Post-transplant events Bone mineral density in children with ... - Nature

Bone Marrow Transplantation (2005) 36, 331–336 & 2005 Nature Publishing Group All rights reserved 0268-3369/05 $30.00

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Post-transplant events Bone mineral density in children with thalassaemia major: determining factors and effects of bone marrow transplantation TF Leung1, ECW Hung1, CWK Lam2, CK Li1, Y Chu1, KW Chik1, MMK Shing1, V Lee1 and PMP Yuen1 1 Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong; and 2Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong

Summary: Osteoporosis and osteopenia affect up to half of patients with thalassaemia major (TM). We investigate the effects of acquired factors and BMT on bone mineral density (BMD) in these patients. In all, 53 patients on regular transfusion (BT group) and 33 patients at 5.771.9 years post transplant (BMT group) were recruited. BMD was measured by dual energy X-ray absorptiometry. Serum concentrations of osteocalcin, bone-specific alkaline phosphatase (ALP), beta-crossLap and urinary cross-linking deoxypyridinoline (DPD) were measured by chemiluminescence and enzyme immunoassay, respectively. Severe BMD deficit (Z-score o2.5) at spine and hip were noted in 62 and 35% of BT group. Serum osteocalcin (b ¼ 0.463; P ¼ 0.006) was predictive of spine BMD, whereas age (b ¼ 0.843; P ¼ 0.007) and urine DPD (b ¼ 0.439; P ¼ 0.037) were associated with hip BMD in BT group. Among BMT patients, post transplant duration (b ¼ 0.450; P ¼ 0.009) and serum bone-specific ALP (b ¼ 0.495; P ¼ 0.013) were associated with spine BMD. Severe BMD deficit was less common among BMT than BT patients (6 vs 35%; P ¼ 0.036). The mean (s.d.) osteocalcin levels in BMT and BT groups were 96.4 (72.7) lg/l and 68.9 (40.3) lg/l, respectively (P ¼ 0.037). In conclusion, severe BMD deficit is common in Chinese TM patients and BMT may reverse BMD deficit in these patients. Bone Marrow Transplantation (2005) 36, 331–336. doi:10.1038/sj.bmt.1705053; published online 20 June 2005 Keywords: bone mineral density; thalassaemia major; biochemical marker; children

Osteoporosis and osteopenia are major long-term complications of thalassaemia major (TM). A number of studies have been performed using dual energy X-ray absorptiometry (DEXA) to measure bone mineral density (BMD) in

Correspondence: Dr TF Leung, Department of Paediatrics, 6/F, Prince of Wales Hospital, Shatin, Hong Kong. E-mail: [email protected] Received 18 November 2004; accepted 28 April 2005; published online 20 June 2005

patients with transfusion-dependent thalassaemia.1–5 The prevalence of reduced BMD varied, but Jensen et al1 reported that half of their 82 patients had severely low BMD whereas the other 45% had low bone mass. Angastiniotis et al5 showed that patients with thalassaemia intermedia were not spared, and 75% of them had BMD below 2 s.d. even with transfusion started only later in life. BMD correlates with the risk of fractures. DEXA is currently the most reliable and widely used method for measuring BMD, and this technique assesses bone mass classically at the lumbar spine and proximal femur.6,7 There are well-established normal standards for DEXA measurements for Caucasian and Chinese children.6–8 Both genetic and acquired factors may contribute to the reduction in BMD in TM patients. Concerning the genetic regulation, Sp1 polymorphism in the gene encoding type 1 collagen (major) protein (COLIA1) was found to be associated with the severity of osteopenia at spine and hip in male thalassaemic patients, and the same genetic factor also predicted treatment failure to bisphosphonate.3 Acquired factors contributing to skeletal morbidity include endocrinopathy, direct iron-induced toxicity, bone marrow expansion and the use of iron-chelating therapy.9–12 However, the effects of BMT, being the only curative treatment for TM, on BMD measurements have not been reported. We hypothesise that the diminished BMD seen in TM patients may improve when their disease is cured by BMT. The objectives of this study are to investigate BMD and biochemical markers of bone turnover in TM patients receiving regular blood transfusion (BT) in Hong Kong, to delineate the risk factors for the development of abnormal BMD, and to study the skeletal effects of BMT in these thalassaemic patients.

