骨代谢标志物在骨质疏松症诊治中的应用

骨质疏松症是以骨质量和强度降低为特征的退变性疾病,可导致脆性骨折的发生,但在临床上,经常得不到充分的治疗和诊断。骨代谢标志物（bone turnover marker, BTM）在骨质疏松的诊断及治疗评估中发挥了不可替代的作用,本文就常见BTM及其在骨质疏松症诊治中的应用现状进行综述,为临床上诊治骨质疏松症提供更加详细准确的参考及思路。     

骨代谢标志物在骨质疏松诊疗中的应用指南(2012年版) (日本骨质疏松症学会制定)

近年来,骨代谢标志物临床应用已取得了显著的进展,这些指标的测量,让我们对骨质疏松症的发病机制有一个更好的了解。骨代谢标志物用于选择骨质疏松治疗药物和评价药物疗效。因此,合理应用和评价骨代谢标志物在临床实践中是非常重要的。为了实现这些目标,由日本骨质疏松症学会授权的骨质疏松骨代谢指标应用指南制定委员会,总结骨代谢指标最新研究进展,并提出了骨代谢指标的合理应用。虽然现在骨代谢指标,在骨质疏松症的日常管理工作中具有重要的作用,但由于医保范围的限制,在日本的应用仍不普遍。自日本骨质疏松症学会制定了2001年指南,新的骨代谢指标已列入临床实践。新的促进骨形成的骨质疏松症治疗方法,改变了骨代谢指标在临床实践中的应用。因此,需要调整目前的临床应用方案,提出制定新的2012年指南的建议。     

骨代谢标志物在乳腺癌骨质疏松中的评估价值

目的探究骨代谢标志物在乳腺癌骨质疏松中的诊断价值。方法选取2014年6月至2017年6月在我院住院接受治疗的182例乳腺癌骨质疏松患者为本次研究的研究对象,对本研究对象的骨代谢标志物BALP以及uNTx水平进行检测,统计并对比治疗前后乳腺癌骨质疏松患者骨代谢标志物的变化情况,采用单因素分析方法及多元线性回归分析方法分析影响乳腺癌骨质疏松患者骨代谢标志物水平的因素。结果乳腺癌骨质疏松患者骨代谢标志物BALP以及uNTx水平明显高于正常水平(P0.05),治疗后两者水平均明显低于治疗前(P0.05);单因素分析显示,骨代谢标志物BALP以及uNTx水平与患者骨转移数目呈正相关(P0.05),与骨痛程度无明显联系(P0.05);多元线性回归分析,骨代谢标记物和骨转移数目是影响患者近期疗效的相关因素。结论骨代谢标志物水平与骨质疏松有着密切联系,可作为乳腺癌骨质疏松的理想诊断指标,且该指标相对于影像学检查反应敏感性更强。     

不同骨密度骨质疏松性椎体压缩骨折骨组织形态与骨代谢标志物分析

目的 观察不同骨密度骨质疏松椎体压缩骨折(osteoporotic vertebral compression fracture,OVCF)骨组织形态学特征及骨代谢标志物变化规律.方法 将136例OVCF患者按不同骨密度(T值)分为3组:I组,-3.5相似文献   

