Chondrocalcinosis : risk factors and radiographic phenotype

Abhishek, Abhishek (2012) Chondrocalcinosis : risk factors and radiographic phenotype. PhD thesis, University of Nottingham.

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Objectives: The objectives of this study were to a) examine the distribution of chondrocalcinosis (CC), b) determine the risk factors of CC, and c) examine the radiographic phenotype of osteoarthritis (OA) associated with CC.

Methods: Data from the Genetics of Osteoarthritis and Lifestyle (GOAL) study were used to describe the radiographic distribution of CC, and to conduct a case-control study in which cases with CC were compared with controls without CC. All participants had already completed a detailed questionnaire, been examined by a research metrologist, had radiographs of knees, hands, and pelvis, and had given urine and blood samples. All radiographs had been scored for structural radiographic changes of OA, and for the presence of CC. Frontal plane knee alignment was measured on all knee radiographs. The prevalence (95% confidence interval (CI)) of CC was calculated. The odds ratio (OR) and 95% CI were calculated for risk factors of CC, and for structural changes associated with CC in joints with OA. This was adjusted for age, gender, body mass index (BMI), and OA as appropriate, using logistic regression.

Results: 3170 participants were included in this study. There were 431 cases with CC. The overall prevalence (95%CI) of CC in the GOAL population was 13.7% (12.5% - 14.9%). In the GOAL population, knee was the commonest site of CC. However, 42% of participants with CC did not have any knee involvement. There was evidence for a generalized predisposition to CC. For example, CC at one joint associated with CC at distant joints. Joints with CC clustered together more than would be expected by chance alone. At knees, wrists and hips, bilateral CC was more likely to associate with CC at distant joints than unilateral CC – also supporting the existence of a systemic predisposition to CC.

After adjusting for confounding factors, there was an association between CC and increasing age, lower current BMI, and OA. The association between OA at one joint and CC at the same joint was present for all joints except for the hip. There was no association between CC and gender, diuretic intake, and selected single nucleotide polymorphisms in enzymes involved in pyrophosphate (PPi) metabolism. CC associated with peri-articular calcification, vascular calcification, low cortical bone mineral density (BMD) but not with low cancellous BMD. Self-reported arthroscopy, meniscectomy, knee injury, occupational knee joint loading and knee mal-alignment in the 3rd decade of life associated with knee CC. However, after adjusting for confounding factors including OA, there was no association between either self-reported or radiographically assessed current knee mal-alignment and knee CC.

In joints with OA, the additional presence of CC at the same joint associated with a different radiographic phenotype of structural arthropathy. For example, in knees with OA, knee CC associated with attrition. In hips with OA, hip CC associated negatively with osteophytes, joint space narrowing, and sclerosis at the right hip but not at the left. Similarly, in wrists with OA, wrist CC associated with sclerosis in the right but not in the left wrist; in scapho-trapezioid joints (STJs) with OA wrist CC associated with sclerosis on both sides; in metacarpophalangeal joints with OA, wrist CC associated with cysts in the right but not in the left hand; and in 1st carpometacarpal joint with OA, wrist CC associated with cysts in the left but not in the right hand. In knees with OA, the additional presence of CC at distant joints associated with knee attrition. Those with knee CC + OA were excluded from this analysis to remove any local effects of CC. CC at distant joints did not associate with a distinct structural OA phenotype in other joints examined.

Conclusion: These findings suggest that CC results form a systemic predisposition, and that it commonly occurs at other joints in the absence of knee involvement. Established risk factors of CC such as age, OA, and previous arthroscopy and/or meniscectomy were validated in this study. Several novel risk factors of CC e.g. low current BMI, low cortical BMD, and vascular calcification were identified. Several novel associations of knee CC i.e. early life knee malalignment, self-reported knee injury, and occupational knee loading were also recognised. There was convincing evidence to suggest that in joints with OA, the additional presence of CC modifies the OA phenotype, and that this varies from joint to joint.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Doherty, M.
Zhang, W.
Subjects: W Medicine and related subjects (NLM Classification) > WP Gynecology
R Medicine > RG Gynecology and obstetrics
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Clinical Sciences
Item ID: 12926
Depositing User: EP, Services
Date Deposited: 30 Jul 2013 09:07
Last Modified: 12 Jun 2018 06:57

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