Radiographic Chondrocalcinosis Research Articles

A Narrative Review of Chondrocalcinosis: Clinical Presentation, Diagnosis, and Therapies.

Calcium pyrophosphate deposition disease is categorized into radiographic chondrocalcinosis, acute calcium pyrophosphate arthritis, chronic calcium pyrophosphate arthritis, and osteoarthritis with calcium pyrophosphate deposition. These entities collectively are characterized by the deposition of calcium into joints, which then may cause localized and systemic inflammation, resulting in pain and swelling in the affected joints. Patients with the ANKH gene are more susceptible to the development of CPP arthritis as are those with primary hyperparathyroidism, hypomagnesemia, and hemochromatosis. Radiographic chondrocalcinosis is asymptomatic. Acute calcium pyrophosphate arthritis results in self-limited periods of joint pain and swelling in the affected joint. Along with localized inflammation, there may also be systemic inflammation characterized by fever and elevated inflammatory markers. Chronic calcium pyrophosphate arthritis results in periods of quiescence interrupted by flares that are identical to acute periods of disease. Osteoarthritis associated calcium pyrophosphate arthritis presents with chronic pain well described in osteoarthritis with periods of acute flares. In 2023, a joint effort by the American College of Rheumatology and the European League Against Rheumatism developed guidelines meant to aid in the recognition of calcium pyrophosphate deposition diseases. The diagnosis is made if there is proof of either crowned dens syndrome or synovial fluid analysis demonstrating calcium pyrophosphate crystals or when more than 56 points are summed utilizing the criteria described in the guidelines. Radiographic chondrocalcinosis requires no therapy. Acute calcium pyrophosphate arthritis is treated with the goal of aborting the flare. Treatment options include nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, oral corticosteroids, parenteral corticosteroids, intraarticular corticosteroids, IL-1 inhibitors, or parenteral adrenocorticotropic hormone (ACTH). The goal in treatment for chronic calcium pyrophosphate arthritis is the suppression of acute flares. The drugs used for acute flare treatment may be given as maintenance therapy with the additional options of methotrexate and hydroxychloroquine.

High prevalence of chondrocalcinosis and frequent comorbidity with calcium pyrophosphate deposition disease in patients with seronegative rheumatoid arthritis

BackgroundThe crystal-induced calcium pyrophosphate deposition disease (CPPD) clinically appearing as pseudogout differs from the mere radiographic finding of chondrocalcinosis (CC) but may cause symptoms resembling rheumatoid arthritis (RA).ObjectiveTo study the...

Calcium Pyrophosphate Dihydrate Crystal Deposition in Gouty Tophi.

The coexistence of calcium pyrophosphate dihydrate (CPPD) and monosodium urate monohydrate crystals in gouty tophi has rarely been reported. We undertook this study to investigate CPPD crystal deposits in a series of surgically removed gouty tophi and to identify factors associated with these deposits. Twenty-five tophi from 22 gout patients were analyzed using polarized light microscopy, field emission scanning electron microscopy (FESEM), and μ Fourier transform infrared (μFTIR) spectroscopy. Tophi consisted of multiple lobules separated by fibrous septa and surrounded by a foreign-body giant cell reaction. CPPD crystal aggregates were identified in 9 of 25 tophi from 6 patients. CPPD crystals were dispersed or highly compacted, localized at the edge or inside the tophus lobules, with some lobules completely filled with crystals. Both monoclinic and triclinic CPPD crystal phases were identified using FESEM and μFTIR. Compared to patients without CPPD, those with CPPD-containing tophi were older (mean 60.5 years versus 47.2 years; P = 0.009), and had longer-term gout duration (mean 17.0 years versus mean 9.0 years; P < 0.05) and tophi duration (mean 10.0 years versus mean 4.6 years; P < 0.01). None of the patients had radiographic chondrocalcinosis of the knee or wrist. CPPD crystal formation seems to be a late and frequent event of tophus maturation, occurring more frequently with aging, and could contribute to the speed of tophus dissolution and the apparent persistence of tophus sometimes observed even after effective, long-lasting urate-lowering therapy.

