Bone characteristics in condylar hyperplasia of the temporomandibular joint: a microcomputed tomography, histology, and Raman microspectrometry study

  • J.-D. Kün-Darbois
    Université Angers, GEROM, IRIS-IBS Institut de Biologie en Santé, Angers, France

    Service de Chirurgie Maxillo-faciale et Stomatologie, CHU d’Angers, Angers, France

    Univ Angers, Nantes Université, Oniris, Inserm, RMeS, REGOS, SFR ICAT, F-49000 Angers, France
    Search for articles by this author
  • H. Bertin
    Service de Chirurgie Maxillo-faciale et Stomatologie, CHU de Nantes, Nantes, France

    Univ Angers, Nantes Université, Oniris, Inserm, RMeS, REGOS, SFR ICAT, F-49000 Angers, France
    Search for articles by this author
  • G. Mouallem
    Service de Chirurgie Maxillo-faciale et Stomatologie, CHU de Nantes, Nantes, France
    Search for articles by this author
  • P. Corre
    Service de Chirurgie Maxillo-faciale et Stomatologie, CHU de Nantes, Nantes, France

    Univ Angers, Nantes Université, Oniris, Inserm, RMeS, REGOS, SFR ICAT, F-49000 Angers, France
    Search for articles by this author
  • T. Delabarde
    Institut Médico-Légal de Paris, Paris, France
    Search for articles by this author
  • D. Chappard
    Correspondence to: GEROM – LHEA, CHU d’Angers, 49933 Angers Cedex, France. Tel: +33 477 53 22 95.
    Université Angers, GEROM, IRIS-IBS Institut de Biologie en Santé, Angers, France

    Univ Angers, Nantes Université, Oniris, Inserm, RMeS, REGOS, SFR ICAT, F-49000 Angers, France
    Search for articles by this author
Published:September 27, 2022DOI:


      Unilateral condylar hyperplasia (UCH) of the temporomandibular joint is a progressive deformation of the mandibular condyle of unknown origin. UCH is characterized by excessive growth of the condylar head and neck, leading to an increase in size and volume. The aim of this study was to investigate the characteristics of the bone in patients with UCH using microcomputed tomography (micro-CT), histology, and Raman microspectroscopy. The mandibular condyles of six patients with UCH were analysed using micro-CT, histology, and Raman microspectrometry and imaging, and the results were compared with those obtained for a normal control subject. Three-dimensional micro-CT models revealed focal abnormalities of the bone microarchitecture, with foci of osteosclerosis. Histological sections showed that these foci included islands of calcified cartilage matrix with live chondrocytes. Raman analysis revealed that the cartilage matrix was more heavily calcified than the bone matrix and that the cartilage could be identified by the phenylalanine (PHE) band of its matrix, as well as by its glycosaminoglycan (GAG) content. The persistence of foci of live and active chondrocytes within the bone matrix is intriguing and appears to be pathognomonic of UCH. These new findings on UCH could help to determine its pathophysiology and thus prevent this disease, which can lead to major facial deformity.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to International Journal of Oral and Maxillofacial Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Nitzan D.W.
        • Katsnelson A.
        • Bermanis I.
        • Brin I.
        • Casap N.
        The clinical characteristics of condylar hyperplasia: experience with 61 patients.
        J Oral Maxillofac Surg. 2008; 66: 312-318
        • Almeida L.E.
        • Zacharias J.
        • Pierce S.
        Condylar hyperplasia: an updated review of the literature.
        Korean J Orthod. 2015; 45: 333-340
        • Obwegeser H.L.
        Condylar hyperactivity.
        Mandibular Growth Anomalies. Springer, 2001: 139-144
        • Obwegeser H.L.
        • Makek M.S.
        Hemimandibular hyperplasia—hemimandibular elongation.
        J Maxillofac Surg. 1986; 14: 183-208
        • Delaire J.
        • Gaillard A.
        • Tulasne J.F.
        [The place of condylectomy in the treatment of hypercondylosis].
        Rev Stomatol Chir Maxillofac. 1983; 84: 11-18
        • Slootweg P.J.
        • Muller H.
        Condylar hyperplasia. A clinico-pathological analysis of 22 cases.
        J Maxillofac Surg. 1986; 14: 209-214
        • Wolford L.M.
        • Movahed R.
        • Perez D.E.
        A classification system for conditions causing condylar hyperplasia.
        J Oral Maxillofac Surg. 2014; 72: 567-595
        • Higginson J.
        • Bartram A.
        • Banks R.
        • Keith D.
        Condylar hyperplasia: current thinking.
        Br J Oral Maxillofac Surg. 2018; 56: 655-662
        • Nolte J.W.
        • Verhoeven T.J.
        • Schreurs R.
        • Bergé S.J.
        • Karssemakers L.H.
        • Becking A.G.
        • Maal T.J.
        3-Dimensional CBCT analysis of mandibular asymmetry in unilateral condylar hyperplasia.
        J Craniomaxillofac Surg. 2016; 44: 1970-1976
        • Sun R.
        • Sun L.
        • Sun Z.
        • Li G.
        • Zhao Y.
        • Ma X.
        • Sun C.
        A three-dimensional study of hemimandibular hyperplasia, hemimandibular elongation, solitary condylar hyperplasia, simple mandibular asymmetry and condylar osteoma or osteochondroma.
        J Craniomaxillofac Surg. 2019; 47: 1665-1675
        • Pripatnanont P.
        • Vittayakittipong P.
        • Markmanee U.
        • Thongmak S.
        • Yipintsoi T.
        The use of SPECT to evaluate growth cessation of the mandible in unilateral condylar hyperplasia.
        Int J Oral Maxillofac Surg. 2005; 34: 364-368
        • Martin-Granizo R.
        • Garcia-Rielo J.M.
        • De la Sen O.
        • Maniegas L.
        • Berguer A.
        • De Pedro M.
        Correlation between single photon emission computed tomography and histopathologic findings in condylar hyperplasia of the temporomandibular joint.
        J Craniomaxillofac Surg. 2017; 45: 839-844
        • Karssemakers L.H.E.
        • Nolte J.W.
        • Tuinzing D.B.
        • Langenbach G.E.J.
        • Becking A.G.
        • Raijmakers P.G.
        Impact of bone volume upon condylar activity in patients with unilateral condylar hyperplasia.
        J Oral Maxillofac Surg. 2018; 76: 2177-2182
        • Mouallem G.