类风湿关节炎患者血清骨代谢标志物水平及炎症因子变化研究

目的探讨类风湿关节炎(rheumatoid arthritis,RA)患者血清骨代谢标志物水平及炎症因子的变化。方法收集RA患者60例和健康对照者20名,再将60例RA患者按照是否合并骨质疏松(osteoporosis,OP)分为OP组(32例)和非OP组(28例)。采用双能X射线骨密度测量仪测骨密度,酶联免疫吸附法测定外周血清白细胞介素(interleukin,IL)-1β、IL-6、IL-17、I型前胶原N-末端前肽(N-terminal propeptide of type I collagen,PINP)、I型胶原C-末端交联顶端肽(type I collagen cross-linked Ctelopeptide,CTX)水平,并详细记录临床、实验室资料。对两组间计量资料采取独立样本t检验进行比较,采用Pearson积差相关法进行相关性分析。结果 (1)RA组与对照组相比,其骨密度、PINP水平普遍较低(P0.05);CTX、IL-1β、IL-17、IL-6水平普遍较高(P0.05)。(2)与非OP组相比,OP组的年龄、病程、IL-1β、IL-17、IL-6水平普遍较高(P0.05),OP组患者CTX、PINP水平虽然高于非OP组,但差异无统计学意义(P0.05)。(3)RA患者外周血血清中IL-1β与红细胞沉降率(erythrocyte sedimentation rate,ESR)成正相关(r=0.423,P0.05),IL-6与C反应蛋白(C-reactive protein,CRP)、ESR、类风湿关节炎患者病情评价(DAS28评分)成正相关(r=0.473、0.370、0.481,P0.05);IL-17与CRP、ESR、DAS28成正相关(r=0.411、0.367、0.468,P0.05);CTX与疾病活动性指标CRP、ESR、DAS28呈正相关(r=0.536、0.488、0.466,P0.05),与病程呈负相关(r=-0.268,P0.05);PINP水平与各疾病活动性指标间均无相关性(P0.05)。结论 RA患者存在较高的OP发生率,且合并OP患者IL-1β、IL-17、IL-6高于未合并OP患者,RA患者中继发OP作用机制可能与炎症因子IL-1β、IL-6、IL-17相关;CTX和PINP与疾病活动和OP密切相关,测定这两个骨代谢指标能够了解RA患者早期骨破坏程度。     

慢性肾脏病患者骨代谢标志物的临床意义

慢性肾脏病矿物质和骨异常(chronic kidney disease-mineral and bone disorder, CKD-MBD)是慢性肾脏病(chronic kidney disease, CKD)的常见并发症之一,引起矿物质代谢紊乱、骨质疏松、骨折及血管钙化的发生,严重影响患者预后。因此,早期的筛查、诊断及治疗十分重要。骨活检因其有创性而未能在临床上广泛开展,CKD-MBD的诊断主要依赖于骨代谢标志物(bone turnover biomakers, BTMs)的测定。既往研究表明,BTMs是评估CKD患者骨转换及患者预后的有力证据。本文就BTMs进行综述,为CKD-MBD的临床诊断与预后评估提供参考。     

PTCH1基因rs28377268多态性与骨质疏松性椎体压缩骨折骨代谢标志物的相关性研究

目的探讨PTCH1基因rs28 377 268位点多态性与骨质疏松性椎体压缩骨折患者骨代谢标志物的关系。方法选取2016年1月至2016年6月我科脊柱组收治的骨质疏松性椎体压缩骨折患者(骨折组)和脊柱退行性病变骨质疏松患者(对照组)各80例。采用SNa Pshot法进行SNP分型,化学发光法测定骨代谢标志物:骨钙素(osteocalcin,OC)、Ⅰ型胶原羧基端肽β特殊序列(beta-crosslaps of type I collagen cross-linked C-telopeptide,β-CTX)、Ⅰ型前胶原氨基端前肽(procollagen I N-terminal propeptide,P1NP)、25-羟维生素D(25-hydroxyvitamin D,25(OH)D)、甲状旁腺激素(parathyroid hormone,PTH)浓度。比较两组等位基因频率、基因型频率分布及两组骨代谢标志物浓度差异,并分析PTCH1基因rs28 377 268位点多态性与骨代谢标志物浓度的关系。结果骨折组和对照组G、T等位基因频率均为80%、20%,两组GG、GT、TT基因型频率分别为66.25%、27.50%、6.25%和62.50%、35.00%、2.50%,无统计学意义(P0.05)。骨折组中血清OC、PINP、β-CTX及25(OH)D浓度较对照组均无统计学意义,而PTH浓度明显高于对照组(P0.05)。血清OC、PINP、β-CTX及25(OH)D浓度在GG、GT、TT3种基因型之间亦无统计学意义(P0.05),血清PTH浓度在GT、TT基因型中均高于GG基因型,其中TT基因型显著高于GG、GT基因型(P0.05)。结论 PTCH1基因rs28 377 268位点在骨质疏松患者中G、T等位基因的表达频率分别为80%、20%,rs28377268-T等位基因高表达可能间接升高血清PTH浓度,促进骨质疏松发生,增加椎体脆性骨折风险。     

miRNA参与骨代谢调节的作用机制研究进展

微小RNA（microRNA,miRNA）是一组小的非编码RNA,仅含18~22个核苷酸,以对基因表达的负调控作用参与调节一系列发育和生理过程。已有研究表明,miRNA作为一种重要的内源性转录后调节因子,对骨代谢发挥至关重要的调节作用。miRNA通过多种方式调控骨髓间充质干细胞、成骨细胞和破骨细胞等的增殖、分化与功能,为骨发育及维持骨稳态发挥了不可替代的作用。miRNA作为战略靶点或生物标志物在骨质疏松症的诊断和治疗中具有潜在的重要价值。本文综述了近年来发现的在骨代谢中发挥重要作用的miRNA及其作用靶点,以及对成骨/破骨相关信号通路的影响,为骨代谢调节及骨质疏松症的临床治疗提供了新的思路与方向。本文还介绍了miRNA可作为骨质疏松症诊断标志物所面临的问题。     

