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Chondrocalcinosis, Osteophytes and Osteoarthritis

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Chondrocalcinosis, Osteophytes and Osteoarthritis LEADER 499 Osteoarthritis limitations of the standing anteroposte- ................................................................................... rior radiograph for accurate and repro- Ann Rheum Dis: first published as 10.1136/ard.62.6.499 on 1 June 2003. Downloaded from ducible assessment of JSN in patients with OA.8 The issue concerns the import- Chondrocalcinosis, osteophytes and ance of alignment of the central x ray beam with the plane of the medial tibial osteoarthritis plateau in assessment of tibiofemoral compartment joint space width, a de- K D Brandt crease in which is generally taken as an indication of the radiographic severity of ................................................................................... OA and, in serial examinations, of progression of cartilage damage. Fluoro- Crystals, spurs, and osteoarthritis scopically assisted positioning of the joints to align the tibiofemoral compart- Association between OA and the articular surface in vivo.4 Further- ment (that is, with anterior and posterior chondrocalcinosis more, calcium crystals are phlogistic; margins of the medial tibial plateau An association between osteoarthritis their presence within the joint space and superimposed ±1 mm), as with the tech- 9 (OA) and radiographic evidence of chon- synovium may initiate an inflammatory nique described by Buckland-Wright, is drocalcinosis (CC) has been recognised response.5 associated with a more rapid rate of JSN, for years. Crystals of calcium pyrophos- and smaller standard deviation of the phate dihydrate (CPPD) may be found in Radiography of OA rate of narrowing, than protocols that synovial fluid from patients with OA who The paper by Neame et al in this issue of are less effective in providing tibial 10 are relatively asymptomatic as well as the Annals examines the association plateau alignment. Because of subject from those who are experiencing an between knee OA and CC from an epide- to subject variability in the angle of miological perspective.6 Subjects in this acute flare up of joint pain due to an inclination of the tibial plateau relative cross sectional study were defined as attack of pseudogout. Whether CC is the to the horizontal plane, (fortuitous) having OA on the basis of radiographic cause of OA in such people or develops as alignment of the medial plateau with the evidence of a definite osteophyte and a result of changes in metabolism of the plane of the x ray beam occurs in only definite joint space narrowing (JSN, a 11 chondrocyte or in the extracellular ma- about 20–30% of subjects. Indeed, in surrogate for thinning of the articular 6 trix of the articular cartilage is unclear. the Nottingham study the reproduc- cartilage). The authors found an associ- In any event, conditions associated with ibility of repeated measurements of ation between CC and OA in the tibio- minimum joint space width on the same CC, such as hyperparathyroidism, Wil- femoral and patellofemoral compart- ± son’s disease, and haemochromatosis, image ( 0.31 mm for the left medial ments, although patellofemoral CC was tibiofemoral compartment) was consid- are well recognised causes of “second- relatively uncommon and did not occur ary” OA.1 erably greater than the mean annual rate in the absence of concomitant tibiofemo- of JSN in serial images of the same joint Chondrocytes from patients with OA ral CC. who do not exhibit CC produce as much reported by several investigators (0.1–0.2 A strong association was noted be- mm a year).10 pyrophosphate as those from the carti- tween osteophytosis and JSN: a signifi- 2 What is the association between os- lage of patients with CPPD disease. Fur- cant relationship existed between CC teophytosis and OA? Although it is gen- http://ard.bmj.com/ thermore, chondrocytes from human OA and both the total osteophyte score and erally considered that radiographic evi- cartilage exhibit increased sensitivity to the total number of sites within the joint dence of definite osteophytosis is a transforming growth factor β (TGFβ), affected by osteophytosis. In contrast, no requisite for the radiographic diagnosis which has been shown to induce osteo- association was noted between CC and of OA,12 it has been suggested that osteo- phyte formation in murine knee joints, JSN, leading the authors to conclude phytes alone—in the absence of other an effect not seen with insulin-like that the association between OA and CC bony changes of OA in the radiograph growth factor 1.3 TGFβ also stimulates is mediated though an association with (for example, subchondral sclerosis, the secretion of pyrophosphate by on October 2, 2021 by guest. Protected copyright. osteophytes, rather than with JSN. How- subchondral cysts)—may merely reflect chondrocytes, predisposing to formation ever, given that calcium crystals stimu- aging, and not OA.13 14 Furthermore, of pericellular CPPD crystals; the phago- late the synthesis and release from radiographic decreases in the interbone cytosis of which results in the synthesis chondrocytes of potent proteinases that distance in