Results of a 3-year cross-sectional study indicate that boys with more severe hemophilia A have significantly lower mean bone mineral density (BMD) values than boys with moderate or mild manifestations of hemophilia A (P <.05).

Findings showed that 20% of boys with hemophilia A had BMD Z-scores of the lumbar spine between -1 and -2, and 10% had BMD Z-scores ≤-2. Six of the 8 boys with BMD Z-scores between -1 and -2 had severe hemophilia A, and 3 of the 4 boys with BMD Z-scores ≤-2 had severe hemophilia A. Notable BMD loss occurred more in the lumbar spine than the total subcranial BMD, with only 9.1% of the boys demonstrating subcranial Z-scores between -1 and -2 and none having Z-scores ≤-2.

Boys with severe hemophilia A expelled higher levels of calcium in their urine than those with moderate or mild types. Osteocalcin correlated positively with lumbar spine and subcranial BMD-Z scores, with lower levels of osteocalcin found in individuals who had lower BMD Z-scores. Elevated urinary deoxypyridinoline/creatinine correlated with lower lumbar spine and subcranial BMD Z-scores, and was more likely to occur in boys with severe hemophilia A and a history of inhibitors (P <.05).


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The authors stated their study’s results “indicate an uncoupling of bone turnover with decreased bone formation and increased resorption.”

“Patients with hemophilia A, especially those with severe disease and inhibitors, should be targeted toward a more comprehensive skeletal assessment to allow prompt diagnosis and intervention [which includes] adequate Vitamin D levels, dietary calcium intake, and regular physical activity,” they wrote.

Study Methods

Investigators at the Haemophilia Comprehensive Care Centre of Aghia Sophia Children’s Hospital in Athens, Greece, enrolled 51 young boys with hemophilia A in the study, with 41 of the boys on prophylaxis treatments. Of the 51 boys enrolled, 40 had severe hemophilia and 14 had a past medical history of inhibitors, which immune tolerance treatment (ITT) successfully eliminated.

The researchers assessed the boys’ BMDs using dual-energy X-ray absorptiometry (DXA) scans for the lumbar spine and the subcranial total body skeleton. They obtained laboratory bone profiles of the boys using enzyme-linked immunoassay (ELISA), atomic absorption, and electro-chemiluminescence immunoassays to analyze fasting blood and urine samples to ascertain bone turnover.

Serum markers for bone formation included osteocalcin, procollagen type I C-terminal propeptide, and bone alkaline phosphatase. Markers for bone resorption included serum tartrate-resistant acid phosphatase, urinary calcium/creatinine, and urinary deoxypyridinoline/creatinine. Lastly, the researchers measured vitamin D levels and parathormone levels. The investigators compared the lab profiles of the boys with hemophilia A with age- and sex- matched healthy children.

Study Limitations

Limitations of this study included lack of a control group, small sample size, restriction of inclusion according to age and race, and not using a joint assessment tool. The authors also did not consider seasonality affecting metabolic bone markers and vitamin D.

Reference

Pergantou H, Papakonstantinou O, Xafaki P, et al. Uncoupling of bone turnover may compromise skeletal health of young patients with haemophilia A.  J Clin Densitom. Published online August 4, 2021. doi:10.1016/j.jocd.2021.07.011