Intra-articular Mineralization Research Articles

Prevalence of intra-articular mineralization on knee computed tomography: the multicenter osteoarthritis study

The aim of this work was to report the prevalence of computed tomography (CT)-detected intra-articular mineralization. We included participants from the Multicenter Osteoarthritis (MOST) Study. At the 12th year visit of the MOST study, bilateral knee CTs were first obtained. All participants also had posteroanterior and lateral radiographs of bilateral knees and completed standard questionnaires. Knee radiographs were assessed for Kellgren & Lawrence grade (KLG) and radiographic evidence of intra-articular mineralization. CT images were scored using the Boston University Calcium Knee Score (BUCKS) for cartilage, menisci, ligaments, capsule, and vasculature. Prevalence of intra-articular mineralization was computed for the total sample, and stratified by age, sex, race, Body Mass Index (BMI), presence of frequent knee pain, and KLG. We also determined distribution of mineralization in the cartilage and meniscus, and co-localization. 4140 bilateral knees from 2070 participants were included (56.7% female, mean age 61.1 years, mean BMI: 28.8kg/m2). On radiographs 240 knees (5.8%) had intraarticular mineralization, while CT-detected mineralization was present in 9.8% of knees. Prevalence of hyaline articular and meniscus mineralization increased with age and KL grade, and was similar by sex, BMI categories, and comparable in subjects with and without frequent knee pain. Mineralization tended to be ubiquitous in the joint, most commonly involving all three (medial/lateral tibiofemoral and patellofemoral) compartments (3.1%), while the patellofemoral compartment was the most involved compartment in isolation (1.4%). CT of the knee provides greater visualization of intra-articular mineralization than radiographs and allows better localization of the crystal deposition within the joint. Further studies should focus on the co-localization of intra-articular crystal deposition and corresponding magnetic resonance imaging (MRI)-features of knee osteoarthritis (OA).

Intra-articular Mineralization and Association with Osteoarthritis Development and Outcomes

Intra-articular Mineralization and Association with Osteoarthritis Development and Outcomes

Radiographically detectable intra-articular mineralization: Predictor of knee osteoarthritis outcomes or only an indicator of aging? A brief report from the osteoarthritis initiative

ObjectiveTo determine the association between Intra-articular mineralization (IAM) and knee osteoarthritis (OA) outcomes stratified according to participants’ age. MethodsParticipants from the Osteoarthritis Initiative (OAI) with baseline radiographic OA (i.e., Kellgren-Lawrence grade ≥2 with Osteoarthritis Research Society International (OARSI) atlas joint space narrowing (JSN)) in either knee were identified. Both knees and dominant hand baseline radiographs were evaluated for the presence of IAM. Whole-grade OARSI-JSN radiographic progression and increased Western Ontario and McMaster universities osteoarthritis index scores of the knees with baseline radiographic OA (assessed annually) were defined as radiographic and symptomatic progression, respectively. Cox proportional-hazards and longitudinal multilevel regression models investigated radiographic and symptomatic progression, respectively. Results2010 participants with baseline radiographic OA in either one or both knees (N ​= ​2976) were identified. 178 participants had baseline IAM (hand radiographs ​= ​46, knee radiographs ​= ​166, both ​= ​34). An adjusted logistic regression model suggests an association between age and IAM (Odds Ratio: 1.06, 95% Confidence Interval (CI): 1.04–1.08). Presence of any IAM was not associated with whole-grade OARSI-JSN (Hazard Ratio (HR): 1.00, 95% CI: 0.73–1.37) or symptomatic progression (Estimated difference: 1.24, p-value: 0.13) in all participants. Using stratification analysis, in younger participants <60 years old, presence of any IAM was associated with radiographic progression (HR: 1.90, 95% CI: 1.01–3.60). ConclusionAlthough the presence of any radiographic IAM increases with higher age and does not predict knee OA outcomes across the entire sample of OAI participants, it is associated with knee OA radiographic progression in participants aged <60.

Tibial tuberosity transposition advancement for treatment of concomitant cranial cruciate ligament rupture and medial patellar luxation in four feline stifles.