Patients and methods Patient assessment This study recruited all TM patients being managed (with and without BMT) in the paediatric department of a university teaching hospital in Hong Kong. The medical history and details on disease control were obtained from chart review. Specifically, disease-related factors such as pre- and post-BT haemoglobin levels and monthly volume

Bone complications in post-BMT thalassaemia TF Leung et al

332

of BT per kilogram body weight (average for 12 months before study), serum ferritin concentration (average within 6 months) and weekly desferrioxamine (DFO) dose, and time since BMT were recorded. Our centre had the policy to transplant all transfusion-dependent TM who had HLAidentical donors and regardless of their disease severity. The details on BMT outcome and occurrence of endocrine complications for the transplanted patients have been described previously.13,14 Briefly, BMT conditioning most commonly used included busulphan (16 mg/kg), cyclophosphamide (150–200 mg/kg) and antithymocyte globulin (90 mg/kg). GVHD prophylaxis consisted of methotrexate (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6 and 11) and cyclosporin A (1.5 mg/kg every 12-hourly from day 1). Patients in the BMT group were studied X2 years post transplant. All of them were free from any transfusion, medication or transplant-related complication for at least 1 year. None of these patients ever received calcium, vitamin D or bisphosphonate for the treatment or prevention of diminished bone density. Anthropometric factors such as age, sex, weight, height and body mass index were recorded. Pubertal staging of each patient was assessed by physical examination and hormonal profile. Detailed endocrine workup (growth hormone, diabetes mellitus and thyroid, adrenal and gonadal functions) was performed to investigate for any coexisting endocrinopathy if clinically indicated. Patients and their parents gave informed written consent, and the Clinical Research Ethics Committee of our University approved this study prior to its commencement.

As for the markers of bone resorption, serum betacrossLap levels were measured by chemiluminescence immunoassay (Roche Diagnostics, Indianapolis, IN, USA). The urine crosslinking deoxypyridinoline (DPD) levels were measured by sandwich enzyme-linked immunosorbent assay (Quidel, San Diego, CA, USA) and expressed as ratios to creatinine concentrations. The sensitivity of the kits for osteocalcin, bone-specific ALP, beta-crossLap and DPD were 0.5, 0.1, 0.01 mg/l and 1.1 nmol/l, respectively. The investigator responsible for biochemical investigations was unaware of the results for patient assessment, chart review or BMD measurement.

Statistical analysis Demographic, anthropometric and clinical variables were compared between BT and BMT groups by w2 or Fisher’s exact test for proportions and Student’s t-test or Mann– Whitney U test for numerical variables. Absolute BMD values and proportions of patients with severe or mild BMD deficits were analysed by the same methods. The correlations among various clinical and biochemical variables in TM patients and BMD measured at lumbar spine or hip were analysed using Pearson’s coefficients. Multivariate linear regression models were then used to delineate the factors independently associated with BMD values, adjusting for pubertal staging as covariate. All comparisons were made two-tailed, and statistical significance was set at 5%.

BMD measurement

Results

DEXA (Hologic model QDR 4500, Woltham, MA, USA) was used to measure BMD at the lumbar spines (L1–L4; anteroposterior view) and left femoral neck. A single investigator blinded to the clinical status of patients was responsible for all BMD measurements. The mean coefficients of variation for measuring BMD at spine and hip established in our laboratory were 0.47 and 0.94%. Concerning the definition of osteoporosis and osteopenia, the criteria adopted by the World Health Organization were applicable mainly to adults.15 As published data did not support the routine use of T-scores in the categorisation of BMD in children,16 the present study used the terms ‘mild BMD deficit’ (Z-score between 1 and 2.5) and ‘severe BMD deficit’ (Z-score o2.5) in place of osteopenia and osteoporosis. Our patients were classified as having BMD deficits only for those with available Z-scores for BMD as obtained by the limited reference values for BMD in Chinese children.8

Study population

Biochemical markers of bone turnover Paired blood and urine samples were obtained in the morning of DEXA for bone marker analysis. Markers of bone formation including serum osteocalcin and bonespecific alkaline phosphatase (ALP) levels were measured by chemiluminescence immunoassay (Roche Diagnostics, Indianapolis, IN, USA) and by mass concentration assay (Ostaset, Beckman Coulter, Fullerton, USA), respectively. Bone Marrow Transplantation

A total of 86 Chinese TM patients, with a mean (s.d.) age of 14.8 (5.9) years, were recruited. Table 1 summarises the clinical characteristics of 53 patients on regular BT and 33 post-BMT patients. All TM patients in our centre who had HLA-identical donors were transplanted before joining this study, and children in the BT group received 3–4-weekly transfusion as well as regular subcutaneous DFO treatment. Patients in the post transplant group were 5.771.9 years after BMT. Serum ferritin levels in the post-BMT group were significantly reduced by almost 5.5-fold (Po0.001) as compared to the BT group. None of the subjects in BMT or BT group suffered from bone fractures prior to this study.

