Articular chondrocalcinosis in seropositive rheumatoid arthritis. Comparison with a control group

The prevalence of articular chondrocalcinosis was studied in a group of 100 patients with seropositive rheumatoid arthritis (RA). Articular chondrocalcinosis was observed less frequently (3%) than in a control group (19%) of 221 age and sex matched patients with low back pain or extraarticular rheumatism. This difference is statistically significant (p less than 0.001). Articular chondrocalcinosis occurred in the older patients with RA, and was observed in those with the shortest duration of the disease.     

Destructive arthropathy in generalized osteoarthritis with articular chondrocalcinosis.

A destructive arthropathy is much more common when generalized osteoarthritis (GOA) and articular chondrocalcinosis (ACC) coexist than in GOA alone. Fifty-two patients with GOA and ACC were compared to a matched control group with GOA alone. A marked increase in the frequency of a destructive arthropathy was found in the group with both GOA and ACC. Nonweight-bearing joints were often involved in the group with GOA and ACC, whereas they were seldom involved in the group with GOA alone.     

Analysis of the association between chondrocalcinosis and osteoarthritis: a community based study.

OBJECTIVES--To analyse the association between chondrocalcinosis and osteoarthritis (OA) of the hands and knees in an unselected elderly rural population. METHODS--A community based cross sectional study was performed in individuals randomly selected from a previous epidemiological survey on the prevalence of chondrocalcinosis in people older than 60 years from Osona county, Catalonia, northeastern Spain. Radiological OA (grade 2 or more of Kellgren's classification) was evaluated in 26 individuals with chondrocalcinosis and in 104 controls. A total of 18 articular areas of both knees (medial and lateral tibiofemoral compartments) and hands (first, second and third metacarpophalangeal (MCP), first carpometacarpal, trapezium-scaphoid, radiocarpal and distal radioulnar joints) were studied. RESULTS--Radiological changes of OA in the knees were more common in subjects with chondrocalcinosis than in those without it, with an odds ratio adjusted for age and gender (aOR) of 4.3 (95% confidence interval (CI) 1.6 to 11.8, p = 0.005). OA was also more frequent in almost all areas of the hands in individuals with chondrocalcinosis, though the difference reached statistical significance only in the MCP joints (aOR 3.1; 95% CI 1.1 to 8.8; p = 0.033). However, taking into account the side and the different joint compartments analysed, the association between chondrocalcinosis and OA was significant only in the lateral tibiofemoral compartment and the left MCP joints. CONCLUSIONS--In an elderly population unselected for their rheumatic complaints, there was a real association between OA and chondrocalcinosis. This association was particularly relevant in the lateral tibiofemoral compartment of the knee and in the first three left MCP joints.     

Calcium pyrophosphate crystal deposition disease and hyperparathyroidism: a controlled, prospective study.

A prospective, controlled study of patients with primary hyperparathyroidism has been carried out to establish the relation of this endocrinopathy to calcium pyrophosphate dihydrate crystal deposition disease. Eight of 26 patients with documented hyperparathyroidism were found to have chondrocalcinosis compared to four of 104 individuals in the control group (p less than 0.01). Two of these eight patients had confirmed pseudogout attacks shortly after parathyroidectomy. Four other patients, including two without chondrocalcinosis, gave a history of typical pseudogout. Patients with hyperparathyroidism and chondrocalcinosis were significantly older than those without the articular lesion (p = 0.006). We could not delineate specific metabolic abnormalities of hyperparathyroidism which contributed to the development of chondrocalcinosis.     

ARTICULAR CHONDROCALCINOSIS IN A HOSPITAL POPULATION: AN AUSTRALIAN EXPERIENCE

A group of hospital patients aged 55 years or over (53 men, 74 women) were screened for articular chondrocalcinosis (ACC) with high-resolution radiographs of knees, wrists, hands and pelvis. Two men (4%) aged 79 and 86 years had ACC involving knees, wrists and symphysis pubis. Both had clinical joint disease and radiological osteoarthritis (OA). Eighteen women (24%) had ACC with sites affected including the knees (89%), wrists (39%) and symphysis pubis (44%). Metabolic screening did not reveal any predisposing factors in patients with ACC. Symptoms and signs of joint disease were not significantly more common in women with ACC compared to those without ACC, and 44% of those with knee calcification were clinically asymptomatic and had no evidence of OA radiologically. However, the presence of knee ACC significantly increased the risk for OA in the same knee by a factor of three-to-four while knee calcification was associated with the more severe grades of radiographic OA.     

Frequency of chondrocalcinosis of the knees in asymptomatic hyperuricaemia and rheumatoid arthritis: a controlled study.