Concurrence of rheumatoid arthritis and calcium pyrophosphate deposition disease: A case collection and review of the literature

Calcium pyrophosphate deposition disease (CPDD) is arthritis caused by calcium pyrophosphate (CPP) crystal deposition in joints. It is commonly associated with aging as well as a handful of metabolic syndromes. Recent epidemiologic studies suggest a positive association of CPDD and rheumatoid arthritis (RA). Yet how these diseases are related remains unclear. We set out to describe 21 well-characterized patients with both diagnoses. Medical records of patients with both RA and CPDD identified at a single academic practice site were reviewed for age, gender, age of CPDD and RA onset, disease duration, joint involvement, and lab values including rheumatoid factor (RF), cyclic citrullinated peptide antibody (CCP), iron studies, and parathyroid hormone and calcium levels. The mean age of CPDD onset was 69.5 ± 11.4 years, with a mean RA age onset of 53.9 ± 16 years, demonstrating a mean lag of 13.4 ± 10.9 years between diagnoses. The majority of RA patients were diagnosed with CPDD based on the presence of radiographic chondrocalcinosis (15/21). The most commonly involved joint was the knee, followed by the wrist, hip, and shoulder. These data show that the diagnosis of RA often precedes the diagnosis of CPDD. This asynchronous presentation taken together with the classic age of onset for CPDD and typical pattern of joint involvement supports the hypothesis that CPDD develops in RA patients through similar processes as those that cause the idiopathic forms of this disease.

Comparison of ultrasonography and radiography of the wrist for diagnosis of calcium pyrophosphate deposition

ObjectiveUltrasound (US) seems a useful tool for diagnosis of calcium pyrophosphate (CPP) deposition (CPPD). We aimed to compare the performance of US and conventional radiography of the wrist for diagnosis of CPPD. MethodsPatients with CPP crystals identified in synovial fluid (SF) (knee, hip, shoulder, ankle or wrist) were consecutively included and compared to patients without CPP crystals in synovial fluid considered as controls. As recommended, we used the term chondrocalcinosis (CC) to assess imaging features suggesting CPPD. In all patients, US and radiographic assessment of CC of the wrists was performed by two distinct operators blinded each other (one operator by imaging modality). The two operators were blinded to clinical data, SF analysis and US or radiography findings. ResultsWe included 32 CPPD patients and 26 controls. Among CPPD patients, US revealed CC in 30 (93.7%) and radiography in 17 (53.1%) (P<0.001). The sensitivity and specificity of US for the diagnosis of CPPD were 94% and 85%, respectively; the positive likelihood ratio (LR+) was 6.1. The sensitivity and specificity of radiography were 53.1% and 100%, respectively. At joints level independently of SF analysis, US revealed CC in 35 joints without radiographic CC whereas X-rays showed CC in 3 joints without US CC. The κ coefficient between US and radiography for CC was moderate: 0.33 (0.171–0.408). ConclusionOur study suggests that wrist US should be considered as a relevant tool for the diagnosis of CPPD, with higher sensitivity than radiography for detecting CPP deposits.

Does Chondrocalcinosis Associate With a Distinct Radiographic Phenotype of Osteoarthritis in Knees and Hips? A Case–Control Study

To examine if knee chondrocalcinosis (CC), hip CC, or CC at distant joints associates with a distinct radiographic phenotype of osteoarthritis (OA) in knees or hips. We conducted a case-control study using data from the Genetics of Osteoarthritis and Lifestyle (GOAL) study (n = 3,170). All participants of the GOAL study had radiographs of knees, hands, and pelvis, which have been scored for CC and for individual radiographic features of OA. For this study, cases had radiographic OA and CC, and controls had radiographic OA without CC at the index joint. Data for knees and hips were analyzed separately. Binary logistic regression was used to examine the association between each radiographic phenotype and CC in joints with OA. Generalized estimating equation analysis was used to account for correlated data. Knee CC, and CC at any distant joint (without knee CC), associated with attrition in knee OA (adjusted odds ratio 2.32 [95% confidence interval 1.42-3.79] and 2.42 [1.41-4.13], respectively). There was no association between knee CC and osteophytosis or joint space narrowing (JSN) in knees with OA. Hip CC associated negatively with the summated osteophyte score and minimum JSN in hip OA. However, in hips with OA, CC did not associate with cysts or sclerosis. Additionally, distant joint CC did not associate with any structural change in hip OA. This study demonstrates that knee CC and CC at distant joints associate with attrition in knee OA, and hip CC associates with a milder hip OA phenotype. There was no evidence that CC associates with a hypertrophic OA phenotype.

