Effect of Denosumab Compared With Risedronate on Bone Strength in Patients Initiating or Continuing Glucocorticoid Treatment

Piet Geusens; Melissa S.A.M. Bevers; Bert van Rietbergen; Osvaldo D. Messina; Eric Lespessailles; Beatriz Oliveri; Roland Chapurlat; Klaus Engelke; Arkadi Chines; Shuang Huang; Kenneth G. Saag; Joop P. van den Bergh

doi:10.1002/jbmr.4551

Effect of Denosumab Compared With Risedronate on Bone Strength in Patients Initiating or Continuing Glucocorticoid Treatment

Piet Geusens (Corresponding author)
, Melissa S.A.M. Bevers
, Bert van Rietbergen
, Osvaldo D. Messina
, Eric Lespessailles
, Beatriz Oliveri
, Roland Chapurlat
, Klaus Engelke
, Arkadi Chines
, Shuang Huang
, Kenneth G. Saag
, Joop P. van den Bergh

Orthopaedic Biomechanics

Onderzoeksoutput: Bijdrage aan tijdschrift › Tijdschriftartikel › Academic › peer review

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In a randomized clinical trial in patients initiating glucocorticoid therapy (GC-I) or on long-term therapy (GC-C), denosumab every 6 months increased spine and hip bone mineral density at 12 and 24 months significantly more than daily risedronate. The aim of this study was to evaluate the effects of denosumab compared with risedronate on bone strength and microarchitecture measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in GC-I and GC-C. A subset of 110 patients had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia at baseline and at 12 and 24 months. Cortical and trabecular microarchitecture were assessed with standard analyses and failure load (FL) with micro-finite element analysis. At the radius at 24 months, FL remained unchanged with denosumab and significantly decreased with risedronate in GC-I (−4.1%, 95% confidence interval [CI] −6.4, −1.8) and, in GC-C, it significantly increased with denosumab (4.3%, 95% CI 2.1, 6.4) and remained unchanged with risedronate. Consequently, FL was significantly higher with denosumab than with risedronate in GC-I (5.6%, 95% CI 2.4, 8.7, p < 0.001) and in GC-C (4.1%, 95% CI 1.1, 7.2, p = 0.011). We also found significant differences between denosumab and risedronate in percentage changes in cortical and trabecular microarchitectural parameters in GC-I and GC-C. Similar results were found at the tibia. To conclude, this HR-pQCT study shows that denosumab is superior to risedronate in terms of preventing FL loss at the distal radius and tibia in GC-I and in increasing FL at the radius in GC-C, based on significant differences in changes in the cortical and trabecular bone compartments between treatment groups in GC-I and GC-C. These results suggest that denosumab could be a useful therapeutic option in patients initiating GC therapy or on long-term GC therapy and may contribute to treatment decisions in this patient population.

Originele taal-2	Engels
Pagina's (van-tot)	1136-1146
Aantal pagina's	11
Tijdschrift	Journal of Bone and Mineral Research
Volume	37
Nummer van het tijdschrift	6
Vroegere onlinedatum	26 mrt. 2022
DOI's	https://doi.org/10.1002/jbmr.4551
Status	Gepubliceerd - jun. 2022

Bibliografische nota

Financiering

PG reports grants from Amgen, grants and other from AbbVie, grants from Celgene, grants from Lilly, grants from Merck, grants from Pfizer, grants from Roche, grants from UCB, grants from Fresenius, grants from Mylan, and grants from Sandoz outside the submitted work. BR reports personal fees from Scanco Medical AG outside the submitted work. EL reports personal fees from Amgen; personal fees from Lilly; grants, personal fees, and non‐financial support from Celgene; personal fees from Expanscience; personal fees from AbbVie; personal fees from Sublimed; grants, personal fees, and non‐financial support from UCB; and grants, personal fees, and non‐financial support from MSD outside the submitted work. BO reports personal fees from Raffo, personal fees from Baliarda, personal fees from Shire, personal fees from Takeda, personal fees from Gador, personal fees from Amgen, and personal fees from Ultragenyx outside the submitted work. RC reports grants from Amgen during the conduct of the study; grants and personal fees from UCB; personal fees from Lilly; personal fees from BMS; personal fees from AbbVie; personal fees from Pfizer; grants and personal fees from Chugai; personal fees from Sanofi; personal fees from Novartis; and grants and other from Fresenius Kiabi outside the submitted work. AC is employed by Amgen and has equity in Amgen. SH is an employee of and has equity in Amgen. KGS reports grants from Amgen, Horizon Pharma, Swedish Orphan Biovitrum AB, Shanton Pharma Co. LTD, Dyve Bioscience, and LG Chem outside the submitted work. JPB reports grants from Amgen, grants from UCB, and grants from Lilly the outside the submitted work. All authors had full access to the data, and there were no restrictions regarding content to include in the manuscript.

