Background/Purpose:

Calcium pyrophosphate deposition disease (CPDD) is a common cause of both acute and chronic arthritis in the elderly. It is estimated that twenty percent of patients with knee osteoarthritis (OA) have undiagnosed CPDD based on analysis of synovial fluid performed at the time of joint replacement. Calcium pyrophosphate (CPP) crystals can be difficult to identify in synovial fluid, and no biomarkers for CPPD currently exist.

Familial forms of CPDD have been recognized since the original descriptions of this disease. Associated mutations have been identified at one of two loci. One locus (CCAL2) is comprised of mutations in the ANKH protein, which is an ATP/PPi transporter. The second locus (CCAL2) codes for osteoprotegerin (OPG), a decoy receptor for the RANKL/RANK pathway. Little is known about ANKH and OPG levels in synovial fluids of patients with sporadic CPDD and whether these factors might be biomarkers for CPDD. We set out to measure ANKH, OPG and RANKL levels in synovial fluids from patients with chronic knee effusions with and without CPP crystals.

Methods:

Knee synovial fluids were obtained for diagnostic or therapeutic purposes at an academic rheumatology practice from patients with OA or chronic CPDD. No patients had clinical signs or symptoms of active inflammatory arthritis at the time of joint aspiration. De-identified synovial fluids were used with permission from the local IRB. All fluids were examined for crystals using compensated polarized light microscopy by an expert observer (AKR). Cell counts were not performed. Any fluids containing monosodium urate crystals were discarded. Fluids were aliquoted and stored at -20° C. Levels of OPG, ANKH, and RANKL were measured by ELISA and compared in groups with and without CPP crystals by a Mann Whitney test.

Results:

Thirteen synovial fluid samples were analyzed. Seven samples contained CPP crystals and 6 samples did not contain CPP crystals. Levels of ANK, OPG, and RANKL were measurable in all fluids (Table 1). CPDD fluids had statistically higher mean levels of OPG (p <0.026) and similar levels of RANKL compared to OA fluids. Mean ANKH levels were also higher in fluids with CPP crystals compared to OA fluids but this did not reach statistical significance due to the large variability of values. Mean OPG:RANKL ratios were 84.2 in CPDD fluids and 5.0 in OA fluids.

Table 1.

Conclusion:

Synovial fluids from patients with OA or CPDD contain easily measurable quantities of ANKH, OPG, and RANKL. In this small pilot study of well-characterized fluids from patients with and without CPDD, we noted a very high ratio of OPG:RANKL in patients with CPDD. These findings provide additional support for the importance of OPG in CPDD pathogenesis. If validated in a larger study, the OPG:RANKL ratio may be a useful biomarker for CPDD.

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/high-osteoprotegerinrankl-ratios-in-synovial-fluid-correlate-with-the-presence-of-calcium-pyrophosphate-crystals/