Treatment of postmenopausal osteoporosis patients with teriparatide for 24 months reverts forming bone quality indices to premenopausal healthy control values

Paschalis, Eleftherios P.; Gamsjaeger, Sonja; Klaushofer, Klaus; Shane, Elizabeth; Cohen, Adi; Stepan, Jan; Pavo, Imre; Eriksen, Erik F.; Taylor, Kathleen A.; Dempster, David W.

Affiliations

¹Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria

²Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Cente, New York, NY, USA

³Early Onset Osteoporosis Center, Metabolic Bone Diseases Program, Division of Endocrinology, Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, NY, USA

⁴Institute of Rheumatology, Faculty of Medicine 1, Charles University, Prague, Czech Republic

⁵Eli Lilly and Company USA, LLC, Indianapolis, IN, USA

⁶Department of Endocrinology, Pilestredet Park Specialist Center, Oslo, Norway

⁷The Faculty of Dentistry, University of Oslo, Oslo, Norway

⁸Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, NY, USA

⁹Department of Pathology and Cell Biology, College of Physicians and Surgeons of Columbia University, New York, NY, USA

Abstract and keywords

Postmenopausal osteoporosis (PMOP) therapies are frequently evaluated by bone mineral density (BMD) gains against patients receiving placebo (calcium and vitamin D supplementation, a mild bone turnover-suppressing intervention), which is not equivalent to either healthy or treatment-naive PMOP.

The aim of the present observational study was to assess the effects of TPTD treatment in PMOP (20 μg, once daily) at 6 (TPTD 6m; n = 28, age 65 ± 7.3 years), and 24 (TPTD 24m; n = 32, age 67.4 ± 6.15 years) months on bone quality indices at actively forming trabecular surfaces (with fluorescent double labels). Data from the TPTD-treated PMOP patients were compared with those in healthy adult premenopausal women (HC; n = 62, age 40.5 ± 10.6 years), and PMOP receiving placebo (PMOP-PLC; n = 94, age 70.6 ± 4.5 years). Iliac crest biopsies were analyzed by Raman microspectroscopy at three distinct tissue ages: mid-distance between the second label and the bone surface, mid-distance between the two labels, and 1 μm behind the first label. Mineral to matrix ratio (MM), mineral maturity/crystallinity (MMC), tissue water (TW), glycosaminoglycan (GAGs), and pyridinoline (Pyd) content were determined. Outcomes were compared by ANCOVA with subject age and tissue age as covariates, and health status as a fixed factor, followed by Sidak's post-hoc testing (significance assigned to p < 0.05).

Both TPTD groups increased MM compared to PMOP-PLC. While TPTD 6m had values similar to HC, TPTD 24m had higher values compared to either HC or TPTD 6m. Both TPTD groups had lower MMC values compared to PMOP-PLC and similar to HC. TPTD 6m patients had higher TW content compared to HC, while TPTD 24m had values similar to HC and lower than either PMOP-PLC or TPTD 6m. Both TPTD groups had lower GAG content compared to HC group, while TPTD 6m had higher values compared to PMOP-PLC. Finally, TPTD 6m patients had higher Pyd content compared to HC and lower compared to PMOP-PLC, while TPTD 24m had lower values compared to PMOP-PLC and TPTD 6m, and similar to HC group.

The results of the present study indicate that effects of TPTD on forming trabecular bone quality indices depend on treatment duration. At the recommended length of 24 m, TPTD restores bone mineral and organic matrix quality indices (MMC, TW, Pyd content) to premenopausal healthy (HC) levels.

Keywords: Bone quality; Bone formation; Postmenopausal osteoporosis; Teriparatide; Human iliac crest biopsies; Raman spectroscopy

Links

DOI: 10.1016/j.bone.2022.116478

PubMed: 35779845

WoS: 000826578400001

History

Received: 2022-05-11

Revised: 2022-06-24

Accepted: 2022-06-27

Online: 2022-06-29

Cited Works (39)