An association has been reported between urate gout and chondrocalcinosis. Chondrocalcinosis was detected in knee radiographs of 8 of 138 gouty patients compared with none of 142 age matched nongouty normouricaemic controls (p less than 0.025). To define this association further, knee radiographs were examined of 84 patients with asymptomatic hyperuricaemia who had been carefully age matched with the gouty and control groups. Chondrocalcinosis of the knees was detected in only one patient, the difference from the control group not being significant. It therefore appears that there is an association of chondrocalcinosis with gouty arthritis, but not with asymptomatic hyperuricaemia. An association between chondrocalcinosis and rheumatoid arthritis has been suggested, but the studies were not controlled for age. To re-examine this implied association, knee radiographs were inspected of 127 patients with rheumatoid arthritis who had been age matched with the control group. Chondrocalcinosis of the knees was detected in only one patient, a difference from the control group which is not statistically significant.     

Prevalence of rheumatoid arthritis, osteoarthritis, chondrocalcinosis and gouty arthritis at age 79

The prevalence of rheumatic diseases was studied in representative subsamples by interview (n = 134), and by physical (n = 89) and radiographic (n = 81) examination in a representative sample of 79-year-olds in G?teborg, Sweden. The prevalence of rheumatoid arthritis (3-8 ARA criteria) was 10%. Radiographic osteoarthritis (OA) was diagnosed in wrists and/or finger joints of 65% of the probands and in knee joints of 14%. The first metacarpophalangeal (MCP I) joint was more frequently involved in males than in females (p less than 0.05). In females palpable enlargement of distal (DIP) and proximal interphalangeal finger joints correlated (p less than 0.01) to radiographic OA. The degree of heavy work in previous occupations was correlated to radiographic OA of DIP II-V in females (p less than 0.05 and of MCP I in males (p less than 0.05) but not to radiographic or clinical OA in knee joints. Symptoms of OA were reported by 6.1% in the knee and in 4.5% in hip joints. The prevalence of chondrocalcinosis averaged 15% (23% of females and 6% of males). Chondrocalcinosis of the hands occurred in 21% of females but in no males. The prevalence of hyperuricemia was 15% (women 6%, men 29%), and gouty arthritis was found in one woman.     

Chondrocalcinosis in surgically resected joints

To investigate the association between chondrocalcinosis (CC) and osteoarthritis (OA), 338 joint specimens were examined histologically (55 knees and 84 hips surgically resected because of idiopathic OA, 106 control knees obtained postmortem, and 93 fractured hips). The risk for CC in the OA knees was sixfold that of the age- and sex-adjusted control sections. CC occurred much less frequently in the hip than in the knee; the association with OA was less clear-cut. It was not possible to resolve by statistical analysis which of the two pathological processes was the horse and which was the cart.     

Secondary gait changes in patients with medial compartment knee osteoarthritis: increased load at the ankle, knee, and hip during walking

OBJECTIVE: This study tested the hypothesis that gait changes related to knee osteoarthritis (OA) of varied severity are associated with increased loads at the ankle, knee, and hip. METHODS: Forty-two patients with bilateral medial compartment knee OA and 42 control subjects matched for sex, age, height, and mass were studied. Nineteen patients had Kellgren/Lawrence (K/L) radiographic severity grades of 1 or 2, and 23 patients had K/L grades of 3 or 4. Three-dimensional kinematics and kinetics were measured in the hip, knee, and ankle while the subjects walked at a self-selected speed. RESULTS: Patients with more severe knee OA had greater first peak knee adduction moments than their matched control subjects (P = 0.039) and than patients with less severe knee OA (P < 0.001). All patients with knee OA made initial contact with the ground with the knee in a more extended position than that exhibited by control subjects. An increased axial loading rate was present in all joints of the lower extremity. Patients with more severe knee OA had lower hip adduction moments compared with their matched control subjects. CONCLUSION: The secondary gait changes observed among patients with knee OA reflect a potential strategy to shift the body's weight more rapidly from the contralateral limb to the support limb, which appears to be successful in reducing the load at the knee in only patients with less severe knee OA. The increased loading rate in the lower extremity joints may lead to a faster progression of existing OA and to the onset of OA at joints adjacent to the knee. Interventions for knee OA should therefore be assessed for their effects on the mechanics of all joints of the lower extremity.     