Imaging of calcium pyrophosphate deposition disease.

Calcium pyrophosphate deposition disease (CPPD) is a common and clinically heterogeneous form of arthritis caused by the deposition of calcium pyrophosphate (CPP) crystals in articular tissues. The diagnosis of CPPD is supported by the presence of radiographic chondrocalcinosis; yet, conventional radiography detects only about 40% of clinically important CPPD. Here, we critically review the recent literature on imaging in CPPD. New studies inform our use of conventional radiographic screening methodologies for CPPD and provide additional evidence for the utility of diagnostic ultrasound. Recent work also highlights the polyarticular nature of CPPD, its association with tissue damage, and the high prevalence of tendon involvement. While dual energy CT and diffraction-enhanced synchrotron imaging remain research tools, they present potential avenues for improved visualization of CPP deposits. Advances in imaging in CPPD will increase diagnostic accuracy and eventually result in better management of this common form of arthritis.

CT imaging for evaluation of calcium crystal deposition in the knee: initial experience from the Multicenter Osteoarthritis (MOST) study

Role of intra-articular calcium crystals in osteoarthritis (OA) is unclear. Imaging modalities used to date for its evaluation have limitations in their ability to fully characterize intra-articular crystal deposition. Since Computed Tomography (CT) imaging provides excellent visualization of bones and calcified tissue, in this pilot project we evaluated the utility of CT scan in describing intra-articular calcium crystal deposition in the knees. We included 12 subjects with and four subjects without radiographic chondrocalcinosis in the most recent visit from the Multicenter Osteoarthritis (MOST) study, which is a longitudinal cohort of community-dwelling older adults with or at risk for knee OA. All subjects underwent CT scans of bilateral knees. Each knee was divided into 25 subregions and each subregion was read for presence of calcium crystals by a musculoskeletal radiologist. To assess reliability, readings were repeated 4 weeks later. CT images permitted visualization of 25 subregions with calcification within and around the tibio-femoral and patello-femoral joints in all 24 knees with radiographic chondrocalcinosis. Intra-articular calcification was seen universally including meniscal cartilage (most common site involved in 21/24 knees), hyaline cartilage, cruciate ligaments, medial collateral ligament and joint capsule. Readings showed good agreement for specific tissues involved with calcium deposition (kappa: 0.70, 95% CI 0.62-0.80). We found CT scan to be a useful and reliable tool for describing calcium crystal deposition in the knee and therefore potentially for studying role of calcium crystals in OA. We also confirmed that "chondrocalcinosis" is a misnomer because calcification is present ubiquitously.

AB1047 Evidence that a systemic predisposition to chondrocalcinosis exists, and is mediated by osteoarthritis at most but not all joints

BackgroundIt is not known whether radiographic chondrocalcinosis (CC) results from a systemic predisposition or whether the association between CC and osteoarthritis (OA) is joint specific or generalized.ObjectivesTo ascertain if there...

AB1048 Does chondrocalcinosis associate with a different radiographic phenotype of osteoarthritis?

BackgroundSome studies suggest that the structural changes in joints with osteoarthritis (OA) and co-existing radiographic chondrocalcinosis (CC) are distinct from joints with OA alone. However, other studies suggest that there...

Verification of three different MMP-13 isoforms expression in human osteoarthritic cartilage

Verification of three different MMP-13 isoforms expression in human osteoarthritic cartilage

Ex vivo and in vivo magnetic resonance imaging of cartilage canals in swine at predilection sites of osteochondrosis

Ex vivo and in vivo magnetic resonance imaging of cartilage canals in swine at predilection sites of osteochondrosis

Quantitative echogenicity of small intra-articular deposits of calcium, hyaline cartilage thickness and sonographic aspects of the synovium in patients without radiographic chondrocalcinosis

Quantitative echogenicity of small intra-articular deposits of calcium, hyaline cartilage thickness and sonographic aspects of the synovium in patients without radiographic chondrocalcinosis