Year	Entry
2010	Donnelly E, Chen DX, Boskey AL, Baker SP, van der Meulen MCH. Contribution of mineral to bone structural behavior and tissue mechanical properties. Calcif Tiss Int. November 2010;87(5):450-460.
2008	Recker RR, Delmas PD, Halse J, Reid IR, Boonen S, García-Hernandez PA, Supronik J, Lewiecki EM, Ochoa L, Miller P, Hu H, Mesenbrink P, Hartl F, Gasser J, Eriksen EF. Effects of intravenous zoledronic acid once yearly on bone remodeling and bone structure. J Bone Miner Res. January 2008;23(1):6-16.
2003	Paschalis EP, Boskey AL, Kassem M, Eriksen EF. Effect of hormone replacement therapy on bone quality in early postmenopausal women. J Bone Miner Res. June 2003;18(6):955-959.
2016	Boskey AL, Donnelly E, Boskey E, Spevak L, Ma Y, Zhang W, Lappe J, Recker RR. Examining the relationships between bone tissue composition, compositional heterogeneity, and fragility fracture: a matched case-controlled FTIRI study. J Bone Miner Res. May 2016;31(5):1070-1081.
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.
2021	Gamsjaeger S, Fratzl P, Paschalis EP. Interplay between mineral crystallinity and mineral accumulation in health and postmenopausal osteoporosis. Acta Biomater. April 2021;124:374.
2006	Nyman JS, Roy A, Shen X, Acuna RL, Tyler JH, Wang X. The influence of water removal on the strength and toughness of cortical bone. J Biomech. 2006;39(5):931-938.
2000	Jäger I, Fratzl P. Mineralized collagen fibrils: a mechanical model with a staggered arrangement of mineral particles. Biophys J. October 2000;79(4):1737-1746.
2006	Krishnan V, Bryant HU, MacDougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. May 2006;116(5):1202-1209.
2017	Paschalis EP, Gamsjaeger S, Klaushofer K. Vibrational spectroscopic techniques to assess bone quality. Osteoporos Int. August 2017;28(8):2275-2291.
2015	Wagermaier W, Klaushofer K, Fratzl P. Fragility of bone material controlled by internal interfaces. Calcif Tiss Int. September 2015;97(3):201-212.
2011	Paschalis EP, Tatakis DN, Robins S, Fratzl P, Manjubala I, Zoehrer R, Gamsjaeger S, Buchinger B, Roschger A, Phipps R, Boskey AL, Dall'Ara E, Varga P, Zysset P, Klaushofer K, Roschger P. Lathyrism-induced alterations in collagen cross-links influence the mechanical properties of bone material without affecting the mineral. Bone. December 2011;49(6):1232-1241.
1994	Fratzl P, Roschger P, Eschberger J, Abendroth B, Klaushofer K. Abnormal bone mineralization after fluoride treatment in osteoporosis: a small‐angle x‐ray‐scattering study. J Bone Miner Res. October 1994;9(10):1541-1549.
1992	Boskey AL, Pleshko N, Doty SB, Mendelsohn R. Applications of fourier transform infrared (FT-IR) microscopy to the study of mineralization in bone and cartilage. Cell Mater. 1992;2(3):209-220.
1974	Reilly DT, Burstein AH. The mechanical properties of cortical bone. J Bone Joint Surg. 1974;56A(5):1001-1022.
1996	Garnero P, Sornay‐Rendu E, Chapuy M, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res. 1996;11(3):337-349.
2001	Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster J-Y, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mellström D, Oefjord ES, Marcinowska-Suchowierska E, Salmi J, Mulder H, Halse J, Sawicki AZ, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. NEJM. May 10, 2001;344(19):1434-1441.
2016	Paschalis EP, Fratzl P, Gamsjaeger S, Hassler N, Brozek W, Eriksen EF, Rauch F, Glorieux FH, Shane E, Dempster D, Cohen A, Recker R, Klaushofer K. Aging versus postmenopausal osteoporosis: bone composition and maturation kinetics at actively-forming trabecular surfaces of female subjects aged 1 to 84 years. J Bone Miner Res. February 2016;31(2):347-357.
2004	Fratzl P, Gupta HS, Paschalis EP, Roschger P. Structure and mechanical quality of the collagen–mineral nano-composite in bone. J Mater Chem. 2004;14(14):2115-2123.
1996	Fratzl P, Schreiber S, Roschger P, Lafage M, Rodan G, Klaushofer K. Effects of sodium fluoride and alendronate on the bone mineral in minipigs: a small‐angle X‐ray scattering and backscattered electron imaging study. J Bone Miner Res. February 1996;11(2):248-253.
