Editor's choice| Volume 45, ISSUE 1, P1-8.e1, January 2020

Evaluation for Kienböck Disease Familial Clustering: A Population-Based Cohort Study

Published:November 22, 2019DOI:


      Kienböck disease (KD) is rare and its etiology remains unknown. As a result, the ideal treatment is also in question. Our primary purpose was to test the hypothesis that KD would demonstrate familial clustering in a large statewide population with comprehensive genealogical records, possibly suggesting a genetic etiologic contribution. Our secondary purpose was to evaluate for associations between KD and known risk factors for avascular necrosis.


      Patients diagnosed with KD were identified by searching medical records from a comprehensive statewide database, the Utah Population Database. This database contains pedigrees dating back to the early 1800s, which are linked to 31 million medical records for 11 million patients from 1996 to the present. Affected individuals were then mapped to pedigrees to identify high-risk families with an increased incidence of KD relative to control pedigrees. The magnitude of familial risk of KD in related individuals was calculated using Cox regression models. Association of risk factors related to KD was analyzed using conditional logistic regression.


      We identified 394 affected individuals linked to 194 unrelated high-risk pedigrees with increased incidence of KD. The relative risk of developing KD was significantly elevated in first-degree relatives. There was a significant correlation between alcohol, glucocorticoid, and tobacco use and a history of diabetes, and the diagnosis of KD.


      Familial clustering of KD observed in the Utah Population Database cohort indicates a potential genetic contribution to the etiology of the disease. Identification of causal gene variants in these high-risk families may provide insight into the genes and pathways that contribute to the onset and progression of KD.

      Clinical relevance

      This study suggests that there is a potential genetic contribution to the etiology of KD and that the disease has a significant association with several risk factors.

      Key words

      JHS Podcast

      January 1, 2020

      JHS Podcast Episode 46

      Dr. Graham interviews Drs. Nik Kazmers and Mick Jurynec regarding their paper, "Evaluation for Kienböck Disease Familial Clustering: A Population-Based Cohort Study",the lead article in the January 2020 issue of the Journal of Hand Surgery.

