Clinical Care of Bone Health in Patients on the Immune Tolerance Induction’s Protocols With an Immunosuppressive Agent for Inhibitor Eradication in Hemophilia

Abstract

Nowadays, the development of factor VIII and IX inhibitors in patients with hemophilia is considered as the most challenging in the treatment of hemophilia. Immune tolerance induction (ITI) therapy is an approach for eradication of inhibitors. Some ITI protocols are routinely in use for the eradication of inhibitors in patients with hemophilia. Moreover, such a therapeutic regimen may facilitate the tendency to reduced bone density in patients with inhibitor. This study scheduled to investigate whether that predisposing role of ITI protocols with an immunosuppressive agent has considered or not. By a literature review, published ITI protocols in hemophilia with inhibitors were evaluated. Among them, 51 papers found and studied thoroughly. None of them had performed the bone mineral examination in patients with hemophilia and inhibitor under treatment. Since there are 2 coexisting facilitating factors in these protocols, considering the bone mineral density study for patients with inhibitor who are undergoing ITI protocols with an immunosuppressive agent is recommended.

Low Bone Mineral Density in Hemophiliacs

“…Clinical studies should more often also address patients with factor inhibitors, since the literature shows that these have hardly been considered. Some of the immune tolerance induction (ITI) protocols use one or more immunosuppressive agents for the eradication of inhibitors associated with the side-effect of reduced BMD, thus further pushing patients toward osteoporosis (40). It will also be interesting to see if patients treated with emicizumab, a recombinant, humanized, bispecific monoclonal antibody that restores the function of FVIII by bridging activated FIX and FX, develop a bone phenotype or not.…”

“…The main risk factors predisposing to reduced bone density include smoking, alcoholism, vitamin D deficiency, and some drugs such as exogenous glucocorticoid excess, anticoagulants of warfarin, and heparin (40).…”

Therapeutic Effects of Kefir Peptides on Hemophilia-Induced Osteoporosis in Mice With Deficient Coagulation Factor VIII

“…An earlier single institutional cross-sectional study (n = 88) indicated that low BMD became more prevalent with the increasing severity of hemophilia in PWH <50 years, and a large proportion of PWH ≥50 years (no association with the severity of hemophilia) had osteoporosis; thus, adult PWH ≥50 years should receive routine osteoporosis detection (Kempton et al, 2014). Immune tolerance induction (ITI) is routinely used for the treatment of hemophilia with an inhibitor in PWH; however, such a therapeutic regimen has been reported to facilitate the reduction of BMD in patients with an inhibitor (Rezaieyazdi and Mansouritorghabeh, 2020). Few studies have evaluated the effects of anti-osteoporotic treatment in PWH, except ibandronate, a common bisphosphonate used for the treatment of postmenopausal osteoporosis (Anagnostis et al, 2013).…”