Dual targeting of CD19 and CD22 against B-ALL using a novel high-sensitivity aCD22 CAR.

CAR T cells recognizing CD19 effectively treat relapsed and refractory B-ALL and DLBCL. However, CD19 loss is a frequent cause of relapse. Simultaneously targeting a second antigen, CD22, may decrease antigen escape, but is challenging: its density is approximately 10-fold less than CD19, and its large structure may hamper immune synapse formation. The characteristics of the optimal CD22 CAR are underexplored. We generated 12 distinct CD22 antibodies and tested CARs derived from them to identify a CAR based on the novel 9A8 antibody, which was sensitive to low CD22 density and lacked tonic signaling. We found no correlation between affinity or membrane proximity of recognition epitope within Ig domains 3-6 of CD22 with CART function. The optimal strategy for CD19/CD22 CART co-targeting is undetermined. Co-administration of CD19 and CD22 CARs is costly; single CARs targeting CD19 and CD22 are challenging to construct. The co-expression of two CARs has previously been achieved using bicistronic vectors. Here, we generated a dual CART product by co-transduction with 9A8-41BBζ and CAT-41BBζ (obe-cel), the previously described CD19 CAR. CAT/9A8 CART eliminated single- and double-positive target cells in vitro and eliminated CD19- tumors in vivo. CAT/9A8 CART is being tested in a phase I clinical study (NCT02443831).

Performance of microbial inoculation and tricalcium phosphate on nitrogen retention and conversion: Core microorganisms and enzyme activity during kitchen waste composting.

The substantial release of NH3 during composting leads to nitrogen (N) losses and poses environmental hazards. Additives can mitigate nitrogen loss by adsorbing NH3/NH4, adjusting pH, and enhancing nitrification, thereby improving compost quality. Herein, we assessed the effects of combining bacterial inoculants (BI) (1.5%) with tricalcium phosphate (CA) (2.5%) on N retention, organic N conversion, bacterial biomass, functional genes, network patterns, and enzyme activity during kitchen waste (KW) composting. Results revealed that adding of 1.5%/2.5% (BI + CA) significantly (p < 0.05) improved ecological parameters, including pH (7.82), electrical conductivity (3.49 mS/cm), and N retention during composting. The bacterial network properties of CA (265 node) and BI + CA (341 node) exhibited a substantial niche overlap compared to CK (210 node). Additionally, treatments increased organic N and total N (TN) content while reducing NH4+-N by 65.42% (CA) and 77.56% (BI + CA) compared to the control (33%). The treatments, particularly BI + CA, significantly (p < 0.05) increased amino acid N, hydrolyzable unknown N (HUN), and amide N, while amino sugar N decreased due to bacterial consumption. Network analysis revealed that the combination expanded the core bacterial nodes and edges involved in organic N transformation. Key genes facilitating nitrogen mediation included nitrate reductase (nasC and nirA), nitrogenase (nifK and nifD), and hydroxylamine oxidase (hao). The structural equation model suggested that combined application (CA) and microbial inoculants enhance enzyme activity and bacterial interactions during composting, thereby improving nitrogen conversion and increasing the nutrient content of compost products.

Effect of dietary modulation of fiber and fat level on liver and kidney functions, lipid profile, antioxidant and immune parameters in growing Egyptian geese.

Determining the optimal requirements from dietary fiber and fat for Egyptian geese is a matter of great concern regarding health, production and growth. Therefore, the current study estimated the effects of different dietary fiber and fat levels on functions of liver and kidney, lipid profile, immunity and antioxidant measurements of the growing Egyptian geese. 150 Egyptian goslings (4 weeks old), with almost the same body weights were randomly allocated into 6 groups (25 goslings/group). All groups were subdivided into five replicates, each replicate contains five geese. Liver and kidney functions, immunity and antioxidant parameters were not significantly affected the different studied levels of fiber and fat or by their interaction. Various levels of fiber significantly affected total cholesterol, triglycerides, LDL-cholesterol and VLDL-cholesterol in a concentration-dependent manner and the lowest the lipid profile values were obtained at 12%. In conclusion, the present findings show that use of dietary fiber up to 12% and 5% dietary fat showed no detrimental effects on the immune status and general health of geese and resulted in the preferable lipid profile. This experiment provides a base for further study about the optimal requirements from dietary fiber and fat for the growing Egyptian geese.

