Background/Purpose: Disordered bone remodeling has been implicated in the development of bone erosion in tophaceous gout.  The function of bone cells in the skeleton is regulated by a number of factors, including soluble mediators that influence osteoclast and osteoblast function.  The aim of this study was to determine the relationship between bone erosion and circulating mediators of bone remodeling in people with tophaceous gout.

Methods: One hundred patients with tophaceous gout were prospectively recruited from rheumatology outpatient clinics.  Bone erosion at articular sites was assessed by two readers in conventional computed tomography (CT) scans of the feet using a validated semi-quantitative erosion score, and in plain radiographs (XR) of the hands and feet using a modification of the Sharp-van der Heijde score.  Readers were blinded to all clinical details, including laboratory results.  Hip, spine and total body bone mineral density (BMD) was also measured.  The following soluble mediators of bone remodeling were measured in serum by ELISA: osteoprotegerin (OPG, a soluble decoy receptor for RANKL), sclerostin (an osteocyte-derived Wnt inhibitor), dickkopf-1 (DKK-1, a Wnt inhibitor), and fibroblast growth factor-23 (FGF-23, an osteocyte-derived regulator of phosphorous and vitamin D).

Results: CT bone erosion scores positively correlated with circulating OPG concentrations (r=0.22, p=0.03), and negatively correlated with sclerostin concentrations (r=-0.29, p=0.003).  Similar correlations were observed for XR erosion scores for OPG (r=0.30, p=0.002), and sclerostin (r=-0.21, p=0.04). Neck of femur BMD negatively correlated with OPG concentrations (r=-0.34, p=0.001), and positively correlated with sclerostin concentrations (r=0.24, p=0.02). Similar relationships were observed for total body BMD.  No relationship was observed between bone erosion scores or BMD, and DKK-1 or FGF-23 concentrations.  In linear regression analysis, OPG and sclerostin were independently associated with CT erosion score (p=0.005 for OPG and p=0.003 for sclerostin, R² for model 0.16, p<0.0001).  Similarly, OPG and sclerostin were independently associated with neck of femur BMD (p=0.002 for OPG and p=0.04 for sclerostin, R²for model 0.13, p=0.001).  These relationships persisted after adjusting for eGFR.

Conclusion: In people with tophaceous gout, circulating OPG and sclerostin levels are independently associated with both central and peripheral bone loss.  The direction of the associations does not support a direct role for bone-remodeling factors in pathogenesis of bone erosion, but may reflect compensatory or repair mechanisms to maintain bone homeostasis at both central and peripheral sites.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-mediators-of-bone-remodeling-in-patients-with-tophaceous-gout/