Sclerostin Linked to Bone Issues, Disease Severity in Children With Hemophilia A, Study Says

The levels of sclerostin, a protein that regulates bone formation, may be linked to disease severity and reflect bone alterations in children with hemophilia A, a study suggests.

The study, “Serum Sclerostin Level and Bone Mineral Density in Pediatric Hemophilic Arthropathy,” was published in The Indian Journal of Pediatrics.

Hemophilia is a genetic blood disorder that affects the body’s ability to form blood clots to prevent excessive bleeding. In hemophilia A, this inability is caused by the lack of a specific clotting protein, called factor VIII (FVIII), due to mutations in the FVIII gene. When spontaneous bleeding episodes happen in the joints, patients may develop arthropathy, or joint disease.

Previous studies have shown that a significant number of patients with hemophilia are also affected by osteoporosis, a disease that weakens and thins the bones in the body.

“The main factors contributing to the [development] of osteoporosis in hemophilia are prolonged immobilization, lack of weight bearing exercises and co-morbid infections (hepatitis B, hepatitis C and HIV),” the investigators wrote.

This is particularly true for children with hemophilia who have low bone mineral density (BMD) and are at risk of developing not only osteoporosis, but also bone fractures.

Sclerostin is a protein produced by bone cells that is responsible for reducing the formation of bone. Besides hemophilia, it has an effect in other disorders, such as Van Buchem disease, sclerosteosis (rare genetic diseases characterized by excessive bone formation), and rheumatoid arthritis.

In this study, a group of researchers from the Ain Shams University in Cairo, Egypt, set out to determine if the levels of sclerostin in the serum could be linked to the severity of arthropathy and BMD in a group of children with hemophilia A.

The cross-sectional study enrolled 40 boys with hemophilia A and arthropathy between the ages of 5 and 17 years old and 10 age- and sex-matched healthy children.

Patient characteristics, including the degree of FVIII deficiency, frequency of bleeding episodes, treatments received, body mass index (BMI), disease severity, and BMD, were all determined.

Disease severity and BMD were assessed based on the Hemophilia Joint Health Score (HJHS) and on the lumbar spine (LS) Z score, respectively. The levels of sclerostin in the serum were measures in all study participants.

Results showed that sclerostin levels in the serum of children with hemophilia A ranged from 0.03–0.45 ng/ml, which was significantly higher than healthy children (0.0–0.04 ng/ml). LS Z scores ranged from -4.5–1.2 in children with hemophilia A and included 15 (37.5%) children whose LS Z score was low for their age (lower than -2).

In addition, correlation analysis revealed the levels of sclerostin in the serum were directly associated with the patients’ age and disease severity, “indicating that bone metabolism is affected significantly with older age and severity of joint arthropathy,” according to the researchers.

Conversely, a negative but nonsignificant correlation was found between sclerostin levels and BMD, meaning the higher the protein’s levels, the lower the BMD.

Strong negative correlations were found between LS Z scores and HJHS scores, frequency of spontaneous bleeding episodes, and disease severity.

“Serum sclerostin levels are elevated in hemophilic children indicating bone metabolism affection and correlated with clinical parameters including increased age, and HJHS. These findings may have important implications for the management of hemophilic patients, concerning prevention of osteoporosis from early childhood, and the evaluation of different therapies suggest improvement in HJHS with anti-selerostin in hemophilic patients,” the researchers wrote.

“Moreover, increased levels of serum sclerostin may identify hemophilic patients at high risk for developing osteoporosis. We recommend to study serum sclerostin levels in hemophilic children with varying severity for longer periods of time,” they added.