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Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome

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Abstract

Summary

Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point.

Introduction

Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome.

Methods

VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry.

Results

Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3–17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2–15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), −0.5 ± 1.1; p = 0.001) and at 3 months (−0.6 ± 1.1; p < 0.001), but not at 6 months (−0.3 ± 1.3; p = 0.066) or 12 months (−0.3 ± 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup (N = 16; 25 %) had LS BMD Z-scores that were ≤−1.0 at 12 months. In these children, each additional 1,000 mg/m2 of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, −0.71 to −0.07; p = 0.017).

Conclusions

The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤−1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.

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Abbreviations

BMD:

Bone mineral density

CI:

Confidence interval

GFR:

Glomerular filtration rate

GC:

Glucucorticoid

IQR:

Interquartile range

LS:

Lumbar spine

NS:

Nephrotic syndrome

SD:

Standard deviation

VF:

Vertebral fracture

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Acknowledgments

This study was primarily funded by an operating grant from the Canadian Institutes for Health Research (FRN 64285). Additional funding for this work has been provided to Dr. Leanne Ward by the Canadian Institutes for Health Research New Investigator Program, the Canadian Child Health Clinician Scientist Career Enhancement Program, a University of Ottawa Research Chair Award and the CHEO Departments of Pediatrics and Surgery. This work was also supported by the Children's Hospital of Eastern Ontario Research Institute and the University of Alberta Women and Children's Health Research Institute.

The Canadian STOPP Consortium would like to thank the following individuals: The children and their families who participated in the study and without whom the STOPP study would not have been possible. Research Associates who managed the study at the co-ordinating center (the Children's Hospital of Eastern Ontario Ottawa, Ontario): Elizabeth Sykes (STOPP Project Manager), Maya Scharke (STOPP Data Analyst and Database Manager), Monica Tomiak (Statistical Analyses), Victor Konji (STOPP Publications and Presentations Committee Liaison and hand morphometry measurements), Steve Anderson (Children's Hospital of Eastern Ontario Pediatric Bone Health Program Research Manager), Catherine Riddell (STOPP National Study Monitor); Research Associates who took care of the patients from the following institutions: Alberta Children's Hospital, Calgary, Alberta: Eileen Pyra; British Columbia Children's Hospital, Vancouver British Columbia: Terry Viczko, Sandy Hwang, Angelyne Sarmiento; Children's Hospital of Eastern Ontario, Ottawa, Ontario: Heather Cosgrove, Josie MacLennan, Catherine Riddell; Children's Hospital, London Health Sciences Centre, London, Ontario: Leila MacBean, Mala Ramu; McMaster Children's Hospital, Hamilton, Ontario: Susan Docherty-Skippen; IWK Health Center, Halifax, Nova Scotia: Aleasha Warner; Montréal Children's Hospital, Montréal, Québec: Diane Laforte, Maritza Laprise, Ste. Justine Hospital, Montréal, Québec: Claude Belleville, Natacha Gaulin Marion; Stollery Children's Hospital, Edmonton, Alberta: Ronda Blasco, Amanda Mullins, Toronto Hospital for Sick Children, Toronto, Ontario: Michele Petrovic; Winnipeg Children's Hospital, Winnipeg, Manitoba: Dan Catte, Erika Bloomfield. The Research Nurses, Support Staff and all the STOPP collaborators from the various Divisions of Nephrology, Oncology, Rheumatology and Radiology who have contributed to the care of the children enrolled in the study.

Funding

Primary funding source: The Canadian Institutes of Health Research Operating Grants Program (FRN 64285). Additional Funding Sources: The Canadian Child Health Clinician Scientist Program; The Canadian Institutes for Health Research New Investigator Program; The Children's Hospital of Eastern Ontario Research Institute, University of Ottawa; The Women and Children's Health Research Institute, University of Alberta

Conflicts of interest

Dr. Leanne M. Ward has been a consultant to Novartis Pharmaceuticals Corporation, Merck Sharpe & Dohme Corp. and Amgen Inc. in the last 2 years. All other authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Université de Montréal, Montréal, QC, Canada

    V. Phan & N. Alos

  2. University of Manitoba, Winnipeg, MB, Canada

    T. Blydt-Hansen & S. Taback

  3. Children’s Hospital of Eastern Ontario, University of Ottawa, 401 Smyth Rd, Ottawa, ON, K1H 8L1, Canada

    J. Feber, J. Ma, M. Matzinger, N. Shenouda, K. Williams & L. M. Ward

  4. McMaster University, Hamilton, ON, Canada

    S. Arora & S. Atkinson

  5. McGill University, Montréal, QC, Canada

    L. Bell, C. Rodd & F. Rauch

  6. University of Western Ontario, London, ON, Canada

    C. Clarson, G. Filler, J. Grimmer & R. Stein

  7. University of Alberta, Edmonton, AB, Canada

    R. Couch, M. Pinsk & K. Siminoski

  8. Dalhousie University, Halifax, NS, Canada

    E. A. Cummings

  9. University of Toronto, Toronto, ON, Canada

    R. M. Grant & D. Hebert

  10. University of British Columbia, Vancouver, BC, Canada

    B. Lentle

  11. University of Calgary, Calgary, AB, Canada

    J. Midgley & D. Stephure

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  1. V. Phan
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  2. T. Blydt-Hansen
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  3. J. Feber
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  6. S. Atkinson
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  7. L. Bell
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the Canadian STOPP Consortium

Corresponding author

Correspondence to L. M. Ward.