骨代谢标志物在强直性脊柱炎疾病活动性和骨折风险评估中的研究进展

强直性脊柱炎（ankylosing spondylitis,AS）是一种与HLA-B27相关的病因不明的慢性炎症性免疫疾病,该病易侵犯骶髂关节、脊柱骨突以及外周关节,严重者可有骨质疏松及骨折的风险。对于普通AS患者,如何预估患者罹患骨质疏松、甚至发生骨折的风险,以确定哪些患者能从抗骨质疏松症药物治疗中获得最佳益处,是预防骨折发生、降低患者致残率的必然要求。骨代谢标志物可以反映骨的整体转换率,在AS患者的评估强直性脊柱炎疾病活动性及其分型、预测骨折发生的危险性、观察药物治疗疗效等均有重要意义。因此,笔者对骨代谢标志物与AS患者疾病活动性及其与骨质疏松相关性研究进展作一综述。     

骨代谢生化标志物在原发性骨质疏松症药物治疗中的应用

[目的]分析骨代谢生化标志物在骨质疏松症治疗中对药物应用的指导意义,为骨质疏松药物治疗探索一条精准有效地治疗途径。[方法]采用自身前后对照临床研究,56例患者根据Ⅰ型前胶原N-端前肽(P1NP)与β-胶原特殊序列(β-cross Laps)测量值分为低骨转换组(30例)与高骨转换组(26例)。每组随机分别给予2种治疗方案:特立帕肽(20μg/d)与唑来膦酸注射液(5 mg/年),治疗时间为26个周,期间定期观察β-cross Laps、P1NP、腰椎、股骨颈骨密度(BMD)以及VAS疼痛评分的变化情况。[结果]在高、低骨转换组中,特立帕肽治疗后P1NP与β-cross Laps均较治疗前浓度升高(P<0.05),唑来膦酸治疗后P1NP与β-cross Laps均较治疗前浓度降低(P<0.05);低骨转换组特立帕肽治疗后腰椎BMD升高较唑来膦酸显著(P<0.05),高骨转换组唑来膦酸治疗后股骨颈BMD升高较特立帕肽显著(P<0.05);低骨转换组特立帕肽治疗后骨痛缓解优于唑来膦酸(P<0.05),高转换组中两种药物均能缓解骨痛,差异无统计学意义(P>0.05)。[结论]在原发性骨质疏松症治疗中,应以骨生化标志物作为药物选择的依据:低骨转换状态下以促成骨药物为主,高骨转换状态下以抑制骨吸收药物为主。     

儿童骨代谢指标的检查

儿童骨骼是一个充满活力的器官,种族、性别、儿童发育的不同阶段、营养、疾病都影响儿童骨标测量值.骨标志物浓度能早期灵敏地反映骨代谢转换动态状况,评估骨骼代谢疾病的病理生理,以及监测治疗效果.本文综述儿童骨代谢指标检查的方法进展和参考值;包括骨代谢的直接指标如骨碱性磷酸酶、骨钙素、抗酒石酸酸性磷酸、吡啶交联物和交联断肽等,以及骨代谢间接调节指标,特别是最常检测的指标25-羟基维生索D.     

Bone markers in osteoporosis

Current biological markers of bone turnover have proven useful in improving fracture risk assessment and monitoring treatment efficacy in postmenopausal osteoporosis. Recent developments in the field of bone markers include 1) identification of new biochemical markers providing additional information on the complex pathways leading to bone fragility; 2) application of novel technologies such as proteomics for the discovery of novel markers; 3) automation and multiplexing for improving analytical performance and convenience; and 4) refinement of the clinical interpretation of markers. Currently, however, for the management of individual patients, their most established application is to monitor treatment efficacy and possibly to improve fracture risk assessment. The role of bone markers for improving adherence to therapy will need to be investigated in further studies. This brief review discusses these novel technological developments and the recent clinical data on the use of established and new markers in postmenopausal osteoporosis.     