The inheritance of hip osteoarthritis in Iceland

OBJECTIVE: To assess, in a population-wide study in Iceland, the genetic contribution to hip osteoarthritis (OA) leading to total hip replacement (THR). METHODS: Information from 2 population-based databases in Iceland was combined: a national registry of all THRs performed between 1972 and 1996, and a genealogy database of all available Icelandic genealogy records for the last 11 centuries. A genetic contribution to THR for OA was assessed by 1) identifying familial clusters of OA patients with THR, 2) applying the minimum founder test (MFT) to estimate the minimum number of ancestors ("founders") that would account for the genealogy of all 2,713 patients with THR for OA, compared with the average number of founders for control lists, 3) calculating an average pairwise kinship coefficient (KC) for the patient list and control lists, and 4) estimating the relative risk (RR) for THR among relatives of OA patients who have undergone the procedure. One thousand matched control lists, each the same size as the patient list, were created using the genealogy database. RESULTS: A large number of familial clusters of patients with THR for OA were identified. The MFT showed that OA patients descended from fewer founders than did subjects in the control groups (P < 0.001). The average pairwise KC among patients with OA was greater than in the control population (P < 0.001). The RR for THR among siblings of OA patients was 3.05 (95% confidence interval 2.52-3.10). CONCLUSION: This population-based study shows that Icelandic patients with hip replacement for OA are significantly more related to each other than are matched controls drawn from the Icelandic population. These findings support a significant genetic contribution to a common form of OA and encourage the search for genes conferring an increased susceptibility to OA.     

Urinary type II collagen C-telopeptide levels are increased in patients with rapidly destructive hip osteoarthritis

OBJECTIVE: To compare type II collagen degradation using a new urinary specific marker in patients with rapidly destructive and those with slowly progressive hip OA. METHODS: Twelve patients with rapidly destructive and 28 patients with slowly progressive hip OA were included in a prospective, cross sectional case-control study. Urinary levels of C-terminal crosslinking telopeptide of collagen type II (CTX-II) as a marker of cartilage degradation were measured by an ELISA, and urinary free deoxypyridinoline (free DPD), a marker of bone resorption, was measured by high performance liquid chromatography. One x ray evaluation of the hips and urine samples was made in all patients when the diagnosis of OA was established. RESULTS: Patients with hip OA had higher mean (SD) urinary CTX-II levels than 65 healthy age matched controls (492 (232) v 342 (141), p<0.001), but no significant difference was seen for urinary free DPD (p=0.30). Increased urinary CTX-II, but not urinary free DPD, correlated significantly with decreased minimum joint space width assessed by radiograph of the hip. Mean urinary CTX-II levels were significantly higher in patients with rapidly progressive OA than in the slowly progressive group (612 (218) v 441 (221), p=0.015), whereas no significant difference of urinary free DPD was seen between the two groups (p=0.55). CONCLUSION: Patients with hip OA have increased CTX-II degradation as assessed by a new urinary marker. Increased urinary CTX-II levels are associated with rapidly destructive disease, suggesting that this marker might be useful in identifying patients with hip OA at high risk for rapid progression of joint damage.     

The relationship between chondrocalcinosis and osteoarthritis in Saudi Arabia

The association between articular chondrocalcinosis and osteoarthritis was sought by studying 92 patients over the age of 60. Anteroposterior and lateral X-ray projections of knees, hands and wrists were studied for the presence of chondrocalcinosis and osteoarthritis. Of the 92 patients (60 males, 32 females), six had chondrocalcinosis of the knees; two of them also had it in the wrist. The six cases with chondrocalcinosis were compared to the 86 cases without, for the presence of osteoarthritis in the different compartments of the knees, intercarpal joints (IC) and metacarpophalangeal joints (MCP). We found an association between chondrocalcinosis and osteoarthritis of the lateral knee compartment (odd ratio (OR) 10.59, 95% CI 3.47–34.9), second MCP joint (OR 3.27 95% CI 1.44–8.93), third MCP joints (OR 6.92, 95% CI 1.99–25.54) and IC joint (OR 5.69, 95% CI 1.14–29.7). No association was found with overall knee OA, medial knee compartment OA or patellofemoral OA. In conclusion, chondrocalcinosis was associated with OA of the lateral knee compartment, second MCP, third MCP and IC joints. Received: 25 January 2002 / Accepted: 10 June 2002 Correspondence and offprint requests to: Dr Abdurhman S. Al-Arfaj, PO Box 34471, Riyadh 11468, Saudi Arabia. E-mail: asarfaj@ksu.edu.sa     

Osteoarthritis and articular chondrocalcinosis in the elderly.