The role of different dietary Zn sources in modulating heat stress-related effects on some thermoregulatory parameters of New Zealand white rabbit bucks.

The present work was conducted to assess the effect of diets supplementation to heat-stressed buck rabbits with different zinc (Zn) sources on the thermoregulatory and hematobiochemical parameters, and antioxidant status. A total of 24 mature buck rabbits (32-36 weeks of age) were randomly distributed into four groups (6 each). Group 1, non-heat-stressed control (NHSC), was reared in the absence of heat stress (HS) conditions and received the basal diet only. The other three groups (groups 2, 3 and 4) were kept in HS conditions. Group 2, heat-stressed control (HSC), received the basal diet only. The diet supplemented with 75 mg Zn/kg diet either in the inorganic form (Zn sulfate) or in the organic form (Zn picolinate) for groups 3 and 4, respectively. Zn supplementation to rabbits' diets lowered the heat stress-related increase of serum urea, alanine transaminase and malondialdehyde (MDA) concentration. These supplementations also increased the concentration of testosterone under HS conditions. Zn picolinate was more effective than Zn sulfate in restoring serum concentrations of urea, testosterone, and MDA. In conclusion, Zn addition to rabbits' diets from different sources, especially Zn picolinate, exhibits an ameliorative effect against the harmful impact of HS on hematobiochemical parameters and antioxidant status.

Consequences of varying dietary crude protein and metabolizable energy levels on growth performance, carcass characteristics and biochemical parameters of growing geese.

This research aimed to investigate the effect of varying dietary crude protein (CP) and metabolizable energy (ME) quantity on growth, carcass characteristics, biochemical blood parameters and molecular aspects of growing geese. Overall, a total of 180 Egyptian goslings were used in a 2 × 3 factorial design. Two levels of CP (18% and 16%) and three levels of ME (3000, 2900 and 2800 kcal/kg diet) were employed. Growth traits showed no significant differences as a result of different CP or ME levels. Birds fed the higher CP level consumed more feed than the lower. Carcass, dressing, heart, spleen, abdominal fat and thigh percentages within the group fed 18% CP were higher than the other group. Compared with the other ME-based diet, geese fed a low-ME based diet had the highest heart percentage. Feeding growing geese on a 2900 Kcal/kg ME-based diet increased the serum content of total protein and globulin. Geese fed the high-ME diet showed the highest levels of ALP and C4 as compared with other ME levels. Regarding Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), different protein and energy levels did not affect the molecular weight of blood proteins of Egyptian geese during the growing phase. It could be concluded the levels of 16% CP and 2800 kcal/kg ME are enough to maintain the growth performance and the other physiological indices as well as molecular aspects.

Mitigating the detrimental effects of heat stress in poultry through thermal conditioning and nutritional manipulation.

The poultry industry faces several obstacles and challenges, including the changes in global temperature, increase in the per capita demand for meat and eggs, and the emergence and spread of various diseases. Among these, environmental challenges are one of the most severe hurdles impacting the growth and productivity of poultry. In particular, the increasing frequency and severity of heat waves over the past few years represent a major challenge, and this is expected to worsen in the coming decades. Chickens are highly susceptible to high ambient temperatures (thermal stress), which negatively affect their growth and productivity, leading to enormous economic losses. In the light of global warming, these losses are expected to increase in the near future. Specifically, the worsening of climate change and the rise in global temperatures have augmented the adverse effects of heat on poultry production worldwide. At present, the world population is approximately 7.9 billion, and it has been predicted to reach 9.3 billion by 2050 and approximately 11 billion by 2100, implying a great demand for protein supply; therefore, strategies to mitigate future poultry challenges must be urgently devised. To date, several mitigation measures have been adopted to minimize the negative effects of heat stress in poultry. Of these, thermal acclimation at the postnatal stage or throughout the embryonic stages has been explored as a promising approach; however, for large-scale application, this approach warrants further investigation to determine the suitable temperature and poultry age. Moreover, molecular mechanisms governing thermal conditioning are poorly understood. To this end, we sought to expand our knowledge of thermal conditioning in poultry, which may serve as a valuable reference to improve the thermotolerance of chickens via nutritional management and vitagene regulation. Vitagenes regulate the responses of poultry to diverse stresses. In recent years, nutritionists have paid close attention to bioactive compounds such as resveratrol, curcumin, and quercetin administered alone or in combination. These compounds activate vitagenes and other regulators of the antioxidant defense system, such as nuclear factor-erythroid 2-related factor 2. Overall, thermal conditioning may be an effective strategy to mitigate the negative effects of heat stress. In this context, the present review synthesizes information on the adverse impacts of thermal stress, elucidating the molecular mechanisms underlying thermal conditioning and its effects on the acquisition of tolerance to acute heat stress in later life. Finally, the role of some polyphenolic compounds, such as resveratrol, curcumin, and quercetin, in attenuating heat stress through the activation of the antioxidant defense system in poultry are discussed.

