Reduced hip bone mineral density is associated with high levels of calciprotein particles in patients with Fabry disease

Abstract

Calciprotein particles (CPP) are nanoscale mineralo-protein aggregates that help stabilize excess mineral in the circulation. We examined the relationship between CPP and bone mineral density in Fabry disease patients. We found an inverse correlation with total hip and femoral neck density, but none with lumbar spine. Purpose Calciprotein particles (CPP) are colloidal mineral-protein complexes made up primarily of the circulating glycoprotein fetuin-A, calcium, and phosphate. They form in extracellular fluid and facilitate the stabilization, transport, and clearance of excess minerals from the circulation. While most are monomers, they also exist in larger primary (CPP-I) and secondary (CPP-II) form, both of which are reported to be raised in pathological states. This study sought to investigate CPP levels in the serum of patients with Fabry disease, an X-linked systemic lysosomal storage disorder that is associated with generalized inflammation and low bone mineral density (BMD). Methods We compared serum CPP-I and CPP-II levels in 59 patients with Fabry disease (37 female) with levels in an agematched healthy adult cohort (n=28) and evaluated their association with BMD and biochemical data obtained from routine clinical review. Results CPP-I and CPP-II levels were higher in male Fabry disease patients than female sufferers as well as their corresponding sex-and age-matched controls. CPP-II levels were inversely correlated with BMD at the total hip and femoral neck, but not the lumbar spine. Regression analyses revealed that these associations were independent of common determinants of BMD, but at the femoral neck, a significant association was only found in female patients. Conclusion Low hip BMD was associated with high CPP-II in patients with Fabry disease, but further work is needed to investigate the relevance of sex-related differences and to establish whether CPP measurement may aid assessment of bone disease in this setting.

Assessing Osteopenia and Osteoporosis with Dual-energy X-ray Absorptiometry Studies in Fabry Disease

“…CPP are colloidal mineral-protein complexes that form in extracellular uid and facilitate the stabilization, transport, and clearance of excess minerals from the circulation. CPP exist in primary (CPP-I) and secondary (CPP-II) form, both of which are reported to be raised in pathological states [17]. One study that looked at mouse models of FD with impaired functioning of the medullary thick ascending limb of the nephron, observed that a decrease in plasma calcium induced an increase in PTH, leading to secondary hyperparathyroidism, which resulted in accelerated bone resorption [18].…”