2005	Boskey AL, DiCarlo E, Paschalis E, West P, Mendelsohn R. Comparison of mineral quality and quantity in iliac crest biopsies from high- and low-turnover osteoporosis: an FT-IR microspectroscopic investigation. Osteoporos Int. December 2005;16(12):2031-2038.
2017	Hernandez CJ, van der Meulen MCH. Understanding bone strength is not enough. J Bone Miner Res. June 2017;32(6):1157-1162.
2009	Gourion‐Arsiquaud S, Faibish D, Myers E, Spevak L, Compston J, Hodsman A, Shane E, Recker RR, Boskey ER, Boskey AL. Use of FTIR spectroscopic imaging to identify parameters associated with fragility fracture. J Bone Miner Res. September 2009;24(9):1565-1571.
2001	Boskey AL. Bone mineralization. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:5-1–5-33.
2003	Boskey A. Bone mineral crystal size. Osteoporos Int. September 2003;14(suppl 5):S16-S20.
2011	Thompson WR, Modla S, Grindel BJ, Czymmek KJ, Kirn-Safran CB, Wang L, Duncan RL, Farach-Carson MC. Perlecan/Hspg2 deficiency alters the pericellular space of the lacunocanalicular system surrounding osteocytic processes in cortical bone. J Bone Miner Res. March 2011;26(3):618-629.
2011	Gamsjaeger S, Buchinger B, Zwettler E, Recker R, Black D, Gasser JA, Eriksen EF, Klaushofer K, Paschalis EP. Bone material properties in actively bone-forming trabeculae in postmenopausal women with osteoporosis after three years of treatment with once-yearly zoledronic acid. J Bone Miner Res. January 2011;26(1):12-18.
2010	Gamsjaeger S, Masic A, Roschger P, Kazanci M, Dunlop JWC, Klaushofer K, Paschalis EP, Fratzl P. Cortical bone composition and orientation as a function of animal and tissue age in mice by raman spectroscopy. Bone. August 2010;47(2):392-399.
2006	Durchschlag E, Paschalis EP, Zoehrer R, Roschger P, Fratzl P, Recker R, Phipps R, Klaushofer K. Bone material properties in trabecular bone from human iliac crest biopsies after 3‐ and 5‐year treatment with risedronate. J Bone Miner Res. October 2006;21(10):1581-1590.
2006	Ma YL, Zeng Q, Donley DW, Ste‐Marie L, Gallagher JC, Dalsky GP, Marcus R, Eriksen EF. Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF‐II immunoreactivity in postmenopausal women with osteoporosis. J Bone Miner Res. June 2006;21(6):855-864.
2004	Paschalis EP, Shane E, Lyritis G, Skarantavos G, Mendelsohn R, Boskey AL. Bone fragility and collagen cross‐links. J Bone Miner Res. December 2004;19(12):2000-2004.
2001	Paschalis EP, Verdelis K, Doty SB, Boskey AL, Mendelsohn R, Yamauchi M. Spectroscopic characterization of collagen cross‐links in bone. J Bone Miner Res. October 2001;16(10):1821-1828.
2003	Gao H, Ji B, Jäger IL, Arzt E, Fratzl P. Materials become insensitive to flaws at nanoscale: lessons from nature. Proc Natl Acad Sci USA. May 13, 2003;100(10):5597-5600.
2015	Granke M, Does MD, Nyman JS. The role of water compartments in the material properties of cortical bone. Calcif Tiss Int. September 2015;97(3):292-307.
2016	Paschalis EP, Gamsjaeger S, Fratzl-Zelman N, Roschger P, Masic A, Brozek W, Hassler N, Glorieux FH, Rauch F, Klaushofer K, Fratzl P. Evidence for a role for nanoporosity and pyridinoline content in human mild osteogenesis imperfecta. J Bone Miner Res. May 2016;31(5):1050-1059.
2015	McNerny EMB, Gong B, Morris MD, Kohn DH. Bone fracture toughness and strength correlate with collagen cross-link maturity in a dose-controlled lathyrism mouse model. J Bone Miner Res. March 2015;30(3):455-464.
2019	Bouxsein ML, Eastell R, Lui L-Y, Wu LA, de Papp AE, Grauer A, Marin F, Cauley JA, Bauer DC, Black DM; FNIH Bone Quality Project. Change in bone density and reduction in fracture risk: a meta-regression of published trials. J Bone Miner Res. April 2019;34(4):632-642.
1997	Paschalis EP, Betts F, DiCarlo E, Mendelsohn R, Boskey AL. FTIR microspectroscopic analysis of human iliac crest biopsies from untreated osteoporotic bone. Calcif Tiss Int. December 1997;61(6):487-492.
2018	Dempster DW, Zhou H, Recker RR, Brown JP, Recknor CP, Lewiecki EM, Miller PD, Rao SD, Kendler DL, Lindsay R, Krege JH, Alam J, Taylor KA, Melby TE, Ruff VA. Remodeling- and modeling-based bone formation with teriparatide versus denosumab: a longitudinal analysis from baseline to 3 months in the AVA study. J Bone Miner Res. 2018;33(2):298-306.