Dystrophic calcinosis: structural and morphological composition, and evaluation of ethylenediaminetetraacetic acid ('EDTA') for potential local treatment.
Calcinosis
Calcium deposits
EDTA treatment
Scleroderma
Systemic Sclerosis
Journal
Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438
Informations de publication
Date de publication:
22 May 2024
22 May 2024
Historique:
received:
14
02
2024
accepted:
20
04
2024
medline:
23
5
2024
pubmed:
23
5
2024
entrez:
22
5
2024
Statut:
epublish
Résumé
To perform a detailed morphological analysis of the inorganic portion of two different clinical presentations of calcium-based deposits retrieved from subjects with SSc and identify a chemical dissolution of these deposits suitable for clinical use. Chemical analysis using Fourier Transform IR spectroscopy ('FTIR'), Raman microscopy, Powder X-Ray Diffraction ('PXRD'), and Transmission Electron Microscopy ('TEM') was undertaken of two distinct types of calcinosis deposits: paste and stone. Calcinosis sample titration with ethylenediaminetetraacetic acid ('EDTA') assessed the concentration at which the EDTA dissolved the calcinosis deposits in vitro. FTIR spectra of the samples displayed peaks characteristic of hydroxyapatite, where signals attributable to the phosphate and carbonate ions were all identified. Polymorph characterization using Raman spectra were identical to a hydroxyapatite reference while the PXRD and electron diffraction patterns conclusively identified the mineral present as hydroxyapatite. TEM analysis showed differences of morphology between the samples. Rounded particles from stone samples were up to a few micron in size, while needle-like crystals from paste samples reached up to 0.5 µm in length. Calcium phosphate deposits were effectively dissolved with 3% aqueous solutions of EDTA, in vitro. Complete dissolution of both types of deposit was achieved in approximately 30 min using a molar ratio of EDTA/HAp of ≈ 300. Stone and paste calcium-based deposits both comprise hydroxyapatite, but the constituent crystals vary in size and morphology. Hydroxyapatite is the only crystalline polymorph present in the SSc-related calcinosis deposits. Hydroxyapatite can be dissolved in vitro using a dosage of EDTA considered safe for clinical application. Further research is required to establish the optimal medium to develop the medical product, determine the protocol for clinical application, and to assess the effectiveness of EDTA for local treatment of dystrophic calcinosis.
Sections du résumé
BACKGROUND
BACKGROUND
To perform a detailed morphological analysis of the inorganic portion of two different clinical presentations of calcium-based deposits retrieved from subjects with SSc and identify a chemical dissolution of these deposits suitable for clinical use.
METHODS
METHODS
Chemical analysis using Fourier Transform IR spectroscopy ('FTIR'), Raman microscopy, Powder X-Ray Diffraction ('PXRD'), and Transmission Electron Microscopy ('TEM') was undertaken of two distinct types of calcinosis deposits: paste and stone. Calcinosis sample titration with ethylenediaminetetraacetic acid ('EDTA') assessed the concentration at which the EDTA dissolved the calcinosis deposits in vitro.
RESULTS
RESULTS
FTIR spectra of the samples displayed peaks characteristic of hydroxyapatite, where signals attributable to the phosphate and carbonate ions were all identified. Polymorph characterization using Raman spectra were identical to a hydroxyapatite reference while the PXRD and electron diffraction patterns conclusively identified the mineral present as hydroxyapatite. TEM analysis showed differences of morphology between the samples. Rounded particles from stone samples were up to a few micron in size, while needle-like crystals from paste samples reached up to 0.5 µm in length. Calcium phosphate deposits were effectively dissolved with 3% aqueous solutions of EDTA, in vitro. Complete dissolution of both types of deposit was achieved in approximately 30 min using a molar ratio of EDTA/HAp of ≈ 300.
