Teriparatide Followed by Denosumab in Premenopausal Idiopathic Osteoporosis: Bone Microstructure and Strength by HR-pQCT.
BONE MICROSTRUCTURE
BONE STRENGTH
DENOSUMAB
PREMENOPAUSAL OSTEOPOROSIS
TERIPARATIDE
Journal
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISSN: 1523-4681
Titre abrégé: J Bone Miner Res
Pays: United States
ID NLM: 8610640
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
revised:
17
10
2022
received:
06
07
2022
accepted:
03
11
2022
pubmed:
7
11
2022
medline:
10
1
2023
entrez:
6
11
2022
Statut:
ppublish
Résumé
Premenopausal women with idiopathic osteoporosis (PreMenIOP) have marked deficits in skeletal microstructure. We have reported that sequential treatment with teriparatide and denosumab improves central skeletal bone mineral density (BMD) by dual-energy X-ray absorptiometry and central QCT in PreMenIOP. We conducted preplanned analyses of high-resolution peripheral quantitative computed tomography (HR-pQCT) scans from teriparatide and denosumab extension studies to measure effects on volumetric BMD (vBMD), microarchitecture, and estimated strength at the distal radius and tibia. Of 41 women enrolled in the parent teriparatide study (20 mcg daily), 34 enrolled in the HR-pQCT study. HR-pQCT participants initially received teriparatide (N = 24) or placebo (N = 10) for 6 months; all then received teriparatide for 24 months. After teriparatide, 26 enrolled in the phase 2B denosumab extension (60 mg q6M) for 24 months. Primary outcomes were percentage change in vBMD, microstructure, and stiffness after teriparatide and after denosumab. Changes after sequential teriparatide and denosumab were secondary outcomes. After teriparatide, significant improvements were seen in tibial trabecular number (3.3%, p = 0.01), cortical area and thickness (both 2.7%, p < 0.001), and radial trabecular microarchitecture (number: 6.8%, thickness: 2.2%, separation: -5.1%, all p < 0.02). Despite increases in cortical porosity and decreases in cortical density, whole-bone stiffness and failure load increased at both sites. After denosumab, increases in total (3.5%, p < 0.001 and 3.3%, p = 0.02) and cortical vBMD (1.7% and 3.2%; both p < 0.01), and failure load (1.1% and 3.6%; both p < 0.05) were seen at tibia and radius, respectively. Trabecular density (3.5%, p < 0.001) and number (2.4%, p = 0.03) increased at the tibia, while thickness (3.0%, p = 0.02) increased at the radius. After 48 months of sequential treatment, significant increases in total vBMD (tibia: p < 0.001; radius: p = 0.01), trabecular microstructure (p < 0.05), cortical thickness (tibia: p < 0.001; radius: p = 0.02), and whole bone strength (p < 0.02) were seen at both sites. Significant increases in total vBMD and bone strength parameters after sequential treatment with teriparatide followed by denosumab support the use of this regimen in PreMenIOP. © 2022 American Society for Bone and Mineral Research (ASBMR).
Substances chimiques
Denosumab
4EQZ6YO2HI
Teriparatide
10T9CSU89I
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, U.S. Gov't, P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
35-47Subventions
Organisme : FDA HHS
ID : R01 FD003902
Pays : United States
Organisme : FDA HHS
ID : R01 FD005114
Pays : United States
Organisme : NIAMS NIH HHS
ID : K24 AR052665
Pays : United States
Informations de copyright
© 2022 American Society for Bone and Mineral Research (ASBMR).
Références
Cohen A, Liu XS, Stein EM, et al. Bone microarchitecture and stiffness in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab. 2009;94(11):4351-4360.
Cohen A, Recker RR, Lappe J, et al. Premenopausal women with idiopathic low-trauma fractures and/or low bone mineral density. Osteoporos Int. 2012;23(1):171-182.
Cohen A, Dempster DW, Recker RR, et al. Abnormal bone microarchitecture and evidence of osteoblast dysfunction in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab. 2011;96(10):3095-3105.
Cohen A, Lang TF, McMahon DJ, et al. Central QCT reveals lower volumetric BMD and stiffness in premenopausal women with idiopathic osteoporosis, regardless of fracture history. J Clin Endocrinol Metab. 2012;97(11):4244-4252.
Liu XS, Cohen A, Shane E, et al. Individual trabeculae segmentation (ITS)-based morphological analysis of high-resolution peripheral quantitative computed tomography images detects abnormal trabecular plate and rod microarchitecture in premenopausal women with idiopathic osteoporosis. J Bone Miner Res. 2010;25(7):1496-1505.
Liu XS, Cohen A, Shane E, et al. Bone density, geometry, microstructure, and stiffness: relationships between peripheral and central skeletal sites assessed by DXA, HR-pQCT, and cQCT in premenopausal women. J Bone Miner Res. 2010;25(10):2229-2238.
Cohen A, Shiau S, Nair N, et al. Effect of teriparatide on bone remodeling and density in premenopausal idiopathic osteoporosis: a phase II trial. J Clin Endocrinol Metabol. 2020;105(10):e3540-e3556.