Bone mineral density and bone turnover markers in children with chronic renal failure

Bone mineral density (BMD) at lumbar spine (L₂-L₄) was measured by dual-energy X-ray absorptiometry (DEXA) in 21 children with predialysis chronic renal failure (CRF) and 44 children with end-stage renal failure (ESRF) on regular hemodialysis. BMD results were expressed as Z-scores. Osteopenia was documented in 13 predialysis patients (61.9%) and 26 patients (59.1%) with ESRF. No significant correlation was observed between Z-scores and the duration of CRF or estimated creatinine clearance. In osteopenic children there was a negative correlation between Z-scores and serum phosphorus (r=–0.61, P=0.004), intact parathyroid hormone (iPTH) (r=–0.47, P=0.03), and bone-specific alkaline phosphatase (r=–0.52, P=0.02) and a positive correlation with total calcium (r=0.41, P=0.07) and 25-hydroxycholecalciferol (r=0.53, P=0.02). Osteopenic children who had iPTH values 200 pg/ml were more osteopenic than those who had lower iPTH levels (P=0.006). In conclusion, osteopenia, assessed by DEXA, is frequent in children with CRF. It occurs early irrespective of the duration or the severity of CRF. In children with ESRF the degree of osteopenia is correlated with laboratory markers of renal osteodystrophy and patients with biochemical findings of secondary hyperparathyroidism are more osteopenic than the others.     

Bone metabolism in galactosemia

Classical galactosemia is an autosomal recessively inherited disorder of galactose metabolism. Treatment consists of life-long dietary restriction of galactose. Despite treatment, long-term complications occur such as a decreased bone mineral density (BMD). A decreased BMD might be the result of either dietary deficiencies secondary to the galactose-restricted diet or unknown intrinsic factors. In this study, 40 children with classical galactosemia (13 males and 27 females, aged 3-17 years) on dietary treatment were included to gain insight in the bone metabolism of galactosemics. We found weight and height Z scores significantly decreased in galactosemics. Mean areal BMD Z scores of lumbar spine and of femoral neck as measured by Dual energy X-ray Absorptiometry (DXA) were -0.6 (P < 0.001) and -0.3 (P = 0.066), respectively. Mean volumetric BMD of the femoral neck was significant lower in galactosemics (P < 0.001). The recommended dietary allowances (RDA) for calcium, magnesium, zinc, vitamin D, and protein were met in all patients. Mean serum levels of calcium, phosphate, magnesium, zinc, 1,25-dihydroxy vitamin D (1,25OHD), parathormone (PTH), 17-beta estradiol, bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were normal. Serum levels of IGF-1 Z score, carboxylated osteocalcin (cOC), N-terminal telopeptide (NTX), and C-terminal telopeptide (CTX) were significantly lower in galactosemics than in control subjects. The different bone markers were strongly correlated. The low levels of IGF-1 Z score, formation marker cOC, and resorption markers NTX and CTX suggest a decreased bone metabolism in galactosemics.     

Bone metabolism markers and hungry bone syndrome after parathyroidectomy in dialysis patients with secondary hyperparathyroidism

Objective

To explore the short-term variation in bone metabolic markers and the characteristics of hungry bone syndrome (HBS) after parathyroidectomy (PTX) with forearm autotransplantation in uremic patients with secondary hyperparathyroidism (SHPT) and to provide a basis for the pathogenesis, diagnosis and treatment of metabolic bone disease in SHPT.

Methods

A total of 115 patients with SHPT receiving PTX from July 2015 to December 2017, hospitalized at the First Affiliated Hospital of Nanjing Medical University, were enrolled in our study. We retrospectively analyzed the baseline clinical data, the levels of bone metabolism markers before and on the third day after PTX, and the risk factors predicting HBS.

Results

Preoperative baseline data showed that the levels of bone metabolic markers such as bone metabolism-regulating hormones: iPTH, calcitonin (CT); bone formation markers: phosphatase (ALP), osteocalcin (OC); bone resorption markers: type I collagen cross-linked N-telopeptides (NTX), type I collagen cross-linked C-telopeptides (CTX), tartrate-resistant acid phosphatase 5b (TRAP-5b) were all increased compared to normal levels. The levels of postoperative serum iPTH, CT, CTX and TRAP-5b decreased significantly compared to preoperative levels, while the levels of OC and ALP increased significantly. Of the 115 patients, 101 (87.8%) developed HBS after PTX. High preoperative serum ALP and low preoperative serum calcium level independently predicted the occurrence of HBS. Younger preoperative age, high preoperative serum ALP and iPTH level independently predicted the severity of HBS.