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Geusens, P., Bevers, M. S. A. M., van Rietbergen, B., Messina, O. D., Lespessailles, E., Oliveri, B., Chapurlat, R., Engelke, K., Chines, A., Huang, S., Saag, K. G., & van den Bergh, J. P. (2022). Effect of Denosumab Compared With Risedronate on Bone Strength in Patients Initiating or Continuing Glucocorticoid Treatment. Journal of Bone and Mineral Research, 37(6), 1136-1146. https://doi.org/10.1002/jbmr.4551

@article{09a0a4b8871c4229978226bf7b4dd8f5,

title = "Effect of Denosumab Compared With Risedronate on Bone Strength in Patients Initiating or Continuing Glucocorticoid Treatment",

abstract = "In a randomized clinical trial in patients initiating glucocorticoid therapy (GC-I) or on long-term therapy (GC-C), denosumab every 6 months increased spine and hip bone mineral density at 12 and 24 months significantly more than daily risedronate. The aim of this study was to evaluate the effects of denosumab compared with risedronate on bone strength and microarchitecture measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in GC-I and GC-C. A subset of 110 patients had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia at baseline and at 12 and 24 months. Cortical and trabecular microarchitecture were assessed with standard analyses and failure load (FL) with micro-finite element analysis. At the radius at 24 months, FL remained unchanged with denosumab and significantly decreased with risedronate in GC-I (−4.1\%, 95\% confidence interval [CI] −6.4, −1.8) and, in GC-C, it significantly increased with denosumab (4.3\%, 95\% CI 2.1, 6.4) and remained unchanged with risedronate. Consequently, FL was significantly higher with denosumab than with risedronate in GC-I (5.6\%, 95\% CI 2.4, 8.7, p < 0.001) and in GC-C (4.1\%, 95\% CI 1.1, 7.2, p = 0.011). We also found significant differences between denosumab and risedronate in percentage changes in cortical and trabecular microarchitectural parameters in GC-I and GC-C. Similar results were found at the tibia. To conclude, this HR-pQCT study shows that denosumab is superior to risedronate in terms of preventing FL loss at the distal radius and tibia in GC-I and in increasing FL at the radius in GC-C, based on significant differences in changes in the cortical and trabecular bone compartments between treatment groups in GC-I and GC-C. These results suggest that denosumab could be a useful therapeutic option in patients initiating GC therapy or on long-term GC therapy and may contribute to treatment decisions in this patient population.",

keywords = "BONE STRENGTH, DENOSUMAB, GLUCOCORTICOID-INDUCED OSTEOPOROSIS, HIGH-RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY (HR-pQCT), RISEDRONATE, Bone and Bones, Radius, Bone Density, Humans, Glucocorticoids/adverse effects, Risedronic Acid/pharmacology, Denosumab/pharmacology, Tibia/diagnostic imaging",

author = "Piet Geusens and Bevers, \{Melissa S.A.M.\} and \{van Rietbergen\}, Bert and Messina, \{Osvaldo D.\} and Eric Lespessailles and Beatriz Oliveri and Roland Chapurlat and Klaus Engelke and Arkadi Chines and Shuang Huang and Saag, \{Kenneth G.\} and \{van den Bergh\}, \{Joop P.\}",

year = "2022",

month = jun,

doi = "10.1002/jbmr.4551",

language = "English",

volume = "37",

pages = "1136--1146",

journal = "Journal of Bone and Mineral Research",

issn = "0884-0431",

publisher = "Oxford University Press",

number = "6",

}

Geusens, P, Bevers, MSAM , van Rietbergen, B, Messina, OD, Lespessailles, E, Oliveri, B, Chapurlat, R, Engelke, K, Chines, A, Huang, S, Saag, KG & van den Bergh, JP 2022, 'Effect of Denosumab Compared With Risedronate on Bone Strength in Patients Initiating or Continuing Glucocorticoid Treatment', Journal of Bone and Mineral Research, vol. 37, nr. 6, blz. 1136-1146. https://doi.org/10.1002/jbmr.4551

Effect of Denosumab Compared With Risedronate on Bone Strength in Patients Initiating or Continuing Glucocorticoid Treatment. / Geusens, Piet (Corresponding author); Bevers, Melissa S.A.M.; van Rietbergen, Bert et al.
In: Journal of Bone and Mineral Research, Vol. 37, Nr. 6, 06.2022, blz. 1136-1146.

Onderzoeksoutput: Bijdrage aan tijdschrift › Tijdschriftartikel › Academic › peer review

TY - JOUR

T1 - Effect of Denosumab Compared With Risedronate on Bone Strength in Patients Initiating or Continuing Glucocorticoid Treatment

AU - Geusens, Piet

AU - Bevers, Melissa S.A.M.

