{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:05:27Z","timestamp":1791515127436,"version":"4.3.4"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T00:00:00Z","timestamp":1577145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1041456"],"award-info":[{"award-number":["GNT1041456"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Osteolysis adjacent to total hip replacement (THR) prostheses is a major cause of their eventual failure. Periprosthetic osteolysis is associated with the production of bioactive particles, produced by the wear of articulating prosthesis surfaces. Wear particles invade the periprosthetic tissue, inducing inflammation and bone resorption. Previous studies have shown that osteocytes, the most numerous cell type in mineralised bone, can respond to wear particles of multiple orthopaedic material types. Osteocytes play important roles in bone resorption, regulating bone resorption by osteoclasts and directly through osteocytic osteolysis, also known as perilacunar remodelling. In this study, we perform a histological analysis of bone biopsies obtained from cohorts of male and female patients undergoing either primary THR surgery or revision THR surgery for aseptic loosening. The osteocyte lacunae area (Ot.Lac.Ar) and percentage lacunar area\/bone area (%Ot.Lac.Ar\/B.Ar) were significantly larger overall in revision THR bone than bone from similar sites in primary THR. Analysis by patient gender showed that increased Ot.Lac.Ar, indicative of increased perilacunar remodelling, was restricted to female revision samples. No significant differences in osteoclast parameters were detectable between the cohorts. These findings suggest previously unrecognised gender-specific mechanisms of bone loss in orthopaedic wear particle-induced osteolysis in humans.<\/jats:p>","DOI":"10.3390\/jcm9010053","type":"journal-article","created":{"date-parts":[[2019,12,25]],"date-time":"2019-12-25T11:07:48Z","timestamp":1577272068000},"page":"53","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evidence for Gender-Specific Bone Loss Mechanisms in Periprosthetic Osteolysis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-5791","authenticated-orcid":false,"given":"Renee T.","family":"Ormsby","sequence":"first","affiliation":[{"name":"Biomedical Orthopaedic Research Group, Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucian B.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, SA 5000, Australia"},{"name":"Department of Orthopaedics & Trauma, Royal Adelaide Hospital, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roumen","family":"Stamenkov","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics & Trauma, Royal Adelaide Hospital, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Findlay","sequence":"additional","affiliation":[{"name":"Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3123-9861","authenticated-orcid":false,"given":"Gerald J.","family":"Atkins","sequence":"additional","affiliation":[{"name":"Biomedical Orthopaedic Research Group, Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,24]]},"reference":[{"key":"ref_1","unstructured":"(2019, June 30). Australian Orthopaedic Association National Joint Replacement Registry Annual Report 2017. Available online: https:\/\/aoanjrr.sahmri.com\/annual-reports-2017."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1186\/ar2170","article-title":"Aseptic loosening of total joint replacements: Mechanisms underlying osteolysis and potential therapies","volume":"9","author":"Darwech","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1097\/00003086-200112000-00008","article-title":"Osteolysis: Basic science","volume":"393","author":"Jacobs","year":"2001","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s11420-006-9003-6","article-title":"The central role of wear debris in periprosthetic osteolysis","volume":"2","author":"Purdue","year":"2006","journal-title":"HSS J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"93","DOI":"10.5312\/wjo.v2.i10.93","article-title":"Role of polyethylene particles in peri-prosthetic osteolysis: A review","volume":"2","author":"Atkins","year":"2011","journal-title":"World J. Orthop."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1302\/2046-3758.55.BJR-2016-0086","article-title":"The pathobiology and pathology of aseptic implant failure","volume":"5","author":"Athanasou","year":"2016","journal-title":"Bone Jt. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s10787-013-0192-6","article-title":"Periprosthetic osteolysis after total hip replacement: Molecular pathology and clinical management","volume":"21","author":"Howie","year":"2013","journal-title":"Inflammopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1136\/pgmj.2006.053215","article-title":"Femoral osteolysis following total hip replacement","volume":"83","author":"Dattani","year":"2007","journal-title":"Postgrad Med. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1302\/0301-620X.80B3.0800531","article-title":"Cellular profile and cytokine production at prosthetic interfaces-study of tissues retrieved from revised hip and knee replacements","volume":"80b","author":"Goodman","year":"1998","journal-title":"J. Bone Jt. Surg. Br. Vol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s00402-015-2196-8","article-title":"Metal ions as inflammatory initiators of osteolysis","volume":"135","author":"Magone","year":"2015","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.arth.2005.04.001","article-title":"Revision total hip arthroplasty in hip joints with metallosis: A single-center experience with 31 cases","volume":"20","author":"Chang","year":"2005","journal-title":"J. Arthroplast."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1002\/jbm.b.33243","article-title":"Wear particles and ions from cemented and uncemented titanium-based hip prostheses-a histological and chemical analysis of retrieval material","volume":"103","author":"Grosse","year":"2015","journal-title":"J. Biomed. Mater. Res. Part B Appl. Biomater."