CONCLUSIONS
CONCLUSIONS
Stone and paste calcium-based deposits both comprise hydroxyapatite, but the constituent crystals vary in size and morphology. Hydroxyapatite is the only crystalline polymorph present in the SSc-related calcinosis deposits. Hydroxyapatite can be dissolved in vitro using a dosage of EDTA considered safe for clinical application. Further research is required to establish the optimal medium to develop the medical product, determine the protocol for clinical application, and to assess the effectiveness of EDTA for local treatment of dystrophic calcinosis.
Identifiants
pubmed: 38778407
doi: 10.1186/s13075-024-03324-7
pii: 10.1186/s13075-024-03324-7
doi:
Substances chimiques
Edetic Acid
9G34HU7RV0
Durapatite
91D9GV0Z28
Calcium Chelating Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102Subventions
Organisme : Seventh Framework Programme
ID : 310637 SMILEY
Informations de copyright
© 2024. The Author(s).
Références
Marzano A, et al. Dystrophic calcinosis cutis in subacute lupus. Dermatology. 1999;198(1):90–2.
pubmed: 10026412
doi: 10.1159/000018074
Boulman N, Slobodin G, Rozenbaum M, Rosner I. Seminars in arthritis and rheumatism. Elsevier; 2005. p. 805–12.
Valenzuela A, Chung L. Calcinosis: pathophysiology and management. Curr Opin Rheumatol. 2015;27(6):542–8.
pubmed: 26352733
doi: 10.1097/BOR.0000000000000220
Herrick AL, Gallas A. Systemic sclerosis-related calcinosis. Journal of Scleroderma and Related Disorders. 2016;1(2):194–203.
doi: 10.5301/jsrd.5000211
Fernandez-Flores A. Calcinosis cutis: critical review. Acta Dermatovenerol Croat. 2011;19(1):0–0.
Giuggioli D, et al. Use of Neem oil and Hypericum perforatum for treatment of calcinosis-related skin ulcers in systemic sclerosis. J Int Med Res. 2020;48(4):0300060519882176.
pubmed: 31875751
doi: 10.1177/0300060519882176
Bartoli F, et al. Calcinosis in systemic sclerosis: subsets, distribution and complications. Rheumatology. 2016;55(9):1610–4.
pubmed: 27241706
doi: 10.1093/rheumatology/kew193
Valenzuela A, Chung L. Management of calcinosis associated with systemic sclerosis. Current treatment options in rheumatology. 2016;2:85–96.
doi: 10.1007/s40674-016-0035-x
Traineau H, et al. Treatment of calcinosis cutis in systemic sclerosis and dermatomyositis: a review of the literature. J Am Acad Dermatol. 2020;82(2):317–25.
pubmed: 31302187
doi: 10.1016/j.jaad.2019.07.006
Fink C.W, Baum J. Treatment of Calcinosis Universalis with Chelating Agent. Am J Dis Child. 1963;105(4):390–2.
Winder P.R, Curtis A.C. Edathamil in the Treatment of Scleroderma and Calcinosis Cutis. Arch Derm. 1960;82(5):732–6.
pubmed: 13785770
doi: 10.1001/archderm.1960.01580050074009
Maniscalco BS, Taylor KA. Calcification in coronary artery disease can be reversed by EDTA–tetracycline long-term chemotherapy. Pathophysiology. 2004;11(2):95–101.
pubmed: 15364120
doi: 10.1016/j.pathophys.2004.06.001
Lei Y, et al. Efficacy of reversal of aortic calcification by chelating agents. Calcif Tissue Int. 2013;93:426–35.
pubmed: 23963635
doi: 10.1007/s00223-013-9780-0
Sultan-Bichat N, et al. Treatment of calcinosis cutis by extracorporeal shock-wave lithotripsy. J Am Acad Dermatol. 2012;66(3):424–9.
pubmed: 21745699
doi: 10.1016/j.jaad.2010.12.035
Sparsa A, et al. Treatment of cutaneous calcinosis in CREST syndrome by extracorporeal shock wave lithotripsy. J Am Acad Derm. 2005;53(5, Supplement):S263–5.
