The prevention and treatment of glucocorticoid-induced osteopaenia in juvenile rheumatic disease: A randomised double-blind controlled trial

British Society for Paediatric and Adolescent Rheumatology UK

Research output: Contribution to journalArticle

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Abstract

Background Children and young people (CYP) with chronic rheumatic conditions; Juvenile Idiopathic Arthritis, Juvenile Systemic Lupus Erythematosus, Juvenile Dermatomyositis and Juvenile Vasculitis, treated with steroids, have low bone density, increased fracture risk and are likely to have suboptimal peak bone mass. There is currently no evidence base for the management of steroid-induced bone loss in children with rheumatic diseases. Methods We undertook a multi-centre double dummy double-blind randomised placebo controlled trial to investigate whether the bisphosphonate risedronate was superior to alfacalcidol or calcium and vitamin D supplementation in the prevention and treatment of steroid-induced osteopaenia in these children. Patients were stratified and randomised in a 1:1 ratio, into: placebo; alfacalcidol; risedronate. The primary outcome was the change in lumbar spine bone mineral density z score (LSaBMDz) measured by dual energy x-ray absorptiometry at one year. Secondary outcome was fracture rate. Results Two hundred and seventeen patients were recruited to the study. Seventy seven placebo, 71 alfacalcidol, and 69 risedronate. Highly statistically significant differences were observed in the change in LSaBMDz between the placebo and risedronate groups; 0.274, 95% CI (0.061, 0.487) (p < 0.001) and between the risedronate and the alfacalcidol groups; 0.326 95% CI (0.109, 0.543) (p < 0.001). The difference observed between the alfacalcidol and placebo group was not statistically significant. Highly statistically significant differences were seen in the change in Total Body Less Head aBMD-Z Score between the placebo and risedronate groups (p < 0.01) but not between the alfacalcidol and risedronate groups. No significant differences in fracture frequency, adverse or serious adverse reactions were observed between the groups. Conclusions Children and adolescents receiving steroids for rheumatic diseases benefit from prophylactic treatment with bisphosphonates to increase LSaBMD. Alfacalcidol is ineffective.
Original languageEnglish
Pages (from-to)79-87
Number of pages9
JournalEClinicalMedicine - published by THE LANCET
Volume12
DOIs
Publication statusPublished - 01 Jul 2019

Fingerprint

Rheumatic Diseases
Glucocorticoids
Placebos
Steroids
Diphosphonates
Bone Density
Therapeutics
Bone and Bones
Juvenile Arthritis
Vasculitis
Risedronate Sodium
alfacalcidol
Vitamin D
Systemic Lupus Erythematosus
Spine
Randomized Controlled Trials
Head
X-Rays
Calcium

Keywords

  • Bisphosphonates
  • Clinical trial
  • Juvenile idiopathic arthritis
  • Osteoporosis
  • Steroids

Cite this

@article{258699b107434ae6a5fca5216c607b3e,
title = "The prevention and treatment of glucocorticoid-induced osteopaenia in juvenile rheumatic disease: A randomised double-blind controlled trial",
abstract = "Background Children and young people (CYP) with chronic rheumatic conditions; Juvenile Idiopathic Arthritis, Juvenile Systemic Lupus Erythematosus, Juvenile Dermatomyositis and Juvenile Vasculitis, treated with steroids, have low bone density, increased fracture risk and are likely to have suboptimal peak bone mass. There is currently no evidence base for the management of steroid-induced bone loss in children with rheumatic diseases. Methods We undertook a multi-centre double dummy double-blind randomised placebo controlled trial to investigate whether the bisphosphonate risedronate was superior to alfacalcidol or calcium and vitamin D supplementation in the prevention and treatment of steroid-induced osteopaenia in these children. Patients were stratified and randomised in a 1:1 ratio, into: placebo; alfacalcidol; risedronate. The primary outcome was the change in lumbar spine bone mineral density z score (LSaBMDz) measured by dual energy x-ray absorptiometry at one year. Secondary outcome was fracture rate. Results Two hundred and seventeen patients were recruited to the study. Seventy seven placebo, 71 alfacalcidol, and 69 risedronate. Highly statistically significant differences were observed in the change in LSaBMDz between the placebo and risedronate groups; 0.274, 95{\%} CI (0.061, 0.487) (p < 0.001) and between the risedronate and the alfacalcidol groups; 0.326 95{\%} CI (0.109, 0.543) (p < 0.001). The difference observed between the alfacalcidol and placebo group was not statistically significant. Highly statistically significant differences were seen in the change in Total Body Less Head aBMD-Z Score between the placebo and risedronate groups (p < 0.01) but not between the alfacalcidol and risedronate groups. No significant differences in fracture frequency, adverse or serious adverse reactions were observed between the groups. Conclusions Children and adolescents receiving steroids for rheumatic diseases benefit from prophylactic treatment with bisphosphonates to increase LSaBMD. Alfacalcidol is ineffective.",
keywords = "Bisphosphonates, Clinical trial, Juvenile idiopathic arthritis, Osteoporosis, Steroids",
author = "{British Society for Paediatric and Adolescent Rheumatology UK} and Madeleine Rooney and Nick Bishop and J. Davidson and Beresford, {Michael W.} and Clarissa Pilkington and Donagh, {Janet Mc} and Sue Wyatt and J. Gardner-Medwin and Rangaraj Satyapal and Jacqui Clinch and H. Foster and Mark Elliott and Rejina Verghis",
year = "2019",
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The prevention and treatment of glucocorticoid-induced osteopaenia in juvenile rheumatic disease: A randomised double-blind controlled trial. / British Society for Paediatric and Adolescent Rheumatology UK.

