{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T23:41:45Z","timestamp":1781826105197,"version":"3.54.5"},"update-to":[{"DOI":"10.12688\/f1000research.2-266.v1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T00:00:00Z","timestamp":1402963200000}}],"reference-count":120,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T00:00:00Z","timestamp":1402963200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Total joint replacement surgery is being performed on an increasingly large part of the population. Clinical longevity of implants depends on their osseointegration, which is influenced by the load, the characteristics of the implant and the bone-implant interface, as well as by the quality and quantity of the surrounding bone. Aseptic loosening due to periprosthetic osteolysis is the most frequent known cause of implant failure. Wear of prosthetic materials results in the formation of numerous particles of debris that cause a complex biological response. Dual-energy X-ray Absorptiometry (DXA) is regarded as an accurate method to evaluate Bone Mineral Density (BMD) around hip or knee prostheses. Further data may be provided by a new device, the Bone Microarchitecture Analysis (BMA), which combines bone microarchitecture quantification and ultra high resolution osteo-articular imaging. Pharmacological strategies have been developed to prevent bone mass loss and to extend implant survival. Numerous trials with bisphosphonates show a protective effect on periprosthetic bone mass, up to 72 months after arthroplasty. Strontium ranelate has been demonstrated to increase the osseointegration of titanium implants in treated animals with improvement of bone microarchitecture and bone biomaterial properties.<\/ns4:p>","DOI":"10.12688\/f1000research.2-266.v2","type":"journal-article","created":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T12:52:35Z","timestamp":1403009555000},"page":"266","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Periprosthetic bone loss: diagnostic and therapeutic approaches"],"prefix":"10.12688","volume":"2","author":[{"given":"Loredana","family":"Cavalli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Brandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2014,6,17]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"1436-41","DOI":"10.1016\/j.bone.2010.01.379","article-title":"Strontium Ranelate improves implant osseointegration.","volume":"46","author":"L Maimoun","year":"2010","journal-title":"Bone."},{"key":"ref-2","first-page":"50-55","article-title":"Ibandronate and cementless total hip arthroplasty: densitometric measurement of periprosthetic bone mass and new therapeutic approach to the prevention of aseptic loosening.","volume":"9","author":"M Muratore","year":"2012","journal-title":"Clin Cases Miner Bone Metab."},{"key":"ref-3","doi-asserted-by":"crossref","first-page":"575-84","DOI":"10.2106\/00004623-198365050-00001","article-title":"The synovial-like membrane at the bone-cement interface in loose total hip replacements and its proposed role in bone lysis.","volume":"65","author":"S Goldring","year":"1983","journal-title":"J Bone Joint Surg Am."},{"key":"ref-4","doi-asserted-by":"crossref","first-page":"612-8","DOI":"10.2106\/00004623-197658050-00005","article-title":"Extensive localized bone resorption in the femur following total hip replacement.","volume":"58","author":"W Harris","year":"1976","journal-title":"J Bone Joint Surg Am."},{"key":"ref-5","doi-asserted-by":"crossref","first-page":"912-9","DOI":"10.2106\/00004623-198668060-00014","article-title":"Localized osteolysis in stable non-septic total hip replacement.","volume":"68","author":"M Jasty","year":"1986","journal-title":"J Bone Joint Surg Am."},{"key":"ref-6","first-page":"599-605","article-title":"Aseptic loosening in total hip implants: the role of polyethylene wear debris.","volume":"34","author":"E Boynton","year":"1991","journal-title":"Can J Surg."},{"key":"ref-7","first-page":"79-87","article-title":"Il Disodio Clodronato riduce il riassorbimento periprotesico in impianti non cementati nelle fasi precoci: studio prospettico con controllo.","volume":"28","author":"L Massari","year":"2002","journal-title":"GIOT."},{"key":"ref-8","first-page":"71-78","article-title":"Bisfosfonati e protesi articolari. Up-to-date 2005","author":"G Iolascon","year":"2005"},{"key":"ref-9","first-page":"95-102","article-title":"Collagen texture and osteocyte distribution in lamellar bone.","volume":"100","author":"G Marotti","year":"1995","journal-title":"Ital J Anat Embryol."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"331-339","DOI":"10.1007\/s002239900536","article-title":"Osteocyte-bone lining cell system at the origin of steady ionic current in damaged amphibian bone.","volume":"63","author":"A Rubinacci","year":"1998","journal-title":"Calcif Tissue Int."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"1823-1834","DOI":"10.1007\/s00198-011-1797-5","article-title":"Bisphosphonates for periprosthetic bone loss after joint arthroplasty: a meta-analysis of 14 randomized controlled trials.","volume":"23","author":"T Lin","year":"2012","journal-title":"Osteoporos Int."