls (1.34 ± 0.11 [1.06-1.52]) (p < 0.001), and correlated with BMD. TBS and BMD values correlated with age, indicating that thalassemia negatively affects both bone quality and quantity, especially as the patient gets older. TBS was 1.02 ± 0.11 [0.80-1.28] in the osteoporotic thalassemic patients, 1.08 ± 0.12 [0.82-1.30] in the osteopenic ones and 1.15 ± 0.10 [0.96-1.26] in those with normal BMD. No gender differences were found (males: 1.02 ± 0.13 [0.80-1.30], females 1.05 ± 0.11 [0.80-1.30]), nor between patients with and without endocrine-metabolic disorders affecting bone metabolism. Our findings from a large population with thalassemia major show that TBS is a valuable tool to assess noninvasively bone quality, and it may be related to fragility fracture risk in thalassemic osteopathy.