Teriparatide followed by denosumab in premenopausal idiopathic osteoporosis: bone microstructure and strength by HR-pQCT

wbldb

Agarwal, Sanchita¹; Shiau, Stephanie²; Kamanda-Kosseh, Mafo¹; Bucovsky, Mariana¹; Kil, Nayoung¹; Lappe, Joan M.³; Stubby, Julie³; Recker, Robert R.³; Guo, X. Edward⁴; Shane, Elizabeth¹; Cohen, Adi¹

Teriparatide followed by denosumab in premenopausal idiopathic osteoporosis: bone microstructure and strength by HR-pQCT

J Bone Miner Res. January 2023;38(1):35-47

©2022 American Society for Bone and Mineral Research (ASBMR)

Affiliations

¹Department of Medicine, Columbia University Vagelos College of Physicians & Surgeons, New York, NY, USA

²Department of Biostatistics & Epidemiology, Rutgers School of Public Health, Piscataway, NY, USA

³Department of Medicine, Creighton University Medical Center, Omaha, NE, USA

⁴Bone Bioengineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY, USA
Abstract and keywords

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.

Keywords: PREMENOPAUSAL OSTEOPOROSIS; TERIPARATIDE; DENOSUMAB; BONE MICROSTRUCTURE; BONE STRENGTH
Links

DOI: 10.1002/jbmr.4739

PubMed: 36335582

WoS: 000890724000001
History

Received: 2022-07-06

Revised: 2022-10-17

Accepted: 2022-11-03

Cited Works (31)

Year	Entry
2010	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. May 2010;25(5):983-993.
2007	MacNeil JA, Boyd SK. Accuracy of high-resolution peripheral quantitative computed tomography for measurement of bone quality. Med Eng Phys. December 2007;29(10):1096-1105.
2008	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. June 2008;42(6):1203-1213.
2021	Ramchand SK, David NL, Lee H, Bruce M, Bouxsein ML, Leder BZ, Tsai JN. 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. January 2021;36(1):41-51.
2002	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. June 2002;30(6):842-848.
2017	Tsai JN, Nishiyama KK, Lin D, Yuan A, Lee H, Bouxsein ML, Leder BZ. Effects of denosumab and teriparatide transitions on bone microarchitecture and estimated strength: the DATA-Switch HR-pQCT study. J Bone Miner Res. October 2017;32(10):2001-2009.
2010	Seeman E, Delmas PD, Hanley DA, Sellmeyer D, Cheung AM, Shane E, Kearns A, Thomas T, Boyd SK, Boutroy S, Bogado C, Majumdar S, Fan M, Libanati C, Zanchetta J. Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res. August 2010;25(8):1886-1894.
2008	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. March 2008;23(3):392-399.
1998	Laib A, Häuselmann HJ, Rüegsegger P. In vivo high resolution 3D-QCT of the human forearm. Technol Health Care. 1998;6(5-6):329-337.
2013	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. April 2013;28(4):736-745.
2008	Vico L, Zouch M, Amirouche A, Frère D, Laroche N, Koller B, Laib A, Thomas T, Alexandre C. High‐resolution pQCT analysis at the distal radius and tibia discriminates patients with recent wrist and femoral neck fractures. J Bone Miner Res. November 2008;23(11):1741-1750.
2015	Tsai JN, Uihlein AV, Burnett-Bowie S-AM, Neer RM, Zhu Y, Derrico N, Lee H, Bouxsein ML, Leder BZ. 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. January 2015;30(1):39-45.
2010	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. September 2010;47(3):519-528.
2013	Nishiyama KK, Shane E. Clinical imaging of bone microarchitecture with HR-pQCT. Curr Osteoporos Rep. June 2013;11(2):147-155.
2009	Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. NEJM. August 20, 2009;361(8):756-765.
2010	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. April 2010;25(4):882-890.
2011	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 HT‐pQCT study. J Bone Miner Res. January 2011;26(1):50-62.
2014	Kawalilak CE, Johnston JD, Olszynski WP, Kontulainen SA. Characterizing microarchitectural changes at the distal radius and tibia in postmenopausal women using HR-pQCT. Osteoporos Int. August 2014;25(8):2057-2066.
2008	Liu XS, Sajda P, Saha PK, Wehrli FW, Bevill G, Keaveny TM, Guo XE. Complete volumetric decomposition of individual trabecular plates and rods and its morphological correlations with anisotropic elastic moduli in human trabecular bone. J Bone Miner Res. February 2008;23(2):223-235.
2012	Liu XS, Stein EM, Zhou B, Zhang CA, Nickolas TL, Cohen A, Thomas V, McMahon DJ, Cosman F, Nieves J, Shane E, Guo XE. 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. February 2012;27(2):263-272.
2022	Chiba K, Okazaki N, Kurogi A, Watanabe T, Mori A, Suzuki N, Adachi K, Era M, Yokota K, Inoue T, Yabe Y, Furukawa K, Kondo C, Tsuda K, Ota S, Isobe Y, Miyazaki S, Morimoto S, Sato S, Nakashima S, Tashiro S, Yonekura A, Tomita M, Osaki M. Randomized controlled trial of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate in patients with postmenopausal osteoporosis: the TERABIT study. Bone. July 2022;160:116416.
2014	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 Tiss Int. March 2014;94(3):269-281.
1999	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. July 1999;14(7):1167-1174.
2007	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. October 2007;41(4):505-515.
1995	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. January 1995;28(1):69-81.
1999	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. April 1999;14(4):536-545.
2001	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. January 2001;16(1):157-165.
2010	Liu XS, Cohen A, Shane E, Stein E, Rogers H, Kokolus SL, Yin PT, McMahon DJ, Lappe JM, Recker RR, Guo XE. 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. July 2010;25(7):1496-1505.
2011	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. June 1, 2011;48(6):1291-1297.
2010	Liu XS, Zhang XH, Sekhon KK, Adams MF, McMahon DJ, Bilezikian JP, Shane E, Guo XE. High-resolution peripheral quantitative computed tomography can assess microstructural and mechanical properties of human distal tibial bone. J Bone Miner Res. April 2010;25(4):746-756.
2010	Liu XS, Cohen A, Shane E, Yin PT, Stein EM, Rogers H, Kokolus SL, McMahon DJ, Lappe JM, Recker RR, Lang T, Guo XE. 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. October 2010;25(10):2229-2238.

Cited By (1)

Year	Entry
2023	Cooper DML, Harrison KD, Hiebert BD, King GA, Panahifar A, Zhu N, Swekla KJ, Pivonka P, Chapman LD, Arnason T. Daily administration of parathyroid hormone slows the progression of basic multicellular units in the cortical bone of the rabbit distal tibia. Bone. November 2023;176:116864.