Prophylaxis May Help to Preserve Bone Mineral Density in Children
Bone mineral density — the amount of minerals in bone tissue — is markedly lower in children with moderate and severe hemophilia than their healthy peers as a result of recurrent bleeding episodes that damage their joints, according to a small, single-center study in India.
Preventive, or prophylactic, treatment was also found to significantly lower hemarthrosis — joint bleeds — compared with on-demand therapy, and to delay the progression of bone mineral loss in these patients.
The study, “Evaluation of bone mineral density (BMD) and the effect of type of factor replacement therapy on BMD in children with hemophilia: A single-center observational study,” was published in the journal Pediatric Hematology and Oncology.
In people with hemophilia, recurrent hemarthrosis can result in arthropathy, a form of joint disease that can cause disability. Hemophilic arthropathy has been associated with low bone mineral density (BMD), a parameter that is frequently used as an indicator of fracture risk and of osteoporosis, a disease that causes bones to become weak and brittle.
Children with hemophilia are more likely to have low BMD, bone fractures, and develop osteoporosis. The main factors that contribute to low BMD in hemophilia are prolonged immobilization to treat joint bleeds, lack of weight bearing exercises, and limited physical activity.
Relatively little published data exists on BMD for hemophilia patients living in India, the researchers noted, and how factor replacement therapy use — prophylaxis versus on-demand — affects BMD in children with hemophilia is largely unknown.
Scientists at the All India Institute of Medical Sciences in New Delhi compared the BMD of children there with moderate or severe hemophilia A or B at the study’s start (a baseline measure) with that recorded six months later at a follow-up visit.
They enrolled 39 patients — 35 children (89.7%) with hemophilia A and four (10.3%) with hemophilia B — and for comparison 40 healthy age-matched children as a control group.
Six of the patients (15.4%) had moderate hemophilia, defined as between 1% and 5% (0.01–0.05 international units per milliliter or IU/ml) of clotting factor activity in their blood, and 33 (84.6%) had severe disease, marked by less than 1% (0.01 IU/ml) factor activity.
At the study’s start, 11 children who were not on any type of therapy were started on secondary prophylaxis. Of note, secondary prophylaxis is when the factor is infused regularly once the patient has had several bleeds in a single joint, while primary prophylaxis is started at an early age to prevent bleeding.
Of the other 28 children (71.8%), all receiving factor replacement therapy at baseline, 19 (48.7%) were on primary or secondary prophylaxis and nine (23.1%) used the therapy on-demand.
BMD was measured by dual-energy X‐ray absorptiometry — a type of X-ray scan that can be used to determine bone density — and measures were expressed as Z-scores. Researchers classified BMD as normal when Z-scores were higher than −2, and low when they were −2 or less.
A significantly greater prevalence of low BMD at the lumbar spine was found among patients than healthy children (41% vs. 15%). Similar differences in density were also seen at the total hip (38.5% vs 15%), and in the total body (30.8% vs 10%).
Each joint was assigned a range-of-motion (ROM) score, which measures the distance and direction that a joint can stretch. The sum of the scores for each joint ranged from zero (normal joints) to 36.
Higher BMD Z-scores, meaning better bone mineral density, were associated with fewer episodes of joint bleed, a lower number of target joints, and a lower total joint ROM score. Target joints are those with at least three spontaneous bleeds within a six-month period.
Further analysis showed that at baseline, the prophylaxis group had significantly higher BMD Z-scores at the lumbar spine, total hip, and total body region than did children in the no-therapy and on-demand therapy groups.
BMD Z-scores rose after six months of prophylaxis, but not with the on-demand regimen. Preventative treatment also lowered the number of joint bleeds, the proportion of children with target joints, the number of target joints, and the total joint ROM score.
“Our study indicates that children with moderate and severe hemophilia in India are more prone to develop low BMD as compared to normal children of same age which is attributed to recurrent target joint bleeding resulting into progression of arthropathy and consequent immobilization,” the scientists wrote.
“Joint disability due to hemophilic arthropathy,” they added, “seems to be the most important predisposing factor for low BMD as the resulting impaired physical activity and prolonged immobilization aggravate osteopenic [bone-weakening] changes” in patients.
Their study’s findings also show “that prophylaxis is better than on-demand therapy as it markedly decreases bleeding episodes into joints and prevents onset or reduces severity of hemophilic arthropathy, thereby retarding progression of bone mineral loss,” the researchers wrote.
Because previous studies reported no differences in BMD between people on prophylaxis and on-demand therapy, additional studies with larger numbers of patients and longer follow-up are warranted to validate these findings, the team noted.