Case series summaryThree cats (four stifles) were diagnosed with varying grades of medial patellar luxation and stifle instability in cranial tibial thrust. Radiographs showed periarticular osteophytosis, intra-articular mineralization and opacification encroachment of the infrapatellar fat pad. Stifle exploration revealed either partial (n = 2) or complete (n = 2) cranial cruciate ligament tear and medial meniscal injury in all cases. Medial meniscectomy, partial parasagittal patellectomy, femoral trochleoplasty and tibial tuberosity transposition advancement using a 6 mm cage, two-fork plate and 4 mm spacer were performed in four stifles. Screws (2.0 mm) and washers were used in the cranial cage ears rather than conventional 2.4 mm screws. By the 2-week recheck, lameness was minimal and stifles were stable. Radiographic follow-up at 8 weeks showed appropriate progression of osseous union in all cases. One cat experienced a major complication, suffering tibial fracture following a lapse in exercise restriction, and revision surgery was performed successfully with subsequent osseus union of the osteotomy site. At the mid-term follow-up, all cats had a return to previous level of function, as assessed by both owner questionnaire and clinical evaluation.Relevance and novel informationTibial tuberosity transposition and advancement has been shown to be successful in dogs for the treatment of concomitant medial patellar luxation and cranial cruciate ligament rupture. To date, there have been no reports of tibial tuberosity transposition and advancement in cats. A benefit of this approach is concomitant alignment of the extensor mechanism and neutralization of the femorotibial shear force. Our case series describes successful use of tibial tuberosity transposition advancement in cats.

Can Dual-Energy Computed Tomography Be Used to Identify Early Calcium Crystal Deposition in the Knees of Patients With Calcium Pyrophosphate Deposition?

To assess the ability of dual-energy computed tomography (DECT) in identifying early calcium crystal deposition in menisci and articular cartilage of the knee, depending on the presence/absence of chondrocalcinosis seen on conventional CT. One hundred thirty-two knee DECT scans from patients with suspected crystal-associated arthropathy were reviewed and assigned to a calcium pyrophosphate deposition (CPPD) group (n = 50) or a control group (n = 82). Five DECT attenuation parameters were measured in preset regions of interest (ROIs) in menisci and articular cartilage and compared between groups using linear mixed models with adjustment for confounders. Subgroup analysis, excluding ROIs with chondrocalcinosis seen on conventional CT, was performed. In both menisci and articular cartilage, and for all 5 DECT attenuation parameters, calcified ROIs in CPPD patients showed significantly higher values than ROIs in controls (P ≤ 0.036). Conversely, noncalcified ROIs in CPPD patients were comparable with those in controls (P ≥ 0.09). While specific DECT parameters yielded good accuracy (area under the curve [AUC] 0.87-0.88) in differentiating calcified ROIs in CPPD patients from ROIs in controls, DECT failed to distinguish between noncalcified ROIs in CPPD patients and controls (AUC 0.58-0.59). While DECT has the potential to characterize knee intraarticular mineralization, this technique cannot yet accurately identify early calcium crystal deposition that is not visible as chondrocalcinosis on conventional CT.

Non-invasive characterization of intra-articular mineralization using dual-energy computed tomography

Non-invasive characterization of intra-articular mineralization using dual-energy computed tomography

Epidemiology of intraarticular mineralization on knee dual energy computed tomography in two cohorts: the multicenter osteoarthritis study

Purpose: Computed tomography (CT) has a higher sensitivity for the detection of intraarticular mineralization in comparison with commonly used imaging technique in knee osteoarthritis (OA) including radiographs and MRI. The role of intra-articular mineralization in knee OA has been unclear, contributed to by inadequate imaging assessment of this phenomenon. The aim of this study is to report the prevalence of CT-detected intra-articular mineralization in older adults with or at risk of knee OA.

Intra-articular mineralization on knee CT increases risk of knee pain in the most study

Purpose: Intra-articular (i.a.) calcium crystal deposition is common in knee osteoarthritis (OA), particularly in end-stage disease. Low-grade inflammation related to crystals may contribute to knee pain, including pain fluctuation. However, results on this matter have been conflicting in prior studies. Detection of chondrocalcinosis has relied on radiographs to date, which have low sensitivity, and this may have limited the ability to adequately assess the relation of chondrocalcinosis to knee pain.

Reliability of a new scoring system for intraarticular mineralization of the knee: Boston University Calcium Knee Score (BUCKS)

