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Predictors of bone loss in childhood hematologic malignancies: a prospective study

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Abstract

Summary

Twenty-nine children with malignancies and age, gender-matched controls were prospectively studied over 14 months. Patients had higher parathyroid hormone (PTH) levels and fat mass, lower bone mass, and bone mass increments at follow-up than controls. Lean mass, age at diagnosis, systemic and intrathecal therapy were predictors of bone mass changes on adjusted analyses.

Introduction

Children with hematologic malignances have low bone mass. We prospectively investigated anthropometric, clinical, and hormonal predictors of changes in bone mass in children receiving cancer therapy.

Methods

Twenty-nine children, mean age of 9 ± 2.9 years and 32 age and gender-matched controls, were studied. Seven had completed their course 40 ± 22 weeks prior, while 22 were still receiving therapy for 80 ± 28 weeks. Age at diagnosis, calcium intake, exercise activity, systemic corticosteroids in dexamethasone (Dex) dose, and methotrexate (MTX), and intrathecal MTX therapy received within follow-up period were assessed. Routine chemistries, PTH, 25-hydroxy vitamin D (25-OHD), bone remodeling markers, bone mass, and body composition were measured at baseline and 14 months.

Results

Patients had lower exercise activity, sun exposure, and bone markers levels than controls. They had higher PTH levels and fat mass, lower bone mass at the spine, hip, and total body, and lower increments at these sites on follow-up. Predictors of bone mass changes on univariate analyses were: age at diagnosis (R = −0.50 to −0.44, p < 0.05), Dex–MTX doses (R = −0.58 to −0.41, p < 0.05), intrathecal therapy (p < 0.03),% changes in lean mass (R = 0.37 to 0.54, p < 0.04), 25-OHD levels (R = 0.39, p < 0.03), and PTH levels (R = −0.47 to −0.41, p < 0.05). Lean mass, age at diagnosis, systemic and intrathecal therapy were predictors of bone mass changes on adjusted analyses.

Conclusion

This study provides insight into the pathophysiology of bone loss in children receiving cancer therapy and possible interventions to optimize their skeletal health.

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Abbreviations

MTX:

Methotrexate

CS:

Corticosteroids

Dex:

Dexamethasone

S-Ca:

Serum calcium

S-P:

Serum phosphorus

S-Mg:

Serum magnesium

S-Cr:

Serum creatinine

TSP:

Total serum protein

PTH:

Parathyroid hormone

25-OHD:

25-hydroxy vitamin D

ALKP:

Alkaline phosphatase

S-Osteocalcin:

Serum osteocalcin

S-Crosslaps:

Serum crosslaps

BMD:

Bone mineral density

BMC:

Bone mineral content

BMAD:

Bone mineral adjusted density

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Acknowledgments

We would like to thank the children and their parents for study participation and acknowledge Ms Randa Shahine for assistance in study progress, Ms Samia Mroueh for BMD analyses, and Ms Carmen Hajj-Chahine for the hormonal assays. This study was supported by an investigator-initiated grant funded by Novartis Pharmaceuticals.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Calcium Metabolism and Osteoporosis Program, Division of Endocrinology, Department of Internal Medicine, American University of Beirut Medical Center, PO BOX: 11–0236, Riad El Solh, 1107 2020, Beirut, Lebanon

    Ghada El-Hajj Fuleihan, A. Arabi, L. E.-O. Daouk, T. Ghalayini & J. Chaiban

  2. Children Cancer Center, Department of Pediatrics, American University of Beirut Medical Center, Beirut, Lebanon

    S. Muwakkit & M. Abboud

Authors
  1. Ghada El-Hajj Fuleihan
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  2. S. Muwakkit
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  3. A. Arabi
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  4. L. E.-O. Daouk
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  5. T. Ghalayini
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  6. J. Chaiban
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  7. M. Abboud
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Corresponding author

Correspondence to Ghada El-Hajj Fuleihan.

Appendix I

Appendix I

Hormonal assays

Serum 25-OHD was measured by a competitive protein-binding assay, RIA (radioimmunoassay) with inter- and intra-assay CV (coefficient of variation) between 5% and 8.2% for values between 15.6 and 60.5 ng/ml (IDS, Immuno-Diagnostic Systems, Boldon, UK), 1,25-(OH)2D by RIA with inter- and intra-assay CV between 9.3% and 13.6% for values between 8.6 and 56.8 pg/ml, serum PTH with ELSA-PTH, IRMA (immunoradiometric assay) with inter-and intra-assay CV <7% for values between 6 and 887 pg/ml (CIS Bio International, Gif-sur-Yvette, France), serum C-TX by ECLIA (electrochemiluminescence immunoassay) (Elecsys) with inter- and intra-assay CV between 1% and 5.5% for values between 140 and 359 pg/ml (Roche Diagnostics), serum OC by IRMA (immunoradiometric assay) (CIS Bio International, Gif-Sur-Yvette, France), with inter- and intra-assay CV between 1.2% and 5.2% for values between 20.4 and 220 ng/ml, TSH by ECLIA (Elecsys) with inter- and intra-assay CV between 4.3% and 5.3% for values between 0.2 and 7.9 μU/ml, FT4 by ECLIA (Elecsys) with inter- and intra-assay CV between 2.77% and 4.08% for values between 1 and 3.2 ng/dl, testosterone by RIA (CIS Bio International, Gif-Sur-Yvette, France), with inter- and intra-assay CV between 3.8% and 7.5% for values between 46 and 763 ng/dl, estradiol by IRMA with inter- and intra-assay CV between 3.5% and 4.9% for values between 347 and 2,609 pg/ml (CIS Bio International, Gif-Sur-Yvette, France), IGF1 by IRMA with inter-and intra-assay CV between 3.2% and 5.9% at values between 39.1 and 509 ng/ml (CIS Bio International, Gif-Sur-Yvette, France).

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El-Hajj Fuleihan, G., Muwakkit, S., Arabi, A. et al. Predictors of bone loss in childhood hematologic malignancies: a prospective study. Osteoporos Int 23, 665–674 (2012). https://doi.org/10.1007/s00198-011-1605-2

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  • DOI: https://doi.org/10.1007/s00198-011-1605-2

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