OsteoArthritis and Cartilage (2004) 12, S53–S54
`© 2003 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
`doi:10.1016/j.joca.2003.09.003
`
`International
`Cartilage
`Repair
`Society
`
`Workshop
`
`Are osteophytes good or bad?
`C-J. Menkes MD† and N. E. Lane MD‡*
`†Universite´ Rene´ Descartes, Hoˆpital Cochin, 27 rue du Faubourg Saint Jacques, 75014 Paris France
`‡Division of Rheumatology, University of California at San Francisco, San Francisco, California 94143, U.S.A.
`
`Key words: Osteophyte, Osteoarthritis, Growth factors, Animal model.
`
`There are three types of osteophytes: the traction spur,
`a physiologic response at the insertion of tendons and
`ligaments;
`the inflammatory spur,
`represented by the
`syndesmophyte at the insertion of ligaments and tendons
`to bone as seen in ankylosing spondylitis; and the real
`osteophyte – or better, osteochondrophyte – arising in the
`synovium overlying bone at the junctional zone. The osteo-
`chondrophyte is believed to form from metaplasia of syn-
`ovium into cartilage with the formation of chondroblasts and
`cartilage at the margin of articular surface1–4.
`The osteophyte myth is represented by the supposed
`diagnostic relevance of tibial spine hypertrophy. In reality,
`tibial spines are not
`ligamentous insertions or traction
`spurs, and the peaking of the tibial spines is not a relevant
`diagnostic finding1. The osteophytes can be considered to
`be an adaptive reaction of the joint to cope with instability.
`Osteophytes splint the joint and may play a compensatory
`role in the redistribution of
`forces to provide articular
`cartilage protection. It has been shown, at the time of total
`knee replacement, that removal of osteophytes from the
`arthritic compartment significantly increased the varus-
`valgus motion, and subsequent removal of osteophytes
`from the nonosteoarthritic compartment further increased
`motion. Therefore, these data suggest that osteophytes
`appear to stabilize osteoarthritic knees but can cause fixed
`deformity5.
`The formation of osteophytes is linked to growth factors.
`Uchino et al.6 demonstrated that both transforming growth
`factor-♢1 (TGF-♢1) and basic fibroblast growth factor (bFGF)
`are expressed in osteophytes of
`the femoral head in
`osteoarthritis (OA). In a murine model of OA, osteophytes
`develop after repeated injections of TGF-♢1 in the knee and
`after sustained overexpression of TGF-♢ in the joint follow-
`ing TGF-♢ gene transfer7,8. Interestingly, cartilage lesions
`are correlated with the degree of osteophyte formation. A
`few studies have shown that bone scintigraphy is a good
`marker for growing, active osteophytes and may predict, to
`some extent, the future disintegration of the joint9,10.
`Clinically, osteophytes of the knee are associated with
`pain and predict pain more accurately than the narrowing of
`knee joint space in all radiological views11.
`
`*Address correspondence to: Nancy E. Lane, MD, Associate
`Professor of Medicine, Division of Rheumatology, Box 0868,
`University of California at San Francisco, San Francisco, California
`94143. Tel.: +1-415-206-8189; Fax: +1-415-648-8425; E-mail:
`nelane@itsa.ucsf.edu
`
`The clinical aspects of osteophytes in OA are sum-
`marized by K. Brandt12. According to Dr Brandt, antiresorp-
`tive drugs inhibit the formation of cancellous subchondral
`bone but have no effect on the formation of marginal
`osteophytes. Doxycycline has no effect on osteophytes, but
`some anti-inflammatory drugs, such as glucocorticoids
`that have an anti-anabolic effect,
`inhibit both cartilage
`breakdown and osteophytosis13–15.
`However, osteophytes may represent a manifestation
`of aging in the absence of other bony changes. In most
`cases, they are asymptomatic, but they may be of clinical
`importance. For instance, cervical osteophytes may cause
`dysphagia, and lumbar osteophytes may be responsible for
`nerve root compression with severe pain, requiring surgical
`removal16,17.
`Does the removal of osteophytes accelerate cartilage
`degeneration? Surgeons have shown that after hallux
`rigidus cheilectomy there is no cartilage destruction18. Are
`osteophytes good or bad? It depends where they are
`situated, and it depends on the stage of the disease. At the
`endstage of OA in lower limbs they may be good because
`they stabilize the joint. However, in the spine, most often,
`they are painful, and they are bad.
`
`Discussion
`Participant: Magnetic resonance imaging (MRI) can pro-
`vide interesting information with regard to the evolution of
`osteophytes. As osteophytes evolve, one will typically see
`some focal hyperemic or an edema pattern on an MRI
`scan. And then, as they mature, they can have a low signal
`if they are densely ossified, or even in a late stage, as one
`may see bone marrow replacement going into the osteo-
`phyte. It might be interesting to determine from both longi-
`tudinal and cross-sectional studies the value of MRI in
`showing the relationship between osteophytes and the
`stage of the disease, the symptoms of disease, and drug
`efficacy.
`Dr Menkes: The value of MRI is confirmed by the findings
`in patients who, for some reason, underwent both bone
`scintigraphy and MRI at
`the same time. An increased
`uptake of
`the radioisotope on the bone scan and a
`gadolinium-enhanced imaging on the MRI, corresponding
`to a local hyperactivity, appear to be correlated.