Conclusions

In severe SHPT, both bone formation and resorption were active, which suggested the presence of high-turnover bone diseases characterized by up-regulation of osteoclasts-osteoblasts functionally coupling activation in the patients. PTX could promote osteoblast activity and reduce osteoclast activity. HBS was common after PTX. Preoperative higher serum ALP and lower calcium were independent predictors of the occurrence of HBS. Younger patients with higher preoperative ALP and PTH may need to closely monitor serum calcium levels and intensive calcium supplementation after PTX.

     

Biochemical markers of bone metabolism in infants and children under intravenous corticosteroid therapy

The short-term effects of corticosteroids (CS) administered intravenously (IV) on biochemical parameters of bone metabolism were followed in infants and children. Forty-nine patients from 2 months to 10 years of age, admitted to Pediatrics Department for bronchiolitis, viral-associated wheezing and croup, were treated with IV hydrocortisone or methylprednisolone (10 or 2 mg/Kg/day, respectively) for 3 days. Blood and fasting urine were collected on admission (day 1), 2 days later (day 3) and 12 days after the end of therapy (day 15). Fifty-one children of similar age and gender without respiratory problems or bone diseases were used as controls. On day 3, suppression of the bone formation markers osteocalcin (OC) (P < 0.001) and total alkaline phosphatase (ALP) (P < 0.05) was observed, but not of the bone resorption markers of hydroxyproline, pyridinoline and calcium excretion (UHyp/UCr, UPYD/UCr and UDPD/UCr, UCa/UCr). Significant decreases were indicated in serum phosphate (Pi) and the maximum renal tubular Pi reabsorption (TmP/GFR) compared to basal (P < 0.001). No significant changes were noticed in the circulating levels of calcium (Ca), parathyroid hormone (iPTH), 25OHD, 24,25(OH)₂D, 1,25(OH)₂D, the insulin-like growth factor-I (IGF-I) and its binding protein-3 (IGFBP-3). Two weeks after therapy, the increase of OC to higher than basal (P < 0.01) indicated a probable activation of the osteoblasts. Serum Pi and the TmP/GFR index values that had significantly decreased by day 3 returned to pretreatment levels by day 15. When assessing the effects of the CS in relation to age, no changes were detected in the levels of OC and total ALP in the <12-month-old children, but a fall of OC was observed in the >1-year-old group (P < 0.001). In contrast to the OC, the effects on serum and renal tubular reabsorption of phosphate were similar for both groups. In conclusion, short-term IV administered CS led to significant but reversible inhibition of bone formation markers, especially detectable in the >1-year-old children, without affecting the bone resorption ones. The adverse effects on phosphate metabolism were also significant, but temporal and irrespective of age.     

慢性肾盂肾炎患者骨代谢研究

目的 了解慢性肾盂肾炎患的骨代谢情况。方法 对31例慢性肾盂肾炎患进行了有关骨密度(Ward’s、Neck、Troch、L2-4)、血清骨钙素(BGP)、尿脱氧吡啶啉(DPD)、肾小球滤过率(TGFR)、血β2-MG、尿β2-MG等项目的检查,并将结果输入计算机,进行t检验及r直线相关等统计学处理。结果 患组血BGP(7．041±5．743ng／ml)、尿DPD(6．058±2．245nM／nMCr)、Ward’s三角部位骨密度(0．838±0．223g／cm^2)与对照组相比(分别为3．354±0．765ng／ml、4．596±1．621nM／nMCr、0.936±0．076g／cm^2)经t检验具有显差异性(P<0．05或P<0．01);而Neck、Troch、L2-4部位骨密度、血清Ca、P、Mg、AKP、BUN、Cr等项检查,患组与对照组无明显差异(P>0．05);患组Ward’s三有部位骨密度与TGFR、血β2-MG、尿β2-MG具有明显相关性(r系数分别为0．567、-0．500、-0．334,P<0.05)。结论 慢性肾盂肾炎患,即使没有发展到慢性肾功能不全阶段,也已存在骨代谢异常,应及早采取措施,避免骨质疏松的发生。     

