Efficacy of pamidronate in children with low bone mineral density during and after chemotherapy for acute lymphoblastic leukemia and non-Hodgkin lymphoma

Jae Min Lee; Ji Eun Kim; Soon Hwan Bae; Jeong Ok Hah

doi:10.5045/br.2013.48.2.99

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Original Article

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Blood Res 2013; 48(2):

Published online June 25, 2013

https://doi.org/10.5045/br.2013.48.2.99

Efficacy of pamidronate in children with low bone mineral density during and after chemotherapy for acute lymphoblastic leukemia and non-Hodgkin lymphoma

Jae Min Lee, Ji Eun Kim, Soon Hwan Bae, and Jeong Ok Hah^*

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Department of Pediatrics, College of Medicine, Yeungnam University, Daegu, Korea.

Correspondence to : Correspondence to Jeong Ok Hah, M.D., Ph.D. Department of Pediatrics, Yeungnam University Hospital, 170, Hyeonchung-ro, Nam-gu, Daegu 705-703, Korea. Tel: +82-53-620-3531, Fax: +82-53-629-2252, johah@med.yu.ac.kr

Received: November 28, 2012; Revised: December 26, 2012; Accepted: May 17, 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Abstract

Background

Reduced bone mineral density (BMD) is a significant sequelae in children receiving chemotherapy for acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). Reduced BMD is associated with an increased risk for fractures. Pamidronate, a second-generation bisphosphonate, has been used to treat osteoporosis in children. This study evaluated the safety and efficacy of pamidronate in children with low BMD during and after chemotherapy for ALL and NHL.

Methods

Between April 2007 and October 2011, 24 children with ALL and NHL were treated with pamidronate. The indication was a decreased BMD Z-score less than -2.0 or bone pain with a BMD Z-score less than 0. Pamidronate was infused at 1 mg/kg/day for 3 days at 1-4 month intervals (pamidronate group, cases). The BMD Z-scores of the cases were compared with those of 10 untreated patients (control group). Lumbar spine BMDs were measured every 6 cycles using dual energy X-ray absorptiometry and Z-scores were calculated. Bone turnover parameters (25-hydroxyvitamin D, alkaline phosphatase, parathyroid hormone, osteocalcin, and type I collagen c-terminal telopeptide) were analyzed.

Results

The median cycle of pamidronate treatment was 12. Increases in BMD Z-scores were significantly higher in the pamidronate group than in the control group (P<0.001). BMD (mg/cm²) increased in all pamidronate-treated cases. Twenty patients who complained of bone pain reported pain relief after therapy. The treatment was well tolerated.

Conclusion

Pamidronate appears to be safe and effective for the treatment of children with low BMD during and after chemotherapy for ALL and NHL.

Keywords Pamidronate, Bone mineral density, Bisphosphonate, ALL, NHL, Corticosteroids

Article

Original Article

Blood Res 2013; 48(2): 99-106

Published online June 25, 2013 https://doi.org/10.5045/br.2013.48.2.99

Efficacy of pamidronate in children with low bone mineral density during and after chemotherapy for acute lymphoblastic leukemia and non-Hodgkin lymphoma

Jae Min Lee, Ji Eun Kim, Soon Hwan Bae, and Jeong Ok Hah^*

Department of Pediatrics, College of Medicine, Yeungnam University, Daegu, Korea.

Correspondence to:Correspondence to Jeong Ok Hah, M.D., Ph.D. Department of Pediatrics, Yeungnam University Hospital, 170, Hyeonchung-ro, Nam-gu, Daegu 705-703, Korea. Tel: +82-53-620-3531, Fax: +82-53-629-2252, johah@med.yu.ac.kr

Received: November 28, 2012; Revised: December 26, 2012; Accepted: May 17, 2013

Abstract

Background

Methods

Results

Conclusion

Pamidronate appears to be safe and effective for the treatment of children with low BMD during and after chemotherapy for ALL and NHL.

Keywords: Pamidronate, Bone mineral density, Bisphosphonate, ALL, NHL, Corticosteroids

Abstract

Fig 1.

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Figure 1.

(A) Changes in the bone mineral density (BMD) Z-scores. Graph shows the BMD Z-scores for each patient in the control and pamidronate groups at baseline and after follow-up. Eight of the 10 control group patients had decreased BMD Z-scores, and 22 of the 24 pamidronate group patients had increased BMD Z-scores. (B) Changes in BMD (mg/cm²). Graph shows the BMD for each patient in the control and pamidronate groups at baseline and after follow-up. The BMDs of all pamidronate group patients increased after pamidronate therapy; however, the BMDs of 8 control group patients (N=10) decreased.

Blood Research 2013; 48: 99-106https://doi.org/10.5045/br.2013.48.2.99

Fig 2.

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Figure 2.

(A) The monthly BMD Z-score increases in the control and pamidronate groups were -0.024±0.097 and +0.193±0.201, respectively (P<0.001). The median, 25^th and 75^th percentiles (box), and ranges of BMD changes (whiskers) are shown. (B) Changes in the BMD per month (mg/cm²/month) in the control and pamidronate groups were -0.29±4.31 and +11.92±6.98, respectively (P<0.001). The median, 25^th and 75^th percentiles (box), and ranges of the BMD changes (whiskers) are shown.

Blood Research 2013; 48: 99-106https://doi.org/10.5045/br.2013.48.2.99

Table 1 . Patient characteristics..

P values were calculated using the chi-square or Fisher's exact test..

Abbreviations: ALL, acute lymphoblastic leukemia; ABL, acute biphenotypic leukemia; NHL, non-Hodgkin lymphoma; DXA, dual energy X-ray absorptiometry; HSCT, hematopoietic stem cell transplantation; AON, aseptic osteonecrosis..

Table 2 . Pamidronate therapy outcomes..

Values are shown as the mean±SD..

Abbreviation: BMD, bone mineral density..

Table 3 . Factors that affect bone mineral density and pamidronate treatment outcomes..

Values are shown as the mean±SD..

Abbreviations: HSCT, hematopoietic stem cell transplantation; AON, aseptic osteonecrosis; ALL, acute lymphoblastic leukemia; ABL, acute biphenotypic leukemia; NHL, non-Hodgkin lymphoma..

Table 4 . Changes in biochemical values after pamidronate treatment..

Values are shown as the mean±SD..

Abbreviations: ALP, alkaline phosphatase; 25-OHD, 25-hydroxyvitamin D; PTH, parathyroid hormone; ICTP, type I collagen C-terminal telopeptide..