Shane E, Shiau S, Recker RR, et al. Denosumab after teriparatide in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metabol. 2021;107(4):e1528-e1540.
Agarwal S, Shane E, Lang T, et al. Spine volumetric BMD and strength in premenopausal idiopathic osteoporosis: effect of teriparatide followed by denosumab. J Clin Endocrinol Metabol. 2022;107(7):e2690-e2701.
Laib A, Häuselmann HJ, Rüegsegger P. In vivo high resolution 3D-QCT of the human forearm. Technol Health Care. 1998;6:329-337.
Nishiyama KK, Shane E. Clinical imaging of bone microarchitecture with HR-pQCT. Curr Osteoporos Rep. 2013;11(2):147-155.
Hildebrand T, Laib A, Müller R, Dequeker J, Rüegsegger P. Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus. J Bone Miner Res. 1999;14(7):1167-1174.
MacNeil JA, Boyd SK. Accuracy of high-resolution peripheral quantitative computed tomography for measurement of bone quality. Med Eng Phys. 2007;29(10):1096-1105.
Hansen S, Shanbhogue V, Folkestad L, Nielsen MMF, Brixen K. Bone microarchitecture and estimated strength in 499 adult Danish women and men: a cross-sectional, population-based high-resolution peripheral quantitative computed tomographic study on peak bone structure. Calcif Tissue Int. 2014;94(3):269-281.
Vico L, Zouch M, Amirouche A, et al. High-resolution pQCT analysis at the distal radius and tibia discriminates patients with recent wrist and femoral neck fractures. J Bone Miner Res. 2008;23(11):1741-1750.
Bacchetta J, Boutroy S, Vilayphiou N, et al. Early impairment of trabecular microarchitecture assessed with HR-pQCT in patients with stage II-IV chronic kidney disease. J Bone Miner Res. 2009;25(4):849-857.
Seeman E, Delmas PD, Hanley DA, et al. Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res. 2010;25(8):1886-1894.
Kawalilak C, Johnston J, Olszynski W, Kontulainen S. Characterizing microarchitectural changes at the distal radius and tibia in postmenopausal women using HR-pQCT. Osteoporos Int. 2014;25(8):2057-2066.
Liu XS, Zhang XH, Sekhon KK, et al. High-resolution peripheral quantitative computed tomography can assess microstructural and mechanical properties of human distal tibial bone. J Bone Miner Res. 2010;25(4):746-756.
Agarwal S, Rosete F, Zhang C, et al. In vivo assessment of bone structure and estimated bone strength by first- and second-generation HR-pQCT. Osteoporosis Int. 2016;27(10):2955-2966.
Nishiyama KK, Cohen A, Young P, et al. Teriparatide increases strength of the peripheral skeleton in premenopausal women with idiopathic osteoporosis: a pilot HR-pQCT study. J Clin Endocrinol Metab. 2014;99(7):2418-2425.
Sode M, Burghardt AJ, Pialat J-B, Link TM, Majumdar S. Quantitative characterization of subject motion in HR-pQCT images of the distal radius and tibia. Bone. 2011;48(6):1291-1297.
Buie HR, Campbell GM, Klinck RJ, MacNeil JA, Boyd SK. Automatic segmentation of cortical and trabecular compartments based on a dual threshold technique for in vivo micro-CT bone analysis. Bone. 2007;41(4):505-515.
Burghardt AJ, Buie HR, Laib A, Majumdar S, Boyd SK. Reproducibility of Direct Quantitative Measures of Cortical Bone Microarchitecture of the Distal Radius and Tibia by HR-pQCT. Bone. 2010;47(3):519-528.
Müller R, Rüegsegger P. Three-dimensional finite element modelling of non-invasively assessed trabecular bone structures. Med Eng Phys. 1995;17(2):126-133.
Van Rietbergen B, Weinans H, Huiskes R, Odgaard A. A new method to determine trabecular bone elastic properties and loading using micromechanical finite-element models. J Biomech. 1995;28(1):69-81.
MacNeil JA, Boyd SK. Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone. 2008;42(6):1203-1213.
Pistoia W, van Rietbergen B, Lochmüller E-M, Lill CA, Eckstein F, Rüegsegger P. Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images. Bone. 2002;30(6):842-848.
Macdonald HM, Nishiyama KK, Kang J, Hanley DA, Boyd SK. Age-related patterns of trabecular and cortical bone loss differ between sexes and skeletal sites: a population-based HR-pQCT study. J Bone Miner Res. 2011;26(1):50-62.
Boutroy S, Van Rietbergen B, Sornay-Rendu E, Munoz F, Bouxsein ML, Delmas PD. Finite element analysis based on in vivo HR-pQCT images of the distal radius is associated with wrist fracture in postmenopausal women. J Bone Miner Res. 2008;23(3):392-399.
Nishiyama KK, Macdonald HM, Buie HR, Hanley DA, Boyd SK. Postmenopausal women with osteopenia have higher cortical porosity and thinner cortices at the distal radius and tibia than women with normal aBMD: an in vivo HR-pQCT study. J Bone Miner Res. 2010;25(4):882-890.