BMD in BT-dependent thalassaemia Table 2 shows the BMD results for patients in the BT and BMT groups. Z-scores for BMD measurements were not available for 19 (36%) patients in the BT group and 11 (33%) patients in the BMT group. About 90% of TM patients receiving regular transfusion had mild BMD deficit, whereas BMD in 62 and 35% of them exceeded the values for severe BMD deficit at the spine and hip, respectively. The diagnosis of severe BMD deficit at either lumbar spine or left hip was not associated with gender (P ¼ 0.410 and 0.071), onset of puberty (P ¼ 0.096 and


333 Table 1 Clinical characteristics of patients in blood transfusion (BT) and post-BMT groups Characteristica

BT (n ¼ 53) BMT (n ¼ 33)

Age (year) Male gender, n (%) Weight (kg) Height (cm) Body mass index (kg/m2)

14.475.9 27 (51) 36.0711.0 139.2717.2 18.172.7

15.675.8 15 (45) 38.6712.5 145.7717.3 17.772.9

0.346 0.620 0.331 0.096 0.576

20 (38)

11 (33)

0.260

7 (13) 26 (49)

9 (27) 13 (39)

14 (26) 14 (26) 1 (2)

13 (39) 12 (36) 1 (3)

0.144 0.329 1.000

0 1 (2)

0 1 (3)

1.000 1.000

740173770

134871144

P-value

Table 3 Univariate analyses for factors associated with BMD measured at lumbar spine and left hip in transfusion-dependent TM patients Factor

Pubertal development Tanner stage 1 (pre-pubertal), n (%) Tanner stage 2 or 3, n (%) Tanner stage 4 or 5, n (%) Any endocrinopathy, n (%) Hypogonadism, n (%) Growth hormone deficiency, n (%) Hypothyroidism, n (%) Diabetes mellitus, n (%) Serum ferritin (pmol/l) a

o0.001

Spine BMD

Age Body weight Body height Body mass index Pre-transfusion haemoglobin Post-transfusion haemoglobin Transfusion requirementa Serum ferritin concentration Weekly DFO dose Serum bone-specific ALP Serum osteocalcin Serum beta-crossLap Urine DPD

Hip BMD

r

P

r

P

0.680 0.746 0.752 0.399 0.146 0.195 0.071 0.080 0.605 0.472 0.555 0.376 0.617

o0.001 o0.001 o0.001 0.003 0.297 0.162 0.613 0.569 o0.001 0.001 o0.001 0.007 o0.001

0.469 0.609 0.633 0.308 0.093 0.174 0.009 0.014 0.486 0.467 0.388 0.278 0.543

0.001 o0.001 o0.001 0.028 0.518 0.222 0.947 0.921 o0.001 0.001 0.006 0.056 o0.001

a

Expressed in terms of average transfusion volume per kilogram body weight per month.

Results expressed in mean7s.d. or number (percentage).

Table 4 Univariate analyses for factors associated with BMD measured at lumbar spine and left hip in the post-BMT patients Table 2 A comparison of absolute BMD and BMD scores in TM children with blood transfusion (BT) and BMT BMD resultsa

BT (n ¼ 53)

Absolute BMD values (g/cm2) Spine 0.63670.115 Hip 0.65370.121 Classify by BMD scoreb Spine BMD score o1 Spine BMD score o2.5 Hip BMD score o1 Hip BMD score o2.5

31/34 (91) 21/34 (62) 23/26 (88) 9/26 (35)

BMT (n ¼ 33)

Factor

P-value

0.68470.155 0.70670.149

0.102 0.092

19/22 (86) 8/22 (36) 7/16 (44) 1/16 (6)

0.117 0.063 0.004 0.036

a

Expressed in either mean7s.d. or number (percentage). The denominators under the BT and BMT groups denote the numbers of patients having Z-scores for BMD. The baseline characteristics of these selected patients with Z-scores were the same as those for the whole BT or BMT group.