      Loading ...
      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 Journal of Hand Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Kienböck R.
        Über traumatische malazie des mondbeins und ihre folgezustände: Entartungsformen und kompressionsfrakturen.
        Fortschr Geb Röntgenstr. 1910; Band XVI: 77-103
        • Squitieri L.
        • Petruska E.
        • Chung K.C.
        Publication bias in Kienböck’s disease: systematic review.
        J Hand Surg Am. 2010; 35: 359-367.e5
      1. NIH National Center for Advancing Translational Sciences, Genetic and Rare Diseases Information Center. Kienböck’s disease.
        (Available from:)
        • Lichtman D.M.
        • Pientka II, W.F.
        • Bain G.I.
        Kienböck disease: moving forward.
        J Hand Surg Am. 2016; 41: 630-638
        • Stahl S.
        • Santos Stahl A.
        • Rahmanian-Schwarz A.
        • et al.
        An international opinion research survey of the etiology, diagnosis, therapy and outcome of Kienböck’s disease (KD).
        Chir Main. 2012; 31: 128-137
        • Lluch A.
        • Garcia-Elias M.
        Etiology of Kienböck disease.
        Tech Hand Up Extrem Surg. 2011; 15: 33-37
        • Bain G.I.
        • MacLean S.B.
        • Yeo C.J.
        • Perilli E.
        • Lichtman D.M.
        The etiology and pathogenesis of Kienböck disease.
        J Wrist Surg. 2016; 5: 248-254
        • Beckenbaugh R.D.
        • Shives T.C.
        • Dobyns J.H.
        • Linscheid R.L.
        Kienböck’s disease: the natural history of Kienböck’s disease and consideration of lunate fractures.
        Clin Orthop Relat Res. 1980; 149: 98-106
        • Afshar A.
        • Aminzadeh-Gohari A.
        • Yekta Z.
        The association of Kienböck’s disease and ulnar variance in the Iranian population.
        J Hand Surg Eur Vol. 2013; 38: 496-499
        • Goeminne S.
        • Degreef I.
        • De Smet L.
        Negative ulnar variance has prognostic value in progression of Kienböck’s disease.
        Acta Orthop Belg. 2010; 76: 38-41
        • Stahl S.
        • Stahl A.S.
        • Meisner C.
        • et al.
        Critical analysis of causality between negative ulnar variance and Kienböck disease.
        Plast Reconstr Surg. 2013; 132: 899-909
        • Mennen U.
        • Sithebe H.
        The incidence of asymptomatic Kienböck’s disease.
        J Hand Surg Eur Vol. 2009; 34: 348-350
        • Chung K.C.
        • Spilson M.S.
        • Kim M.H.
        Is negative ulnar variance a risk factor for Kienböck’s disease? A meta-analysis.
        Ann Plast Surg. 2001; 47: 494-499
        • Rhee P.C.
        • Jones D.B.
        • Moran S.L.
        • Shin A.Y.
        The effect of lunate morphology in Kienböck disease.
        J Hand Surg Am. 2015; 40: 738-744
        • Viegas S.F.
        • Wagner K.
        • Patterson R.
        • Peterson P.
        Medial (hamate) facet of the lunate.
        J Hand Surg Am. 1990; 15: 564-571
        • Gelberman R.H.
        • Bauman T.D.
        • Menon J.
        • Akeson W.H.
        The vascularity of the lunate bone and Kienböck’s disease.
        J Hand Surg Am. 1980; 5: 272-278
        • Pichler M.
        • Putz R.
        The venous drainage of the lunate bone.
        Surg Radiol Anat. 2003; 24: 372-376
        • Williams C.S.
        • Gelberman R.H.
        Vascularity of the lunate : anatomic studies and implications for the development of osteonecrosis.
        Hand Clin. 1993; 9: 391-398
        • Lamas C.
        • Carrera A.
        • Proubasta I.
        • Llusa M.
        • Majo J.
        • Mir X.
        The anatomy and vascularity of the lunate: considerations applied to Kienböck’s disease.
        Chir Main. 2007; 26: 13-20
        • Razemon J.P.
        Kienböck’s disease radiology [in French].
        Ann Radiol (Paris). 1982; 25: 353-358
        • Glueck C.J.
        • Freiberg R.A.
        • Wang P.
        Heritable thrombophilia-hypofibrinolysis and osteonecrosis of the femoral head.
        Clin Orthop Relat Res. 2008; 466: 1034-1040
        • Shah K.N.
        • Racine J.
        • Jones L.C.
        • Aaron R.K.
        Pathophysiology and risk factors for osteonecrosis.
        Curr Rev Musculoskelet Med. 2015; 8: 201-209
        • Nakamura R.
        • Tanaka Y.
        • Imaeda T.
        • Miura T.
        The influence of age and sex on ulnar variance.
        J Hand Surg Br. 1991; 16: 84-88
        • D’Hoore K.
        • De Smet L.
        • Verellen K.
        • Vral J.
        • Fabry G.
        Negative ulnar variance is not a risk factor for Kienböck’s disease.
        J Hand Surg Am. 1994; 19: 229-231
        • Garcia-Elias M.
        • An K.N.
        • Cooney W.P.
        • Linscheid R.L.
        Lateral closing wedge osteotomy for treatment of Kienböck’s disease : a clinical and biomechanical study of the optimum correcting angle.
        Chir Main. 1998; 17: 283-290
        • Mirabello S.C.
        • Rosenthal D.I.
        • Smith R.J.
        Correlation of clinical and radiographic findings in Kienböck’s disease.
        J Hand Surg Am. 1987; 12: 1049-1054
        • Therkelsen F.
        • Andersen K.
        Acta Chir Scand. 1949; 97: 503-526
        • Templeman D.C.
        • Engber W.D.
        Kienböck’s disease—Case report of familial occurrence.