In: EClinicalMedicine - published by THE LANCET, Vol. 12, 01.07.2019, p. 79-87.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The prevention and treatment of glucocorticoid-induced osteopaenia in juvenile rheumatic disease: A randomised double-blind controlled trial

AU - British Society for Paediatric and Adolescent Rheumatology UK

AU - Rooney, Madeleine

AU - Bishop, Nick

AU - Davidson, J.

AU - Beresford, Michael W.

AU - Pilkington, Clarissa

AU - Donagh, Janet Mc

AU - Wyatt, Sue

AU - Gardner-Medwin, J.

AU - Satyapal, Rangaraj

AU - Clinch, Jacqui

AU - Foster, H.

AU - Elliott, Mark

AU - Verghis, Rejina

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Background Children and young people (CYP) with chronic rheumatic conditions; Juvenile Idiopathic Arthritis, Juvenile Systemic Lupus Erythematosus, Juvenile Dermatomyositis and Juvenile Vasculitis, treated with steroids, have low bone density, increased fracture risk and are likely to have suboptimal peak bone mass. There is currently no evidence base for the management of steroid-induced bone loss in children with rheumatic diseases. Methods We undertook a multi-centre double dummy double-blind randomised placebo controlled trial to investigate whether the bisphosphonate risedronate was superior to alfacalcidol or calcium and vitamin D supplementation in the prevention and treatment of steroid-induced osteopaenia in these children. Patients were stratified and randomised in a 1:1 ratio, into: placebo; alfacalcidol; risedronate. The primary outcome was the change in lumbar spine bone mineral density z score (LSaBMDz) measured by dual energy x-ray absorptiometry at one year. Secondary outcome was fracture rate. Results Two hundred and seventeen patients were recruited to the study. Seventy seven placebo, 71 alfacalcidol, and 69 risedronate. Highly statistically significant differences were observed in the change in LSaBMDz between the placebo and risedronate groups; 0.274, 95% CI (0.061, 0.487) (p < 0.001) and between the risedronate and the alfacalcidol groups; 0.326 95% CI (0.109, 0.543) (p < 0.001). The difference observed between the alfacalcidol and placebo group was not statistically significant. Highly statistically significant differences were seen in the change in Total Body Less Head aBMD-Z Score between the placebo and risedronate groups (p < 0.01) but not between the alfacalcidol and risedronate groups. No significant differences in fracture frequency, adverse or serious adverse reactions were observed between the groups. Conclusions Children and adolescents receiving steroids for rheumatic diseases benefit from prophylactic treatment with bisphosphonates to increase LSaBMD. Alfacalcidol is ineffective.

AB - Background Children and young people (CYP) with chronic rheumatic conditions; Juvenile Idiopathic Arthritis, Juvenile Systemic Lupus Erythematosus, Juvenile Dermatomyositis and Juvenile Vasculitis, treated with steroids, have low bone density, increased fracture risk and are likely to have suboptimal peak bone mass. There is currently no evidence base for the management of steroid-induced bone loss in children with rheumatic diseases. Methods We undertook a multi-centre double dummy double-blind randomised placebo controlled trial to investigate whether the bisphosphonate risedronate was superior to alfacalcidol or calcium and vitamin D supplementation in the prevention and treatment of steroid-induced osteopaenia in these children. Patients were stratified and randomised in a 1:1 ratio, into: placebo; alfacalcidol; risedronate. The primary outcome was the change in lumbar spine bone mineral density z score (LSaBMDz) measured by dual energy x-ray absorptiometry at one year. Secondary outcome was fracture rate. Results Two hundred and seventeen patients were recruited to the study. Seventy seven placebo, 71 alfacalcidol, and 69 risedronate. Highly statistically significant differences were observed in the change in LSaBMDz between the placebo and risedronate groups; 0.274, 95% CI (0.061, 0.487) (p < 0.001) and between the risedronate and the alfacalcidol groups; 0.326 95% CI (0.109, 0.543) (p < 0.001). The difference observed between the alfacalcidol and placebo group was not statistically significant. Highly statistically significant differences were seen in the change in Total Body Less Head aBMD-Z Score between the placebo and risedronate groups (p < 0.01) but not between the alfacalcidol and risedronate groups. No significant differences in fracture frequency, adverse or serious adverse reactions were observed between the groups. Conclusions Children and adolescents receiving steroids for rheumatic diseases benefit from prophylactic treatment with bisphosphonates to increase LSaBMD. Alfacalcidol is ineffective.

KW - Bisphosphonates

KW - Clinical trial

KW - Juvenile idiopathic arthritis

KW - Osteoporosis

KW - Steroids

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U2 - 10.1016/j.eclinm.2019.06.004

DO - 10.1016/j.eclinm.2019.06.004

M3 - Article

AN - SCOPUS:85068261750

VL - 12

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EP - 87

JO - EClinicalMedicine - published by THE LANCET

JF - EClinicalMedicine - published by THE LANCET

SN - 2589-5370

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