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"579-586","DOI":"10.1302\/0301-620X.83B4.11223","article-title":"Hip disease and the prognosis of total hip replacements. A review of 53,698 primary total hip replacements reported to the Norwegian Arthroplasty Register 1987\u201399.","volume":"83","author":"O Furnes","year":"2001","journal-title":"J Bone Joint Surg Br."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"953-958","DOI":"10.2106\/JBJS.E.00120","article-title":"Proximal femoral allograft treatment of Vancouver type-B3 periprosthetic femoral fractures after total hip arthroplasty.","volume":"88","author":"A Maury","year":"2006","journal-title":"J Bone Joint Surg Am."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"1166-1169","DOI":"10.1016\/j.injury.2012.03.024","article-title":"Femoral replacement for salvage of periprosthetic fracture around a total hip replacement.","volume":"43","author":"A McLean","year":"2012","journal-title":"Injury: Int J Care Injured."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"783-8","DOI":"10.1016\/j.arth.2011.08.019","article-title":"A Biomechanical Comparison of Periprosthetic Femoral Fracture Fixation in Normal and Osteoporotic Cadaveric Bone.","volume":"27","author":"H Demos","year":"2012","journal-title":"J Arthroplasty."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1186\/ar2170","article-title":"Aseptic loosening of total joint replacements: mechanisms underlying osteolysis and potential therapies.","volume":"9","author":"Y Abu-Amer","year":"2007","journal-title":"Arthritis Res Ther."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"83-92","DOI":"10.1002\/jor.1100120111","article-title":"In vivo inflammatory response to polymethylmethacrylate particulate debris: effect of size, morphology, and surface area.","volume":"12","author":"H Gelb","year":"1994","journal-title":"J Ortho Res."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"463-473","DOI":"10.1002\/(SICI)1097-4636(199604)30:4<463::AID-JBM4>3.0.CO;2-N","article-title":"Effect of size, concentration, surface area, and volume of polymethylmethacrylate particles on human macrophages in vitro.","volume":"30","author":"O Gonzalez","year":"1996","journal-title":"J Biomed Mater Res."},{"key":"ref-19","first-page":"60-67","article-title":"Composition and morphology of wear debris in failed uncemented total hip replacement.","volume":"76","author":"A Shanbhag","year":"1994","journal-title":"J Bone Joint Surg Br."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"1041-1048","DOI":"10.1016\/S0736-0266(03)00081-0","article-title":"Mitogen-activated protein (MAP) kinases mediate PMMA-induction of osteoclasts.","volume":"21","author":"S Abbas","year":"2003","journal-title":"J Orthop Res."},{"key":"ref-21","first-page":"26-34","article-title":"Cytokine and matrix metalloproteinase expression in pigmented villonodular synovitis may mediate bone and cartilage destruction.","volume":"18","author":"R O\u2019Keefe","year":"1998","journal-title":"Iowa Orthop J."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"21-28","DOI":"10.5507\/bp.2002.004","article-title":"Particle disease. A comprehensive theory of periprosthetic osteolysis: a review.","volume":"146","author":"J Gallo","year":"2002","journal-title":"Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"129-34","DOI":"10.1016\/j.arth.2005.04.014","article-title":"Changes of the biochemical markers of bone turnover and periprosthetic bone remodeling after cemented hip arthroplasty.","volume":"21","author":"M Arabmotlagh","year":"2006","journal-title":"J Arthroplasty."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"291-297","DOI":"10.3109\/17453670903074467","article-title":"Periprosthetic DXA after total hip arthroplasty with short vs. ultra-short custom-made femoral stems: 37 patients followed for 3 years.","volume":"80","author":"C Albanese","year":"2009","journal-title":"Acta Orthop."},{"key":"ref-25","first-page":"339-46","article-title":"Closeness of fit of uncemented stems improves the strain distribution in the femur.","volume":"13","author":"J Hua","year":"1995","journal-title":"J Orthop Res."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"20-6","DOI":"10.1302\/0301-620X.86B1.14637","article-title":"Changes in bone mineral density in the proximal femur after cementless total hip arthroplasty. A five-year longitudinal study.","volume":"86","author":"W Brodner","year":"2004","journal-title":"J Bone Joint Surg Br."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"281-9","DOI":"10.1007\/s00198-003-1546-5","article-title":"Periprosthetic bone remodeling of two types of uncemented femoral implant with proximal hydroxyapatite coating: a 3-year follow-up study addressing the influence of prosthesis design and preoperative bone density on periprosthetic bone loss.","volume":"15","author":"A Rahmy","year":"2004","journal-title":"Osteoporos Int."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"60-5","DOI":"10.1007\/BF00434103","article-title":"Course of bone mineral content changes around cementless Zweym\u00fcller total hip arthroplasty. A 4-year follow-up study.","volume":"116","author":"P Korovessis","year":"1997","journal-title":"Arch Orthop Trauma Surg."