pubmed: 16227105
doi: 10.1016/j.jaad.2005.04.010
Blumhardt S, et al. Safety and efficacy of extracorporeal shock wave therapy (ESWT) in calcinosis cutis associated with systemic sclerosis. Clin Exp Rheumatol. 2016;34(5):177–80.
pubmed: 27494629
Fahmy F, Evans D, Devaraj V. Microdrilling of digital calcinosis. Eur J Plast Surg. 1998;21:378–80.
doi: 10.1007/s002380050122
Lapner MA, Goetz TJ. High-speed burr debulking of digital calcinosis cutis in scleroderma patients. The Journal of Hand Surgery. 2014;39(3):503–10.
pubmed: 24559627
doi: 10.1016/j.jhsa.2013.12.003
Motlaghzadeh Y, et al. Regression of calcinosis cutis after inkless tattoo in a patient with dermatomyositis: therapeutic potential of microneedling. Osteoporos Int. 2022;33(11):2449–52.
pubmed: 35881144
doi: 10.1007/s00198-022-06501-z
Al-Mayouf SM, Alsonbul A, Alismail K. Localized calcinosis in juvenile dermatomyositis: successful treatment with intralesional corticosteroids injection. Int J Rheum Dis. 2010;13(3):e26–8.
pubmed: 20704606
doi: 10.1111/j.1756-185X.2010.01483.x
Nowaczyk J, Zawistowski M, Fiedor P. Local, non-systemic, and minimally invasive therapies for calcinosis cutis: a systematic review. Arch Dermatol Res. 2022;314(6):515–25.
pubmed: 34165603
doi: 10.1007/s00403-021-02264-5
Chamberlain AJ, Walker NP. Successful palliation and significant remission of cutaneous calcinosis in CREST syndrome with carbon dioxide laser. Dermatol Surg. 2003;29(9):968–70.
pubmed: 12930342
Eleryan MG, et al. Treatment of calcinosis associated with adult and juvenile dermatomyositis using topical sodium thiosulfate via fractionated CO2 laser treatment. Clin Exp Rheumatol. 2019;37(6):1092.
pubmed: 31796160
pmcid: 7108296
Amanzi L, et al. Digital ulcers in scleroderma: staging, characteristics and sub-setting through observation of 1614 digital lesions. Rheumatology (Oxford). 2010;49(7):1374–82.
pubmed: 20400463
doi: 10.1093/rheumatology/keq097
Lin S-Y, Li M-J, Cheng W-T. FT-IR and Raman vibrational microspectroscopies used for spectral biodiagnosis of human tissues. J Spectrosc. 2007;21(1):1–30.
doi: 10.1155/2007/278765
Carden A, Morris MD. Application of vibrational spectroscopy to the study of mineralized tissues (review). J Biomed Opt. 2000;5(3):259–68.
pubmed: 10958610
doi: 10.1117/1.429994
Panda R, et al. FTIR, XRD, SEM and solid state NMR investigations of carbonate-containing hydroxyapatite nano-particles synthesized by hydroxide-gel technique. J Phys Chem Solids. 2003;64(2):193–9.
doi: 10.1016/S0022-3697(02)00257-3
Wang A, et al. Size-controlled synthesis of hydroxyapatite nanorods by chemical precipitation in the presence of organic modifiers. Mater Sci Eng, C. 2007;27(4):865–9.
doi: 10.1016/j.msec.2006.10.001
Penel G, et al. MicroRaman spectral study of the PO4 and CO3 vibrational modes in synthetic and biological apatites. Calcif Tissue Int. 1998;63(6):475–81.
pubmed: 9817941
doi: 10.1007/s002239900561
Berzina-Cimdina L, Borodajenko N. Research of calcium phosphates using Fourier transform infrared spectroscopy. Infrared spectroscopy-materials science, engineering and technology. 2012;12(7):251–63.
