Prospective Biomarkers of Bone Metabolism in Hemophilia A

BMD was measured as Z-scores/T-scores using Dual-Energy X-ray Absorptiometry (DEXA) scanning; specifically looking at Spine, Hip/Neck, and Hip total scores. BMD Z-scores compare what would be expected in someone your age and body size. A Z-score, is a unit of standard deviation, where above 0 would indicate the bones are more dense than expected, while a Z-score below 0 would indicate the bones were less dense.

Hemophilia Joint Health Score (HJHS); with a higher score representing worst outcomes, scores could range from 0 (no problems) to a max score of 120 (severe problems).

Visual Analog Scale (VAS) via the EQ-5D-3L was used to report participants self-rated health. EQ-5D-3L total score ranges from 5 (no problems) to 15 (significant problems). VAS scores could range from 0 (worst health ever) to 100 (best health ever).

cytokines were measured using ELISA/magnetic bead multiplex kits. We calculated concentration change from hour 0 to hour 24. Cytokines: FGF, C-Terminal telopeptide (CTX-1), Dickkopf WNT signaling pathway inhibitor 1(DKK1), Eotaxin, fibroblast growth factor 23(FGF23), interferon gamma, interleukin 13, interleukin 1 beta, interleukin receptor 1 antagonist, interleukin 2, interleukin 4, interleukin 6, interleukin 17, interleukin 8, interleukin 9 Insulin, interferon gamma induced protein 10 (IP10), Leptin, monocyte chemoattractant protein1, monocyte chemoattractant protein1, macrophage inflammatory protein 1a (MIP1a), osteoclasts, Osteoprotegerin, osteopontin, platelet derived growth factors, parathyroid horomone, Recepter activator of nuclear factor kappa-B ligand (RANKL), chemokine ligand 5, sclerostin, transforming growth factor-beta 1, transforming growth factor beta 2, transforming growth factor beta 3, tumor necrosis factor alpha, vascular endothelial growth factor, MIP1b.

VERITAS instrument self-reported compliance with factor replacement regimen. The VERITAS is composed of 6 subsections, where scores range from 1 (best adherence) to 5 (worst adherence). A total score was calculated with the minimum score of 24 (most adherent) and a maximum score of 120 (least adherent)

The HAL is used to assess physical activity; scores range from 42 (severe problems) to 252 (no problems). The ISTH-BAT was used to evaluate bleeding phenotype. Each section was scored using a 0 to 4 scale for each of the 12 subsections. A total score was calculated by taking the sum of each section, resulting in a range of scores from 0 (no bleeding history) to 48 (most extensive clinical intervention for bleeding)

Haem-A-QoL was used to assess various components indicating participants quality of life. Haem-A-QoL is composed of 10 subsections with 3-8 questions in each. Questions are rated from 1 to 5, with 5 being the most negative influence on quality of life. Some questions are worded in the inverse, such that the 1 corresponds to the greatest negative impact on quality of life. In this case, the score is inverted to match the remainder of questions for statistical analysis. A Transformed scores is calculated for each subsection and for the total of all the subjections. The scores range from 0 (best quality of life) to 225 (worst quality of life).