Clinical lessons learned in constitutional hypopituitarism from two decades of experience in a large international cohort.

CONTEXT: The international GENHYPOPIT network collects phenotypical data and screens genetic causes of non-acquired hypopituitarism. AIMS: To describe main phenotype patterns and their evolution through life. DESIGN: Patients were screened according to their phenotype for coding sequence variations in 8 genes: HESX1, LHX3, LHX4, PROP1, POU1F1, TBX19, OTX2 and PROKR2. RESULTS: Among 1213 patients (1143 index cases), the age of diagnosis of hypopituitarism was congenital (24%), in childhood (28%), at puberty (32%), in adulthood (7.2%) or not available (8.8%). Noteworthy, pituitary hormonal deficiencies kept on evolving during adulthood in 49 of patients. Growth Hormone deficiency (GHD) affected 85.8% of patients and was often the first diagnosed deficiency. AdrenoCorticoTropic Hormone deficiency rarely preceded GHD, but usually followed it by over 10 years. Pituitary Magnetic Resonance Imaging (MRI) abnormalities were common (79.7%), with 39.4% pituitary stalk interruption syndrome (PSIS). The most frequently associated extrapituitary malformations were ophthalmological abnormalities (16.1%). Prevalence of identified mutations was 7.3% of index cases (84/1143) and 29.5% in familial cases (n = 146). Genetic analysis in 449 patients without extrapituitary phenotype revealed 36 PROP1, 2 POU1F1 and 17 TBX19 mutations. CONCLUSION: This large international cohort highlights atypical phenotypic presentation of constitutional hypopituitarism, such as post pubertal presentation or adult progression of hormonal deficiencies. These results justify long-term follow-up, and the need for systematic evaluation of associated abnormalities. Genetic defects were rarely identified, mainly PROP1 mutations in pure endocrine phenotypes.

Use of acetylsalicylic acid as an allostatic modulator in the diets of growing Japanese quails exposed to heat stress.

The purpose of this study was to investigate the effect of dietary acetylsalicylic acid (ASA) supplementation on performance, carcasses and some blood metabolites of growing quails exposed to heat stress. Three hundred sixty mix sexed Japanese quail chicks at 2 wk of age with average initial body weight of 77.4 g were randomly allotted to six dietary groups in a 3 × 2 factorial design with three dietary ASA doses (0, 0.5 and 1 g ASA/kg diet) and two ambient temperatures (one normal at 23 ± 2 °C and other high at 33 ± 2 °C). Body weight, daily body weight gain and feed consumption reduced in quails exposed to heat stress (33 °C) during 2-4 wk of age, but not during 4-6 wk of age and during total period (2-6 wk of age). Growth rate and feed utilization were not influenced by ASA supplementation or interaction between ASA supplementation and house temperature at all ages (P > 0.05). All carcass parameters were not affected (P > 0.05) by temperature or dietary ASA or their interactions except dressing percent was decreased (P = 0.025) by ASA. Plasma cholesterol and total lipid were affected by the interaction effect, which were elevated in birds exposed to high ambient temperature (P = 0.004 or 0.022) and ASA supplementation (P = 0.041 or P = 0.003). Glucose concentrations were also influenced by interaction effect, which increased due to ASA supplementation at normal temperature, but were not affected at high temperature. The effect of high ambient temperature or its interaction with ASA did not affect hepatic enzymes and thyroid hormones of growing quails. Diets supplemented with ASA (1000 mg/kg) decreased plasma contents of aspartate transaminase, triiodothyronine (T3) and thyroxin (T4) compared with the control. It is concluded that applications of ASA in quail diets are not suitable in mitigating the disturbances induced by heat stress in the most studied parameters.

Nutritional rickets: vitamin D, calcium, and the genetic make-up.

