Bone mineral and collagen quality in humeri of ovariectomized cynomolgus monkeys given rhPTH(1–34) for 18 months

Paschalis, Eleftherios P.<sup>1</sup>; Burr, David B.<sup>2,3</sup>; Mendelsohn, Richard<sup>4</sup>; Hock, Janet M.<sup>2,5,6</sup>; Boskey, Adele L.<sup>1</sup>

Affiliations

¹Mineralized Tissues Laboratory, Hospital for Special Surgery, New York, New York, USA

²Departments of Anatomy and Cell Biology and Orthopedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA

³Biomechanics and Biomaterials Research Center, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana, USA

⁴Chemistry Department, Rutgers University, Newark, New Jersey, USA

⁵Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana, USA

⁶Current address: Indiana University Schools of Medicine and Dentistry, Indianapolis, Indiana, USA

Abstract and keywords

A recent study of ovariectomized monkeys, treated with recombinant human parathyroid hormone (rhPTH)(1–34) at 1 or 5 mg/kg/day for 18 months or for 12 months followed by 6 months withdrawal from treatment, showed significant differences in the geometry and histomorphometry of cortical bone of the midshaft humerus. To determine the extent to which the rapid bone turnover and cortical porosity induced by rhPTH(1–34) in ovariectomized monkeys modified mineral content, mineral crystal maturity and collagen maturity (cross-link distribution) in the cortical periosteal and endosteal regions, cross-sections of the cortical bone of the mid-humerus, were examined using Fourier transform infrared imaging (FTIRI). FTIRI analyses demonstrated that rhPTH(1–34) altered bone mineral and collagen properties in a dose-dependent manner. Mineral crystal maturity and collagen cross-link ratio (pyridinoline/dehydro-dihydroxylysinonorleucine) on both endosteal and periosteal surfaces decreased relative to ovariectomized animals, consistent with new bone formation. These changes were partially sustained after withdrawal of the higher dose of rhPTH(1–34), suggesting a prolonged after-effect on bone properties for at least two bone remodeling cycles. In conclusion, treatment of ovariectomized monkeys with rhPTH(1–34) had significant effects on cortical bone mineral-to-matrix ratio, mineral crystal maturity, and collagen cross-link ratio. These were fully reversible when the 1-μg rhPTH(1–34) treatment was withdrawn, but only partially reversed when the 5-μg rhPTH(1–34) dose was withdrawn.

Keywords: infrared imaging; bone quality; recombinant human parathyroid hormone (1–34); osteoporosis; ovariectomized monkey

Links

DOI: 10.1359/jbmr.2003.18.4.769

PubMed: 12674338

WoS: 000181744000020

History

Received: 2002-02-19

Revised: 2002-08-06

Accepted: 2002-10-16

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Cited By (21)

Year	Entry
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.
2007	Boskey A, Camacho NP. FT-IR imaging of native and tissue-engineered bone and cartilage. Biomaterials. May 2007;28(15):2465-2478.
2022	Paschalis E, Gamsjaeger S, Burr D. Bone quality in an ovariectomized monkey animal model treated with two doses of teriparatide for either 18 months, or 12 months followed by withdrawal for 6 months. Bone. May 2022;158:116366.
2020	Taylor EA, Donnelly E, Yao X, Johnson ML, Amugongo SK, Kimmel DB, Lane NE. Sequential treatment of estrogen deficient, osteopenic rats with alendronate, parathyroid hormone (1–34), or raloxifene alters cortical bone mineral and matrix composition. Calcif Tiss Int. March 2020;106(3):303-314.
2005	Boskey AL, Mendelsohn R. Infrared analysis of bone in health and disease. J Biomed Opt. May–June 2005;10(3):031102.
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.
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.
2008	Fuchs RK, Allen MR, Ruppel ME, Diab T, Phipps RJ, Miller LM, Burr DB. In situ examination of the time-course for secondary mineralization of Haversian bone using synchrotron Fourier transform infrared microspectroscopy. Matrix Biol. January 2008;27(1):34-41.
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2014	Fonseca H, Moreira-Gonçalves D, Coriolano H-JA, Duarte JA. Bone quality: the determinants of bone strength and fragility. Sports Med. January 2014;44(1):37-53.
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2006	Nagaraja S. Microstructural Stresses and Strains Associated With Trabecular Bone Microdamage [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; December 2006.
2019	Bakr M. Parathyroid Hormone Effect on Facilitating Stress Fracture Repair [PhD thesis]. Brisbane, Australia: Griffith University; July 2019.
2008	Courtland H-W. Intra-Species Variation in Skeletal Mechanical Function is Achieved Through Genetic Regulation of Both the Quality and Morphology of Bone [PhD thesis]. Mount Sinai School of Medicine; 2008.
2019	Beltejar M-JG. Understanding the Genetic Basis for Bone-Matrix Quality [PhD thesis]. University of Rochester; 2019.
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.
2012	Kwaczala AT. Alendronate and PTH Differentially Modulate Bone Quality and Reduce Adiposity in an OVX Rat Model [PhD thesis]. Stony Brook, NY: Stony Brook University; December 2012.
2016	Vrahna C. Investigating the Effects of Downstream Parathyroid Hormone (PTH) Targets on Bone Strength and Quality [PhD thesis]. Melbourne, Australia: The University of Melbourne; December 2016.