The role of intra-articular mineralization in osteoarthritis (OA) is unclear. Its understanding may potentially advance our knowledge of knee OA pathogenesis. We describe and assess the reliability of a novel computed tomography (CT) scoring system, the Boston University Calcium Knee Score (BUCKS) for evaluating intra-articular mineralization. We included subjects from the most recent study visit of the Multicenter Osteoarthritis Study (MOST) Study, a NIH-funded longitudinal cohort of community-dwelling older adults with or at risk of knee OA. All subjects underwent CT of bilateral knees. Each knee was scored at 28 scored locations (14 for cartilage, 6 for menisci, 6 for ligaments, 1 for joint capsule, and 1 popliteal-tibial vessels). A single musculoskeletal radiologist scored cartilage and meniscus subregions, as well as vascular calcifications assigning to each a score ranging from 0 to 3. The joint capsule, medial and lateral posterior meniscal roots, anterior cruciate ligament (ACL)/posterior cruciate ligament (PCL) and 2 collateral ligaments [medial collateral ligament (MCL)/lateral collateral ligament (LCL)] were each scored 0 or 1 for absence or presence of mineralization. To assess reliability, 31 subject CTs were reread 12 weeks later by the same reader and by a second reader and agreement was evaluated using a weighted kappa. The intra-reader reliability ranged from 0.92 for ligaments to 1.0 for joint capsule. The inter-reader reliability ranged from 0.94 for cartilage and ligaments, to 1.0 for joint capsule. BUCKS demonstrated excellent reliability and is a potentially useful CT-based tool for studying the role of calcium crystals in knee OA.

Synovial fluid lubricin increases in canine cruciate ligament rupture

Purpose: Loss of effective joint lubrication contributes to cartilage breakdown in post-traumatic osteoarthritis (PTOA). There are two major lubricants in synovial fluid: hyaluronic acid (HA), which confers viscous properties, and lubricin, which enables low friction boundary lubrication. The absence of functional lubricin results in severe, early onset of polyarthropathy in humans and lubricin knockout mice. Several studies have reported that lubricin decreases in experimental rodent models of PTOA; however, it is unclear whether similar losses are observed in naturally occurring, large animal models of joint injury and osteoarthritis (OA) progression. Naturally occurring cranial cruciate ligament rupture in the dog closely mimics anterior cruciate ligament injury in humans with respect to the development of joint instability and secondary osteoarthritic changes, making this a valuable translational model to study the role of lubricin in PTOA. Here, we investigated lubricin and pro-inflammatory cytokines in canine cranial cruciate ligament rupture (RCCL) and the relationship of these molecules to radiographic evidence of osteoarthritis. Methods: Stifle synovial fluid samples from 30 adult dogs (age 2.5-11 yrs; n=13 neutered males, 14 neutered females, 2 intact males and 1 intact female) sustaining rupture of the cranial cruciate ligament were obtained at the time of surgery and stored in liquid N2 for biobanking purposes. Medical histories, physical examination, and surgical data were obtained from patient medical records, including age, duration of injury prior to presentation, presence of concurrent meniscal injury and whether or not meniscectomy was performed. Stifle synovial fluid samples were also obtained from a cohort of 13 clinically healthy research Beagles (age 2.5 to 5 yrs; intact males). Synovial fluid lubricin levels were quantified using a lubricin sandwich ELISA, and pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α) were measured using a multiplex cytokine panel (Meso Scale Diagnostics, LLC). Pre-operative lateromedial and craniocaudal stifle radiographs were randomized, blinded and scored by two independent observers. A stifle OA scoring system was modified slightly from Innes et al, which evaluated: joint effusion, osteophytosis, intra-articular mineralization, and a global OA score. T-tests were used to analyze biochemical differences between healthy and RCCL joints (α=0.05), and Spearman’s rank-order correlations were performed to determine associations between lubricin and pro-inflammatory cytokines. Results: Lubricin concentrations were nearly six-fold greater in RCCL joints (mean ± SEM = 0.07 ± 0.02 mg/mL) as compared to healthy controls (mean ± SEM = 0.68 ± 0.06mg/mL) (Fig 1A), and this elevation persisted for more than one year after injury (Fig 1B). No significant differences in synovial fluid pro-inflammatory cytokines (IL-2, IL-6, IL8, and TNF-α) were detected between RCCL and healthy joints; however, pro-inflammatory cytokines were all correlated with one another. Duration of injury did not correlate with lubricin concentrations (Spearman’s test, ρ=-0.0205). Lubricin concentrations correlated with the presence of OA, but no associations between the severity of radiographic OA and lubricin levels were detected. Additionally, lubricin levels were not correlated with any of the pro-inflammatory cytokines measured (Table 1). Conclusions: Lubricin was significantly and persistently elevated in joints with RCCL. Interestingly, although pro-inflammatory cytokines in synovial fluid levels were correlated with one another, lubricin levels did not correlate with any pro-inflammatory cytokines. A limitation of this study is that dogs presented with varying degrees of OA and durations of injury prior to surgery, with many animals presenting with a history of lameness or injury of longer than one month. However, to our knowledge, this is the first study to demonstrate that synovial fluid lubricin is significantly increased in a translational, large animal model of knee joint instability. Lubricin may have value as a potential biomarker for knee instability (and perhaps osteoarthritis progression). Lubricin may also be elevated as a protective mechanism in joint instability; however, more mechanistic studies are required to determine the role of elevated synovial fluid lubricin in knee injuries.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Reliability of a new scoring system for intraarticular mineralization of the knee: bucks (Boston University Calcium Knee Score)