BACKGROUND: The prevalence of vitamin D (vitD) deficiency presenting as rickets is increasing worldwide. Insufficient sun exposure, vitD administration, and/or calcium intake are the main causes. However, vitD system-related genes may also have a role. METHODS: Prospective study: 109 rachitic children completed a 6-mo study period or until rachitic manifestations disappeared. Thirty children were selected as controls. Clinical and biochemical data were evaluated at baseline in patients and controls and biochemistry re-evaluated at radiological healing. Therapy was stratified in three different protocols. Fifty-four single-nucleotide polymorphisms (SNPs) of five vitD system genes (VDR, CP2R1, CYP27B1, CYP24A1, and GC) were genotyped and their association with clinical and biochemcial data was analyzed. RESULTS: Therapy response was similar in terms of radiological healing although it was not so in terms of biochemical normalization. Only VDR gene (promoter, start-codon, and intronic genotypes) was rickets-associated in terms of serum 25-OH-D, calcium, radiological severity and time needed to heal. Eight patients with sufficient calcium intake and 25-OH-D levels carried a VDR genotype lacking minor allele homozygous genotypes at SNPs spread along the gene. CONCLUSION: Although patients presented epidemiologic factors strongly contributing to rickets, genetic modulation affecting predisposition, severity, and clinical course is exerted, at least in part, by VDR gene polymorphic variation.

Role of Tamsulosin Therapy after Extracorporeal Shockwave Lithotripsy for Renal Stones: Randomized Controlled Trial.

INTRODUCTION: To evaluate the efficacy of adjunctive tamsulosin therapy after extracorporeal shockwave lithotripsy (SWL) for renal stones. MATERIALS AND METHODS: This prospective study was conducted on patients who underwent single-session SWL for solitary renal stone less than 20 mm. Post-SWL, patients were randomly divided into 2 groups; the tamsulosin group (TG), received a daily dose of tamsulosin 0.4 mg, for a maximum of 12 weeks, with post-SWL traditional analgesia and control group (CG), received the traditional analgesia alone. RESULTS: The study enrolled 271 patients and eventually only 249 (123 in TG and 126 in CG) completed the study. The overall stone free rate was 73.5%: 78.0% in TG and 69.0% in CG (p = 0.108). In TG, 8.1% of patients experienced at least one episode of acute renal/ureteral colic compared with 19.8% of controls (p = 0.008). The mean cumulative analgesia dosage per subject was 313 mg in TG and 346 mg in CG (p < 0.001). Overall, 14 patients developed steinstrasse and 6 of them (all in CG) needed urgent intervention (p = 0.031). CONCLUSIONS: Daily tamsulosin therapy does not enhance the clearance of stone fragments but decreases the pain episodes, analgesia dosage and need for adjuvant intervention after SWL for renal stones.

Precocious Puberty Following Traumatic Brain Injury in Early Childhood: A Review of the Literature.

AIMS OF THE REVIEW: The intent of the current manuscript is to review the cases of central precocious puberty (CPP) in early childhood following traumatic brain injury (TBI). SEARCH OF THE LITERATURE: The MEDLINE database was accessed through PubMed in April 2015. Results were not restricted to the date and language of the articles. For the first search we utilized MeSH terms "precocious puberty" in conjunction with "traumatic brain injury" and with "endocrine consequences". Reference lists were reviewed and relevant papers were also consulted to find additional studies and data. In selected cases the corresponding author was contacted by email. RESULTS: In our systematic review, only a few case reports or small case series have highlighted a link between TBI and hypothalamic-pituitary hormone abnormalities. Fourteen reported children were females and 8 were males. The majority of patients reported had severe TBI, assessed by Glasgow Coma Scale or structural injury (skull fractures, intracranial hemorrhage or cerebral injury) reported on computerized tomography or magnetic resonance imaging scans. The pathogenic mechanism of precocious puberty has not yet been determined. An increased pressure on the hypothalamic-pituitary area with loss of normal childhood hypothalamic inhibition of pituitary gonadotropins could be one of the factors responsible for CPP after TBI. CONCLUSIONS: The current review highlights the importance of close clinical follow-up to evaluate the rate of linear growth and pubertal development after TBI. Although, precocious puberty appears to be rare after TBI, prevalence should ideally be assessed by longitudinal follow-up of a large population. Therefore, further multicenter and multidisciplinary studies are required to explore in detail the true incidence and the possible mechanisms of CPP after TBI. Because precocious puberty can be detected on clinical assessment during childhood, a pragmatic approach would be for family physicians to monitor growth and development in children after TBI. Inasmuch as precocity is mediated through the hypothalamic-pituitary pathways, use of LH-RH analogue therapy should be effective in arresting pubertal progression.