One hundred consecutive admissions to an acute geriatric unit were examined for clinical and radiographic evidence of osteoarthritis (OA) and articular chondrocalcinosis (ACC). Thirty-four patients had ACC. This was age related, the prevalence rising from 15% in patients aged 65-74 years to 44% in patients over 84 years. The commonly involved joints were the knee (25%), public symphysis (15%), and wrist (9%). No other aetiological factors predisposing to ACC were found. Of the 25 patients with ACC in the knee 7 had no symptoms or signs and no radiographic evidence of OA at that site. However, the combination of ACC and radiographic OA was characterised by an increase in clinical joint disease. Features of inflammation (joint swelling and joint line tenderness) involving the knee, wrist, and elbow were particularly common in ACC. It is concluded that ACC is common in the elderly and is associated with an increased incidence of joint disease.     

Prevention of cartilage destruction with intraarticular osteoclastogenesis inhibitory factor/osteoprotegerin in a murine model of osteoarthritis

OBJECTIVE: To investigate the effect of osteoclastogenesis inhibitory factor/osteoprotegerin (OPG) on chondrocytes in the development of osteoarthritis (OA) in vivo. METHODS: To determine the role of endogenous OPG in the progression of OA, OA was surgically induced in OPG+/- mice and their wild-type (WT) littermates. To determine the role of exogenous OPG, knee joints of C57BL/6J mice with surgically induced OA were injected intraarticularly with recombinant human OPG (rHuOPG) or vehicle 5 times a week. All mice were euthanized 4 weeks after OA induction; joints were harvested and evaluated immunohistochemically. RESULTS: Although OA changes were induced in both WT and OPG+/- mice, the degenerative changes in the articular cartilage were significantly enhanced in OPG+/- mice. In C57BL/6J mice with surgically induced OA, intraarticular OPG administration protected the articular cartilage from the progression of OA. The Mankin and cartilage destruction scores in OPG-treated animals were approximately 50% of those seen in the control group. Furthermore, OPG administration significantly protected articular cartilage thickness. Findings of the TUNEL assay indicated that rHuOPG prevented chondrocyte apoptosis in joints with surgically induced OA. Results of immunostaining indicated that OPG protein was detected in the synovium and in resident chondrocytes at higher levels in the OPG-treated group than in the control group. CONCLUSION: These data indicate that endogenous OPG had a protective effect against the cartilage destruction that occurs during OA progression. Furthermore, direct administration of rHuOPG to articular chondrocytes prevented cartilage destruction in an experimental murine model of OA via prevention of chondrocyte apoptosis.     

Adenomas of the large intestine after cholecystectomy

The frequency of adenomas of the large intestine in 331 cholecystectomised patients who underwent total colonoscopy was compared with that of a control group of patients with asymptomatic cholelithiasis who were matched for age and sex. Whereas no significant difference in the frequency of adenomas was found between two groups, a subgroup of patients aged 60-80 years with a postcholecystectomy interval of 10 years or greater exhibited a significantly (p less than 0.05) greater frequency of adenomas (38.5%) than matched patients with a postcholecystectomy interval of less than 10 years (21.8%) and matched controls with cholelithiasis (23.7%). This increase in the frequency of adenomas was primarily accounted for by an increase in the percentage of tubular adenomas (p less than 0.05) and corresponded to an increase in the frequency of cancer (p less than 0.05) of the large bowel.     

Further evidence of the role of frizzled-related protein gene polymorphisms in osteoarthritis

OBJECTIVE: To replicate the association of frizzled-related protein (FRZB) non-synonymous polymorphisms with osteoarthritis (OA) susceptibility. METHODS: Three groups of Spanish patients with OA were included: with total joint replacement due to primary OA in the hip (n = 310), or the knee (n = 277), or with hand OA (n = 242). Controls were more than 55 years old and did not show OA (n = 294). SNPs rs288326 (R200W) and rs7775 (R324G) were genotyped. RESULTS: There were no significant differences in allele frequencies between controls and each of the three groups of OA patients. However, allele G of the R324G SNP showed a trend to be more frequent in patients with a clinical OA syndrome at multiple joints (p = 0.07), specifically in women of the total hip replacement group (8.3% in patients without other affected joints, 13.1% with one, 15.9% with two and 24.1% with more than two additional joints, p for trend = 0.008). CONCLUSIONS: No direct replication of previous OA association findings was obtained but the results suggest that the R324G SNP of the FRZB gene may have an effect in OA development in multiple joints, with a specific severe involvement of the hip in women. This phenotype could reconcile previous studies that showed association either with generalised OA or with hip OA in women.     

Chondrocalcinosis in elderly persons

Fifty-eight elderly people were surveyed for chondrocalcinosis with knee, hip and pelvic roent-genograms using Type M industrial x-ray film. Chondrocalcinosis was found in 16 subjects (27.6%), an incidence greater than reported in previous studies. Roentgenograms of the knees alone showed the presence of chondrocalcinosis in 15 subjects. Varus deformity of the knees, increased wrist complaints and wrist involvement with clinical arthritis were significantly more common in subjects with chondrocalcinosis. Symptoms associated with acute inflammatory arthritis were not more common in people with chondrocalcinosis.     