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"386-92","DOI":"10.1080\/17453670610046307","article-title":"Periprosthetic proximal bone loss after uncemented hip arthroplasty is related to stem size: DXA measurements in 138 patients followed for 2\u20137 years.","volume":"77","author":"O Sk\u00f6ldenberg","year":"2006","journal-title":"Acta Orthop."},{"key":"ref-30","first-page":"1651-8","article-title":"Evaluation of a femoral stem with reduced stiffness. A randomized study with use of radiostereometry and bone densitometry.","volume":"84-A","author":"J K\u00e4rrholm","year":"2002","journal-title":"J Bone Joint Surg Am."},{"key":"ref-31","doi-asserted-by":"publisher","first-page":"32-37","DOI":"10.1007\/BF00121253","article-title":"Bone remodeling after total hip arthroplasty using an uncemented anatomic femoral stem: a three-year prospective study using bone densitometry.","volume":"14","author":"J Panisello","year":"2006","journal-title":"J Orthop Surg (Hong Kong)."},{"key":"ref-32","doi-asserted-by":"crossref","first-page":"9-15","DOI":"10.1177\/112070000601603S03","article-title":"Bone remodeling in THA: a comparative DXA scan study conventional implants and a new stemless femoral component. A preliminary report.","volume":"16","author":"C Albanese","year":"2006","journal-title":"Hip Int."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"2211-2217","DOI":"10.1007\/s00264-012-1616-4","article-title":"The cementless Bicontact\u00ae stem in a prospective dual-energy X-ray absorptiometry study.","volume":"36","author":"M Lerch","year":"2012","journal-title":"Int Orthop."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"17-27","DOI":"10.1097\/00003086-197906000-00002","article-title":"\"Modes of failure\" of cemented stem-type femoral components: a radiographic analysis of loosening.","author":"T Gruen","year":"1979","journal-title":"Clin Orthop Relat Res."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"158-61","DOI":"10.1007\/BF01321831","article-title":"Dual X-ray Absorptiometry for the evaluation of bone density from the proximal femur after total hip arthroplasty: analysis, protocols and reproducibility.","volume":"53","author":"C Trevisan","year":"1993","journal-title":"Calcif Tissue Int."},{"key":"ref-36","doi-asserted-by":"crossref","first-page":"1687-98","DOI":"10.2106\/00004623-199811000-00018","article-title":"Bone densitometry in orthopaedic practice.","volume":"80","author":"E Mirsky","year":"1998","journal-title":"J Bone Joint Surg Am."},{"key":"ref-37","doi-asserted-by":"publisher","first-page":"422-7","DOI":"10.1016\/S0883-5403(98)90008-0","article-title":"Bone loss around 2 different types of hip prostheses.","volume":"13","author":"A Spittlehouse","year":"1998","journal-title":"J Arthroplasty."},{"key":"ref-38","doi-asserted-by":"publisher","first-page":"1056-61","DOI":"10.1359\/jbmr.2001.16.6.1056","article-title":"Monitoring of periprosthetic BMD after uncemented total hip arthroplasty with dual-energy X-ray absorptiometry--a 3-year follow-up study.","volume":"16","author":"P Venesmaa","year":"2001","journal-title":"J Bone Min Res."},{"key":"ref-39","doi-asserted-by":"publisher","first-page":"410-416","DOI":"10.3109\/17453674.2011.588860","article-title":"Periprosthetic bone loss after insertion of an uncemented, customized femoral stem and an uncemented anatomical stem. A randomized DXA study with 5-year follow-up.","volume":"82","author":"M Nysted","year":"2011","journal-title":"Acta Orthop."},{"key":"ref-40","doi-asserted-by":"publisher","first-page":"115-21","DOI":"10.1007\/s00223-002-2036-z","article-title":"Pattern of periprosthetic bone remodeling around stable uncemented tapered hip stems: a prospective 84-month follow-up study and a median 156-month cross-sectional study with DXA.","volume":"73","author":"P Aldinger","year":"2003","journal-title":"Calcif Tissue Int."},{"key":"ref-41","doi-asserted-by":"publisher","first-page":"877-85","DOI":"10.1080\/17453670610013169","article-title":"Continuous bone loss around a tapered uncemented femoral stem. A long-term evaluation with DEXA.","volume":"77","author":"H Bod\u00e9n","year":"2006","journal-title":"Acta Orthop."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"1499-504","DOI":"10.1016\/S0140-6736(00)02164-4","article-title":"Poor bone quality or hip structure as risk factors affecting survival of total-hip arthroplasty.","volume":"355","author":"S Kobayashi","year":"2000","journal-title":"Lancet."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"89-92","DOI":"10.1007\/s002640100246","article-title":"Periprosthetic bone mineral density changes with femoral components of differing design philosophy.","volume":"25","author":"C Gibbons","year":"2001","journal-title":"Int Orthop."},{"key":"ref-44","doi-asserted-by":"publisher","first-page":"373-9","DOI":"10.1016\/S0883-5403(97)90192-3","article-title":"Effect of a stemless femoral implant for total hip arthroplasty on the bone mineral density of the proximal femur. A prospective longitudinal study.","volume":"12","author":"E Munting","year":"1997","journal-title":"J Arthroplasty."