Patients with severe hemophilia A should undergo regular bone mineral density (BMD) screenings, according to findings from a study conducted in Bulgaria and published in the journal Folia Medica (Plovdiv).
Individuals with severe hemophilia experience spontaneous bleeding into their weight-bearing joints, which is linked with mutations in the factor VIII (FVIII) gene that lead to complete deficiency of the related clotting protein. Recurrent bleeds into the joints is associated with patients’ developing extensive hemophilic arthropathy early in their lives.
It is well known that men with hemophilia A exhibit a considerable reduction in lumbar spine and total hip BMD, which is observed as early as in childhood. As the patient population with hemophilia ages, related comorbidities as osteopenia and osteoporosis must be considered.
The researchers sought to assess BMD in adults with severe hemophilia A and evaluate a potential link with the bone remodeling biomarkers osteoprotegerin/receptor activator of nuclear factor-κβ ligand (OPG/RANKL), carboxy-terminal telopeptide of type I collagen (CTX-1), vitamin D, and osteocalcin. Study participants were followed up at the Bleeding Disorders Center at St. George University Hospital in Plovdiv, Bulgaria.
A total of 28 male patients with severe hemophilia A were consecutively enrolled in the study. The median participant age was 42.88 years (range, 18 to 71 years). Of these 28 individuals, 16 were aged less than 50 years (11 of whom were receiving on-demand treatment and 5 of whom were receiving primary/secondary prophylaxis). The 12 individuals aged more than 50 years were all receiving on-demand replacement therapy with FVIII products. A total of 33 male age-matched healthy controls were recruited voluntarily to the study. The median patient age in the control group was 38.69 years.
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Levels of bone turnover biomarkers were measured with the use of enzyme-linked immunosorbent assay (ELISA). BMD was evaluated through dual x-ray absorptiometry (DEXA) scans of the lumbar spine and total hip.
Results revealed that the patients with hemophilia A exhibited lower lumbar spine BMD and total hip BMD compared with the controls (–0.955±0.145 g/cm2 vs 1.118±0.790 g/cm2, respectively and –0.840±0.147 g/cm2 vs 0.951±0.075 g/cm2, respectively; P =.05 for both).
Based on DEXA, lumbar spine T-scores were –1.16±1.046 vs 0.14±0.72, respectively, and total hip T-scores were –1.41±0.91 vs 0.40±0.49, respectively (P =.05 for both). Overall, 66% of the participants aged less than 50 years had osteopenia and 8.3% of those in this age group had osteoporosis. In contrast, 50% of the participants aged more than 50 years had osteopenia and 20% had osteoporosis.
Additionally, significantly higher OPG levels were observed in individuals with hemophilia than in controls (123.69±107.05 pg/mL vs 41.98±18.95 pg/mL, respectively; P =.05), along with significantly lower RANKL levels (23.49±29.39 pg/mL vs 131.32±201.27 pg/mL, respectively; P =.05). A positive association was observed between soluble RANKL (sRANKL) level and BMD lumbar spine T-score.
“Our results confirm the importance of regular screening of the bone health of adult patients with hemophilia A,”
the authors emphasized, “and suggest using sRANKL level and ratio as predictors of low BMD,” they concluded.
Ivanova HA, Grudeva-Popova Z, Deneva T, Tsvetkova S, Mateva N. A single-center study of bone mineral density in adult patients with severe hemophilia A in correlation with markers of bone metabolism. Folia Med (Plovdiv). 2023;65(1):87-92. doi:10.3897/folmed.65.e75414