Reliability of a new scoring system for intraarticular mineralization of the knee: bucks (Boston University Calcium Knee Score)

Cross-sectional study of intra-articular mineralization on knee dual-energy computed tomography: the multicenter osteoarthritis study

Cross-sectional study of intra-articular mineralization on knee dual-energy computed tomography: the multicenter osteoarthritis study

Morphological Changes of Osteoarthritis in Feline Stifle Joints and Associations with Intra-articular Mineralization

Morphological Changes of Osteoarthritis in Feline Stifle Joints and Associations with Intra-articular Mineralization

Arterial calcification due to CD73 deficiency (ACDC): imaging manifestations of ectopic mineralization.

Arterial calcification due to CD73 deficiency (ACDC) is a recently identified rare and debilitating adult-onset disorder caused by autosomal recessive NT5E gene mutations. ACDC is characterized by progressive and painful arterial calcifications primarily affecting the lower extremities, as well as calcifications affecting small joint capsules of the hands and feet. In this case report, the authors provide clinical follow-up for one of the first individuals identified by the National Institutes of Health (NIH) as having ACDC, focusing mainly on the imaging manifestations of periarticular joint mineralization, which are bilateral but slightly asymmetric, bulky up to the levels of the metacarpophalangeal and metatarsophalangeal joints, but smaller and more capsular in distribution at the proximal and distal interphalangeal joints, without erosive change or intra-articular mineralization. Differential considerations for similar appearing joint mineralization are provided.

Manifestations of joint disease of domestic carnivores in X-ray view

Changes caused by joint diseases that are manifested in X-ray are very diverse. Some of them are present in all arthroparthies while some are specific to certain diseases. For all the arthropathies it is specific that the duration of a disease significantly influences the presence and intensity of radiological changes. In this paper there analyzed in detail some basic radiological joint diseases manifestations such as: distension of the joint capsule, change of size (width) of the joint space, change of position of corresponding bones within the joint, change in quality of subchondral bone, the appearance of intra-articular mineralization and calcified structures, as well as the presence of perichondral and periarticular bone proliferations. Beside that, there are described in detail arthropathies of different etiology.

Phosphocitrate blocks calcification‐induced articular joint degeneration in a guinea pig model

Calcium deposition occurs frequently in osteoarthritic (OA) joints. However, evidence for a causal role of calcification in cartilage degeneration is inferential. The present study was undertaken to examine the role of calcification in OA disease progression and to evaluate a formulation of phosphocitrate (PC) as a potential therapeutic agent. We have identified a guinea pig OA model in which meniscal calcification appears to correlate with aging and disease progression. We synthesized a new formulation of PC, [CaNa(PC)2(H2O)](n) (CaNaPC), which is a potent antimineralization agent and a specific inhibitor of crystal-induced biologic effects. After weekly treatment of guinea pigs with experimental OA with CaNaPC for 3 months, we examined calcification in menisci and cartilage degeneration. As a control, we examined whether similar CaNaPC treatment had any therapeutic effect in a hemi-meniscectomy model in which there is no known crystal involvement. Meniscal calcification correlated with cartilage degeneration in this animal model. PC treatment led to significant reduction of calcium deposits and arrested OA disease progression. Similar treatment had no effect in the hemi-meniscectomy model. CaNaPC diminishes mineralization in a cutaneous calcergy model and a model of OA in which intraarticular mineralization is a prominent feature. In the OA guinea pig model, inhibition of calcification is accompanied by diminished cartilage degeneration. CaNaPC has no therapeutic effect in the hemi-meniscectomy model. We conclude that pathologic calcification may initiate or amplify processes leading to cartilage degeneration and that CaNaPC may interrupt such a pathway.

Radiographic progression of osteoarthritis of the canine stifle joint: a prospective study.

A radiographic scoring system for features of osteoarthritis of the canine stifle joint was devised. Intra- and inter-rater agreement was assessed by calculation of unweighted kappa statistics. "Global score," "effusion," "osteophytosis," and "intra-articular mineralization" were all features that had acceptable reliability, but "subchondral sclerosis" did not. The scoring system was used in a 13-month prospective study of the radiographic progression of osteoarthritis of the stifle joint, secondary to cranial cruciate ligament deficiency, in 58 dogs. In the index stifle joints all features were characterized by significant change over time, but osteophytosis had the greatest degree of change. In addition, 40% of contralateral joints showed progressive osteophytosis.