Age Body weight Body height Body mass index Years after BMT Pre-transplant haemoglobin Serum ferritin concentration Serum bone-specific ALP Serum osteocalcin Serum beta-crossLap Urine DPD

Spine BMD

Hip BMD

r

P

r

P

0.464 0.778 0.716 0.541 0.526 0.260 0.113 0.393 0.120 0.287 0.639

0.007 o0.001 o0.001 0.001 0.002 0.151 0.530 0.047 0.559 0.155 0.001

0.255 0.726 0.624 0.539 0.507 0.284 0.038 0.143 0.023 0.187 0.535

0.153 o0.001 o0.001 0.001 0.003 0.115 0.832 0.486 0.912 0.361 0.006

b

1.000), pubertal staging (P ¼ 0.176 and 0.960), presence of gonadal failure (P ¼ 0.140 and 0.729) or any type of endocrinopathy (P ¼ 0.140 and 0.729).

Table 5 Multivariate linear regression analyses on clinical and laboratory factorsa associated with BMD at lumbar spine and hip for patients in both the BT and BMT groups

BT group

Factors affecting BMD in thalassaemic patients Tables 3 and 4 summarise the corresponding results for thalassaemic patients in the BT and BMT groups, respectively. In general, demographic data and biochemical bone markers were associated with BMD in the patients. Table 5 summarises the outcomes following multivariate linear regression for those single factors that appeared significant on univariate analyses. Among TM receiving regular BT, multivariate analyses adjusting for pubertal staging revealed that serum osteocalcin (b ¼ 0.463; P ¼ 0.006) was independently predictive of spine BMD, whereas age (b ¼ 0.843; P ¼ 0.007) and urine DPD (b ¼ 0.439; P ¼ 0.037) were associated with hip BMD.

Regression coefficient, b

Factor

Age Body weight Body height Body mass index Years after BMT Weekly DFO dose Serum bone-specific ALP Serum osteocalcin Serum beta-crossLap Urine DPD

BMT group

Spine BMD

Hip BMD

Spine BMD

Hip BMD

0.253 1.446 0.340 0.609 NA 0.077 0.151 0.463y 0.256 0.266

0.843y 0.557 0.439 0.252 NA 0.182 0.025 0.015 ND 0.439w

0.303 0.270 0.755 0.089 0.450y NA 0.495y ND ND 0.181

ND 1.234 0.486 0.365 0.281 NA ND ND ND 0.163

NA ¼ not applicable; ND ¼ not done. a Only included factors that were significantly associated with BMD on univariate analysis (see Tables 3 and 4); multivariate analyses adjusted for pubertal staging as covariate. wPo0.05; yPo0.01.

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The use of DFO, transfusion requirement and degree of iron overload as assessed by serum ferritin were not associated with absolute BMD in our patients. For postBMT patients, linear regression showed that post-BMT duration (b ¼ 0.450; P ¼ 0.009) and serum bone-specific ALP (b ¼ 0.495; P ¼ 0.013) were independently predictive of spine BMD. None of the factors was independently associated with hip BMD.

Effects of BMT on BMD measurements A subgroup of children who underwent BMT for TM were analysed separately and data were compared with the transfusion-dependent group without BMT. The BMD results in these two groups are summarised in Table 2. In general, BMD results were significantly better in the postBMT group. Only 44% of post-BMT children had mild BMD deficit as compared to 88% in the transfusion group (P ¼ 0.004) and 6 vs 35% were in the range of severe BMD deficit (P ¼ 0.036). For absolute BMD at the hip, the result was significant when subgroup analysis was performed in post-pubertal patients (P ¼ 0.044; Figure 1). Table 6 summarises the biochemical bone markers in these BT and BMT groups. Serum osteocalcin, being a marker of P = 0.044

1.1

Absolute BMD (g/cm2)

1.0 0.9 0.8 0.7 0.6 0.5 0.4 BT

BMT Patient group

Figure 1

Box plots of absolute BMD at lumber spine (white) and left hip (shaded) in post-pubertal thalassaemic patients on regular transfusion (BT; n ¼ 30) and following BMT (n ¼ 16).