Clasen AS, Ruyter I. Quantitative determination of type A and type B carbonate in human deciduous and permanent enamel by means of Fourier transform infrared spectrometry. Adv Dent Res. 1997;11(4):523–7.
doi: 10.1177/08959374970110042101
Walters MA, et al. A Raman and infrared spectroscopic investigation of biological hydroxyapatite. J Inorg Biochem. 1990;39(3):193–200.
pubmed: 2168470
doi: 10.1016/0162-0134(90)84002-7
Brundavanam RK, Poinern GEJ, Fawcett D. Modelling the crystal structure of a 30 nm sized particle based hydroxyapatite powder synthesised under the influence of ultrasound irradiation from X-ray powder diffraction data. American Journal of Materials Science. 2013;3(4):84–90.
Mir M, et al. XRD, AFM, IR and TGA study of nanostructured hydroxyapatite. Mater Res. 2012;15(4):622–7.
doi: 10.1590/S1516-14392012005000069
Rusu VM, et al. Size-controlled hydroxyapatite nanoparticles as self-organized organic–inorganic composite materials. Biomaterials. 2005;26(26):5414–26.
pubmed: 15814140
doi: 10.1016/j.biomaterials.2005.01.051
Pon-On W, Meejoo S, Tang IM. Formation of hydroxyapatite crystallites using organic template of polyvinyl alcohol (PVA) and sodium dodecyl sulfate (SDS). Mater Chem Phys. 2008;112(2):453–60.
doi: 10.1016/j.matchemphys.2008.05.082
Wang A, et al. Effects of organic modifiers on the size-controlled synthesis of hydroxyapatite nanorods. Appl Surf Sci. 2007;253(6):3311–6.
doi: 10.1016/j.apsusc.2006.07.025
Chang MC, Douglas WH, Tanaka J. Organic-inorganic interaction and the growth mechanism of hydroxyapatite crystals in gelatin matrices between 37 and 80 °C. J Mater Sci - Mater Med. 2006;17(4):387–96.
pubmed: 16617418
doi: 10.1007/s10856-006-8243-9
Chen F, Wang Z-C, Lin C-J. Preparation and characterization of nano-sized hydroxyapatite particles and hydroxyapatite/chitosan nano-composite for use in biomedical materials. Mater Lett. 2002;57(4):858–61.
doi: 10.1016/S0167-577X(02)00885-6
Suvorova E, Buffat P. Electron Diffraction from Micro- and Nanoparticles of Hydroxyapatite. J Microsc. 1999;196:46–58.
pubmed: 10540256
doi: 10.1046/j.1365-2818.1999.00608.x
O’Connell MS, et al. A Comparative Study of Smear Layer Removal Using Different Salts of EDTA. Journal of Endodontics. 2000;26(12):739–43.
pubmed: 11471645
doi: 10.1097/00004770-200012000-00019
Sreebny LM, Nikiforuk G. Demineralization of hard tissues by organic chelating agents. Science (New York, NY). 1951;113(2941):560.
doi: 10.1126/science.113.2941.560.a
Lin S-Y. Biochemical and molecular aspects of spectral diagnosis in calcinosis cutis. Expert Rev Mol Med. 2014;16: e6.
pubmed: 24618028
doi: 10.1017/erm.2014.6
Hsu VM, Emge T, Schlesinger N. X-ray diffraction analysis of spontaneously draining calcinosis in scleroderma patients. Scand J Rheumatol. 2017;46(2):118–21.
pubmed: 27682520
doi: 10.1080/03009742.2016.1219766
Prudhommeaux F, et al. Variation in the inflammatory properties of basic calcium phosphate crystals according to crystal type. Arthritis Rheum. 1996;39(8):1319–26.
pubmed: 8702440
doi: 10.1002/art.1780390809
Swan A, Dularay B, Dieppe P. A comparison of the effects of urate, hydroxyapatite and diamond crystals on polymorphonuclear cells: relationship of mediator release to the surface area and adsorptive capacity of different particles. J Rheumatol. 1990;17(10):1346–52.