Bone metabolism in cholestatic children before and after living-related liver transplantation--a long-term prospective study

Bone disorders are common in children with end-stage liver diseases, especially those associated with cholestasis. Abnormal hepatocyte function, disordered vitamin D metabolism and calcium-phosphorous homeostasis, malnutrition, and immunosuppressive treatment are potential risk factors of bone tissue pathology before and after transplantation. The aim of the study was to analyze the long-term effect of successful living-related liver transplantation (LRLTx) on skeletal status and bone metabolism in cholestatic children. Eighteen cholestatic children (1.4±0.5yr old; 12 females [F]/6 males [M]) qualified for LRLTx were analyzed; 16 (5F/11M) of them participated in long-term observation (V4). Serum levels of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), cross-linked telopeptide of type 1 collagen (CTx), insulin-like growth factor I (IGF-I), IGF-I binding protein 3 (IGFBP-3), parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were assayed before (V0) and 6mo (V1), 12mo (V2), 18mo (V3), and 4.4yr (V4) after LRLTx. Total body bone mineral content (TBBMC) and total body bone mineral density (TBBMD) were measured by dual-energy X-ray absorptiometry (DXA) at the same pattern. Before LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 levels as well as TBBMC and TBBMD were decreased compared with age-matched control group. The mean serum levels of 25(OH)D and 1,25(OH)(2)D were within reference ranges from V0 to V4. After LRLTx, the OC, P1NP, CTx, IGF-I, and IGFBP-3 as well as TBBMC and TBBMD reached the age-matched reference values. At V4, the level of P1NP decreased below and the PTH increased above the reference range that coincided with reduced Z-scores of both TBBMC (-1.11±1.24) and TBBMD (-1.00±1.19). P1NP and CTx, both measured at V3, correlated with IGF-I at V2 (R=0.86, p=0.014 and R=0.78, p=0.021, respectively) and PTH at V3 for P1NP and V1 for CTx (R=0.64, p=0.048 and R=0.54, p=0.038, respectively). The TBBMC changes between V0 and V4 correlated with IGF-I (R=0.68, p=0.015) and 1,25(OH)(2)D (R=0.54, p=0.025), both assayed at V1. The change of TBBMC Z-scores between V0 and V4 correlated with P1NP at V1 (R=0.69, p=0.002). The TBBMD changes between V0 and V4 correlated with CTx at V1 (R=0.54, p=0.027) and P1NP change between V0 and V1 (R=0.51, p=0.038). In short-term observation, successful LRLTx led to bone metabolism normalization triggered by probable anabolic action of IGF-I and PTH and manifested by TBBMC and TBBMD increases. In long-term horizon, moderately impaired DXA assessed bone status coincided with disturbances in bone metabolism. Bone metabolism markers, especially P1NP and CTx, appeared to be good predictors of changes in bone status evaluated by DXA.     

Bone mass and metabolism in thalassemic children and adolescents treated with different iron-chelating drugs

We evaluated bone mineral density (BMD) and bone turnover in 22 homozygous prepubertal beta-thalassemic patients treated with desferrioxamine. Ten patients underwent treatment with desferrioxamine for the whole study period, while 12 patients stopped desferrioxamine and were then treated with deferiprone (L1). Lumbar and femoral BMD and bone metabolism markers were examined at baseline and after 1 and 3 years of follow up. All patients were prepubertal at baseline and they all became pubertal over the 3 years of follow up. At baseline, the mean lumbar Z score value was –2.048 SD ± 0.75; the Z score was less than –2 SD in 13 children, within –1 and –2 SD in 6, and within 0 and –1 SD in only 3 subjects. A significant BMD increase (P 0.0001) was observed at both the lumbar (+8.466%/year) and the femoral level (average of +3.46%/year at neck and +5.83%/year at the intertrochanteric region) after 3 years, without any significant difference being shown between patients treated with desferrioxamine and those treated with L1. The mean Z score SD values increased to –1.957 ± 0.975 at 1 year (not significantly different from baseline) and to –1.864 ± 1.221 at 3 year follow up (P 0.05 vs baseline); an increase in bone turnover was also observed. These findings show that low BMD, a hallmark of beta-thalassemia, improves significantly when puberty begins; this increase involves different skeletal sites, regardless of pharmacological treatment with different iron-chelating drugs.