Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study

wbldb

Dempster, David W.^1,2; Cosman, Felicia^3,4; Kurland, Etah S.⁴; Zhou, Hua¹; Nieves, Jeri^3,5; Woelfert, Lillian³; Shane, Elizabeth⁴; Plavetić, Katarina¹; Müller, Ralph⁶; Bilezikian, John^4,7; Lindsay, Robert^3,4

Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study

J Bone Miner Res. October 2001;16(10):1846-1853

©2001 American Society for Bone and Mineral Research

Affiliations

¹Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York, USA

²Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York, USA

³Clinical Research Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, New York, USA

⁴Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA

⁵School of Public Health, College of Physicians and Surgeons of Columbia University, New York, New York, USA

⁶Orthopedic Biomechanics Laboratory, Harvard Medical School, and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

⁷Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York, USA
Abstract and keywords

We examined paired iliac crest bone biopsy specimens from patients with osteoporosis before and after treatment with daily injections of 400 U of recombinant, human parathyroid hormone 1–34 [PTH(1–34)]. Two groups of patients were studied. The first group was comprised of 8 men with an average age 49 years. They were treated with PTH for 18 months. The second group was comprised of 8 postmenopausal women with an average age 54 years. They were treated with PTH for 36 months. The women had been and were maintained on hormone replacement therapy for the duration of PTH treatment. Patients were supplemented to obtain an average daily intake of 1500 mg of elemental calcium and 100 IU of vitamin D. The biopsy specimens were subjected to routine histomorphometric analysis and microcomputed tomography (CT). Cancellous bone area was maintained in both groups. Cortical width was maintained in men and significantly increased in women. There was no increase in cortical porosity. There was a significant increase in the width of bone packets on the inner aspect of the cortex in both men and women. This was accompanied by a significant decrease in eroded perimeter on this surface in both groups. Micro‐CT confirmed the foregoing changes and, in addition, revealed an increase in connectivity density, a three dimensional (3D) measure of trabecular connectivity in the majority of patients. These findings indicate that daily PTH treatment exerts anabolic action on cortical bone in patients with osteoporosis and also can improve cancellous bone microarchitecture. The results provide a structural basis for the recent demonstration that PTH treatment reduces the incidence of osteoporosis‐related fractures.

Keywords: parathyroid hormone; osteoporosis; bone microarchitecture; human
Links

DOI: 10.1359/jbmr.2001.16.10.1846

PubMed: 11585349

WoS: 000171142000015
History

Received: 2001-01-10

Revised: 2001-04-09

Accepted: 2001-04-18

Cited Works (19)