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"791-795","DOI":"10.1080\/17453670510045381","article-title":"Measurement of bone mineral density is possible with standard radiographs: a study involving total knee replacement.","volume":"76","author":"M Hernandez-Vaquero","year":"2005","journal-title":"Acta Orthop."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"1595-1601","DOI":"10.1007\/s00402-012-1601-9","article-title":"Osteodensitometry measurements of periprosthetic bone using dual energy X-ray absorptiometry following total knee arthroplasty.","volume":"132","author":"C Windisch","year":"2012","journal-title":"Arch Orthop Trauma Surg."},{"key":"ref-47","doi-asserted-by":"publisher","first-page":"5407-18","DOI":"10.1088\/0031-9155\/49\/24\/001","article-title":"X-ray CT high density artefact suppression in the presence of bones.","volume":"49","author":"J Wei","year":"2004","journal-title":"Phys Med Biol."},{"key":"ref-48","doi-asserted-by":"publisher","first-page":"589-95","DOI":"10.1007\/s00264-007-0389-7","article-title":"Quantitative CT-assisted osteodensitometry of femoral adaptive bone remodelling after uncemented total hip arthroplasty.","volume":"32","author":"R Pitto","year":"2008","journal-title":"Int Orthop."},{"key":"ref-49","doi-asserted-by":"publisher","first-page":"553-62","DOI":"10.1007\/s11517-007-0188-8","article-title":"The reduction of artifacts due to metal hip implants in CT-attenuation corrected PET images from hybrid PET\/CT scanners.","volume":"45","author":"J Kennedy","year":"2007","journal-title":"Med Biol Eng Comput."},{"key":"ref-50","article-title":"Data sheet of the device BMA TMMP D3A Medical Systems"},{"key":"ref-51","doi-asserted-by":"publisher","first-page":"295-301","DOI":"10.1302\/0301-620X.83B2.10108","article-title":"Strain distribution in the proximal human femur. An in vitro comparison in the intact femur and after insertion of reference and experimental femoral stems.","volume":"83","author":"Y Kim","year":"2001","journal-title":"J Bone Joint Surg Br."},{"key":"ref-52","doi-asserted-by":"crossref","first-page":"S22-S30","DOI":"10.1177\/112070000601603S05","article-title":"Biomechanics of a new short-stemmed uncemented hip prosthesis: an in-vitro study in human bone.","volume":"16","author":"F Westphal","year":"2006","journal-title":"Hip Int."},{"key":"ref-53","doi-asserted-by":"crossref","first-page":"71-80","DOI":"10.1177\/112070009900900210","article-title":"The effect of a lateral flare feature on uncemented hip stems.","volume":"9","author":"P Walker","year":"1999","journal-title":"Hip International."},{"key":"ref-54","doi-asserted-by":"publisher","first-page":"166-9","DOI":"10.1007\/s00264-002-0355-3","article-title":"The effect of a lateral flare feature on implant stability.","volume":"26","author":"A Leali","year":"2002","journal-title":"Int Orthop."},{"key":"ref-55","doi-asserted-by":"publisher","first-page":"151-4","DOI":"10.1007\/s00264-004-0554-1","article-title":"Preservation of femoral bone mass after total hip replacements with a lateral flare stem.","volume":"28","author":"A Leali","year":"2004","journal-title":"Int Orthop."},{"key":"ref-56","doi-asserted-by":"crossref","first-page":"322-6","DOI":"10.1177\/230949901202000311","article-title":"Mid-term outcome of a modular, cementless, proximally hydroxyapatite-coated, anatomic femoral stem.","volume":"20","author":"D Cossetto","year":"2012","journal-title":"J Orthop Surg (Hong Kong)."},{"key":"ref-57","doi-asserted-by":"publisher","first-page":"451-75","DOI":"10.1055\/s-0030-1267120","article-title":"Functional results of hip arthroplasty with acrylic prosthesis.","volume":"36-A","author":"R D\u2019Aubigne","year":"1954","journal-title":"J Bone Joint Surg Am."},{"key":"ref-58","first-page":"46-50","article-title":"Australian Orthopaedic Association National Joint Replacement Registry Annual Report.","year":"2010"},{"key":"ref-59","doi-asserted-by":"publisher","first-page":"700-6","DOI":"10.2106\/JBJS.H.01349","article-title":"Comparison of bone mineral density between porous tantalum and cemented tibial total knee arthroplasty components.","volume":"92","author":"Y Minoda","year":"2010","journal-title":"J Bone Joint Surg Am."},{"key":"ref-60","doi-asserted-by":"crossref","first-page":"337-346","DOI":"10.1016\/S0142-9612(02)00324-1","article-title":"Prosthetic particles modify the expression of bone-related proteins by human osteoblastic cells in vitro.","volume":"24","author":"H Zreiqat","year":"2003","journal-title":"Biomaterials."},{"key":"ref-61","doi-asserted-by":"publisher","first-page":"1136-1148","DOI":"10.1359\/JBMR.050206","article-title":"Fibroblasts express RANKL and support osteoclastogenesis in a COX-2-dependent manner after stimulation with titanium particles.","volume":"20","author":"X Wei","year":"2005","journal-title":"J Bone Miner Res."},{"key":"ref-62","first-page":"276-284","article-title":"RANK, RANKL and OPG in inflammatory arthritis and periprosthetic osteolysis.","volume":"4","author":"C Ritchlin","year":"2004","journal-title":"J Musculoskelet Neuronal Interact."},{"key":"ref-63","doi-asserted-by":"publisher","first-page":"5050-5055","DOI":"10.1210\/en.142.12.5050","article-title":"Minireview: the OPG\/RANKL\/RANK system.","volume":"142","author":"S Khosla","year":"2001","journal-title":"Endocrinology."