        • Vernex-Boukerma Z.
        • Longis J.
        • Perrin J.P.
        • Delaire J.
        • Mercier J.M.
        • Corre P.
        Efficacy of proportional condylectomy in a treatment protocol for unilateral condylar hyperplasia: a review of 73 cases.
        J Craniomaxillofac Surg. 2017; 45: 1083-1093
        • Bohuslavizki K.H.
        • Brenner W.
        • Kerscher A.
        • Fleiner B.
        • Tinnemeyer S.
        • Sippel C.
        • Wolf H.
        • Clausen M.
        • Henze E.
        The value of bone scanning in pre-operative decision-making in patients with progressive facial asymmetry.
        Nucl Med Commun. 1996; 17: 562-567
        • Fariña R.
        • Pintor F.
        • Pérez J.
        • Pantoja R.
        • Berner D.
        Low condylectomy as the sole treatment for active condylar hyperplasia: facial, occlusal and skeletal changes. An observational study.
        Int J Oral Maxillofac Surg. 2015; 44: 217-225
        • Ferri J.
        • Raoul G.
        • Potier J.
        • Nicot R.
        [Temporomandibular joint (TMJ): condyle hyperplasia and condylectomy].
        Rev Stomatol Chir Maxillofac Chir Orale. 2016; 117: 259-265
        • Wolford L.M.
        • Mehra P.
        • Reiche-Fischel O.
        • Morales-Ryan C.A.
        • García-Morales P.
        Efficacy of high condylectomy for management of condylar hyperplasia.
        Am J Orthod Dentofacial Orthop. 2002; 121 (discussion 150–151): 136-150
        • Ghawsi S.
        • Aagaard E.
        • Thygesen T.H.
        High condylectomy for the treatment of mandibular condylar hyperplasia: a systematic review of the literature.
        Int J Oral Maxillofac Surg. 2016; 45: 60-71
        • Eslami B.
        • Behnia H.
        • Javadi H.
        • Khiabani K.S.
        • Saffar A.S.
        Histopathologic comparison of normal and hyperplastic condyles.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003; 96: 711-717
        • Gray R.J.
        • Sloan P.
        • Quayle A.A.
        • Carter D.H.
        Histopathological and scintigraphic features of condylar hyperplasia.
        Int J Oral Maxillofac Surg. 1990; 19: 65-71
        • Karssemakers L.H.
        • Nolte J.W.
        • Tuinzing D.B.
        • Langenbach G.E.
        • Raijmakers P.G.
        • Becking A.G.
        Microcomputed tomographic analysis of human condyles in unilateral condylar hyperplasia: increased cortical porosity and trabecular bone volume fraction with reduced mineralisation.
        Br J Oral Maxillofac Surg. 2014; 52: 940-944
        • Lopez D.F.
        • Lopez C.
        • Moreno M.
        • Pinedo R.
        Post-condylectomy histopathologic findings in patients with a positive (99m)Tc methylene diphosphonate single-photon emission computed tomographic diagnosis for condylar hyperplasia.
        J Oral Maxillofac Surg. 2018; 76: 1005-1012
        • Saridin C.P.
        • Raijmakers P.
        • Becking A.G.
        Quantitative analysis of planar bone scintigraphy in patients with unilateral condylar hyperplasia.
        Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007; 104: 259-263
        • Vásquez B.
        • Olate S.
        • Cantín M.
        • Sandoval C.
        • Del Sol M.
        • de Moraes M.
        Histomorphometric analysis of unilateral condylar hyperplasia in the temporomandibular joint: the value of the condylar layer and cartilage island.
        Int J Oral Maxillofac Surg. 2017; 46: 861-866
        • Vásquez B.
        • Olate S.
        • Cantín M.
        • Sandoval C.
        • Fariña R.
        • Del Sol M.
        Histopathological analysis of unilateral condylar hyperplasia: difficulties in diagnosis and characterization of the disease.
        Int J Oral Maxillofac Surg. 2016; 45: 601-609
        • Chappard D.
        Technical aspects: How do we best prepare bone samples for proper histological analysis?.
        in: Heymann D. Bone Cancer: Progression and Therapeutic Approaches. Academic Press, Elsevier Inc., London2009: 203-210
        • Dempster D.W.
        • Compston J.E.
        • Drezner M.K.
        • Glorieux F.H.
        • Kanis J.A.
        • Malluche H.
        • Meunier P.J.
        • Ott S.M.
        • Recker R.R.
        • Parfitt A.M.
        Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee.
        J Bone Miner Res. 2013; 28: 2-17
      1. Alebrahim M.A., Krafft C., Popp J. : Raman imaging to study structural and chemical features of the dentin enamel junction. IOP Conference Series: Materials Science and Engineering. Institute of Physics Publishing, 2015.

