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Ann Rheum Dis: first published as 10.1136/ard.45.7.603 on 1 July 1986. Downloaded from

Annals of the Rheumatic Diseases, 1986; 45, 603-605 Patterns of radiographic abnormalities associated with basic phosphate and calcium dihydrate crystal deposition in the knee

PAUL B HALVERSON AND DANIEL J McCARTY From the Division ofRheumatology, Medical college of Wisconsin, Milwaukee, WI, USA

SUMMARY Radiographs and synovial fluids from 66 knees representing 59 patients with symptomatic osteoarthritis were evaluated to determine the pattern of radiographic abnormali- ties associated with basic (BCP), dihydrate (CPPD), or both crystals together. Crystals were found in 71% of fluids. In general, CPPD crystals correlated with patient age, while BCP crystals correlated with joint degeneration. Synovial fluid BCP and CPPD crystals were found together more often than either alone. Joint compartment narrowing and osteophytes in three compartments are often associated with BCP crystals. Key words: knee osteoarthritis, radiographic changes.

Basic calcium phosphate crystals (BCP) (carbonate obtained for crystal identification and radiographs substituted , octacalcium phosphate, were available. Synovial fluids were examined by and ') are associated with compensated polarised light microscopy, and leuco- various conditions including Milwaukee shoulder cyte counts were determined as described http://ard.bmj.com/ syndrome, calcific periarthritis, and an erosive elsewhere.9 BCP crystals were identified by the polyarticular arthropathy.24 Reports from three binding of radiolabelled diphosphonate, followed by different laboratories have correlated the radiologi- scanning electron microscopy with energy dispersive cal severity of knee joint degeneration with the analysis to determine the calcium to quantity of BCP crystals in joint fluid.5-' The molar ratio as described previously.' Anteropos- prevalence of crystals in joint fluid was also directly terior and lateral radiographs of the knees were read

correlated with the extent of devolutionary changes blindly by both authors. The presence of joint space on October 2, 2021 by guest. Protected copyright. noted radiographically.5 8 The pattern of radio- narrowing and osteophytes in each of the three graphic abnormalities as correlated with the presence (medial and lateral tibiofemoral and patellofemoral) or absence of BCP and/or calcium pyrophosphate compartments of the knee was recorded. The dihydrate (CPPD) crystals in 66 knee joint fluids presence of chondrocalcinosis and femoral cortical from a series of 59 patients with symptomatic erosions (on lateral films) was also noted. Typical osteoarthritis is reported here. osteochondromata or soft tissue calcifications were noted. The Wilcoxon non-parametric ranked sums Materials and methods test was used for statistical comparison of patients ages. x2 Analysis was used to evaluate radiologic All patients were seen because of knee joint findings. symptoms in the rheumatology clinics staffed by the full time faculty of the Medical College of Wiscon- Results sin. Patients were included only if synovial fluid was Complete studies were available on 66 knees in 59 Accepted for publication 19 December 1985. Correspondence to Dr Paul B Halverson, Division of Rheuma- patients. Seven patients had fluid aspirated from tology, Medical College of Wisconsin, 2900 West Oklahoma both knees, and the crystals populations indentified Avenue, Milwaukee, Wisconsin 53215, USA. were concordant in all seven. All synovial fluids had 603 Ann Rheum Dis: first published as 10.1136/ard.45.7.603 on 1 July 1986. Downloaded from

604 Halverson, McCarty Table 1 Synovial fluid crystals and patient characteristics ment in 15/17 knees in group B and 21/22 knees in group D. The presence of diffuse osteophytosis Group, crystals involving all three knee compartments was found in with crystals alone and 13/22 with both A, B, C, D, BCP and 11/17 BCP none BCP CPPD CPPD BCP and CPPD. This was observed in only 1/8 with CPPD alone and 5/19 with no crystals. No of patients 19 14 8 18 The groups were subdivided according to joint No of knee joints 19 17 8 22 none or one compartment Mean age (years) 68-2 66-7 741 75-4 space narrowing in Range 56-92 49-96 47-96 52-80 compared with narrowing in two or three compart- M/F 2/17 3/11 3/5 9/9 ments (interpreted to represent greater joint dam- age). Significantly greater joint damage was found in group D compared with group A (p<0025) or group C (p<0.01), but no difference in joint total leucocyte counts less than 2000 mm3 (2x 109/l) degeneration was noted when groups B and C were and were, therefore, of the 'non-inflammatory' compared (0-05