},{"key":"ref-64","doi-asserted-by":"publisher","first-page":"192-199","DOI":"10.1359\/jbmr.2002.17.2.192","article-title":"In vivo RANK signaling blockade using the receptor activator of NF-kappaB:Fc effectively prevents and ameliorates wear debris-induced osteolysis via osteoclast depletion without inhibiting osteogenesis.","volume":"17","author":"L Childs","year":"2002","journal-title":"J Bone Miner Res."},{"key":"ref-65","first-page":"1405-1412","article-title":"Recombinant adeno-associated virus-mediated osteoprotegerin gene therapy inhibits wear debris-induced osteolysis.","volume":"84-A","author":"M Ulrich-Vinther","year":"2002","journal-title":"J Bone Joint Surg Am."},{"key":"ref-66","doi-asserted-by":"publisher","first-page":"205-16","DOI":"10.1185\/03007995.2013.763779","article-title":"Denosumab, a new pharmacotherapy option for postmenopausal osteoporosis.","volume":"29","author":"R Josse","year":"2013","journal-title":"Curr Med Res Opin."},{"key":"ref-67","doi-asserted-by":"publisher","first-page":"13-20","DOI":"10.1016\/S0736-0266(03)00156-6","article-title":"NF-\u03baB signaling blockade abolishes implant particle-induced osteoclastogenesis.","volume":"22","author":"J Clohisy","year":"2004","journal-title":"J Orthop Res."},{"key":"ref-68","doi-asserted-by":"publisher","first-page":"20077-20082","DOI":"10.1074\/jbc.M208619200","article-title":"Dominant-negative IkappaB facilitates apoptosis of osteoclasts by tumor necrosis factor-alpha.","volume":"278","author":"S Abbas","year":"2003","journal-title":"J Biol Chem."},{"key":"ref-69","doi-asserted-by":"crossref","first-page":"5547-5553","DOI":"10.4049\/jimmunol.171.10.5547","article-title":"Direct inhibition of NF-kappa B blocks bone erosion associated with inflammatory arthritis.","volume":"171","author":"J Clohisy","year":"2003","journal-title":"J Immunol."},{"key":"ref-70","doi-asserted-by":"publisher","first-page":"37219-37222","DOI":"10.1074\/jbc.C400258200","article-title":"The IkappaB kinase (IKK) inhibitor, NEMO-binding domain peptide, blocks osteoclastogenesis and bone erosion in inflammatory arthritis.","volume":"279","author":"S Dai","year":"2004","journal-title":"J Biol Chem."},{"key":"ref-71","doi-asserted-by":"crossref","first-page":"347-355","DOI":"10.2174\/1568008054863808","article-title":"Advances in osteoclast differentiation and function.","volume":"5","author":"Y Abu-Amer","year":"2005","journal-title":"Curr Drug Targets Immune Endocr Metabol Disord."},{"key":"ref-72","doi-asserted-by":"publisher","first-page":"489-495","DOI":"10.1016\/S0165-6147(00)01567-4","article-title":"Src inhibitors: drugs for the treatment of osteoporosis, cancer or both?","volume":"21","author":"M Susva","year":"2000","journal-title":"Trends Pharmacol Sci."},{"key":"ref-73","doi-asserted-by":"publisher","first-page":"54-64","DOI":"10.1016\/S8756-3282(00)00427-0","article-title":"Bone-targeted src SH2 inhibitors block src cellular activity and osteoclast-mediated resorption.","volume":"28","author":"S Violette","year":"2001","journal-title":"Bone."},{"key":"ref-74","doi-asserted-by":"publisher","first-page":"2044-2047","DOI":"10.1002\/art.20383","article-title":"Bisphosphonates: environmental protection for the joint?","volume":"50","author":"S Goldring","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref-75","doi-asserted-by":"publisher","first-page":"31-40","DOI":"10.1002\/jbmr.5650050107","article-title":"Effects of bisphosphonates on isolated rat osteoclasts as examined by reflected light microscopy.","volume":"5","author":"M Sato","year":"1990","journal-title":"J Bone Miner Res."},{"key":"ref-76","doi-asserted-by":"publisher","first-page":"456-461","DOI":"10.1172\/JCI114459","article-title":"Bisphosphonates directly inhibit the bone resorption activity of isolated avian osteoclasts in vitro.","volume":"85","author":"A Carano","year":"1990","journal-title":"J Clin Invest."},{"key":"ref-77","doi-asserted-by":"publisher","first-page":"251-261","DOI":"10.1097\/01.blo.0000238813.95035.1b","article-title":"The cellular and molecular biology of periprosthetic osteolysis.","volume":"454","author":"P Purdue","year":"2007","journal-title":"Clin Orthop Relat Res."},{"key":"ref-78","doi-asserted-by":"publisher","first-page":"2095-2105","DOI":"10.1172\/JCI115539","article-title":"Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure.","volume":"88","author":"M Sato","year":"1991","journal-title":"J Clin Invest."},{"key":"ref-79","doi-asserted-by":"publisher","first-page":"339-346","DOI":"10.1002\/jbmr.5650060405","article-title":"The bisphosphonate alendronate (MK-217) inhibits bone loss due to ovariectomy in rats.","volume":"6","author":"J Seedor","year":"1991","journal-title":"J Bone Miner Res."},{"key":"ref-80","doi-asserted-by":"publisher","first-page":"2577-2586","DOI":"10.1172\/JCI116872","article-title":"The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman primates.","volume":"92","author":"R Balena","year":"1993","journal-title":"J Clin Invest."},{"key":"ref-81","first-page":"236-249","article-title":"Effects of alendronate on particle-induced osteolysis in a rat model.","volume":"84-A","author":"P Millett","year":"2002","journal-title":"J Bone Joint Surg Am."