Biomarkers of bone disease in persons with haemophilia.

INTRODUCTION Persons with haemophilia (PwH) have abnormally low bone density and increased risk of fractures. We previously demonstrated decreased skeletal health in factor VIII (FVIII)-deficient mice. Thus, we hypothesized factor deficiency is an independent risk factor for decreased skeletal health. AIM We seek to identify differences in bone-related cytokine expression among PwH and healthy controls. METHODS We evaluated plasma samples from 79 participants with severe FVIII deficiency and 51 age-matched healthy controls. Plasma samples were assessed for RANKL and OPG, cytokines that regulate bone metabolism, and CTX-1, a biomarker for bone resorption, as well as 10 bone-related cytokines. RESULTS CTX-1 is higher among samples from FVIII-deficient participants compared to controls (P   .05). Levels of TNF-α were lower among PwH < 16 only (P < .05). These differences are not observed in participants with recent factor use. CONCLUSIONS In PwH, markers of bone metabolism and circulating cytokine levels are abnormal. Recent factor use reverses many of these differences suggesting FVIII replacement ameliorates this pathology. This study suggests bone disease present in PwH is intrinsic to FVIII deficiency.