Year	Entry
1998	Kinney JH, Ladd AJC. The relationship between three-dimensional connectivity and the elastic properties of trabecular bone. J Bone Miner Res. May 1998;13(5):839-845.
1987	Lorensen WE, Cline HE. Marching cubes: a high resolution 3D surface construction algorithm. Comput Graph. 1987;21(4):163-169.
1999	Kabel J, Odgaard A, van Rietbergen B, Huiskes R. Connectivity and the elastic properties of cancellous bone. Bone. 1999;24(2):115-120.
2000	Borah B, Dufresne TE, Cockman MD, Gross GJ, Sod EW, Myers WR, Combs KS, Higgins RE, Pierce SA, Stevens ML. Evaluation of changes in trabecular bone architecture and mechanical properties of minipig vertebrae by three‐dimensional magnetic resonance microimaging and finite element modeling. J Bone Miner Res. September 2000;15(9):1786-1797.
1987	Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR. Bone histomorphometry: standardization of nomenclature, symbols, and units: report of the ASBMR histomorphometry nomenclature committee. J Bone Miner Res. December 1987;2(6):595-610.
1994	Guilak F. Volume and surface area measurement of viable chondrocytes in situ using geometric modelling of serial confocal sections. J Microsc (Oxford). March 1994;173(3):245-256.
1997	Lindsay R, Nieves J, Formica C, Henneman E, Woelfert L, Shen V, Dempster D, Cosman F. Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet. August 23, 1997;350(9077):P550-P555.
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.
2000	Oleksik A, Ott SM, Vedi S, Bravenboer N, Compston J, Lips P. Bone structure in patients with low bone mineral density with or without vertebral fractures. J Bone Miner Res. July 2000;15(7):1368-1375.
1995	Boyce RW, Wronski TJ, Ebert DC, Stevens ML, Paddock CL, Youngs TA, Gundersen HJG. Direct stereological estimation of three-dimensional connectivity in rat vertebrae: effect of estrogen, etidronate and risedronate following ovariectomy. Bone. February 1995;16(2):209-213.
1997	Hildebrand T, Rüegsegger P. A new method for the model-independent assessment of thickness in three-dimensional images. J Microsc (Oxford). 1997;185(1):67-75.
1988	Parisien MV, McMahon D, Pushparaj N, Dempster DW. Trabecular architecture in iliac crest bone biopsies: infra-individual variability in structural parameters and changes with age. Bone. 1988;9(5):289-295.
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.
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.
1992	Bradbeer JN, Arlott ME, Meunier PJ, Reeve J. Treatment of osteoporosis with parathyroid peptide (hPTH 1-34) and oestrogen: increase in volumetric density of iliac cancellous bone may depend on reduced trabecular spacing as well as increased thickness of packets of newly formed bone. Clin Endocrinol. September 1992;37(3):282-289.
1997	Odgaard A. Three-dimensional methods for quantification of cancellous bone architecture. Bone. 1997;20(4):315-328.
1997	Ritzel H, Amling M, Pösl M, Hahn M, Delling G. The thickness of human vertebral cortical bone and its changes in aging and osteoporosis: a histomorphometric analysis of the complete spinal column from thirty‐seven autopsy specimens. J Bone Miner Res. January 1997;12(1):89-95.
1993	Odgaard A, Gundersen HJG. Quantification of connectivity in cancellous bone, with special emphasis on 3-D reconstructions. Bone. March–April 1993;14(2):173-182.
1991	Vesterby A, Mosekilde L, Gundersen HJG, Melsen F, Mosekilde L, Holme K, Sørensen S. Biologically meaningful determinants of the in vitro strength of lumbar vertebrae. Bone. 1991;12(3):219-224.

Cited By (52)