        Iowa Orthop J. 1985; 5: 107-109
        • Rubin G.
        • Micha G.
        • Rinott M.G.
        • Wolovelsky A.
        • Shalev S.A.
        • Rozen N.
        Familial occurrence of Kienböck’s disease.
        Orthop Muscular Syst. 2012; 1: 1-2
        • Lichtman D.M.
        • Mack G.R.
        • MacDonald R.I.
        • Gunther S.F.
        • Wilson J.N.
        Kienböck’s disease: the role of silicone replacement arthroplasty.
        J Bone Joint Surg Am. 1977; 59: 899-908
        • Huntsman Cancer Institute, University of Utah
        Utah Population Database. April 18, 2019.
        (Available from:)
        • Goldgar D.E.
        • Cannon-Albright L.A.
        • Oliphant A.
        • et al.
        Chromosome 17q linkage studies of 18 utah breast cancer kindreds.
        Am J Hum Genet. 1993; 52: 743-748
        • Lakhani S.R.
        • Gusterson B.A.
        • Jacquemier J.
        • et al.
        The pathology of familial breast cancer: histological features of cancers in families not attributable to mutations in BRCA1 or BRCA2.
        Clin Cancer Res. 2000; 6: 782-789
        • Miki Y.
        • Swensen J.
        • Shattuck-Eidens D.
        • et al.
        A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.
        Science. 1994; 266: 66-71
        • Tavtigian S.V.
        • Simard J.
        • Rommens J.
        • et al.
        The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.
        Nat Genet. 1996; 12: 333-337
        • Cannon-Albright L.A.
        • Thomas T.C.
        • Bishop D.T.
        • Skolnick M.H.
        • Burt R.W.
        Characteristics of familial colon cancer in a large population data base.
        Cancer. 1989; 64: 1971-1975
        • Slattery M.L.
        • Kerber R.A.
        A comprehensive evaluation of family history and breast cancer risk: the Utah Population Database.
        JAMA. 1993; 270: 1563-1568
        • Slattery M.L.
        • Kerber R.A.
        Family history of cancer and colon-cancer risk—the Utah Population Database.
        J Natl Cancer Inst. 1994; 86: 1618-1626
        • Cannon-Albright L.A.
        • Goldgar D.E.
        • Neuhausen S.
        • et al.
        Localization of the 9p melanoma susceptibility locus (mlm) to a 2-cm region between d9s736 and d9s171.
        Genomics. 1994; 23: 265-268
        • Slager S.L.
        • Skibola C.F.
        • Di Bernardo M.C.
        • et al.
        Common variation at 6p21.31 (bak1) influences the risk of chronic lymphocytic leukemia.
        Blood. 2012; 120: 843-846
        • Kerber R.A.
        Method for calculating risk associated with family history of a disease.
        Genet Epidemiol. 1995; 12: 291-301
        • Kerber R.A.
        • O’Brien E.
        A cohort study of cancer risk in relation to family histories of cancer in the Utah Population Database.
        Cancer. 2005; 103: 1906-1915
        • Abbott D.
        • Brockmeyer D.
        • Neklason D.W.
        • Teerlink C.
        • Cannon-Albright L.A.
        Population-based description of familial clustering of Chiari malformation Type I.
        J Neurosurg. 2018; 128: 460-465
        • Anderson M.B.
        • Curtin K.
        • Wong J.
        • Pelt C.E.
        • Peters C.L.
        • Gililland J.M.
        Familial clustering identified in periprosthetic joint infection following primary total joint arthroplasty: a population-based cohort study.
        J Bone Joint Surg Am. 2017; 99: 905-913
        • Padia R.
        • Alt J.A.
        • Curtin K.
        • et al.
        Familial link of otitis media requiring tympanostomy tubes.
        Laryngoscope. 2017; 127: 962-966
        • Teerlink C.C.
        • Bernhisel R.
        • Cannon-Albright L.A.
        • Rollins M.D.
        A population-based description of familial clustering of hirschsprung disease.
        J Pediatr Surg. 2018; 53: 1355-1359
        • Stahl S.
        • Stahl A.S.
        • Meisner C.
        • Rahmanian-Schwarz A.
        • Schaller H.E.
        • Lotter O.
        A systematic review of the etiopathogenesis of Kienböck’s disease and a critical appraisal of its recognition as an occupational disease related to hand-arm vibration.
        BMC Musculoskelet Disord. 2012; 13: 225
        • Desy N.M.
        • Bernstein M.
        • Harvey E.J.
        • Hazel H.
        Kienböck’s disease and juvenile idiopathic arthritis.
        Mcgill J Med. 2011; 13: 8
        • Jurynec M.J.
        • Sawitzke A.D.
        • Beals T.C.
        • et al.
        A hyperactivating proinflammatory RIPK2 allele associated with early-onset osteoarthritis.
        Hum Mol Genet. 2018; 27: 2383-2391
        • Hoshijima K.
        • Jurynec M.J.
        • Grunwald D.J.
        Precise editing of the zebrafish genome made simple and efficient.
        Dev Cell. 2016; 36: 654-667
        • Samadder N.J.
        • Curtin K.
        • Tuohy T.M.
        • et al.
        Characteristics of missed or interval colorectal cancer and patient survival: a population-based study.
        Gastroenterology. 2014; 146: 950-960
        • Peterson K.
        • Firszt R.
        • Fang J.
        • Wong J.
        • Smith K.R.
        • Brady K.A.
        Risk of autoimmunity in eoe and families: a population-based cohort study.
        Am J Gastroenterol. 2016; 111: 926-932