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Osteoporosis arises from imbalanced activity of osteoclasts and osteoblasts. Since these cell lineages produce the protease, cathepsin Z, the aim of this study was to investigate whether altered cathepsin Z mRNA levels are associated with osteoporosis in clinical samples. Cathepsin Z mRNA in human peripheral blood mononuclear cells was significantly differentially-expressed among non-osteoporotic controls, osteopenia and osteoporosis patients (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and in female osteoporosis patients over the age of 50 years (<jats:italic>P<\/jats:italic>\u2009=\u20090.0016). Cathepsin Z mRNA level strongly correlated with low bone mineral density (BMD) (g\/cm<jats:sup>2<\/jats:sup>), lumbar spine L2-L4 and femoral neck (<jats:italic>T<\/jats:italic>-scores) (<jats:italic>P<\/jats:italic>\u2009=\u20090.0149, 0.0002 and 0.0139, respectively). Importantly, cathepsin Z mRNA was significantly associated with fragility fracture in osteoporosis patients (<jats:italic>P<\/jats:italic>\u2009=\u20090.0018). The levels of cathepsin Z mRNA were not significantly higher in patients with chronic inflammatory disorders in these two groups compared to those without (<jats:italic>P<\/jats:italic>\u2009=\u20090.774 and 0.666, respectively). ROC analysis showed that cathepsin Z mRNA has strong diagnostic value for osteoporosis and osteoporotic fracture. The results show for the first time that cathepsin Z could be a future diagnostic biomarker for osteoporosis including female osteoporosis patients over the age of 50 years.<\/jats:p>","DOI":"10.1038\/s41598-019-46068-0","type":"journal-article","created":{"date-parts":[[2019,7,5]],"date-time":"2019-07-05T10:03:06Z","timestamp":1562320986000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Cathepsin Z as a novel potential biomarker for osteoporosis"],"prefix":"10.1038","volume":"9","author":[{"given":"Ayed A.","family":"Dera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshminarayan","family":"Ranganath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Barraclough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sobhan","family":"Vinjamuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Hamill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong L.","family":"Barraclough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,5]]},"reference":[{"key":"46068_CR1","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nrrheum.2009.260","volume":"6","author":"N Harvey","year":"2010","unstructured":"Harvey, N., Dennison, E. & Cooper, C. 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