Year	Entry
2007	McDonnell P, McHugh PE, O’Mahoney D. Vertebral osteoporosis and trabecular bone quality. Ann Biomed Eng. February 2007;35(2):170-189.
2008	Chappard C, Marchadier A, Benhamou CL. Side-to-side and within-side variability of 3D bone microarchitecture by conventional micro-computed tomography of paired iliac crest biopsies. Bone. July 2008;43(1):203-208.
2008	Nazarian A, Snyder BD, Zurakowski D, Müller R. Quantitative micro-computed tomography: a non-invasive method to assess equivalent bone mineral density. Bone. August 2008;43(2):302-311.
2020	Rooney AM, Bostrom MPG, Dempster DW, Nieves JW, Zhou H, Cosman F. Loading modality and age influence teriparatide-induced bone formation in the human femoral neck. Bone. July 2020;136:115373.
2022	Rooney AM, Dempster DW, Nieves JW, Zhou H, Bostrom MPG, Cosman F. Effects of teriparatide and loading modality on modeling-based and remodeling-based bone formation in the human femoral neck. Bone. April 2022;157:116342.
2023	Ganapathy A, Nieves JW, Keaveny TM, Cosman F. Effects of four-year cyclic versus two-year daily teriparatide treatment on volumetric bone density and bone strength in postmenopausal women with osteoporosis. Bone. February 2023;167:116618.
2013	Boskey AL. Bone composition: relationship to bone fragility and antiosteoporotic drug effects. BoneKEy Rep. December 2013;2:447.
2003	Dufresne TE, Chmielewski PA, Manhart MD, Johnson TD, Borah B. Risedronate preserves bone architecture in early postmenopausal women in 1 year as measured by three-dimensional microcomputed tomography. Calcif Tiss Int. November 2003;73(5):423-432.
2004	Nägele E, Kuhn V, Vogt H, Link TM, Müller R, Lochmüller E-M, Eckstein F. Technical considerations for microstructural analysis of human trabecular bone from specimens excised from various skeletal sites. Calcif Tiss Int. 2004;75(1):15-22.
2016	Hunt HB, Donnelly E. Bone quality assessment techniques: geometric, compositional, and mechanical characterization from macroscale to nanoscale. Clin Rev Bone Miner Metab. September 2016;14(3):133-149.
2008	Chappard C, Marchadier A, Benhamou L. Interindividual and intraspecimen variability of 3-D bone microarchitectural parameters in iliac crest biopsies imaged by conventional micro-computed tomography. J Bone Min Metab. 2008;26(5):506-513.
2002	Borah B, Dufresne TE, Chmielewski PA, Gross GJ, Prenger MC, Phipps RJ. Risedronate preserves trabecular architecture and increases bone strength in vertebra of ovariectomized minipigs as measured by three‐dimensional microcomputed tomography. J Bone Miner Res. July 2002;17(7):1139-1147.
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.
2004	Kozloff KM, Carden A, Bergwitz C, Forlino A, Uveges TE, Morris MD, Marini JC, Goldstein SA. Brittle IV mouse model for osteogenesis imperfecta IV demonstrates postpubertal adaptations to improve whole bone strength. J Bone Miner Res. April 2004;19(4):614-622.
2005	Riggs BL, Parfitt AM. Drugs used to treat osteoporosis: the critical need for a uniform nomenclature based on their action on bone remodeling. J Bone Miner Res. February 2005;20(2):177-184.
2005	Prince R, Sipos A, Hossain A, Syversen U, Ish-Shalom S, Marcinowska E, Halse J, Lindsay R, Dalsky GP, Mitlak BH. Sustained nonvertebral fragility fracture risk reduction after discontinuation of teriparatide treatment. J Bone Miner Res. September 2005;20(9):1507-1513.
2006	Lindsay R, Cosman F, Zhou H, Bostrom MP, Shen VW, Cruz JD, Nieves JW, Dempster DW. A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: early actions of teriparatide. J Bone Miner Res. March 2006;21(3):366-373.
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.
2006	Szulc P, Seeman E, Duboeuf F, Sornay-Rendu E, Delmas PD. Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women. J Bone Miner Res. December 2006;21(12):1856-1863.
2007	Keaveny TM, Donley DW, Hoffmann PF, Mitlak BH, Glass EV, San Martin JA. Effects of teriparatide and alendronate on vertebral strength as assessed by finite element modeling of qct scans in women with osteoporosis. J Bone Miner Res. January 2007;22(1):149-157.
2007	Lindsay R, Zhou H, Cosman F, Nieves J, Dempster DW, Hodsman AB. Effects of a one-month treatment with PTH(1–34) on bone formation on cancellous, endocortical, and periosteal surfaces of the human ilium. J Bone Miner Res. April 2007;22(4):495-502.
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.
2020	Cosman F, McMahon D, Dempster D, Nieves JW. Standard versus cyclic teriparatide and denosumab treatment for osteoporosis: a randomized trial. J Bone Miner Res. February 2020;35(2):219-225.
2020	Henaff CL, Ricarte F, Finnie B, He Z, Johnson J, Warshaw J, Kolupaeva V, Partridge NC. Abaloparatide at the same dose has the same effects on bone as PTH (1‐34) in mice. J Bone Miner Res. April 2020;35(4):714-724.
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.