Clinical spectrum of hypophosphatasia diagnosed in adults

The presentation of hypophosphatasia (HPP) diagnosed in adults demonstrates a wide range of clinical manifestations, many of which are nonspecific. We sought to assess clinical characteristics of adult HPP by evaluation of Mayo Clinic Rochester adults diagnosed with HPP from 1976 through 2008. Subjects were identified by diagnostic code or medical records. Inclusion criteria were age ≥18years at diagnosis; low serum alkaline phosphatase (AP) without bisphosphonate therapy; and one additional element: elevated pyridoxal 5′-phosphate (PLP) or urine phosphoethanolamine (PEA), evidence of osteomalacia, or family history. We were unable to distinguish manifesting carriers from silent unaffected carriers due to lack of a prospective standardized clinical evaluation and the absence of genetic testing. HPP was diagnosed in 22 unrelated adults (median age 49years; 68% women). Most patients (68%) were symptomatic at presentation with features including musculoskeletal pain (41%) or incident fracture (18%). A history of fracture was present in 54%: hip/femoral neck (23%), feet (23%, all women), wrist (18%), and spine (9%, all men). Nine patients (36%) had multiple fractures while 4 (all women) had subtrochanteric femur fractures. Radiographic chondrocalcinosis (27%) and documented pyrophosphate arthropathy (14%) were only observed in women. Median minimum serum AP was 43% below the lower normal limit. Urine PEA was elevated in 15/16 patients (94%). PLP median was 68μg/L (normal, 5–50μg/L) and all (n=8) were above normal. Symptomatic subjects had more fractures and chondrocalcinosis, lower median minimum AP and PLP and higher median PEA levels. Clinical features more common in fracture patients included symptoms at presentation, history of childhood rickets, dental abnormalities, lower median minimum AP and PLP, and higher median urine PEA. Four subjects had iliac crest bone biopsies, with 2/4 specimens consistent with osteomalacia.These results suggest that adult HPP demonstrates a wide spectrum of clinical manifestations including musculoskeletal pain, fractures, chondrocalcinosis and dental anomalies with some overlap in laboratory characteristics in relationship to disease severity. In addition to genetic and environmental factors, gender may influence the clinical expression of HPP.

Chondrocalcinosis is common in the absence of knee involvement

IntroductionWe aimed to describe the distribution of radiographic chondrocalcinosis (CC) and to examine whether metacarpophalangeal joint (MCPJ) calcification and CC at other joints occurs in the absence of knee involvement.MethodsThis was a cross-sectional study embedded in the Genetics of Osteoarthritis and Lifestyle study (GOAL). All participants (n = 3,170) had radiographs of the knees, hands, and pelvis. These were scored for radiographic changes of osteoarthritis (OA), for CC at knees, hips, symphysis pubis, and wrists, and for MCPJ calcification. The prevalence of MCPJ calcification and CC overall, at each joint, and in the presence or absence of knee involvement, was calculated.ResultsThe knee was the commonest site of CC, followed by wrists, hips, and symphysis pubis. CC was more likely to be bilateral at knees and wrists but unilateral at hips. MCPJ calcification was usually bilateral, and less common than CC at knees, hips, wrists, and symphysis pubis. Unlike that previously reported, CC commonly occurred without any knee involvement; 44.4% of wrist CC, 45.9% of hip CC, 45.5% of symphysis pubis CC, and 31.3% of MCPJ calcification occurred in patients without knee CC. Those with meniscal or hyaline articular cartilage CC had comparable ages (P = 0.21), and neither preferentially associated with fibrocartilage CC at distant joints.ConclusionsCC visualized on a plain radiograph commonly occurs at other joints in the absence of radiographic knee CC. Therefore, knee radiographs alone are an insufficient screening test for CC. This has significant implications for clinical practice, for epidemiologic and genetic studies of CC, and for the definition of OA patients with coexistent crystal deposition.

Self‐reported knee malalignment in early adult life as an independent risk for knee chondrocalcinosis