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`C-J. Menkes and N. E. Lane: Are osteophytes good or bad?
`
`Participant: If we accept that osteophytes are the joint’s
`attempt
`to stabilize joint
`instability introduced by the
`osteoarthritic process, there should be some correlation
`between the size or the growth of the osteophyte and other
`criteria of joint change, such as loss of joint space or the
`size of the focal lesions. Do you know whether anyone has
`tried to correlate these or other parameters with the rate of
`progression of osteophyte formation?
`Dr Dougados: In the ECHODIAH study, we evaluated
`radiographic data from 500 patients with hip OA in an effort
`to determine the radiographic findings that would predis-
`pose patients to disease progression. Progression was
`defined by the change in joint space width after 2 years.
`The radiological factors found to be predisposing factors for
`disease progression were the presence at baseline of
`subchondral cysts, osteosclerosis, and osteophytes. We
`found that the absence of osteophytes was associated with
`a higher risk of progression.
`It is possible that the absence of osteophytes is charac-
`teristic of a specific group of patients with rapidly destruc-
`tive OA of
`the hip. When collecting information about
`osteophytes, it is interesting to take into account other
`localizations of the disease.
`Dr Buckland-Wright: I wonder if this is not something that
`has been described previously, by the South African sur-
`geons, who characterized the atrophic and hypertrophic
`forms of OA. The atrophic form, which is non-osteophyte
`forming, is highly destructive with rapid progression, and
`the hypertrophic form is osteophyte forming with a low rate
`of progression.
`
`References
`1. Alexander CJ. Osteoarthritis: a review of old myths and
`current concepts. Skeletal Radiol 1990;19:327–33.
`2. Moskowitz
`R.
`Bone
`remodeling
`in
`osteo-
`arthritis: subchondral and osteophytic responses.
`Osteoarthritis Cartilage 1999;7:323–4.
`3. Oni OO, Boyd I. The origin of the periarticular osteo-
`phytes of osteoarthritic knee joints. Afr J Med Sci
`1998;27:23–5.
`4. Moskowitz RW, Goldberg VM. Osteophyte evolution:
`studies in an experimental partial meniscectomy
`model. J Rheumatol 1987;14:166-8.
`5. Pottenger LA, Phillips FM, Draganich LF. The effect of
`marginal osteophytes on reduction of varus-valgus
`instability in osteoarthritic knees. Arthritis Rheum
`1990;33:853–8.
`
`6. Uchino M, Izumi T, Tominaga T, Wakita R, Minchara H,
`Sekiguchi M, et al. Growth factor expression in
`the osteophytes of
`the human femoral head in
`osteoarthritis. Clin Orthop 2000;377:119–25.
`7. Van den Berg WB. Osteophyte formation in osteo-
`arthritis. Osteoarthritis Cartilage 1999;7:333.
`8. Van Beuningen HM, Glansbeek HL, Van der Kraan
`PM, Van den Berg WB. Osteoarthritis-like changes
`in the murine knee joint
`resulting from intra-
`articular transforming growth factor-beta injections.
`Osteoarthritis Cartilage 2000;1:25–33.
`9. Van Osch GJ, Van der Kraan PM, Van Valburg AA, Van
`den Berg WB. The relation between cartilage dam-
`age and osteophyte size in a murine model
`for
`osteoarthritis in the knee. Rheumatol
`Int 1996;
`16:115–9.
`10. Dieppe PA, Cushnagan J, Young P, Kirwan J. Bone
`scintigraphy predicts the progression of joint space
`narrowing in osteoarthritis of the knee. Ann Rheum
`Dis 1993;52:557–63.
`11. Cicuttini FM, Baker J, Hart DJ, Spector TD. Association
`of pain with radiological changes in different compart-
`ments and views of
`the knee joint. Osteoarthritis
`Cartilage 1996;4:143–7.
`12. Brandt KD. Osteophytes in osteoarthritis. Clinical
`aspects. Osteoarthritis Cartilage 1999;7:334–5.
`13. Yu LP, Smith GN Jr., Brandt KD, Myers SL, O’Connor
`BL, Brandt DA. Reduction of the severity of canine
`osteoarthritis by prophylactic treatment with oral
`doxycycline. Arthritis Rheum 1992;35:1150–9.
`14. Pelletier JP, Martel-Pelletier J. Protective effects of
`corticosteroids on cartilage lesions and osteophyte
`formation
`in
`the Pond-Nuki
`dog model
`of
`osteoarthritis. Arthritis Rheum 1989;32:181–93.
`15. Devogelaer JP, Manicourt DH. Osteophytes and
`osteoarthritis progression. Effects of nonsteroidal
`antiinflammatory drugs. Osteoarthritis Cartilage
`1999;7:336–7.
`16. Strasser G, Schima W, Schober E, Pokieser P, Kaider
`A, Denk DH. Cervical osteophytes impinging on the
`pharynx: importance of size and concurrent disorders
`for development of aspiration. Am J Roentgenol
`2000;174:449–53.
`17. Lamer TJ. Lumbar spine pain originating from vertebral
`osteophytes. Reg Anesth Pain Med 1999;24:347–51.
`18. Mann RA, Clanton TO. Hallux rigidus: treatment by
`cheilectomy. J Bone Joint Surg 1988;30:400–6.
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