2021	Weigl M, Kocijan R, Ferguson J, Leinfellner G, Heimel P, Feichtinger X, Pietschmann P, Grillari J, Zwerina J, Redl H, Hackl M. Longitudinal changes of circulating miRNAs during bisphosphonate and teriparatide treatment in an animal model of postmenopausal osteoporosis. J Bone Miner Res. June 2021;36(6):1131-1144.
2023	Rooney AM, McNeill TJ, Ross FP, Bostrom MPG, van der Meulen MCH. PTH treatment increases cortical bone mass more in response to compression than tension in mice. J Bone Miner Res. January 2023;38(1):59-69.
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.
2011	Silva BC, Costa AG, Cusano NE, Kousteni S, Bilezikian JP. Catabolic and anabolic actions of parathyroid hormone on the skeleton. J Endocrinol Invest. November 2011;34(10):801-810.
2003	Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ; PaTH Study Investigators. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. NEJM. September 25, 2003;349(13):1207-1215.
2007	Canalis E, Giustina A, Bilezikian JP. Mechanisms of anabolic therapies for osteoporosis. NEJM. August 30, 2007;357(9):905-916.
2012	Rizzoli R, Chapurlat RD, Laroche J-M, Krieg MA, Thomas T, Frieling I, Boutroy S, Laib A, Bock O, Felsenberg D. Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis. Osteoporos Int. January 2012;23(1):305-315.
2016	Langdahl B, Ferrari S, Dempster DW. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis. Ther Adv Musculoskel Dis. December 2016;8(6):225-235.
2007	Yuan Y. The Differential Effects of Two Critical Osteoclastogenesis Stimulating Factors on Bone Biomechanics [PhD thesis]. Clemson, SC: Clemson University; May 2007.
2008	Livingston EW. Risedronate Prevents Early Bone Loss Resulting from Whole-Body Irradiation [Master's thesis]. Clemson, SC: Clemson University; August 2008.
2003	Kim CH. In Vivo Trabecular Bone Response to Mechanical Loading and Parathyroid Hormone Stimulation [PhD thesis]. Columbia University; 2003.
2018	Chen JTH. Alterations in Bone Tissue Properties With Parathyroid Hormone Treatment [PhD thesis]. Ithaca, NY: Cornell University; May 2018.
2018	Hunt HB. Characterization of Material Properties, Microarchitecture, and Mechanics of Bone from Subjects With Type 2 Diabetes Mellitus [PhD thesis]. Ithaca, NY: Cornell University; December 2018.
2020	Rooney A. Interactions Among Estrogen Receptor-Alpha, Parathyroid Hormone, and Mechanical Loading in Skeletal Health [PhD thesis]. Ithaca, NY: Cornell University; December 2020.
2020	Ziemian SN. The Roles of Subchondral Bone Mass, Stiffness, and Remodeling in Load-Induced Osteoarthritis Development [PhD thesis]. Ithaca, NY: Cornell University; August 2020.
2005	Stauber M. Volumetric Spatial Decomposition of Porous Microstructures: A Framework for Element Based Analysis of Trabecular Bone [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2005.
2008	Nazarian A. Relative Interaction of Material and Structure in Normal and Pathologic Bone [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2008.
2010	Müller T. Bioimaging and Biomechanics of Bone Competence and Implant Stability [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2010.
2012	Christen DB. Nonlinear Failure Prediction in Human Bone: A Clinical Approach Based on High Resolution Imaging [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2012.
2019	Bakr M. Parathyroid Hormone Effect on Facilitating Stress Fracture Repair [PhD thesis]. Brisbane, Australia: Griffith University; July 2019.
2013	Wong AKO. A Tri-Modality Comparison of Volumetric Bone Measure Quantification Using 1.0 Tesla Peripheral Magnetic Resonance Imaging, Peripheral Quantitative Computed Tomography and Highresolution-Peripheral Quantitative Computed Tomography Images [PhD thesis]. Hamilton, ON: McMaster University; October 2013.
2012	Acerbo AS. Local Chemical and Nanostructural Properties of Rat Cortical Bone Are Altered by Osteoporosis and Pharmaceutical Treatments [PhD thesis]. Stony Brook, NY: Stony Brook University; August 2012.
2014	Colombo A. La micro-architecture de l’os trabéculaire en croissance: Variabilité tridimensionnelle normale et pathologique analysée par microtomodensitométrie [PhD thesis]. Université de Bordeaux; December 15, 2014.
2005	Kozloff KM. Influence of a Collagen Mutation of the Mechanical Nature of Bone: Governing Factors in a Disease Model for Osteogenesis Imperfecta Type IV [PhD thesis]. University of Michigan; 2005.
2021	Tseng W-J. Structural and Mechanical Responses to Intermittent Parathyroid Hormone Treatment, Discontinuation and Cyclic Administration Regimens [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2021.
2020	Hiebert B. The Development of a Cortical Bone Turnover Model: Parathyroid Hormone Effects in the Rabbit [Master's thesis]. University of Saskatchewan; July 2020.
2022	Sales EdS. The Spatio-Temporal Behavior of Basic Multicellular Units in a PTH-Induced Cortical Bone Remodeling Rabbit Model [Master's thesis]. University of Saskatchewan; August 2022.