},{"key":"ref-82","first-page":"313","article-title":"Effects of alendronate in total hip arthroplasty. Proceedings of the South African Orthopaedic Association.","volume":"81","author":"A Lyons","year":"1999","journal-title":"J Bone Joint Surg Br."},{"key":"ref-83","doi-asserted-by":"publisher","first-page":"1-8","DOI":"10.1016\/j.orthres.2004.06.004","article-title":"Effect of pamidronate on bone turnover and implant migration after total hip arthroplasty: a randomized trial.","volume":"23","author":"J Wilkinson","year":"2005","journal-title":"J Orthop Res."},{"key":"ref-84","doi-asserted-by":"publisher","first-page":"4105-4115","DOI":"10.1016\/j.biomaterials.2003.11.024","article-title":"Osteoblast proliferation and maturation by bisphosphonates.","volume":"25","author":"G Im","year":"2004","journal-title":"Biomaterials."},{"key":"ref-85","first-page":"71-78","article-title":"Bisfosfonati e protesi articolari. Up-to-date 2005","author":"G Iolascon","year":"2005"},{"key":"ref-86","doi-asserted-by":"publisher","first-page":"2-19","DOI":"10.1016\/j.bone.2011.04.022","article-title":"Bisphosphonates: the first 40 years.","volume":"49","author":"R Russell","year":"2011","journal-title":"Bone."},{"key":"ref-87","doi-asserted-by":"publisher","first-page":"253-266","DOI":"10.2147\/TCRM.S7688","article-title":"Targeted approaches in the treatment of osteoporosis: differential mechanism of action of denosumab and clinical utility.","volume":"8","author":"L Cavalli","year":"2012","journal-title":"Ther Clin Risk Manag."},{"key":"ref-88","doi-asserted-by":"publisher","first-page":"1294-1301","DOI":"10.1210\/jc.2004-0952","article-title":"Severely suppressed bone turnover: a potential complication of alendronate therapy.","volume":"90","author":"C Odvina","year":"2005","journal-title":"J Clin Endocrinol Metab."},{"key":"ref-89","doi-asserted-by":"publisher","first-page":"1736-1740","DOI":"10.1359\/jbmr.090408","article-title":"Bilateral fractures of the femur diaphysis in a patient with rheumatoid arthritis on long-term treatment with alendronate: clues to the mechanism of increased bone fragility.","volume":"24","author":"M Somford","year":"2009","journal-title":"J Bone Miner Res."},{"key":"ref-90","doi-asserted-by":"publisher","first-page":"460-462","DOI":"10.3109\/17453674.2010.492766","article-title":"Histology of an undisplaced femoral fatigue fracture in association with bisphosphonate treatment: Frozen bone with remodelling at the crack.","volume":"81","author":"P Aspenberg","year":"2010","journal-title":"Acta Orthop."},{"key":"ref-91","doi-asserted-by":"publisher","first-page":"887-894","DOI":"10.1007\/s00198-008-0754-4","article-title":"Changes in non-enzymatic glycation and its association with altered mechanical properties following 1-year treatment with risendronate or alendronate.","volume":"20","author":"S Tang","year":"2009","journal-title":"Osteoporos Int."},{"key":"ref-92","doi-asserted-by":"publisher","first-page":"672-678","DOI":"10.1002\/jbmr.560","article-title":"Reduced cortical bone compositional heterogeneity with bisphosphonate treatment in postmenopausal women with intertrochanteric and subtrochanteric fractures.","volume":"27","author":"E Donnelly","year":"2012","journal-title":"J Bone Miner Res."},{"key":"ref-93","doi-asserted-by":"publisher","first-page":"2267-2294","DOI":"10.1002\/jbmr.253","article-title":"Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research.","volume":"25","author":"E Shane","year":"2010","journal-title":"J Bone Miner Res."},{"key":"ref-94","doi-asserted-by":"publisher","first-page":"1055-1061","DOI":"10.1124\/jpet.102.035295","article-title":"Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid.","volume":"302","author":"J Wood","year":"2002","journal-title":"J Pharmacol Exp Ther."},{"key":"ref-95","doi-asserted-by":"publisher","first-page":"2267-2294","DOI":"10.1002\/jbmr.253","article-title":"Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research.","volume":"25","author":"E Shane","year":"2010","journal-title":"J Bone Miner Res."},{"key":"ref-96","doi-asserted-by":"publisher","first-page":"354-360","DOI":"10.1007\/s00223-008-9131-8","article-title":"Alendronate reduces bone toughness of ribs without significantly increasing microdamage accumulation in dogs following 3 years of daily treatment.","volume":"82","author":"M Allen","year":"2008","journal-title":"Calcif Tissue Int."},{"key":"ref-97","doi-asserted-by":"publisher","first-page":"1288-1292","DOI":"10.1002\/jor.20895","article-title":"Effects of 1 to 3 years\u2019 treatment with alendronate on mechanical properties of the femoral shaft in a canine model: implications for subtrochanteric femoral fracture risk.","volume":"27","author":"D Burr","year":"2009","journal-title":"J Orthop Res."},{"key":"ref-98","doi-asserted-by":"publisher","first-page":"613-620","DOI":"10.1359\/jbmr.2000.15.4.613","article-title":"Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib.","volume":"15","author":"T Mashiba","year":"2000","journal-title":"J Bone Miner Res."},{"key":"ref-99","doi-asserted-by":"publisher","first-page":"385-390","DOI":"10.1302\/0301-620X.94B3.27999","article-title":"Atypical femoral fractures and bisphosphonate treatment: experience in two large United Kingdom teaching hospitals.","volume":"94-B","author":"R Thompson","year":"2012","journal-title":"J Bone Joint Surg Br."