Table 6 Serum and urine bone markers in TM patientsa on regular blood transfusion (BT) and following BMT Markers Serum bone-specific ALP (mg/l) Serum osteocalcin (mg/l) Serum beta-crossLap (mg/l) Urine DPD (nmol/mmol Cr)

BT (n ¼ 50) BMT (n ¼ 26) P-value 66.9740.4 68.9740.3 1.3970.67 20.2712.0

71.2742.6 96.4772.7 1.4970.85 17.478.5

0.675 0.037 0.602 0.242

ALP ¼ alkaline phosphatase; Cr ¼ creatinine. Results expressed as mean7s.d. a Morning blood and urine samples were not available in three BT and seven BMT patients. Bone Marrow Transplantation

bone formation, was significantly higher among patients who underwent BMT (P ¼ 0.037). The effects of time post transplant on BMD measurements were also studied. The mean (s.d.) ages of TM patients X6 years following BMT (n ¼ 13) and those transplanted for o6 years (n ¼ 20) were 16.7 (5.0) years and 14.9 (6.3) years (P ¼ 0.359). However, absolute BMD values were significantly higher in the former group at lumbar spine (mean (s.d.): 0.804 (0.134) vs 0.606 (0.114) g/cm2; P ¼ 0.0002) and left hip (mean (s.d.): 0.828 (0.120) vs 0.627 (0.108 g/cm2; Po0.0001). This effect of post-BMT duration on BMD measurements remained significant on linear regression when adjusted for pubertal staging, age and anthropometric parameters (P ¼ 0.013 for spine; P ¼ 0.012 for hip).

Discussion This cross-sectional study investigates the acquired factors determining BMD in a cohort of Chinese patients with TM. We confirm that severe BMD deficit (ie equivalent to osteoporosis in adults) is a common complication (62% at spine and 35% at hip). Among these patients, age and biochemical markers of bone turnover in serum and urine are useful indicators of absolute BMD. On the other hand, anthropometric variables, disease-related factors (eg transfusion requirement or extent of iron overload) or the dosage of DFO treatment were not independent factors that determine BMD. This study also investigates the possible benefits of BMT on BMD measurements in TM patients. This study shows for the first time that transplanted patients had lower prevalence of BMD deficits as compared to those on regular BT. The proportion of TM patients having subnormal BMD also decreases with increasing duration after BMT, and this may be related to increased bone formation as shown by the increase in serum osteocalcin levels in the BMT group. The proportion of our TM patients having BMD deficits, up to 62% at lumbar spines, is consistent with the literature.1–5 Bone problems may be present even in welltransfused and chelated patients. Various factors contribute to the development of osteoporosis. TM causes marrow expansion, changing the architecture of the bones especially in areas such as the axial skeleton. The treatment for TM, that is, regular BT to suppress ineffective haematopoiesis, leads to iron overload in internal organs such as the pituitary gland and the pancreas. Involvement of the pituitary gland may disrupt the growth hormone and the gonadotrophin/sex hormone axes. Deficient growth hormone secretion, growth hormone insensitivity and hypogonadotrophic hypogonadism have all been demonstrated in TM patients.17–19 As a result, bone growth and puberty may be delayed, thereby reducing BMD and the peak bone mass. In this study, 26% of TM patients on regular BT had endocrinopathy. In particular, growth hormone deficiency and diabetes mellitus were diagnosed only in 3% of patients, and none of them suffered from hypothyroidism (Table 1). These figures are much lower than the reported ones for Caucasian patients. One possible explanation is that our patients were relatively young at the time of