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/00003086-199807000-00026","article-title":"Variation in cytokines induced by particles from different prosthetic materials","volume":"352","author":"Haynes","year":"1998","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1016\/0142-9612(96)00013-0","article-title":"Histomorphological reaction of bone to different concentrations of phagocytosable particles of high-density polyethylene and ti-6al-4v alloy in vivo","volume":"17","author":"Goodman","year":"1996","journal-title":"Biomaterials"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chiu, R., Ma, T., Smith, R.L., and Goodman, S.B. (2008). Ultrahigh molecular weight polyethylene wear debris inhibits osteoprogenitor proliferation and differentiation in vitro. J. Biomed. Mater. Res. Part A.","DOI":"10.1002\/jbm.a.32001"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S0142-9612(99)00211-2","article-title":"Phagocytosis of wear debris by osteoblasts affects differentiation and local factor production in a manner dependent on particle composition","volume":"21","author":"Lohmann","year":"2000","journal-title":"Biomaterials"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1002\/jbm.a.31794","article-title":"Allocation of nonbirefringent wear debris: Darkfield illumination associated with pixe microanalysis reveals cobalt deposition in mineralized bone matrix adjacent to cocr implants","volume":"87","author":"Busse","year":"2008","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3672","DOI":"10.1016\/j.biomaterials.2009.03.035","article-title":"The induction of a catabolic phenotype in human primary osteoblasts and osteocytes by polyethylene particles","volume":"30","author":"Atkins","year":"2009","journal-title":"Biomaterials"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.actbio.2016.01.016","article-title":"Evidence that osteocyte perilacunar remodelling contributes to polyethylene wear particle induced osteolysis","volume":"33","author":"Ormsby","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.coph.2016.02.003","article-title":"Osteocytes: The master cells in bone remodelling","volume":"28","author":"Prideaux","year":"2016","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/jbmr.320","article-title":"The amazing osteocyte","volume":"26","author":"Bonewald","year":"2011","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/jbmr.1567","article-title":"Demonstration of osteocytic perilacunar\/canalicular remodeling in mice during lactation","volume":"27","author":"Qing","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1002\/jbmr.1646","article-title":"Matrix metalloproteinase-13 is required for osteocytic perilacunar remodeling and maintains bone fracture resistance","volume":"27","author":"Tang","year":"2012","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1002\/jbmr.2003","article-title":"Sclerostin regulates release of bone mineral by osteocytes by induction of carbonic anhydrase 2","volume":"28","author":"Kogawa","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"59","DOI":"10.4248\/ijos.09019","article-title":"Osteocyte remodeling of the perilacunar and pericanalicular matrix","volume":"1","author":"Qing","year":"2009","journal-title":"Int. J. Oral Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1210\/en.2015-1345","article-title":"A role for the calcitonin receptor to limit bone loss during lactation in female mice by inhibiting osteocytic osteolysis","volume":"156","author":"Clarke","year":"2015","journal-title":"Endocrinology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.actbio.2019.01.047","article-title":"Osteocytes respond to particles of clinically-relevant conventional and cross-linked polyethylene and metal alloys by up-regulation of resorptive and inflammatory pathways","volume":"87","author":"Ormsby","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1359\/JBMR.051103","article-title":"Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice","volume":"21","author":"Lane","year":"2006","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"172","DOI":"10.5312\/wjo.v6.i2.172","article-title":"Biological response to prosthetic debris","volume":"6","author":"Bitar","year":"2015","journal-title":"World J. Orthop."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1302\/0301-620X.81B4.0810582","article-title":"Polyethylene wear, osteolysis and acetabular loosening with an ha-coated hip prosthesis. A follow-up of 94 consecutive arthroplasties","volume":"81","author":"Rokkum","year":"1999","journal-title":"J. Bone Jt. Surg. Br. Vol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/jor.21554","article-title":"Review of periprosthetic osteolysis in total joint arthroplasty: An emphasis on host factors and future directions","volume":"30","author":"Beck","year":"2012","journal-title":"J. Orthopaed Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1097\/00003086-200012000-00005","article-title":"The john charnley award. Wear is a function of use, not time","volume":"i7","author":"Schmalzried","year":"2000","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.bone.2013.01.025","article-title":"Osteocytes remove and replace perilacunar mineral during reproductive cycles","volume":"54","author":"Wysolmerski","year":"2013","journal-title":"Bone"},{"key":"ref_34","first-page":"135","article-title":"The influence of pregnancy and lactation on maternal bone health: A systematic review","volume":"8","author":"Salari","year":"2014","journal-title":"J. Fam. Reprod Health"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"R53","DOI":"10.1530\/EJE-14-0424","article-title":"Bone metabolic changes during pregnancy: A period of vulnerability to osteoporosis and fracture","volume":"172","author":"Tarin","year":"2015","journal-title":"Eur. J. Endocrinol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00198-002-1329-4","article-title":"Endogenous hormones and bone turnover markers in pre- and perimenopausal women: Swan","volume":"14","author":"Sowers","year":"2003","journal-title":"Osteoporos. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s11914-010-0014-3","article-title":"Reproductive hormones and bone","volume":"8","author":"Nicks","year":"2010","journal-title":"Curr. Osteoporos Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e00415-18","DOI":"10.1128\/mBio.00415-18","article-title":"Novel insights into staphylococcus aureus deep bone infections: The involvement of osteocytes","volume":"9","author":"Yang","year":"2018","journal-title":"MBio"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/1759720X16687480","article-title":"Diabetes and bone health: Latest evidence and clinical implications","volume":"9","author":"Sundararaghavan","year":"2017","journal-title":"Ther. Adv. Musculoskelet Dis."},{"key":"ref_40","first-page":"4184190","article-title":"The effect of tobacco smoking on musculoskeletal health: A systematic review","volume":"2018","author":"Haddad","year":"2018","journal-title":"J. Environ. Public Health"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s42000-018-0018-4","article-title":"Obesity and bone metabolism","volume":"17","author":"Savvidis","year":"2018","journal-title":"Horm. (Athens)"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/1\/53\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:45:28Z","timestamp":1760190328000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/1\/53"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,24]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["jcm9010053"],"URL":"https:\/\/doi.org\/10.3390\/jcm9010053","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,24]]}}}