pubmed: 2174972
Chiou HJ, et al. Correlations among mineral components, progressive calcification process and clinical symptoms of calcific tendonitis. Rheumatology. 2010;49(3):548–55.
pubmed: 20032222
doi: 10.1093/rheumatology/kep359
Flora S, Mittal M, Mehta A. Heavy metal induced oxidative stress & its possible reversal by chelation therapy. Indian J Med Res. 2008;128(4):501.
pubmed: 19106443
Poggio C, et al. Decalcifying capability of irrigating solutions on root canal dentin mineral content. Contemporary Clinical Dentistry. 2015;6(2):201–5.
pubmed: 26097355
pmcid: 4456742
doi: 10.4103/0976-237X.156046
Koçak S, et al. Influence of Diode Laser Application on the Efficiency of QMiX and EDTA Solutions in Removing Smear Layer. Photomed Laser Surg. 2015;33(11):564–7.
pubmed: 26389792
doi: 10.1089/pho.2015.3910
Sitashi P, Pan WH, Zhan L. Chelating agent effects on root canal smear layer removal and relevant impact factors. Chinese Journal of Tissue Engineering Research. 2013;17(12):2249–56.
Gao S, et al. Nano-scratch behavior of human root canal wall dentin lubricated with EDTA pastes. Tribol Int. 2013;63:169–76.
doi: 10.1016/j.triboint.2012.03.010
Arslan H, et al. Effect of agitation of EDTA with 808-nanometer diode laser on removal of smear layer. Journal of Endodontics. 2013;39(12):1589–92.
pubmed: 24238453
doi: 10.1016/j.joen.2013.07.016
Poggio C, et al. Decalcifying effect of different ethylenediaminetetraacetic acid irrigating solutions and tetraclean on root canal dentin. Journal of Endodontics. 2012;38(9):1239–43.
pubmed: 22892742
doi: 10.1016/j.joen.2012.06.010
Poggio C, et al. In vitro antibacterial activity of different endodontic irrigants. Dent Traumatol. 2012;28(3):205–9.
pubmed: 22051159
doi: 10.1111/j.1600-9657.2011.01074.x
Torabinejad M, et al. A New Solution for the Removal of the Smear Layer. Journal of Endodontics. 2003;29(3):170–5.
pubmed: 12669874
doi: 10.1097/00004770-200303000-00002
Vemuri S, et al. Effect of different final irrigating solutions on smear layer removal in apical third of root canal: A scanning electron microscope study. J Conserv Dent. 2016;19(1):87–90.
pubmed: 26957801
pmcid: 4760023
doi: 10.4103/0972-0707.173207
Nerness AZ, et al. Effect of triple antibiotic paste with or without ethylenediaminetetraacetic acid on surface loss and surface roughness of radicular dentine. Odontology. 2016;104(2):170–5.
pubmed: 25556157
doi: 10.1007/s10266-014-0191-0
Abu Zeid S.T.H, Khafagi M.G, Abou Neel E.A. Effect of root canal medications on maturation and calcification of root canal dentin hydroxyapatite. Spectroscopy Letters. 2016;49(2):135–9.
doi: 10.1080/00387010.2015.1099109
Çiçek E, Keskin Ö. The effect of the temperature changes of EDTA and MTAD on the removal of the smear layer: A scanning electron microscopy study. Scanning. 2015;37(3):193–6.
pubmed: 25739528
doi: 10.1002/sca.21198
Lanigan R, Yamarik T. Final report on the safety assessment of EDTA, calcium disodium EDTA, diammonium EDTA, dipotassium EDTA, disodium EDTA, TEA-EDTA, tetrasodium EDTA, tripotassium EDTA, trisodium EDTA, HEDTA, and trisodium HEDTA. Int J Toxicol. 2001;21:95–142.