assessment (ie 23% were p10 years), and only a few of them suffer from severe endocrine dysfunctions. The use of iron-chelating therapy is another important factor for skeletal complications, and DFO has been shown to have a direct toxic effect on bone growth.11,12 Our study suggests the potential benefits of BMT in reversing the bone complications in TM. Although several studies reported the usefulness of bisphosphonates in treating bone complications for TM,20,21 there has not been any report on whether BMD in these patients would improve spontaneously after BMT. Our post transplant TM patients had a significantly lower rate of BMD deficits in their left hips. We also observed a trend towards improvement in BMD for the spine. Overall, there was a 5.8-fold reduction in severe BMD deficit among post-BMT patients. Patients who survived longer (eg X6 years) following BMT also had better BMD even when adjusted for their pubertal staging and anthropometry. In a separate study, our group has recently conducted follow-up BMD measurements in 12 post-BMT patients and 12 thalassaemics on regular BT about 18 months after the present cross-sectional evaluation. All subjects did not receive calcium, vitamin D or bisphosphonate between these evaluations. Among post-BMT patients, there were significant increases in BMD at spine (mean (s.d.): 0.695 (0.139) to 0.732 (0.130) g/cm2; P ¼ 0.001) and hip (0.725 (0.172) to 0.771 (0.180) g/cm2; P ¼ 0.001) during follow-up. On the other hand, we observed significant improvement in BMD only at spine (0.617 (0.108) to 0.655 (0.094) g/cm2; P ¼ 0.042) but not hip (P ¼ 0.203) among transfusiondependent TM patients (unpublished data). These preliminary findings support the view that BMT appears to be able to improve the acquisition of bone mass among TM patients. However, this follow-up period was still relatively short in detecting clinically significant changes in BMD. The exact reasons accounting for BMD improvement post transplant are unclear. The benefit of BMT on skeletal problem in TM may be related to the enhanced bone formation, as the mean osteocalcin level was significantly elevated by 40% in the post transplant group while there was no difference in the level of bone resorption between two groups. Other possible reasons include reduced marrow expansion and the discontinuation of iron-chelating agents. A reduction in the direct toxic effects resulting from iron accumulation may also be responsible, as serum ferritin levels were much lower among the post transplant patients. On the other hand, we reported recently that endocrine problems were very common among Chinese post transplant TM patients.14 The relative importance of these factors on BMD has to be determined. It would be important to conduct longitudinal study to follow changes in BMD and other bone markers before and serially after BMT to confirm the findings observed in the present crosssectional study. Results from the present study and from our unpublished follow-up study as described above suggest important treatment implication for bone problems in TM patients. Subnormal BMD is very common among transfusiondependent patients, and severe BMD deficit is present in at least one-third of the cases. From our unpublished data, we may not detect any serial improvement in BMD when these

335

children grow up. On the other hand, we expect to find significant BMD improvement among TM patients following BMT. These suggests that aggressive therapies to improve bone mass should be given to regularly transfused TM patients to try to prevent clinical events such as bone fractures in the long run, whereas a more conservative approach with close BMD monitoring may be adopted for post-BMT patients with mild-to-moderate BMD deficit. Randomised controlled trials with sufficiently long followup period are needed to validate this possible treatment algorithm. The main limitation of this study relates to its crosssectional design. TM patients on regular BT may differ in relation to factors such as anthropometry and different extent of pubertal development as compared to post-BMT cases. Although we did not serially monitor BMD among the same group of post-BMT patients from before transplant, our finding of a better BMD among TM patients who survived BMT longer (eg X6 years) supports a beneficial role of BMT on bone-related complications in TM. Prospective long-term cohort study comparing BMD between pre- and post-BMT patients is needed to definitely answer this research question. Another limitation is that Z-scores for BMD were not available for 19 (36%) patients in the BT group and 11 (33%) patients in the BMT group. The World Health Organization defines osteoporosis quantitatively as a measurement of BMD that is more than 2.5 s.d. below the mean peak value for young adults (ie by T-score), whereas osteopenia is classified as having a T-score for BMD between 1 and 2.5.15 However, it may be misleading to apply this criterion to diagnose osteoporosis and osteopenia in children.16 In that study, nearly 90% of children were erroneously diagnosed to have low BMD based on a DEXA scan. The most frequent error (62%) was the use of T-score (s.d. score compared with young adults) to diagnose osteoporosis, which is inappropriate for children. Z-score (s.d. score compared with age and sex-matched controls) should be used instead. Thus, this study adopted the terms ‘severe’ and ‘mild’ BMD deficits. As a result of this potential error, we classified TM patients as having BMD deficits only for those with available Z-scores. In conclusion, BMD deficits are common in Chinese patients with TM. Patients’ age and biochemical bone markers but not disease-related factors predict low BMD in these patients. Decreased BMD in TM patients may improve following BMT, and those transplanted for X6 years had higher absolute BMD values as compared to patients with shorter post-transplant duration.

Acknowledgements We thank Iris HS Chan and Chung Yi Li for their technical assistance in measuring biochemical bone markers.

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