AU - van Rietbergen, Bert

AU - Messina, Osvaldo D.

AU - Lespessailles, Eric

AU - Oliveri, Beatriz

AU - Chapurlat, Roland

AU - Engelke, Klaus

AU - Chines, Arkadi

AU - Huang, Shuang

AU - Saag, Kenneth G.

AU - van den Bergh, Joop P.

PY - 2022/6

Y1 - 2022/6

N2 - In a randomized clinical trial in patients initiating glucocorticoid therapy (GC-I) or on long-term therapy (GC-C), denosumab every 6 months increased spine and hip bone mineral density at 12 and 24 months significantly more than daily risedronate. The aim of this study was to evaluate the effects of denosumab compared with risedronate on bone strength and microarchitecture measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in GC-I and GC-C. A subset of 110 patients had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia at baseline and at 12 and 24 months. Cortical and trabecular microarchitecture were assessed with standard analyses and failure load (FL) with micro-finite element analysis. At the radius at 24 months, FL remained unchanged with denosumab and significantly decreased with risedronate in GC-I (−4.1%, 95% confidence interval [CI] −6.4, −1.8) and, in GC-C, it significantly increased with denosumab (4.3%, 95% CI 2.1, 6.4) and remained unchanged with risedronate. Consequently, FL was significantly higher with denosumab than with risedronate in GC-I (5.6%, 95% CI 2.4, 8.7, p < 0.001) and in GC-C (4.1%, 95% CI 1.1, 7.2, p = 0.011). We also found significant differences between denosumab and risedronate in percentage changes in cortical and trabecular microarchitectural parameters in GC-I and GC-C. Similar results were found at the tibia. To conclude, this HR-pQCT study shows that denosumab is superior to risedronate in terms of preventing FL loss at the distal radius and tibia in GC-I and in increasing FL at the radius in GC-C, based on significant differences in changes in the cortical and trabecular bone compartments between treatment groups in GC-I and GC-C. These results suggest that denosumab could be a useful therapeutic option in patients initiating GC therapy or on long-term GC therapy and may contribute to treatment decisions in this patient population.

AB - In a randomized clinical trial in patients initiating glucocorticoid therapy (GC-I) or on long-term therapy (GC-C), denosumab every 6 months increased spine and hip bone mineral density at 12 and 24 months significantly more than daily risedronate. The aim of this study was to evaluate the effects of denosumab compared with risedronate on bone strength and microarchitecture measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in GC-I and GC-C. A subset of 110 patients had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia at baseline and at 12 and 24 months. Cortical and trabecular microarchitecture were assessed with standard analyses and failure load (FL) with micro-finite element analysis. At the radius at 24 months, FL remained unchanged with denosumab and significantly decreased with risedronate in GC-I (−4.1%, 95% confidence interval [CI] −6.4, −1.8) and, in GC-C, it significantly increased with denosumab (4.3%, 95% CI 2.1, 6.4) and remained unchanged with risedronate. Consequently, FL was significantly higher with denosumab than with risedronate in GC-I (5.6%, 95% CI 2.4, 8.7, p < 0.001) and in GC-C (4.1%, 95% CI 1.1, 7.2, p = 0.011). We also found significant differences between denosumab and risedronate in percentage changes in cortical and trabecular microarchitectural parameters in GC-I and GC-C. Similar results were found at the tibia. To conclude, this HR-pQCT study shows that denosumab is superior to risedronate in terms of preventing FL loss at the distal radius and tibia in GC-I and in increasing FL at the radius in GC-C, based on significant differences in changes in the cortical and trabecular bone compartments between treatment groups in GC-I and GC-C. These results suggest that denosumab could be a useful therapeutic option in patients initiating GC therapy or on long-term GC therapy and may contribute to treatment decisions in this patient population.

KW - BONE STRENGTH

KW - DENOSUMAB

KW - GLUCOCORTICOID-INDUCED OSTEOPOROSIS

KW - HIGH-RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY (HR-pQCT)

KW - RISEDRONATE

KW - Bone and Bones

KW - Radius

KW - Bone Density

KW - Humans

KW - Glucocorticoids/adverse effects

KW - Risedronic Acid/pharmacology

KW - Denosumab/pharmacology

KW - Tibia/diagnostic imaging

UR - https://www.scopus.com/pages/publications/85129066577

U2 - 10.1002/jbmr.4551

DO - 10.1002/jbmr.4551

M3 - Article

C2 - 35340062

SN - 0884-0431

VL - 37

SP - 1136

EP - 1146

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

IS - 6

ER -

Effect of Denosumab Compared With Risedronate on Bone Strength in Patients Initiating or Continuing Glucocorticoid Treatment

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