Additional information

The Canadian STeroid-associated Osteoporosis in the Pediatric Population (STOPP) Consortium (a pan-Canadian, pediatric bone health working group)

#Principal investigator; *Executive Committee Member; §Publications and Presentations Committee Member

Coordinating center

Children's Hospital of Eastern Ontario, Ottawa, Ontario: Leanne M. Ward#*§ (Study Principal Investigator), Janusz Feber*§ (Nephrology), Jacqueline Halton*§ (Oncology), Roman Jurencak (Rheumatology), MaryAnn Matzinger (Radiology, Central Radiograph Analyses), Johannes Roth (Rheumatology), Nazih Shenouda§ (Radiology, Central Radiograph Analyses)

Ottawa Hospital Research Institute, Ottawa Methods Centre Ottawa, Ontario: David Moher*§ (Research Methods), Tim Ramsay (Statistical Analyses)

Participating centers

Alberta Children's Hospital, Calgary, Alberta: David Stephure (Site Principal Investigator), Reinhard Kloiber (Radiology), Victor Lewis (Oncology), Julian Midgley (Nephrology), Paivi Miettunen (Rheumatology)

British Columbia Children's Hospital, Vancouver, British Columbia: David Cabral* (Site Principal Investigator), David B. Dix (Oncology), Kristin Houghton (Rheumatology), Helen R. Nadel (Radiology)

British Columbia Women's and Children's Hospital and Health Sciences Center, Vancouver, British Columbia: Brian C. Lentle§ (Radiology)

Brock University, Faculty of Applied Health Sciences, St. Catharines, Ontario: John Hay§ (Physical Activity Measurements)

Children's Hospital, London Health Sciences Centre, University of Western Ontario, London, Ontario: Robert Stein (Site Principal Investigator), Elizabeth Cairney (Oncology), Cheril Clarson (Bone Health), Guido Filler (Nephrology) §, Joanne Grimmer (Nephrology), Keith Sparrow (Radiology)

IWK Health Center, Halifax, Nova Scotia: Elizabeth Cummings (Site Principal Investigator), Conrad Fernandez (Oncology), Adam M. Huber§ (Rheumatology), Bianca Lang*§ (Rheumatology), Kathy O'Brien (Radiology)

McMaster Children's Hospital, Hamilton, Ontario: Stephanie Atkinson*§ (Site Principal Investigator), Steve Arora (Nephrology), Ronald Barr§ (Oncology), Craig Coblentz (Radiology), Peter B. Dent (Rheumatology), Maggie Larche (Rheumatology), Colin Webber* (Radiology),

Montréal Children's Hospital, Montréal, Québec: Celia Rodd§ (Site Principal Investigator), Sharon Abish (Oncology), Lorraine Bell (Nephrology), Rosie Scuccimarri (Rheumatology)

Shriners Hospital for Children, Montréal, Québec: Frank Rauch*§ (Co-Chair, Publications and Presentations Committee and Ancillary Studies Committee), Francis Glorieux*

Ste. Justine Hospital, Montréal, Québec: Nathalie Alos* (Site Principal Investigator), Josée Dubois (Radiology), Caroline Laverdière (Oncology), Véronique Phan (Nephrology), Claire Saint-Cyr (Rheumatology)

Stollery Children's Hospital, Edmonton, Alberta: Robert Couch* (Site Principal Investigator), Janet Ellsworth (Rheumatology), Claire LeBlanc (Rheumatology), Maury Pinsk (Nephrology), Kerry Siminoski§ (Radiology), Beverly Wilson (Oncology)

Toronto Hospital for Sick Children, Toronto, Ontario: Ronald Grant* (Site Principal Investigator), Martin Charron (Radiology), Diane Hebert (Nephrology)

Université de Sherbrooke, Department of family medicine, Sherbrooke, Québec: Isabelle Gaboury*§ (Biostatistics)

Winnipeg Children's Hospital, Winnipeg, Manitoba: Shayne Taback§ (Site Principal Investigator), Tom Blydt-Hansen (Nephrology), Sara Israels (Oncology), Kiem Oen (Rheumatology), Martin Reed (Radiology)

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Phan, V., Blydt-Hansen, T., Feber, J. et al. Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome. Osteoporos Int 25, 627–637 (2014). https://doi.org/10.1007/s00198-013-2466-7

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