Macdonald HM, Nishiyama KK, Hanley DA, Boyd SK. Changes in trabecular and cortical bone microarchitecture at peripheral sites associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis. Osteoporos Int. 2010;22(1):357-362.
Tsai J, Uihlein A, Burnett-Bowie S, et al. Effects of two years of teriparatide, denosumab, or both on bone microarchitecture and strength (DATA-HRpQCT study). J Clin Endocrinol Metabol. 2016;101(5):2023-2030.
Tsai JN, Uihlein AV, Burnett-Bowie SAM, et al. Comparative effects of teriparatide, denosumab, and combination therapy on peripheral compartmental bone density, microarchitecture, and estimated strength: the DATA-HRpQCT study. J Bone Miner Res. 2015;30(1):39-45.
Hansen S, Hauge EM, Jensen J-EB, Brixen K. Differing effects of PTH 1-34, PTH 1-84 and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis. An 18 month open-labeled observational study using HR-pQCT. J Bone Miner Res. 2013;28(4):736-745.
Chiba K, Okazaki N, Kurogi A, et al. Randomized controlled trial of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate in patients with postmenopausal osteoporosis: the TERABIT study. Bone. 2022;160:116416.
Paggiosi MA, Yang L, Blackwell D, et al. Teriparatide treatment exerts differential effects on the central and peripheral skeleton: results from the MOAT study. Osteoporos Int. 2018;29(6):1367-1378.
Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756-765.
Chavassieux P, Portero-Muzy N, Roux JP, et al. Reduction of cortical bone turnover and erosion depth after 2 and 3 years of denosumab: iliac bone histomorphometry in the FREEDOM trial. J Bone Miner Res. 2019;34(4):626-631.
Tsai JN, Nishiyama KK, Lin D, et al. Effects of denosumab and teriparatide transitions on bone microarchitecture and estimated strength: the DATA-switch HR-pQCT study. J Bone Miner Res. 2017;32(10):2001-2009.
Liu D, Manske SL, Kontulainen SA, et al. Tibial geometry is associated with failure load ex vivo: a MRI, pQCT and DXA study. Osteoporos Int. 2007;18(7):991-997.
Liu XS, Sajda P, Saha PK, et al. Complete volumetric decomposition of individual trabecular plates and rods and its morphological correlations with anisotropic elastic moduli in human trabecular bone. J Bone Min Res. 2008;23(2):223-235.
Liu XS, Shane E, McMahon DJ, Guo XE. Individual trabecula segmentation (ITS)-based morphological analysis of microscale images of human tibial trabecular bone at limited spatial resolution. J Bone Miner Res. 2011;26(9):2184-2193.
Liu XS, Stein EM, Zhou B, et al. Individual trabecula segmentation (ITS)-based morphological analyses and microfinite element analysis of HR-pQCT images discriminate postmenopausal fragility fractures independent of DXA measurements. J Bone Miner Res. 2012;27(2):263-272.
Garita B, Maligro J, Sadoughi S, et al. Microstructural abnormalities are evident by histology but not HR-pQCT at the periosteal cortex of the human tibia under CVD and T2D conditions. Med Novel Technol Dev. 2021;10:100062.
Hirano T, Burr DB, Turner CH, Sato M, Cain RL, Hock JM. Anabolic effects of human biosynthetic parathyroid hormone fragment (1-34), LY333334, on remodeling and mechanical properties of cortical bone in rabbits. J Bone Miner Res. 1999;14(4):536-545.
Burr DB, Hirano T, Turner CH, Hotchkiss C, Brommage R, Hock JM. Intermittently administered human parathyroid hormone(1-34) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgus monkeys. J Bone Miner Res. 2001;16(1):157-165.
Minisola S, Cipriani C, Grotta GD, et al. Update on the safety and efficacy of teriparatide in the treatment of osteoporosis. Ther Adv Musculoskeletal Dis. 2019;11:1759720X19877994.
Burghardt AJ, Kazakia GJ, Ramachandran S, Link TM, Majumdar S. Age- and gender-related differences in the geometric properties and biomechanical significance of intracortical porosity in the distal radius and tibia. J Bone Miner Res. 2010;25(5):983-993.
Paschalis EP, Glass EV, Donley DW, Eriksen EF. Bone mineral and collagen quality in iliac crest biopsies of patients given teriparatide: new results from the fracture prevention trial. J Clin Endocrinol Metabol. 2005;90(8):4644-4649.
Garnero P, Bauer DC, Mareau E, et al. Effects of PTH and alendronate on type I collagen isomerization in postmenopausal women with osteoporosis: the PaTH study. J Bone Miner Res. 2008;23(9):1442-1448.
Ramchand SK, David NL, Lee H, et al. Effects of combination Denosumab and high-dose teriparatide administration on bone microarchitecture and estimated strength: the DATA-HD HR-pQCT study. J Bone Miner Res. 2021;36(1):41-51.