Interplay between mineral crystallinity and mineral accumulation in health and postmenopausal osteoporosis

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Gamsjaeger, S.¹; Fratzl, P.²; Paschalis, E. P.¹

Interplay between mineral crystallinity and mineral accumulation in health and postmenopausal osteoporosis

Acta Biomater. April 2021;124:374

©2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Affiliations

¹Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Heinrich Collin Str. 30, Vienna A-1140, Austria

²Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, Potsdam 14476, Germany
Abstract and keywords

Osteoporosis is characterized by an imbalance between bone formation and resorption rates, resulting in bone loss. For ethical reasons, effects of antiosteoporosis drugs are compared against patients receiving vitamin D and calcium supplementation which is a mild antiresorptive regimen. Bone formation may be resolved into two phases: the initial formation of mineral crystals (primary nucleation) and the subsequent mineral accumulation (secondary nucleation and mineral growth) on them. In this study, we used Raman microspectroscopic analysis of iliac crest biopsies from healthy females (N = 108), postmenopausal osteoporosis patients receiving vitamin D and calcium supplementation (PMOP-S; N = 66), and treatment-naïve postmenopausal osteoporosis patients (PMOP-TN; N = 12) to test the hypothesis that at forming trabecular surfaces, mineral maturity / crystallinity of the youngest crystallites associates with the amount of subsequent mineral accumulation. The surfaces of analysis were chosen based on the presence of fluorescent double labels, defining three distinct tissue ages. The results indicated that when adjusted for age and tissue age, there were no differences in amount of mineral formed between healthy females and either PMOP-S or PMOP-TN, while both PMOP-S and PMOP-TN had larger crystallites compared to healthy females. Moreover, significant differences existed between PMOP-S and PMOP-TN in size of initial crystals formed as well as rate of mineral accumulation and maturation. These findings suggest an additional mechanism that may contribute to the decreased mineral content evident in PMOP, and provide a potential target for the development of new interventions.

Statement of Significance: We used Raman microspectroscopic analysis of iliac crest biopsies from healthy females and postmenopausal osteoporosis patients (PMOP) receiving placebo to test the hypothesis that at forming trabecular surfaces, mineral maturity / crystallinity (MMC) of the youngest crystallites associates with the amount of subsequent mineral accumulation. This can affect bone mechanical properties as larger crystallites have been shown to result in compromised mechanical attributes; and larger crystallites grow slower compared to smaller ones. The results of the present analysis indicate that increased MMC of the youngest formed mineral may contribute to the bone mineral loss evident in PMOP and the accompanying increased fracture risk independently of bone turnover rate.

Keywords: Raman microspectroscopy; Postmenopausal osteoporosis; Bone loss; Bone formation; Mineral maturity/crystallinity; Mineral content
Links

DOI: 10.1016/j.actbio.2021.02.011

PubMed: 33582361

WoS: 000632754400003
History

Received: 2020-09-16

Revised: 2021-02-5

Accepted: 2021-02-5

Online: 2021-02-11

Cited Works (34)

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.
1999	Mendelsohn R, Paschalis EP, Boskey AL. Infrared spectroscopy, microscopy, and microscopic imaging of mineralizing tissues: spectra-structure correlations from human iliac crest biopsies. J Biomed Opt. January 1999;4(1):14-21.
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.
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.
2010	Gourion-Arsiquaud S, Allen MR, Burr DB, Vashishth D, Tang SY, Boskey AL. Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone. March 2010;46(3):666-672.
1993	Grynpas M. Age and disease-related changes in the mineral of bone. Calcif Tiss Int. February 1993;53(suppl 1):S57-S64.
1981	Chatterji S, Wall JC, Jeffery JW. Age-related changes in the orientation and particle size of the mineral phase in human femoral cortical bone. Calcif Tiss Int. December 1981;33(6):567-574.
2015	Mandair GS, Morris MD. Contributions of Raman spectroscopy to the understanding of bone strength. BoneKEy Rep. January 7, 2015;4:620.
2012	Donnelly E, Meredith DS, Nguyen JT, Gladnick BP, Rebolledo BJ, Shaffer AD, Lorich DG, Lane JM, Boskey AL. Reduced cortical bone compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fractures. J Bone Miner Res. March 2012;27(3):672-678.
2008	Roschger P, Paschalis EP, Fratzl P, Klaushofer K. Bone mineralization density distribution in health and disease. Bone. March 2008;42(3):456-466.
2001	Roschger P, Grabner BM, Rinnerthaler S, Tesch W, Kneissel M, Berzlanovich A, Klaushofer K, Fratzl P. Structural development of the mineralized tissue in the human L4 vertebral body. J Struct Biol. November 2001;136(2):126-136.
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.
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.
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.
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.
2003	Currey JD. The many adaptations of bone. J Biomech. 2003;36(10):1487-1495.
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.
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.
2001	Boskey AL. Bone mineralization. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:chap 5.
2003	Boskey A. Bone mineral crystal size. Osteoporos Int. September 2003;14(suppl 5):S16-S20.
2020	Taylor EA, Donnelly E. Raman and Fourier transform infrared imaging for characterization of bone material properties. Bone. October 2020;139:115490.
1996	Paschalis EP, DiCarlo E, Betts F, Sherman P, Mendelsohn R, Boskey AL. FTIR microspectroscopic analysis of human osteonal bone. Calcif Tiss Int. December 1996;59(6):480-487.
1997	Paschalis EP, Betts F, DiCarlo E, Mendelsohn R, Boskey AL. FTIR microspectroscopic analysis of normal human cortical and trabecular bone. Calcif Tiss Int. December 1997;61(6):480-486.
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.
1984	Currey JD. Effects of differences in mineralization on the mechanical properties of bone. Philos Trans R Soc Lond B Biol Sci. February 13, 1984;304(1121):509-518.
2013	Gourion-Arsiquaud S, Lukashova L, Power J, Loveridge N, Reeve J, Boskey AL. Fourier transform infrared imaging of femoral neck bone: reduced heterogeneity of mineral-to-matrix and carbonate-to-phosphate and more variable crystallinity in treatment-naive fracture cases compared with fracture-free controls. J Bone Miner Res. January 2013;28(1):150-161.
2007	Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR; HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. NEJM. May 3, 2007;356(18):1809-1822.
2011	Morris MD, Mandair GS. Raman assessment of bone quality. Clin Orthop Relat Res. August 2011;469:2160-2169.
2002	Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet. June 1, 2002;359(9321):1929-1936.
1997	McCalden RW, McGeough JA, Court-Brown CM. Age-related changes in the compressive strength of cancellous bone: the relative importance of changes in density and trabecular architecture. J Bone Joint Surg. March 1997;79A(3):421-427.
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.
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.

Cited By (2)

Year	Entry
2022	Paschalis EP, Gamsjaeger S, Klaushofer K, Shane E, Cohen A, Stepan J, Pavo I, Eriksen EF, Taylor KA, Dempster DW. Treatment of postmenopausal osteoporosis patients with teriparatide for 24 months reverts forming bone quality indices to premenopausal healthy control values. Bone. September 2022;162:116478.
2022	Gamsjaeger S, Rauch F, Glorieux FH, Paschalis EP. Cortical bone material / compositional properties in growing children and young adults aged 1.5–23 years, as a function of gender, age, metabolic activity, and growth spurt. Bone. December 2022;165:116548.