Selected highlights of the VIII International Symposium of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) on Growth, Puberty and Endocrine Complications in Thalassaemia. Auditorium of the Sultan Qaboos University (SQU) Muscat (Sultanate of Oman), 20th of December 2014.

The VIII ICET-A International Symposium was held in Muscat (Sultanate of Oman) on the 20th of December, 2014. The symposium included four sessions on a wide range of topics covering growth disorders and endocrine complications in thalassaemia. Despite the fact that endocrine complications are very common in multi-transfused thalassaemia patients a recent survey conducted by the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) in 2014 in Acitrezza (Catania, Italy) showed that the major difficulties reported by hematologists or pediatricians experienced in thalassaemias or thalassaemia syndromes in following endocrine complications included: Lack of familiarity with medical treatment of endocrine complications, interpretation of endocrine tests, lack of collaboration and on-time consultation between thalassaemic centres supervised by haematologists and endocrinologists. Endocrine monitoring of growth, pubertal development, reproductive ability and endocrine function in general are essential to achieve a good quality of life as well as controlling the pain which results from the defects of bone structure, all of which increase with the age of patients. Such comprehensive care is best provided by coordinated, multidisciplinary teams working in expert centres. The multidisciplinary team must include an endocrinologist, preferably someone experienced in the management of hormonal deficiencies caused early in life by transfusion-induced iron overload.

Trace Minerals in Laying Hen Diets and Their Effects on Egg Quality.

With the advancement in the egg industry sector, egg quality has assumed great significance in certain countries. Enhancements in the nutritional value of eggs may have direct affirmative consequences for daily nutrient intake and therefore for human health. Thus, affirmative improvement in egg quality boosts consumer preferences for eggs. Also, the improvement in eggshell quality can avoid the disposal of broken eggs and consequently economic losses. Therefore, poultry nutrition and mineral supplements have a significant impact on egg quality. Minerals are crucial in poultry feed for a number of biological processes, including catalytic, physiologic, and structural processes. For instance, they contribute to the biological processes necessary for forming and developing eggshells. To produce high-quality eggs for sale, diets must therefore contain the right amount of minerals. This review aims to highlight the role of both organic and inorganic minerals in improving egg quality, in addition to reviewing the interactions of mineral supplements with intestinal microbiota and subsequent effects on the egg quality.

Performance and economic efficiency of laying hens in response to adding zeolite to feed and litter.

This study investigated the effect of different levels of zeolite in laying hen (Silver Montazah) diet and litter on productive performance, egg quality criteria, and economics during the second stage of production (40-56 wk of age). An experiment with a 3 × 4 factorial design was performed to study the effects of four levels of zeolite (0, 10, 15, and 20 g/kg feed) in the diet and three levels of zeolite (0, 1.5, and 2 kg/m2) in the litter. Adding zeolite to diet and litter significantly improved final BW and BW change, egg number, egg weight, egg mass, laying rate, feed consumption (FC), and feed conversion ratio (FCR), as well as egg quality criteria when compared to the unsupplemented group. Additionally, adding zeolite at a level of 2 kg /m2 litter and 20 g/kg diet achieved the greatest enhancement in productive performance features. Therefore, it can be suggested that the greatest results were obtained in laying farms when zeolite was added as a litter addition and as a supplement to feed.

The relationship between eggshell color, hatching traits, fertility, mortality, and some qualitative aspects of Japanese quail (Coturnix japonica) eggs.