the tibiofemoral compart- of matrix metalloproteinases by 15 can degrade the cartilage matrix (see ment may be related to age, raising the chondrocytes.4 These enzymes partici- above) and that accelerated degenera- possibility that, had age been taken into pate directly in the breakdown of the tion of cartilage has been observed in account in the Nottingham study, a rela- extracellular matrix of the cartilage and joints of animals with experimentally tionship between CC and joint space activate latent proenzymes and growth induced OA after intra-articular injec- width might have been revealed. factors that cause further structural tion of CPPD crystals,7 the apparent lack damage. Calcium crystals also decrease of association between CC and articular Chondrocalcinosis as a risk factor for the synthesis of proteinase inhibitors, cartilage damage might have been due to OA such as tissue inhibitors of metallopro- the insensitivity of radiography for de- Is CC a risk factor for the progression of teinases, exacerbating tissue damage.4 tection of CC or of the radiographic pro- knee OA? Can the presence of CC be used In addition to the effects of CPPD tocol employed in the epidemiological to predict which subjects with radio- crystals on cartilage cited above, calcium study for detection of cartilage loss (that graphic evidence of OA will progress crystals may produce direct mechanical is, JSN). radiographically or clinically (for exam- damage to articular cartilage. Addition Possibly, more rigorous radioanatomi- ple, with increasing severity of joint pain of CPPD crystals to the solution bathing cal positioning than can be achieved and diminution of function)? Although cartilage plugs that were subjected to with the conventional weightbearing the presence of CPPD crystals in synovial mechanical wear in vitro increased pro- extended anteroposterior view of the fluid from patients with knee OA was teoglycan loss from the cartilage matrix, knee would have shown an association associated with increased disability,16 suggesting that crystals present in syno- between CC and JSN. Considerable inter- and an association has been reported vial fluid may cause increased wear of est has been focused recently on the between the presence of CPPD crystals in www.annrheumdis.com 500 LEADER synovial fluid and severe radiographic that convert pyrophosphate to 6 Neame RL, Carr AJ, Muir K, Doherty M. UK 17 18 21 community prevalence of knee changes of OA, others have not found orthophosphate and increase the solu- Ann Rheum Dis: first published as 10.1136/ard.62.6.499 on 1 June 2003. Downloaded from 22 chondrocalcinosis: evidence that correlation an association between CC and radio- bility of CPPD crystals, the authors with osteoarthritis is through a shared graphic severity of OA.19 However, these suggest that the association might have association with osteophyte. Ann Rheum Dis 2003;62:513. studies were all cross sectional, rather been due to iatrogenic hypomagnesae- 7 Fam A, Morava-Protence I, Purcell C, Young than longitudinal and, as mentioned mia. It might be possible to test this B, Bunring P, Lewis A. Acceleration of above, the sensitivity of radiography for hypothesis in the large prospective study experimental lapine osteoarthritis by calcium pyrophosphate microcrystalline synovitis. the detection of CPPD crystals in articu- of the natural history of OA soon to be Arthritis Rheum 1995;38:201–10. lar structures is poor. initiated with support from the National 8 Brandt KD, Mazzuca SA, Conrozier T, Dacre In their paper, Neame et al note that Institutes of Health (NIH) and the phar- JE, Peterfy CG, Provvedini D, et al. Which is the best radiologic/radiographic protocol for increases in osteophytosis and bone maceutical industry, in which an attempt a clinical trial of a structure-modifying drug in remodelling were the most common will be made to identify surrogate patients with knee osteoarthritis? Proceedings changes found in patients with knee OA biomarkers for incident OA and for the of January 17–18, 2002 Workshop in Toussus-le-Noble, France. J Rheumatol and CC who were followed up progression of established OA in 5000 2002;29:1308–20. longitudinally.6 It is important to re- subjects over a four year period of obser- 9 Buckland-Wright JC. Protocols for member that the pathogenetic mecha- vation. For this purpose a cohort of sub- radiography. In: Brandt KD, Doherty M, Lohmander SL, eds. Osteoarthritis. Oxford: nisms underlying osteophytosis are dif- jects will be established that would be Oxford University Press, 1998:578–80. ferent from those that result in the well well suited to a prospective analysis 10 Vignon E, Piperno M, Le Graverand MP, recognised changes in subchondral bone examining whether diuretic treatment Mazzuca SA, Brandt KD, Mathieu P, et al. Measurement of radiographic joint space in OA, in which both the formation and predisposes to CC, osteophytosis, or inci- width in the tibiofemoral compartment of the resorption of bone are accelerated. Fur- dent or progressive OA. Thus, the careful osteoarthritic knee: comparison of standing thermore, the increased turnover of epidemiological observations of Neame anteroposterior and Lyon Schuss views.
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