},{"key":"ref-100","doi-asserted-by":"publisher","first-page":"1289-1295","DOI":"10.1302\/0301-620X.93B10.26924","article-title":"Long-term bisphosphonate usage and subtrochanteric insufficiency fractures: a cause for concern?","volume":"93","author":"R Yoon","year":"2011","journal-title":"J Bone Joint Surg Br."},{"key":"ref-101","doi-asserted-by":"publisher","first-page":"679-686","DOI":"10.1302\/0301-620X.92B5.22941","article-title":"A rational approach to management of alendronate-related subtrochanteric fractures.","volume":"92","author":"S Das De","year":"2010","journal-title":"J Bone Joint Surg Br."},{"key":"ref-102","doi-asserted-by":"publisher","first-page":"994-7","DOI":"10.1302\/0301-620X.94B7.28778","article-title":"A rare case of a bisphosphonate-induced peri-prosthetic femoral fracture.","volume":"94","author":"M Cross","year":"2012","journal-title":"J Bone Joint Surg Br."},{"key":"ref-103","doi-asserted-by":"publisher","first-page":"232","DOI":"10.2484\/rcr.v3i4.232","article-title":"Subtrochanteric femoral insufficiency fracture following bisphosphonate therapy for osseous metastases.","volume":"3","author":"L Bush","year":"2008","journal-title":"Radiol Case Rep."},{"key":"ref-104","doi-asserted-by":"publisher","first-page":"565-567","DOI":"10.1080\/17453670710015580","article-title":"Subtrochanteric displaced insufficiency fracture after long-term alendronate therapy--a case report.","volume":"79","author":"A Sayed-Noor","year":"2008","journal-title":"Acta Orthop."},{"key":"ref-105","doi-asserted-by":"publisher","first-page":"224-231","DOI":"10.1016\/j.injury.2007.08.036","article-title":"An emerging pattern of subtrochanteric stress fractures: a long-term complication of alendronate therapy?","volume":"39","author":"E Kwek","year":"2008","journal-title":"Injury."},{"key":"ref-106","doi-asserted-by":"publisher","first-page":"349-353","DOI":"10.1302\/0301-620X.89B3.18146","article-title":"Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution.","volume":"89","author":"S Goh","year":"2007","journal-title":"J Bone Joint Surg Br."},{"key":"ref-107","doi-asserted-by":"crossref","first-page":"249-254","DOI":"10.1177\/145749691210100405","article-title":"Salmon calcitonin (MIACALCIC NS 200 IU) in prevention of bone loss after hip replacement.","volume":"101","author":"I Arnala","year":"2012","journal-title":"Scand J Surg."},{"key":"ref-108","doi-asserted-by":"publisher","first-page":"405-408","DOI":"10.1007\/BF00301940","article-title":"25 years of salmon calcitonin; from synthesis to therapeutic use.","volume":"57","author":"M Azria","year":"1995","journal-title":"Calcif Tissue Int."},{"key":"ref-109","first-page":"S149","article-title":"Calcitonin-salmon nasal spray reduces the incidence of new vertebral fractures in postmenopausal women. Three-year interim results of the PROOF study.","volume":"12","author":"J Stock","year":"1997","journal-title":"J Bone Miner Res."},{"key":"ref-110","doi-asserted-by":"publisher","first-page":"2012-20","DOI":"10.1359\/jbmr.040906","article-title":"Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats.","volume":"19","author":"P Ammann","year":"2004","journal-title":"J Bone Miner Res."},{"key":"ref-111","doi-asserted-by":"publisher","first-page":"176-9","DOI":"10.1016\/S8756-3282(01)00484-7","article-title":"Strontium ranelate inhibits bone resorption while maintaining bone formation in alveolar bone in monkeys (Macaca fascicularis).","volume":"29","author":"J Buehler","year":"2001","journal-title":"Bone."},{"key":"ref-112","doi-asserted-by":"publisher","first-page":"906-11","DOI":"10.1053\/meta.2002.33360","article-title":"Long-term treatment with strontium ranelate increases vertebral bone mass without deleterious effect in mice.","volume":"51","author":"P Delannoy","year":"2002","journal-title":"Metabolism."},{"key":"ref-113","doi-asserted-by":"publisher","first-page":"115-23","DOI":"10.1016\/S8756-3282(03)00115-7","article-title":"S12911-2 reduces bone loss induced by short-term immobilization in rats.","volume":"33","author":"M Hott","year":"2003","journal-title":"Bone."},{"key":"ref-114","doi-asserted-by":"publisher","first-page":"607-15","DOI":"10.1002\/jbmr.5650080512","article-title":"An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats.","volume":"8","author":"P Marie","year":"1993","journal-title":"J Bone Miner Res."},{"key":"ref-115","doi-asserted-by":"publisher","first-page":"11-7","DOI":"10.1016\/S0014-2999(02)02040-X","article-title":"In vitro effects of S12911-2 on osteoclast function and bone marrow macrophage differentiation.","volume":"450","author":"R Baron","year":"2002","journal-title":"Eur J Pharmacol."},{"key":"ref-116","doi-asserted-by":"crossref","first-page":"517-23","DOI":"10.1016\/8756-3282(96)00080-4","article-title":"The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro.","volume":"18","author":"E Canalis","year":"1996","journal-title":"Bone."},{"key":"ref-117","doi-asserted-by":"publisher","first-page":"1082-7","DOI":"10.1359\/jbmr.2003.18.6.1082","article-title":"S 12911-2 inhibits osteoclastic bone resorption in vitro.","volume":"18","author":"N Takahashi","year":"2003","journal-title":"J Bone Miner Res."