Abstract
Summary
Human chitotriosidase (Chit) increases during the osteoclast differentiation and their activity. We demonstrated that serum Chit was significantly higher in osteoporotic subjects than in healthy control ones and revealed a negative correlation between Chit and bone mineral density (BMD). This is the first study showing a correlation between Chit and severe postmenopausal osteoporosis.
Introduction
Mammalian chitinases exert important biological roles in the monocyte lineage and chronic inflammatory diseases. In particular, Chit seems to promote bone resorption in vitro. No in vivo studies have been performed to confirm this finding. We aim to evaluate Chit activity in postmenopausal women affected by severe osteoporosis.
Methods
In this cross-sectional study, 91 postmenopausal women affected by osteoporosis and 61 with either osteopenia or normal BMD were screened. All subjects were assessed by dual-energy X-ray absorptiometry (DXA) and X-ray vertebral morphometry. Osteoporotic subjects were considered eligible if they were affected by at least one vertebral osteoporotic fracture (group A = 57 subjects). Osteopenic or healthy subjects were free from osteoporotic fractures (group B = 51 subjects). Enzymatic Chit and serum β-CrossLaps (CTX) were measured in the whole population.
Results
Group A showed higher serum levels of beta-CTX compared to group B (0.40 ± 0.26 ng/mL vs 0.29 ± 0.2 ng/mL, p = 0.022). Chit was significantly higher in group A than in group B (1042 ± 613 nmol/mL/h vs 472 ± 313 nmol/mL/h, p < 0.001, respectively) even after adjustment for age (p < 0.001). Spearman correlation test revealed a negative correlation between Chit and BMD at each site (lumbar spine: r = −0.38, p = 0.001, femoral neck: r = −0.35, p = 0.001, total femur: r = −0.39, p < 0.001). Furthermore, a positive correlation between Chit and PTH was observed (r = 0.26, p = 0.013). No significant correlation was found between Chit and beta-CTX (r = 0.12, p = 0.229). After a multivariate analysis, a positive correlation between severe osteoporosis and Chit (p < 0.001), beta-CTX (p = 0.013), and age (p < 0.001) was observed.
Conclusion
This is the first clinical study showing a correlation between Chit and severe postmenopausal osteoporosis. Larger and prospective studies are needed to evaluate if Chit may be a promising clinical biomarker and/or therapeutic monitor in subjects with osteoporosis.
Similar content being viewed by others
References
Hlaing TT, Compston JE (2014) Biochemical markers of bone turnover - uses and limitations. Ann Clin Biochem 51:189–202. doi:10.1177/0004563213515190
Garnero P (2014) New developments in biological markers of bone metabolism in osteoporosis. Bone 66:46–55. doi:10.1016/j.bone.2014.05.016
Palermo A, Strollo R, Maddaloni E, Tuccinardi D, D’Onofrio L, Briganti SI, Defeudis G, De Pascalis M, Lazzaro MC, Colleluori G, Manfrini S, Pozzilli P, Napoli N (2014) Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity. Clin Endocrinol (Oxf). doi:10.1111/cen.12672
Boot RG, Blommaart EF, Swart E, Ghauharali-van der Vlugt K, Bijl N, Moe C, Place A, Aerts JM (2001) Identification of a novel acidic mammalian chitinase distinct from chitotriosidase. J Biol Chem 276:6770–6778. doi:10.1074/jbc.M009886200
Van Eijk M, Voorn-Brouwer T, Scheij SS, Verhoeven AJ, Boot RG, Aerts JM (2010) Curdlan-mediated regulation of human phagocyte-specific chitotriosidase. FEBS Lett 584:3165–3169. doi:10.1016/j.febslet.2010.06.001
Guan S-P, Mok Y-K, Koo K-N, Chu KL, Wong WS (2009) Chitinases: biomarkers for human diseases. Protein Pept Lett 16:490–498
Di Rosa M, Tibullo D, Vecchio M, Nunnari G, Saccone S, Di Raimondo F, Malaguarnera L (2014) Determination of chitinases family during osteoclastogenesis. Bone 61:55–63. doi:10.1016/j.bone.2014.01.005
Hollak CE, van Weely S, van Oers MH, Aerts JM (1994) Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. J Clin Invest 93:1288–1292. doi:10.1172/JCI117084
Orchard PJ, Lund T, Miller W, Rothman SM, Raymond G, Nascene D, Basso L, Cloyd J, Tolar J (2011) Chitotriosidase as a biomarker of cerebral adrenoleukodystrophy. J Neuroinflammation 8:144. doi:10.1186/1742-2094-8-144