Quail, one of the most important sources of meat and eggs, can aid in the reduction of the meat crisis if they are raised and cared for by small farmers. The current study investigated the impact of eggshell color variety on egg quality traits and hatching parameters of Japanese quail Coturnix japonica eggs. Therefore, 1,075 eggs were collected from female quails when they were 10-wk old. These eggs were distributed based on the color of their eggshells into 5 different classifications: eggshell with color type 1, very dark distributed brown spots on brown eggshell; eggshell with color type 2, small black spots on a white eggshell; eggshell with color type 3, widespread brown spots on brown eggshell; eggshell with color type 4, bubble egg, pin dotted on grayish brown color eggshell; and eggshell with color type 5, small brown spots on very clearly white eggshell. The characteristics of hatchability, internal and external egg quality, and the rate of embryonic death were then determined. The results showed that the percentage of fertility and commercial and scientific hatchability was greatly affected by eggshell color. There were also variations in the percentage of hatched chicks', early mortality rates, and late mortality rates based on eggshell color. According to the results of the current study, eggshell color has a significant impact on egg weight, egg width, and percentages of eggshell, yolk, and albumen but has no effect on shape index, egg length, or egg elongation. Based on the results, eggshells with color types 2 and 3 were recommended for use in hatching procedures due to their high levels of fertility (92.01 and 91.63%, respectively), scientific hatchability (82.92 and 83.93%, respectively), commercial hatchability (76.56 and 77.32%, respectively), and hatched chick (5.50 and 6.70, respectively). In addition, the late embryonic mortality rate was 0.00% for eggshells with color type 3. Therefore, the color of the eggshell can be employed as a key factor in guiding the eggs that are produced, whether they are going to be consumed at the table or used for hatching, to make breeding easier.

Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies.

Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells limits the efficacy of immunotherapeutic approaches. The T cell receptor expresses one of two highly homologous chains [T cell receptor ß-chain constant (TRBC) domains 1 and 2] in a mutually exclusive manner, making it a promising target. Here we demonstrate specificity redirection by rational design using structure-guided computational biology to generate a TRBC2-specific antibody (KFN), complementing the antibody previously described by our laboratory with unique TRBC1 specificity (Jovi-1) in targeting broader spectrum of T cell malignancies clonally expressing either of the two chains. This permits generation of paired reagents (chimeric antigen receptor-T cells) specific for TRBC1 and TRBC2, with preclinical evidence to support their efficacy in T cell malignancies.

Penile length and genital anomalies in Egyptian male newborns: epidemiology and influence of endocrine disruptors.

This is an attempt to establish the normal stretched penile length and prevalence of male genital anomalies in full-term neonates and whether they are influenced by prenatal parental exposure to endocrine-disrupting chemicals. A thousand newborns were included; their mothers were subjected to the following questionnaire: parents' age, residence, occupation, contact with insecticides and pesticides, antenatal exposure to cigarette smoke or drugs, family history of genital anomalies, phytoestrogens intake and history of in vitro fertilization or infertility. Free testosterone was measured in 150 neonates in the first day of life. Mean penile length was 3.4±0.37 cm. A penile length <2.5 cm was considered micropenis. Prevalence of genital anomalies was 1.8% (hypospadias 83.33%). There was a higher rate of anomalies in those exposed to endocrine disruptors (EDs; 7.4%) than in the non-exposed (1.2%; p<0.0001; odds ratio 6, 95% confidence interval 2-16). Mean penile length showed a linear relationship with free testosterone and was lower in neonates exposed to EDs.

Osteoporosis in thalassemia major: an update and the I-CET 2013 recommendations for surveillance and treatment.

In recent years, the issue of osteopenia/osteoporosis in children, adolescents and young adults with thalassaemia major (TM) has attracted much attention because it is a prominent cause of morbidity despite adequate transfusion and iron chelation therapy. The reported frequency of osteoporosis, even in well treated TM patients varies from 13.6% to 50% with an additional 45% affected by osteopenia. The pathogenesis of TM-induced osteoporosis is multifactorial. Genetic and acquired factors play role in demineralization of bones in thalassemia. Osteoporosis is characterized by low bone mass and disruption of bone architecture, resulting in reduced bone strength and increased risk of fractures. The significant predictors of fracture prevalence include male gender, hypothyroidism, age, lack of spontaneous puberty in females, active hepatitis, heart disease and diabetes. The early identification of osteopenia and osteoporosis is of paramount importance. This is because delayed diagnosis and inadequate treatment have led to severe osteoporosis, skeletal abnormalities, fractures, spinal deformities, nerve compression and growth failure. dequate hormonal replacement, has been posponed, Effective iron chelation adequate hormonal replacement, improvement of hemoglobin levels, calcium and vitamin D administration and physical activity are currently the main measures for the management of the disease. The use of bisphosphonates in TM patients with osteoporosis is increasing and their positive effect in improving bone mineral density is encouraging. The recommendations of the International Network on Growth Disorders and Endocrine Complications in Thalassaemia (I-CET) for diagnosis and management of osteoporosis in TM are also briefly included in this review.