Does anti-IgE therapy prevent chronic allergic asthma-related bone deterioration in asthmatic mice?

Abstract

Current evidence on the association between allergic diseases and bone metabolism indicates asthma may be a potential risk factor for bone health. Using anti-IgE has been proven effective in allergic asthma treatment with a good safety profile; however, its effects on bone health are unknown. Thus, we aimed to investigate whether: (i) chronic allergic asthma (CAA) causes any meaningful changes in bone, and if any, (ii) anti-IgE therapy prevents any CAA-induced adverse alteration. A murine model was used to study CAA. Thirty-two BALB/c male-mice were assigned into four groups (eight-mice/group): Control, CAA (treated with saline), CAA + 100 µg of anti-IgE (CAA + 100AIgE), and CAA + 200 µg of anti-IgE (CAA + 200AIgE) groups. After immunization, saline or anti-IgE was performed intraperitoneally for 8-weeks (in five-sessions at 15-days interval). Three-point bending test was used for the mechanical analysis. Bone calcium (Ca²⁺) and phosphorus (P³⁻) as well as Ca/P ratio were evaluated using inductively-coupled plasma-mass-spectrometer (ICP-MS). Compared to control, reductions observed in yield and ultimate moments, rigidity, energy-to-failure, yield and ultimate stresses, elastic modulus, toughness, and post-yield toughness parameters of the CAA group were found significant (P < 0.05). Similar declines were also detected regarding bone Ca²⁺, P³⁻ and Ca/P ratio (P < 0.05). Compared to control, we observed that 200 µg administration of anti-IgE in CAA + 200AIgE group hindered CAA-related impairments in mineral and mechanical characteristics of bone, while 100 µg in CAA + 100AIgE failed to do so. Our results showed CAA may cause bone loss, leading to a decrease in bone strength, and anti-IgE administration may dose-dependently inhibit these impairments in bone.

Introduction

Asthma is a chronic inflammatory airway disorder that has many clinical phenotypes in which various cells, factors, and mechanisms are involved. It is recognized as a complex condition with differences in severity, history, comorbidities, and treatment response (Saetta and Turato, 2001, Shin et al., 2009). Since immunoglobulin (Ig) E plays a central role in disease pathogenesis, attention has been focused on regulating IgE production (Kang et al., 2010, Ohta et al., 2017, Licari et al., 2017). Owing to its proven efficacy and safety profile, U.S. Food and Drug Administration and European Union approved anti-IgE use in patients with moderate-to-severe persistent allergic asthma (FDA, 2016, EPAR, 2020).

There is limited data on the effects of asthma morbidity on bone metabolism. Accumulated evidence has demonstrated an association between airway hyperresponsiveness (AHR) or asthma and several factors regarding bone metabolism. Findings have revealed a significant negative correlation between reduced bone mineral density, serum vitamin-D, serum total or ionized calcium levels and the severity and exacerbation frequencies of AHR or asthma (Freishtat et al., 2010, Nagdeote et al., 2011, Chinellato et al., 2011, Jung et al., 2014, Hussein et al., 2019). Given that lifelong persistence of asthma developed in adulthood and evidence regarding bone metabolism, asthma morbidity can be a potential risk factor for bone health. There is no data on revealing the status of both the disease and anti-IgE therapy on mechanical and compositional characteristics of bone. We, therefore, aimed to explore whether chronic allergic asthma (CAA) causes any meaningful changes in mechanical features and mineral composition (MC) of bone. Owing to the uncertainty about the effects of anti-IgE therapy on bone, we also examined whether anti-IgE therapy hinders any CAA-induced adverse alteration in MC and/or mechanics of bone. To the best of our knowledge, this is the first paper studying the effects of asthma morbidity and anti-IgE therapy on mechanical and mineral characteristics of bone in an experimental-chronic inhalational exposure model of CAA in mice.