},{"key":"ref-118","doi-asserted-by":"publisher","first-page":"1291-300","DOI":"10.1111\/j.1476-5381.2009.00305.x","article-title":"Osteoblasts play key roles in the mechanisms of action of strontium ranelate.","volume":"157","author":"T Brennan","year":"2009","journal-title":"Br J Pharmacol."},{"key":"ref-119","doi-asserted-by":"publisher","first-page":"1419-25","DOI":"10.1359\/jbmr.070607","article-title":"Strontium ranelate treatment improves trabecular and cortical intrinsic bone tissue quality, a determinant of bone strength.","volume":"22","author":"P Ammann","year":"2007","journal-title":"J Bone Miner Res."},{"key":"ref-120","doi-asserted-by":"publisher","first-page":"578-82","DOI":"10.1002\/jor.21050","article-title":"Strontium ranelate treatment enhances hydroxyapatite-coated titanium screws fixation in osteoporotic rats.","volume":"28","author":"Y Li","year":"2010","journal-title":"J Orthop Res."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/2-266\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/2-266\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/2-266\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T15:00:14Z","timestamp":1543849214000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/2-266\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,17]]},"references-count":120,"URL":"https:\/\/doi.org\/10.12688\/f1000research.2-266.v2","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.4823.r7008","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.4823.r5158","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.4823.r5158","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.4823.r7008","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,17]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/2-266\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.4823.r5158, Jason K.F. Wong, Institute of Inflammation and Repair, University of Manchester, Manchester, UK, 13 Aug 2014, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/2-266\/v2#referee-response-5158","order":0,"name":"referee-response-5158","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.1270.r4886, Javad Parvizi, Department of Orthopaedics, Rothman Institute, Thomas Jefferson University Hospital, Philadelphia, PA, USA, 27 May 2014, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/2-266\/v1#referee-response-4886","order":1,"name":"referee-response-4886","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Loredana Cavalli<\/b>; \n<i>Posted: 27 May 2014<\/i>; The authors would like to thank the referee for&nbsp;his response.As regards BMA technique, it is not currently widespread for a clinical use, except in few research centers specialized in bone diseases, like ours at Orthopedic Trauma Center&nbsp;in Florence, Italy. As its entrance is very recent, and its potential applications are very wide, it is not yet available a protocol to compare this technique with other ones for peri-prosthetic bone study. So, at the end of the paragraph\n<i> Imaging techniques for the evaluation etc., <\/i>before the last sentence\n<i>, <\/i>we would add: &quot;\n<i>Although not currently widespread, except in few research centers specialized in bone diseases<\/i>, the employment of BMA...&quot;&nbsp;About metal subtraction option in X-ray and CT imaging, as it represents a real&nbsp;possibility to correct artifacts, we are preparing a brief paragraph to add: thank you for the suggestion!&nbsp;OPG and RANK-Fc were the first molecular strategy, so we would cite them, adding the sentence &quot;\n<i>but the successful preclinical findings, i.e. the ability to prevent and reverse wear debris-induced osteolysis, have not been confirmed by clinical trials<\/i>&quot;.&nbsp;Regarding Strontium Ranelate, we would add: &quot;\n<i>In particular, SrRan has been shown to enhance preosteoblastic cell replication and osteoblastic differentiation and to decrease abilities of osteo&shy;blasts to induce osteoclastogenesis, both through &nbsp;the calcium-sensing receptor and an increase in the OPG\/RANKL ratio <\/i>(new ref.: Brennan TC, Rybchyn MS, Green W, Atwa S, Conigrave AD, Mason RS. Osteoblasts play key roles in the mechanisms of action of strontium ranelate. \n<i>Br J Pharmacol<\/i>. 2009;157(7):1291\u20131300).&quot;&nbsp;In the conclusions, the sentence &quot;\n<i>Dual-energy X-ray Absorptiometry allow to evaluate bone density around hip or knee prosthesis, and further data may be provided by the new device called Bone Microarchitecture Analysis<\/i>.&quot; can be added after the second paragraph.We will provide&nbsp;a new version of the paper with all these corrections as soon as possible.","URL":"https:\/\/f1000research.com\/articles\/2-266\/v2#referee-comment-840","order":2,"name":"referee-comment-840","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.4823.r7008, P Edward Purdue, Division of Research, Hospital for Special Surgery, New York, NY, USA, 15 Jan 2015, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/2-266\/v2#referee-response-7008","order":3,"name":"referee-response-7008","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}