Differential effects of abaloparatide and teriparatide on hip cortical volumetric BMD by DXA-based 3D modeling

Winzenrieth, R.; Ominsky, M. S.; Wang, Y.; Humbert, L.; Weiss, R. J.

Affiliations

¹Galgo Medical, Carrer de París, 179 2°, Barcelona 08036, Spain

²Radius Health, Inc., 950 Winter Street, Waltham, MA 02451, USA

Abstract and keywords

Summary: In postmenopausal osteoporotic women in ACTIVE, abaloparatide reduced fracture risk and increased areal bone mineral density (BMD) more than teriparatide at the hip and wrist. DXA-based 3D modeling showed significantly greater increases in hip cortical volumetric BMD with abaloparatide versus teriparatide. This may explain differences reported in aBMD by DXA.

Introduction: In ACTIVE, abaloparatide (ABL) increased bone mineral density (BMD) shown by dual-energy X-ray absorptiometry (DXA) while reducing fracture incidence in postmenopausal osteoporotic women. Changes in DXA BMD with ABL, 80 μg, were significantly greater than with open-label teriparatide (TPTD), 20 μg, at cortical sites including total hip, femoral neck, and 1/3 distal radius. The purpose of this study was to better understand the relative effects of ABL and TPTD on cortical and cancellous compartments in the proximal femur.

Methods: Hip DXA images from a subset of randomly selected patients in the ACTIVE trial (n = 250/arm) were retrospectively analyzed using three-dimensional modeling methods (3D-SHAPER software) to evaluate changes from baseline at months 6 and 18.

Results: Similar significant increases in trabecular volumetric BMD (vBMD, + 9%) and cortical thickness (+ 1.5%) were observed with ABL and TPTD by 3D-DXA at 18 months. In contrast, only ABL significantly increased cortical vBMD versus baseline (+ 1.3%), and changes in both cortical vBMD and cortical surface BMD were significantly greater with ABL versus TPTD. In the TPTD group, changes in cortical vBMD were inversely correlated with changes in serum CTX (carboxy-terminal telopeptide of type I collagen) and PINP (procollagen type I N-terminal propeptide), suggesting that higher bone turnover may have attenuated cortical gains.

Conclusion: These results suggest previously reported differences in areal BMD increases between ABL and TPTD may be due to differential effects on cortical vBMD. Further studies are warranted to investigate how these differences affect therapeutic impact on hip strength in postmenopausal women with osteoporosis.

Keywords: Abaloparatide; Cortical volumetric BMD; Dual-energy X-ray absorptiometry; Osteoporosis; Teriparatide; 3D modeling

Links

DOI: 10.1007/s00198-020-05806-1

PubMed: 33496831

WoS: 000611917200002

History

Received: 2020-09-22

Accepted: 2020-12-17

Online: 2021-01-26

Cited Works (9)

Year	Entry
2017	Humbert L, Martelli Y, Fonollà R, Steghöfer M, Di Gregorio S, Malouf J, Romera J, del Río Barquero LM. 3D-DXA: assessing the femoral shape, the trabecular macrostructure and the cortex in 3D from DXA images. IEEE Trans Med Imaging. January 2017;36(1):27-39.
2005	Mayhew PM, Thomas CD, Clement JG, Loveridge N, Beck TJ, Bonfield W, Burgoyne CJ, Reeve J. Relation between age, femoral neck cortical stability, and hip fracture risk. Lancet. July 9, 2005;366(9480):129-135.
2010	Zebaze RMD, Ghasem-Zadeh A, Bohte A, Iuliano-Burns S, Mirams M, Price RI, Mackie EJ, Seeman E. Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet. May 15, 2010;375(9727):1729-1736.
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.
2003	Jiang Y, Zhao JJ, Mitlak BH, Wang O, Genant HK, Eriksen EF. Recombinant human parathyroid hormone (1–34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res. November 2003;18(11):1932-1941.
2003	Misof BM, Roschger P, Cosman F, Kurland ES, Tesch W, Messmer P, Dempster DW, Nieves J, Shane E, Fratzl P, Klaushofer K, Bilezikian J, Lindsay R. Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab. January 2003;88(3):1150-1156.
2016	Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, Alexandersen P, Zerbini CAF, Hu M-y, Harris AG, Fitzpatrick LA, Cosman F, Christiansen C; ACTIVE Study Investigators. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. August 16, 2016;316(7):722-733.
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.
2020	Watts NB, Hattersley G, Fitzpatrick LA, Wang Y, Williams GC, Miller PD, Cosman F. Correction to: Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis. Osteoporos Int. May 2020;31(5):1017-1018.

Cited By (2)

Year	Entry
2021	Beck B, Harding A, Weeks B, Humbert L, Winzenrieth R. Response to "Concerns regarding the use of 3D-DXA". Bone. August 2021;149:115936.
2021	Dempster DW, Zhou H, Rao SD, Recknor C, Miller PD, Leder BZ, Annett M, Ominsky MS, Mitlak BH. Early effects of abaloparatide on bone formation and resorption indices in postmenopausal women with osteoporosis. J Bone Miner Res. April 2021;36(4):644-653.