Radiographic abnormalities associated with crystal deposition in the knee 605 collagenase activities were often found in these crystals appear to correlate mainly with devolution- fluids, and BCP crystals stimulated both synthesis ary joint changes, while CPPD crystals in joint fluid and secretion of these enzymes from tissue cultured appear to correlate chiefly with age. synovial fibroblasts. This mechanism may represent one such positive feedback loop.t6 References The simultaneous occurrence of BCP and CPPD 1 McCarty D J, Halverson P B. Basic calcium phosphate (, has been previously reported as 'mixed crystal octacalcium phosphate, tricalcium phosphate) crystal de- disease'.t7 18 In the present study 18/40 (45%) of position disease. In: McCarty D J, ed. Arthritis and allied fluids containing crystals had 'mixed crystal disease'. conditions. 10th ed. Philadelphia: Lea and Febiger, 1985: 1547-64. Gibilisco and his associates found an incidence of 2 Halverson P B, McCarty D J, Cheung H S, Ryan L M. 43% and patients with radiological evidence of Milwaukee shoulder syndrome: eleven additional cases with chondrocalcinosis were excluded from this study involvement of the knee in seven (basic calcium phosphate population.8 Thus the prevalence of both BCP and crystal deposition disease). Semin Arthritis Rheum 1984; 14: 36-44. CPPD crystals together is more common than the 3 Faure G, Daclusi G. Calcified tendonitis: a review. Atnn Rheutn prevalence of either type of crystal alone. Dis 1983: 42: 50-3. Identification of BCP crystals remains difficult. 4 Schumacher H R, Miller J L, Ludvico C. Jcsscr R A. Erosivc According to Paul et al alizarin red staining is a arthritis associatcd with apatitc crystal deposition. Arthritis Rheum 1981; 24: 31-7. highly sensitive but non-specific screening 5 Halvcrson P B. McCarty D J. ldcntification of hydroxyapatite procedure.6 Its clinical usefulness without more crystals in synovial fluid. Arthritis Rheum 1979:, 22: 389-95. specific confirmatory methods remains uncertain.7 6 Paul H, Reginato A J, Schumacher H R. Alizarin red S staining The 1-diphosphonate (EH- as a screcning test to detcct calcium compounds in synovial [14C]ethane-l-hydroxy-l, fluid. Arthritis Rheum 1983: 26: 191-2(X). DP) binding test is sensitive to 2 [.g of standard 7 Bardin T, Bucki B, Dryll A, Lansaman J. Ryckewaert A. hydroxyapatite crystals/ml. Concentrations of Alizarin red staining of synovial fluid (SF). Similar results in crystals not detectable by [14C]EHDP binding may osteoarthritis (OA) and rheumatoid arthritis (RA). Arthritis give positive results by alizarin red staining, making Rheum 1985; 28 (suppl): S53. 8 Gibilisco P A, Schumacher H R, Hollander J L, Soper K A. comparison of our data with other published results Synovial fluid crystals in ostcoarthritis. Arthritis Rheum 1985; difficult. 28: 511-5. In a previous study of 11 patients with Milwaukee 9 McCarty D J. Synovial fluid. In: McCarty D J, ed. Arthritis and allied conditions. l()th cd. Philadelphia: Lea and Febigcr. 1985: shoulder syndrome we found that seven had involve- 54-75. ment of their knees as well. The abnormalities were 10 Ropes M W, Bauer W. Synovial fluid changes in joint diseases.

not those of typical osteoarthritis in that three had Boston: Harvard University Press, 1953. http://ard.bmj.com/ lateral rather than medial compartment narrowing 11 Ryan L M, McCarty D J. Calcium pyrophosphate crystal deposition disease; pseudogout; articular chrondrocalcinosis. and five had chondrocalcinosis. Three patients in In: McCarty D J, ed. Arthritis and allied conditions. 10th ed. the present study had shoulder abnormalities com- Philadelphia: Lea and Febiger, 1985: 1515-46. patible with Milwaukee shoulder syndrome. One of 12 Dieppe P A, Crocker P, Huskisson E C, Willoughby D A. these knees had lateral compartment narrowing and Apatite deposition disease: a new arthropathy. Lancet 1976; i: 266-9. another had chondrocalcinosis. The question of 13 Schumacher H R, Smolyo A P, Tse R L, Maurer K. Arthritis whether or not the radiological pattern of knee joint associated with apatite crystals. Ann Intern Med 1977; 87: degeneration is distinctive in patients with Mil- 411-6. on October 2, 2021 by guest. Protected copyright. waukee shoulder syndrome cannot be answered 14 Dieppe P A, Crocker P R, Corkc C F, Doylc D V. Huskisson E C, Willoughby D A. Synovial fluid crystals. Q J Med 1979; 48: from the data presented here but will require further 533-53. study. 15 Dicppc P A. Dohcrty M, MacFarlanc D G. Hutton C W, In summary, crystals are often present in synovial Bradfield J W, Watt l. Apatitc associatcd destructive arthritis. fluid from osteoarthritic joints. There is no distinc- Br J Rheumatol 1984; 23: 84-91. 16 Cheung H S, Halverson P B, McCarty D J. Garancis J C. tive pattern of radiographic abnormality that accom- Release of collagenase, neutral protease, and prostaglandins panies BCP crystal deposition, but the presence of from cultured synovial cells by hydroxyapatite and calcium knee joint compartment narrowing, particularly in pyrophosphate dihydrate. Arthritis Rheum 1981; 24: 1338-44. the presence of three compartment osteophytosis, is 17 Dieppe P A, Doyle D V, Huskisson E C, Willoughby D A, Crocker P R. Mixed crystal deposition disease and osteoarthri- very suggestive. The findings are similar when both tis. Br Med J 1978; i: 150. BCP and CPPD are present except that radiological 18 Doylc D V, Dieppe P A, Crockcr P R, lbc K. Mixed crystal chondrocalcinosis is often seen. Joint fluid BCP deposition in an ostcoarthritic joint. J Pathol 1977: 123: 1-5.