        • Nyman J.S.
        • Makowski A.J.
        • Patil C.A.
        • Masui T.P.
        • O’Quinn E.C.
        • Bi X.
        • Guelcher S.A.
        • Nicollela D.P.
        • Mahadevan-Jansen A.
        Measuring differences in compositional properties of bone tissue by confocal Raman spectroscopy.
        Calcif Tissue Int. 2011; 89: 111-122
        • Roschger A.
        • Gamsjaeger S.
        • Hofstetter B.
        • Masic A.
        • Blouin S.
        • Messmer P.
        • Berzlanovich A.
        • Paschalis E.P.
        • Roschger P.
        • Klaushofer K.
        • Fratzl P.
        Relationship between the v2PO4/amide III ratio assessed by Raman spectroscopy and the calcium content measured by quantitative backscattered electron microscopy in healthy human osteonal bone.
        J Biomed Opt. 2014; 19065002
        • Pascaretti-Grizon F.
        • Guillaume B.
        • Terranova L.
        • Arbez B.
        • Libouban H.
        • Chappard D.
        Maxillary sinus lift with beta-tricalcium phosphate (beta-TCP) in edentulous patients: a nanotomographic and Raman study.
        Calcif Tissue Int. 2017; 101: 280-290
        • Paschalis E.P.
        • Fratzl P.
        • Gamsjaeger S.
        • Hassler N.
        • Brozek W.
        • Eriksen E.F.
        • Rauch F.
        • Glorieux F.H.
        • Shane E.
        • Dempster D.
        • Cohen A.
        • Recker R.
        • Klaushofer K.
        Aging versus postmenopausal osteoporosis: bone composition and maturation kinetics at actively-forming trabecular surfaces of female subjects aged 1 to 84 years.
        J Bone Miner Res. 2015; 31: 347-357
        • Gamsjaeger S.
        • Mendelsohn R.
        • Klaushofer K.
        • Paschalis E.P.
        Vibrational spectroscopic analysis of hard tissues.
        in: Salzer R. Siesler H.W. Infrared and Raman Spectroscopic Imaging. Second edition. Wiley-VCH, Weinheim, Germany2014: 153-180
        • Akkus O.
        • Adar F.
        • Schaffler M.B.
        Age-related changes in physicochemical properties of mineral crystals are related to impaired mechanical function of cortical bone.
        Bone. 2004; 34: 443-453
        • Morris M.D.
        • Mandair G.
        Raman assessment of bone quality.
        Clin Orthop Relat Res. 2011; 469: 2160-2169
        • Hodder S.C.
        • Rees J.I.
        • Oliver T.B.
        • Facey P.E.
        • Sugar A.W.
        SPECT bone scintigraphy in the diagnosis and management of mandibular condylar hyperplasia.
        Br J Oral Maxillofac Surg. 2000; 38: 87-93
        • Lineaweaver W.
        • Vargervik K.
        • Tomer B.S.
        • Ousterhout D.K.
        Posttraumatic condylar hyperplasia.
        Ann Plast Surg. 1989; 22: 163-172
        • Mahajan M.
        Unilateral condylar hyperplasia—a genetic link? Case reports.
        Natl J Maxillofac Surg. 2017; 8: 58-63
        • Chen Y.
        • Ke J.
        • Long X.
        • Meng Q.
        • Deng M.
        • Fang W.
        • Li J.
        • Cai H.
        • Chen S.
        Insulin-like growth factor-1 boosts the developing process of condylar hyperplasia by stimulating chondrocytes proliferation.
        Osteoarthr Cartil. 2012; 20: 279-287
        • Raijmakers P.G.
        • Karssemakers L.H.
        • Tuinzing D.B.
        Female predominance and effect of gender on unilateral condylar hyperplasia: a review and meta-analysis.
        J Oral Maxillofac Surg. 2012; 70: e72-e76
        • Goulart D.R.
        • Sigua-Rodriguez E.A.
        • Farina R.
        • Olate S.
        Condylar hyperplasia in a monozygotic twin girl: an argument about etiology.
        J Craniofac Surg. 2018; 29: 599-602
        • Ji H.
        • Li J.
        • Shao J.
        • He D.
        • Liu Y.
        • Fei W.
        • Luo E.
        Histopathologic comparison of condylar hyperplasia and condylar osteochondroma by using different staining methods.
        Oral Surg Oral Med Oral Pathol Oral Radiol. 2017; 123: 320-329
        • Horobin R.
        • Kiernan J.
        Conn’s biological stains: a handbook of dyes, stains and fluorochromes for use in biology and medicine.
        Taylor & Francis,, 2020
        • Poole A.
        The relationship between toluidine blue staining and hexuronic acid content of cartilage matrix.
        Histochem J. 1970; 2: 425-430
        • Sawicki W.
        • Moskalewski S.
        Hoechst 33342 staining coupled with conventional histological technique.
        Stain Technol. 1989; 64: 191-196
        • Russe P.
        • Pascaretti-Grizon F.
        • Aguado E.
        • Goyenvale E.
        • Filmon R.
        • Baslé M.F.
        • Chappard D.
        Does milling one-piece titanium dental implants induce osteocyte and osteoclast changes?.
        Morphologie. 2011; 95: 51-59
      2. Fosca M., Basoli V., Della Bella E., Russo F., Vadalà G., Alini M., Rau J.V., Verrier S. : Raman spectroscopy in skeletal tissue disorders and tissue engineering: present and prospective. Tissue Eng Part B Rev 2022 Jan 5. doi: 〈10.1089/ten.teb.2021.0139〉, 2022.