Ultrasonographic study of Achilles tendon and plantar fascia in chondrocalcinosis

OBJECTIVE: To investigate by high frequency grey-scale ultrasonography (US) and power Doppler sonography (PDS) the modality and frequency of involvement of the Achilles tendon and plantar fascia in chondrocalcinosis (CC), and to correlate these findings with clinical complaints and radiographic evidence. METHODS: The heels of 57 consecutive patients with CC were evaluated by US, PDS, and radiography. One control group of 50 consecutive patients with osteoarthritis (OA) without signs of CC was studied in the same way. A second control group of 50 healthy subjects underwent only US/PDS examination. All subjects also underwent clinical assessment. RESULTS: US revealed Achilles tendon calcifications in 57.9% of those with CC, but none in the control groups. Plantar fascia calcifications were observed in 15.8% of CC and in 2% of OA cases, but not in healthy controls. US showed no significant difference in postero-inferior and inferior calcaneal enthesophytosis between subjects with CC (59.6% and 61.4%, respectively) and those with OA (46% and 44%, respectively). Such alterations were also present, in lower percentages, in the healthy controls. Posterior and inferior calcaneal erosions were absent in all groups. Achilles enthesopathy was found in 22.8% of patients with CC (14.9% of heels, with vascular signals in 11.4% of heels on PDS). Deep retrocalcaneal bursitis was found in 10.5% of patients with CC (7% of heels, with vascular signals in 5.2% of heels on PDS). Plantar fasciitis was found in 40.3% of patients with CC (36% of heels, with vascular signals in 2.6% of heels on PDS) and in 14% of OA patients, but not in healthy controls. No significant correlation was found between talalgia or sex of patients and presence of calcifications. A significant correlation was observed between talalgia and Achilles enthesopathy (r = 0.78, p < 0.0001), deep retrocalcaneal bursitis (r = 0.7, p < 0.0001), and plantar fasciitis (r = 0.31, p < 0.001). A significant correlation between talalgia and vascular signals on PDS was observed in Achilles enthesopathy (r = 0.91, p < 0.0001) and deep retrocalcaneal bursitis (r = 0.65, p < 0.0001). The presence of vascular signals on PDS was significantly associated with the presence of tendinous and bursal grey-scale US alterations. Achilles tendon calcifications were 39% sensitive, 100% specific, and 77% accurate for the presence of CC, whereas plantar fascia calcifications were 15% sensitive, 98% specific, and 54% accurate. Excellent agreement was found between US and radiography in detecting Achilles tendon calcifications (k = 0.86), plantar fascia calcifications (k = 0.77), postero-inferior enthesophytosis (k = 0.90), and inferior enthesophytosis (k = 0.83). CONCLUSION: Calcaneal tendon calcifications are frequent and asymptomatic findings in patients with CC, and they have a high specificity for this disease. US shows high agreement with radiography in depicting calcifications and enthesophytosis. Inflammatory changes of the calcaneal soft tissues are frequently observed by US and PDS in patients with chondrocalcinosis.     

Prevalence of articular chondrocalcinosis in elderly subjects in a rural area of Catalonia.

OBJECTIVES--To undertake an epidemiological survey of the prevalence of radiological chondrocalcinosis in the elderly population of Osona, a rural area of Catalonia, north east Spain. METHODS--Knee and wrist radiographs were performed on 261 subjects (141 women, 120 men) aged at least 60 years, who attended a series of 35 general practitioners for various medical problems. RESULTS--Twenty seven subjects had articular chondrocalcinosis, which represents a crude prevalence of 10%. Articular chondrocalcinosis was more often observed in women than in men (14 v 6%). Articular chondrocalcinosis increases in occurrence with age, rising from 7% in subjects aged 60-69 years to 43% in subjects older than 80 years. A similar occurrence of articular chondrocalcinosis was noted in the indigenous population, in which several cases of familial chondrocalcinosis have previously been reported, and in subjects born in other areas of Spain. All but one subject with articular chondrocalcinosis had chondrocalcinosis of the knee. The occurrence of rheumatic disorders did not differ significantly between subjects with articular chondrocalcinosis and those without. CONCLUSIONS--Articular chondrocalcinosis is an age related disorder, which could partly explain the discrepancies in its prevalence reported in previous studies. In most subjects with articular chondrocalcinosis recruited from an unselected population the clinical manifestations are probably mild or even absent.