PS1107 IMPACT OF SEVERITY OF THE DISEASE AND FVIII INHIBITOR ON BONE MINERAL DENSITY AND BONE TURNOVER MARKER IN CHILDREN WITH HEMOPHILIA A
Authors: Xafaki P. , Doulgeraki A. , Pergantou H. , Komitopoulou A. , Michalopoulou A. , Dettoraki A. , Athanasopoulou H. , Platokouki H. 
Published: June 2019

Background:

Recurrent hemarthroses, and prolonged immobilization may predispose to low bone mineral density in children with hemophilia. Furthermore, adequate dietary calcium intake is a major determinant of bone mass accrual.

Aims:

To evaluate the impact of severity of the disease and history of FVIII inhibitor on bone density and bone turnover markers in children with hemophilia A.

Methods:

Children with hemophilia A (severe FVIII: <1 iu/dl, moderate: ≤ 1‐ 5 iu/dl), aged 6–18 years, were evaluated for bone mineral density (BMD) and bone turnover markers. Positive FVIII inhibitor (>0.6 BU, Bethesda units) history was recorded. Patients were categorized into three groups. Group I: severe cases with inhibitor, II: severe cases without inhibitor and III: moderate cases. Dual‐energy X‐Ray absorptiometry (DXA) of total body (TB) and/or lumbar spine (LS) was applied for BMD measurement and expressed as z‐score (low for chronological age, z‐score ≤ ‐2). Bone resorption [urinary deoxypyridinoline/cretinine (uDPD/uCr), urinary excretion of calcium (uCa/uCr), tartrate‐resistant acid phosphatase (Trap)] and bone formation markers [serum total and bone specific alkaline phosphatase (ALP, bALP), osteocalcin and carboxy‐terminal propeptides of type I collagen], as well as vitamin D, parathormone and serum Ca were measured. All patients completed a validated questionnaire about their dietary calcium intake.

Results:

Fifty one children with hemophilia A (severe 40), mean age: 11.7 ± 3.6 years, were included. Fourteen children (27.4%) had history of FVIII inhibitor. Mean z‐score for LS BMD was −0.51 ± 0.98 [4/40 (10%) had z‐score ≤ ‐2 and 8/40 (20%) had z‐score between −1 and −2)]. Mean z‐score for TB BMD was 0.18 ± 0.85 [none had z‐score ≤ ‐2 and 4/44 (9.1%) had z‐score between −1 and −2)]. Significant difference was found in mean TB and LS BMD between severe and moderate cases (0.81 ± 0.13 vs 0.94 ± 0.18, p = 0.017). Furthermore, hemophilic children with history of inhibitor had lower mean BMD both on TB (0.74 ± 0.069 vs 0.88 ± 0.16, p = 0.005) and LS measurement site (0.66 ± 0.7 vs 0.87 ± 0.24, p = 0.013). Mean TB and LS BMD was significantly higher in group I compared to groups II and III (p < 0.05). On the other hand, patients with severe hemophilia had increased levels of uCa/uCr compared to children with moderate disease (0.35 ± 0.27 vs 0.17 ± 0.08, p < 0.05). In addition, mean value of uDPD/uCr was increased in children with history of inhibitor in comparison to non inhibitor (40.49 ± 11.1 vs 29.09 ± 15.04, p = 0.014). Group I had higher uDPD/uCr values (p < 0.05) compared to group II and group III (40.49 ± 11.1 vs 30.7 ± 16.3 and 24.78 ± 10.54). No differences were observed in other bone markers among all groups. The dietary calcium intake was adequate (> of EAR, Estimated Average Requirement) in only 19% of children, but no differences in both LS and TB BMD were revealed. Nevertheless, children with inadequate calcium intake had significant increased (p < 0.05) ALP/bALP, compared to the rest of patients.

Summary/Conclusion:

In our study, 10% of children with Haemophilia A had low for chronological age LS BMD. Severe disease and history of FVIII inhibitor seem to burden bone health, as measured with DXA. Resorption markers were found to be impaired. Homeostasis of calcium seem to overweigh low dietary intake. Severe cases, especially those with history of inhibitor, are in higher risk to develop bone metabolic disturbances; thus, close monitoring of bone status seems to be necessitated.