        • Dehring K.A.
        • Crane N.J.
        • Smukler A.R.
        • McHugh J.B.
        • Roessler B.J.
        • Morris M.D.
        Identifying chemical changes in subchondral bone taken from murine knee joints using Raman spectroscopy.
        Appl Spectrosc. 2006; 60: 1134-1141
        • Kumar R.
        • Grønhaug K.M.
        • Afseth N.K.
        • Isaksen V.
        • de Lange Davies C.
        • Drogset J.O.
        • Lilledahl M.B.
        Optical investigation of osteoarthritic human cartilage (ICRS grade) by confocal Raman spectroscopy: a pilot study.
        Anal Bioanal Chem. 2015; 407: 8067-8077
        • Hassler N.
        • Roschger A.
        • Gamsjaeger S.
        • Kramer I.
        • Lueger S.
        • van Lierop A.
        • Roschger P.
        • Klaushofer K.
        • Paschalis E.P.
        • Kneissel M.
        • Papapoulos S.
        Sclerostin deficiency is linked to altered bone composition.
        J Bone Miner Res. 2014; 29: 2144-2151
        • Kazanci M.
        • Fratzl P.
        • Klaushofer K.
        • Paschalis E.
        Complementary information on in vitro conversion of amorphous (precursor) calcium phosphate to hydroxyapatite from Raman microspectroscopy and wide-angle X-ray scattering.
        Calcif Tissue Int. 2006; 79: 354-359
        • Gamsjaeger S.
        • Klaushofer K.
        • Paschalis E.P.
        Raman analysis of proteoglycans simultaneously in bone and cartilage.
        J Raman Spectrosc. 2014; 45: 794-800
        • Chappard D.
        • Guillaume B.
        • Teman G.
        • Kün-Darbois J.D.
        Raman spectroscopic analysis and imaging in two cases of benign cementoma: comparison with dental and bone tissues.
        J Raman Spectrosc. 2020; 51: 1044-1055
        • Aguado E.
        • Goyenvalle E.
        • Guintard C.
        • Chappard D.
        Bone grafted with β-TCP granules in the rabbit: a microcomputed tomographic, histologic, Raman microspectrometric, and Raman imaging study.
        J Raman Spectrosc. 2020; 51: 2435-2446
        • Gaifulina R.
        • Nunn A.D.
        • Draper E.R.
        • Strachan R.K.
        • Blake N.
        • Firth S.
        • Thomas G.M.
        • McMillan P.F.
        • Dudhia J.
        Intra-operative Raman spectroscopy and ex vivo Raman mapping for assessment of cartilage degradation.
        Clin Spectrosc. 2021; 3100012
        • Feng X.
        Chemical and biochemical basis of cell-bone matrix interaction in health and disease.
        Curr Chem Biol. 2009; 3: 189-196
        • Viguet-Carrin S.
        • Garnero P.
        • Delmas P.
        The role of collagen in bone strength.
        Osteoporos Int. 2006; 17: 319-336
        • Wilusz R.E.
        • Sanchez-Adams J.
        • Guilak F.
        The structure and function of the pericellular matrix of articular cartilage.
        Matrix Biol. 2014; 39: 25-32
        • Albro M.B.
        • Bergholt M.S.
        • St-Pierre J.P.
        • Vinals Guitart A.
        • Zlotnick H.M.
        • Evita E.G.
        • Stevens M.M.
        Raman spectroscopic imaging for quantification of depth-dependent and local heterogeneities in native and engineered cartilage.
        NPJ Regen Med. 2018; 3: 1-11
        • Ferraro V.
        • Gaillard-Martinie B.
        • Sayd T.
        • Chambon C.
        • Anton M.
        • Santé-Lhoutellier V.
        Collagen type I from bovine bone. Effect of animal age, bone anatomy and drying methodology on extraction yield, self-assembly, thermal behaviour and electrokinetic potential.
        Int J Biol Macromol. 2017; 97: 55-66
        • Cao H.
        • Xu S.Y.
        Purification and characterization of type II collagen from chick sternal cartilage.
        Food Chem. 2008; 108: 439-445
        • Hessle H.
        • Engvall E.
        Type VI collagen. Studies on its localization, structure, and biosynthetic form with monoclonal antibodies.
        J Biol Chem. 1984; 259: 3955-3961