To determine if self-reported current and early adult life knee malalignment is associated with knee chondrocalcinosis (CC). A case-control study embedded in the Genetics of Osteoarthritis and Lifestyle (GOAL) study was performed. A validated self-reported line-drawing instrument was mailed to 3,022 participants of GOAL, inquiring about knee malalignment (straight, valgus, varus) in their third decade (20s) and currently. Self-reported weight in 20s and present weight and height measured at the initial visit were used to calculate body mass index (BMI) in 20s and currently. Occupational risk was present if participants self-reported mechanically demanding activities in their longest held job. Cases were participants with radiographic CC at any tibiofemoral (TF) joints. Osteoarthritis was defined as a Kellgren/Lawrence score of ≥3 at TF joints or patellofemoral joints. Odds ratio (OR), adjusted OR, and 95% confidence interval (95% CI) were calculated for associations with knee CC. A total of 2,167 participants responded to the questionnaire, of which 7.5% respondents had knee CC. Knee CC was associated with self-reported varus (adjusted OR 1.77 [95% CI 1.05, 2.98]) and any knee malalignment in 20s (adjusted OR 1.64 [95% CI 1.02, 2.64]). This association was not restricted to the mechanically loaded TF compartment. There was no association between current knee malalignment and knee CC. Age (adjusted OR 1.73 [95% CI 1.36, 2.19]) and knee OA (adjusted OR 2.88 [95% CI 1.89, 4.38]) were associated with knee CC. There was no association between BMI in 20s (adjusted OR 1.14 [95% CI 0.92, 1.42]), occupational risk (adjusted OR 1.32 [95% CI 0.94, 1.85]), and knee CC. Early life knee malalignment, predominantly varus, is an independent risk factor for knee CC. This association is not restricted to the mechanically loaded compartment, implying a generalized predisposition throughout the knee.

Lower prevalence of chondrocalcinosis in Chinese subjects in Beijing than in white subjects in the United States: The Beijing Osteoarthritis Study

Chondrocalcinosis, which can promote joint inflammation and cartilage degeneration, is highly prevalent in elderly white subjects. Data on its prevalence are scarce in other ethnic populations. This study was undertaken to compare the prevalence of chondrocalcinosis in Chinese subjects with that in white subjects. We recruited a random sample of Beijing residents ages >or=60 years. Participants underwent standard weight-bearing anteroposterior knee radiography and posteroanterior hand radiography using the protocols developed in the Framingham Osteoarthritis Study. Radiographic chondrocalcinosis was defined as present in a knee or wrist when there was evidence of definite linear cartilage calcification. We compared the prevalence of chondrocalcinosis in Chinese subjects with that in white subjects using age-standardized prevalence ratios. We used identical methods to collect samples of tap water from 2 cities and measured their levels of calcium, magnesium, and phosphate in the same laboratory. Chinese subjects had a much lower prevalence of knee chondrocalcinosis (1.8% in men, 2.7% in women) than did white subjects (6.2% in men, 7.7% in women), with the age-standardized prevalence ratio being 0.34 (95% confidence interval [95% CI] 0.20-0.54) and 0.43 (95% CI 0.31-0.59) in men and women, respectively. Wrist chondrocalcinosis was rare in elderly Chinese subjects (prevalence 0.3% in men and 1.0% in women), with the age-standardized prevalence ratio being 0.06 (95% CI 0.01-0.18) in Chinese men and 0.18 (95% CI 0.10-0.30) in Chinese women. Calcium levels in the tap water in Beijing were 15-fold higher than in Framingham, whereas no difference was found in magnesium and phosphate levels. Knee chondrocalcinosis and wrist chondrocalcinosis are far less common in Chinese subjects in Beijing than in US white subjects in Framingham, Massachusetts. Given the current lack of understanding of the etiology of chondrocalcinosis, further epidemiologic studies of the impact of genetic and environmental factors on occurrence of chondrocalcinosis are indicated.

Calcium crystal-associated diseases.

The significance of calcium-containing crystals is unknown. Circumstantial evidence suggests that crystals are associated with more severe arthritis. Addition of calcium pyrophosphate dihydrate crystals to a lapine meniscectomy model of osteoarthritis resulted in greater damage to cartilage compared with meniscectomy alone. Elimination of calcium pyrophosphate dihydrate crystals may occur extracellularly by enzymatic degradation. Spermine and spermidine both enhance the degradative activity of alkaline phosphatase on crystals. In familial calcium pyrophosphate dihydrate crystal deposition disease, genetic heterogeneity is likely because one family demonstrated a linkage to chromosome 8q, whereas another did not. Tumoral deposition of calcium pyrophosphate dihydrate crystals may occur in single locations without radiographic chondrocalcinosis in other joints. Hydroxyapatite crystals are found in the ligamenta flava from surgical specimens but not as tumoral depositions. Magnesium whitlockite crystals have been found not only in osteoarthritic articular cartilage but also in normal cartilage, suggesting that these crystals may be nonpathologic in at least some cases.