Van Eijk M, van Roomen CPAA, Renkema GH, Bussink AP, Andrews L, Blommaart EF, Sugar A, Verhoeven AJ, Boot RG, Aerts JM (2005) Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity. Int Immunol 17:1505–1512. doi:10.1093/intimm/dxh328
Young E, Chatterton C, Vellodi A, Winchester B (1997) Plasma chitotriosidase activity in Gaucher disease patients who have been treated either by bone marrow transplantation or by enzyme replacement therapy with alglucerase. J Inherit Metab Dis 20:595–602
Ries M, Schaefer E, Lührs T, Mani L, Kuhn J, Vanier MT, Krummenauer F, Gal A, Beck M, Mengel E (2006) Critical assessment of chitotriosidase analysis in the rational laboratory diagnosis of children with Gaucher disease and Niemann-Pick disease type A/B and C. J Inherit Metab Dis 29:647–652. doi:10.1007/s10545-006-0363-3
Boot RG, Hollak CEM, Verhoek M, Alberts C, Jonkers RE, Aerts JM (2010) Plasma chitotriosidase and CCL18 as surrogate markers for granulomatous macrophages in sarcoidosis. Clin Chim Acta 411:31–36. doi:10.1016/j.cca.2009.09.034
Kzhyshkowska J, Gratchev A, Goerdt S (2007) Human chitinases and chitinase-like proteins as indicators for inflammation and cancer. Biomark Insights 2:128–146
Pagliardini V, Pagliardini S, Corrado L, Lucenti A, Panigati L, Bersano E, Servo S, Cantello R, D’Alfonso S, Mazzini L (2014) Chitotriosidase and lysosomal enzymes as potential biomarkers of disease progression in amyotrophic lateral sclerosis: a survey clinic-based study. J Neurol Sci. doi:10.1016/j.jns.2014.12.016
Cho SJ, Weiden MD, Lee CG (2015) Chitotriosidase in the pathogenesis of inflammation, interstitial lung diseases and COPD. Allergy Asthma Immunol Res 7:14–21. doi:10.4168/aair.2015.7.1.14
Elmonem MA, Makar SH, van den Heuvel L, Abdelaziz H, Abdelrahman SM, Bossuyt X, Janssen MC, Cornelissen EA, Lefeber DJ, Joosten LA, Nabhan MM, Arcolino FO, Hassan FA, Gaide Chevronnay HP, Soliman NA, Levtchenko E (2014) Clinical utility of chitotriosidase enzyme activity in nephropathic cystinosis. Orphanet J Rare Dis 9:155. doi:10.1186/s13023-014-0155-z
Vedder AC, Cox-Brinkman J, Hollak CE, Linthorst GE, Groener JE, Helmond MT, Scheij S, Aerts JM (2006) Plasma chitotriosidase in male Fabry patients: a marker for monitoring lipid-laden macrophages and their correction by enzyme replacement therapy. Mol Genet Metab 89:239–244. doi:10.1016/j.ymgme.2006.04.013
Chang MK, Raggatt L-J, Alexander KA, Kuliwaba JS, Fazzalari NL, Schroder K, Maylin ER, Ripoll VM, Hume DA, Pettit AR (2008) Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol 181:1232–1244
Vi L, Baht GS, Whetstone H, Ng A, Wei Q, Poon R, Mylvaganam S, Grynpas M, Alman BA (2014) Macrophages promote osteoblastic differentiation in-vivo: implications in fracture repair and bone homeostasis. J Bone Miner Res. doi:10.1002/jbmr.2422
Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E,Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176
Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E,Morinaga T, Higashio K (1998) Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139:1329–1337. doi:10.1210/endo.139.3.5837
Cho SW, Soki FN, Koh AJ, Eber MR, Entezami P, Park SI, van Rooijen N, McCauley LK (2014) Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone. Proc Natl Acad Sci U S A 111:1545–1550. doi:10.1073/pnas.1315153111
Boot RG, Renkema GH, Verhoek M, Strijland A, Bliek J, de Meulemeester TM, Mannens MM, Aerts JM (1998) The human chitotriosidase gene. Nature of inherited enzyme deficiency. J Biol Chem 273:25680–25685
Acknowledgments
We thank Mrs. Cinzia Antonacci, Department of Laboratory medicine, Campus Biomedico of Rome, for her assistance in laboratory work and Prof. Salvatore Musumeci, Institute of Biomolecular Chemistry, National Research Council (CNR), Catania, Italy, for his useful help in the discussion.
Conflict of interests
None.
Author information
Authors and Affiliations
Corresponding author
Additional information
M. Musumeci, A. Palermo, V. Denaro and S. Manfrini contributed equally to this work.
Rights and permissions
About this article
Cite this article
Musumeci, M., Palermo, A., D’Onofrio, L. et al. Serum chitotriosidase in postmenopausal women with severe osteoporosis. Osteoporos Int 27, 711–716 (2016). https://doi.org/10.1007/s00198-015-3254-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-015-3254-3