Polyarticular osteoarthritis - Two major phenotypes hypothesized

ArthroCare Pty Ltd, P.O. Box 6, Mount Lawley, and Department of Medicine, University of Western Australia, Australia.
Medical Hypotheses (Impact Factor: 1.15). 02/2006; 66(2):315-8. DOI: 10.1016/j.mehy.2005.08.028
Source: PubMed

ABSTRACT Osteoarthritis is the commonest form of arthritis, at least amongst Caucasians and is frequently polyarticular. Genetic factors are now considered pivotal in the aetiopathogenesis of polyarticular osteoarthritis (POA). This document proposes a nexus between the gene most commonly mutated amongst Caucasian peoples, notably the HFE gene and an appreciable subset of POA patients who have a clinically recognisable OA phenotype. It is hypothesised that there are at least 2 major POA phenotypes each of which is associated with discrete genotypes. Type 1 POA characterized by Heberden's or Bouchard's nodes with prominent DIP, PIP, knee joint (medial compartment) and Great toe MTP joint involvement corresponds to the putative nodal generalized form of OA or NGOA (proposed Type 1 POA phenotype). As yet no genetic marker has been defined for this POA subset. The second is a hitherto less well recognized phenotype characterized by involvement of the index and/or middle finger metacarpophalangeal (MCP2,3) joints and the elbows, ankles and possibly the intertarsal and tarsometatarsal joints. The hip and knee joints may sometimes also be involved. This different joint distribution corresponds closely to the pattern observed in the arthropathy that often accompanies hereditary haemochromatosis. It is predicted that mutations in the HFE gene will associate strongly with the proposed Type 2 POA phenotype and serve as a genetic marker for this clinically recognisable subset.

  • [Show abstract] [Hide abstract]
    ABSTRACT: To respond to a pre-specified set of questions posed by the United States Food and Drug Administration (FDA) on defining the disease state to inform the clinical development of drugs, biological products, and medical devices for the prevention and treatment of osteoarthritis (OA). An Osteoarthritis Research Society International (OARSI) Disease State working group was established, comprised of representatives from academia and industry. The Working Group met in person and by teleconference on several occasions from the Spring of 2008 through the Autumn of 2009 to develop consensus-based, evidence-informed responses to these questions. A report was presented at a public forum in December 2009 and accepted by the OARSI Board of Directors in the Summer of 2010. An operational definition of OA was developed incorporating current understanding of the condition. The structural changes that characterize OA at the joint level were distinguished from the patients' experience of OA as the 'disease' and 'illness', respectively. Recommendations were made regarding the evaluation of both in future OA clinical trials. The current poor understanding of the phenotypes that characterize OA was identified as an important area for future research. The design and conduct of clinical trials for new OA treatments should address the heterogeneity of the disease, treatment-associated structural changes in target joints and patient-reported outcomes.
    Osteoarthritis and Cartilage 03/2011; 19(5):478-82. DOI:10.1016/j.joca.2010.09.013 · 4.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hereditary Haemochromatosis is a common inherited disorder, which primarily affects populations of northern European origin. Individuals homozygous for the C282Y mutation in the HFE gene product have up to a 30 percent chance of developing significant disease as a result of iron overload. Arthropathy is arguably the most disabling complication of iron overload in this disorder. Here we review the clinical and pathophysiological aspects of arthropathy in Hereditary Haemochromatosis. © 2011 by the American College of Rheumatology.
    01/2012; 64(1):9-14. DOI:10.1002/acr.20501
  • [Show abstract] [Hide abstract]
    ABSTRACT: HintergrundDie generalisierte Osteoarthrose (GOA) wird in der Literatur unterschiedlich definiert. Ebenso kontrovers ist die Diskussion über die Zusammenhänge zwischen GOA und Heberden-Arthrose (HA). Beide Fragestellungen wurden daher an einem Patientengut überprüft, für das in einer genealogischen Studie an 931 Familienmitgliedern eine familiäre Disposition nachgewiesen werden konnte. Material und MethodenAn 106 Patienten mit einer HA und 109 Kontrollpersonen wurden je Patient 70Gelenke bzw. Wirbelsäulensegmente mittels charakteristischer funktioneller und 44Gelenke bzw. Wirbelsäulenabschnitte mittels röntgenologischer Parameter untersucht. ErgebnisseDie GOA betrifft sowohl die kleinen und großen Gelenke als auch die Wirbelsäule. Dieses Phänomen ist umso ausgeprägter, je mehr Fingergelenke im Sinne einer Heberden- und Bouchard-Arthrose verändert sind. SchlussfolgerungDie GOA betrifft den gesamten Bewegungsapparat. Die unterschiedliche Manifestation an einzelnen Gelenken und Wirbelsäulenabschnitten ist wahrscheinlich auf multifaktorielle lokale und systemische Faktoren zurückzuführen. In einer früheren Untersuchung konnte für die untersuchte Population eine genetische Disposition mit einer maximalen Prävalenz der HA von 30% gesichert werden. Da die HA als genetischer Marker für die GOA angesehen werden kann, ist die gleiche Aussage für die Häufigkeit der GOA anzunehmen. BackgroundThe definition of generalized osteoarthritis in the literature is just as controversial as the discussion about correlations between GOA and Heberden’s nodes (HN). Therefore, both questions were investigated in patients with proven heredity in a genealogical study of 931 family members. Material and methodsIn 106 patients with HN and 109 control subjects, 70 joints and spinal segments were investigated with respect to characteristic functional parameters. In addition, 44 joints and spinal segments were investigated radiologically. ResultsGOA affects both the small and large joints as well as the spine. This phenomenon is the more pronounced the more finger joints are affected by Heberden’s and Bouchard’s nodes. ConclusionsGOA affects the entire musculoskeletal system. The varying manifestation in individual joints and spinal segments is probably attributable to multifactorial local and systemic factors. In an earlier study, a genetic disposition with a maximum HA prevalence of 30% was identified in the study population. Since HA is considered a genetic marker for GOA, it can be assumed that the same is true of GOA prevalence. SchlüsselwörterGeneralisierte Arthrose-Heberden-Arthrose-Bouchard-Arthrose-Arthrosedisposition-Polyarthrose KeywordsGeneralized osteoarthritis-Heberden’s nodes-Bouchard’s nodes-Disposition to osteoarthritis-Polyarthritis
    Zeitschrift für Rheumatologie 08/2010; 69(6):544-549. DOI:10.1007/s00393-010-0643-z · 0.46 Impact Factor