Hemophilia A BMD Change And Influencing Factors

Background and objectives:Osteoporosis means bone that has both reduced bone mineral density (BMD) and impaired quality or structural integrity, resulting in increased fracture risks. Multiple researches suggested that hemophilia patients had greater risks of developing decreased BMD. Variables associated might include lower activity levels, HCV or HIV exposures, lower vitamin D levels, decreased joint range of motion and history of inhibitor. Previous research result showed that low osteocalcin levels predominated in the group with low BMD in hemophilia children, which indicated a diminished osteoblastic bone formation activity. While other research result differed in that a high bone resorption not balanced by a comparable bone formation might explain the decrease of BMD in adult hemophilia patients. Proper clinical interventions have yet to be defined to maintain the BMD of hemophilia patients. The Objectives of this study are, to evaluate BMD levels of hemophilia A (HA) patients, the possible variables associated, and the possible pathogenesis.Methods:Hemophilia A patients without inhibitors were enrolled from hemophilia center, PUMC hospital, from January to June,2012. All patients singed the consent forms and completed the evaluations.1) Clinical information was collected using Chinese hemophilia questionnaire.2) BMD was determined following dual energy x-ray absorptiometry (DXA) lab instructions. BMD absolute values, T-scores and Z-scores were recorded. Patients were divided into two groups of Z-scores above and below-2.3) Blood samples for bone turnover samples were collected during9am to9:30am. Carboxy terminal cross linked telopeptide of type I collagen (CTx) was measured for bone absorption, while amino terminal propeptide of type I pro-collagen (P1NP) was measured for bone formation. Bone turnover markers were measured using electrochemiluminescence immunoassay (ECLIA).4) FVⅢ:C was determined using a One Stage partial thromboplastin time-based assay. FVⅢ inhibitor was determined using Bethesda assay. Results:1. Of all48patients, the average of bilateral hip BMD was below1g/cm2, with average Z-score negative. There was no significant differences in BMD between severe and moderate hemophilia patients at all measured sites.2. No significant differencewas observed in patients with Z-score above-2and those below-2in aspects of fractures.3. In the on-demand treatment group, patients with Z-score above-2had higher physical activity levels compared with those below-2(OR10.652,95%CI1.456-77.92), and a lower incidence of long-term immobility history (OR0.057,95%CI0.003-0.972).4. In the prophylaxis treatment group, physical activity level was significantly higher in the Z-score>-2group than those in the Z-score≤-2group, whether while they were still on on-demand treatment (3.4±01.5vs2.4±0.9, P=0.029) or while switched to on prophylaxis (4.0±0.0vs3.1±0.8, P=0.009).5. Of all39patients,4were proved to have Vitamin D insufficiency (10.3%),34were proved to have Vitamin D deficiency (87.2%).6. Of all39patients, serum3-CTx was found to be significantly related to BMD Z-scores (r=-0.409,P=0.010). While there was no significant relation found between serum calcium,25-OH-VitD, or tP1NP and BMD.Conclusions:1. The average bilateral hip DXA measurements were well below those of ethnic-, age-and sex-compared population. No significant difference in BMD was observed between severe and moderate hemophilia patients.2. The decrease in BMD did not necessarily lead to an increase in fracture incidence.3. For those on on-demand treatment, physical activity level appeared to be a protective factor, while a history of long-term immobility a risk factor. For those on secondary prophylaxis, physical activity levels before and after prophylaxis were significantly related to BMD.4. Secondary prophylaxis alone had not proved to be a protective factor for the BMD of hemophilia patients.5. A high incidence of vitamin D insufficiency and deficiency were noticed among hemophilia patients. However, Vitamin D levels were not significantly related to BMD.6. The possible pathogenesis of BMD decrease in hemophilia patients might be an increase in osteoclastic activity, which was not accompanied by a comparable increase in osteoblastic bone formation.