Calcium phosphate particulates increase friction in the rat knee joint.

OBJECTIVE: Basic calcium phosphate (BCP) particulates are commonly found in cartilage and synovial fluid of osteoarthritis (OA) joints with the amount of BCP correlating with knee OA severity. How cartilage mineralization affects joint degeneration has yet to be determined. The objective of this study was to determine whether BCP in the synovial fluid affects the rat knee joint coefficient of friction (COF). METHODS: The COFs of knees from both hind limbs of four mature male rats were measured post mortem using a pendulum apparatus with an infrared tracking system. The three conditions evaluated were (1) the naïve state, (2) after the injection of 100 µL of phosphate buffered saline (PBS) (sham) and (3) after the injection of 100 µL of a 1 mg/mL BCP suspension. The decrease in the pendulum amplitude (decay) was fit using two friction models: (1) a one parameter Stanton linear decay model and (2) a two parameters combination Stanton linear decay and viscous damping exponential decay model. RESULTS: The COF increased 17.6% after injection of BCP compared to the naïve (P = 0.0012) and 16.0% compared to the saline injected (P = 0.0018) joints as derived from the one parameter model. The COF did not differ between naïve and saline injected joints. Results from the two parameters model showed a similar increase in COF after injection of BCP while the viscous damping was not significantly different between conditions. CONCLUSIONS: The increased joint friction with BCP particulates suggests BCPs may play a role in articular surface degradation and OA development.

Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species.

Matrix γ-carboxyglutamate (Gla) protein (MGP) is an important local inhibitor of vascular calcification, which can undergo two post-translational modifications: vitamin K-dependent γ-glutamate carboxylation and serine phosphorylation. While carboxylation is thought to have effects upon binding of calcium-ions, phosphorylation is supposed to affect the cellular release of MGP. Since both modifications can be exerted incompletely, various MGP species can be detected in the circulation. MGP levels were measured with two commercially available competitive and two novel sandwich assays in healthy controls, in patients with rheumatic disease, aortic valve disease, and end-stage renal disease, as well as in volunteers after vitamin K supplementation (VKS) and treatment with vitamin K antagonists (VKA). Major differences were found between the MGP assays, including significantly different behaviour with regard to vascular disease and the response to VKA and VKS. The dual-antibody assay measuring non-phosphorylated, non-carboxylated MGP (dp-ucMGP) was particularly sensitive for these changes and would be suited to assess the vascular vitamin K status. We conclude that the different assays for particular circulating MGP species allows the assessment of various aspects of the MGP system.

Methotrexate as an alternative therapy for chronic calcium pyrophosphate deposition disease: an exploratory analysis.

OBJECTIVE: To evaluate the effectiveness of methotrexate (MTX), which works not only as an immunosuppressant, but also as a potent antiinflammatory agent, as an alternative therapeutic option for patients with severe calcium pyrophosphate deposition disease (CPDD) who fail to respond to standard therapy with nonsteroidal antiinflammatory drugs and/or glucocorticoids. METHODS: We analyzed, in 2 university hospitals in Switzerland, consecutive patients with CPDD that was resistant to classic treatment and were subsequently treated with MTX. Before and after initiation of MTX therapy, we quantified the frequency of pseudogout attacks, pain intensity, the number of swollen and tender joints, and inflammatory biomarkers. Clinical and biologic side effects of MTX and patients satisfaction with MTX treatment were also evaluated. RESULTS: The study included 5 patients treated with low dosages of MTX (5-20 mg/week). The mean followup time with MTX was 50.4 months (range 6-81 months). All patients reported an excellent clinical response, with marked improvement within a mean period of 7.4 weeks. A significant decrease in pain intensity (P < 0.0001), swollen and tender joint counts (P < 0.0001), and frequency of attacks was observed. The biomarkers of inflammation decreased markedly when systematically analyzed (3 patients). No significant side effects were reported. CONCLUSION: This study suggests that MTX could be a valuable therapeutic option for severe CPDD that is refractory to conventional therapy.

Acceleration of experimental lapine osteoarthritis by calcium pyrophosphate microcrystalline synovitis.

OBJECTIVE: To investigate the effects of chronic calcium pyrophosphate dihydrate (CPPD) synovitis on the development of osteoarthritic (OA) lesions in an animal model. METHODS: OA was induced in the right knees of 30 male New Zealand white rabbits by partial lateral meniscectomy and section of the fibular collateral and sesamoid ligaments (PLM/LS), followed by 8 weekly intraarticular (IA) injections of 1 mg (low-dose) or 10 mg (high-dose) of CPPD crystals in 3 sets of experiments (10 rabbits each). The contralateral left knees served as controls: experiment 1 PLM/LS alone, experiment 2 8 weekly IA injections of CPPD crystals alone, and experiment 3 sham surgery plus 8 weekly IA injections of CPPD crystals. RESULTS: At 8 weeks, repeated IA injections of low-dose and high-dose CPPD crystals into meniscectomized right knees resulted in more severe OA than in meniscectomized but noninjected left knees (experiment 1) (P = 0.003 and P = 0.001, respectively). One-fourth of the meniscectomized knees (11 of 40), both CPPD-injected and noninjected, showed embedded synovial cartilage shards. CONCLUSION: The data demonstrate a worsening effect of chronic CPPD crystal-induced synovitis on experimental OA produced in the rabbit knees by PLM/LS, and support a possible role for CPPD microcrystalline inflammation in the progression of OA lesions in clinical CPPD crystal deposition disease.