Fluticasone Propionate/Anti-IgE Combination Preserves Bone Mechanical and Mineral Integrity Better than Monotherapies or Anti-TNF-α in Mice with Ovalbumin-Induced Allergic Airway Inflammation.

Allergic asthma is among the type 2-driven chronic inflammatory allergic diseases. Osteoimmunological findings indicate that shared systemic immune mediators and persistent inflammation can disrupt skeletal homeostasis and promote bone fragility. Treatment commonly includes inhaled corticosteroids like fluticasone propionate (FP) to suppress inflammation, with anti-immunoglobulin E (anti-IgE) biologics added to interrupt the IgE-mediated allergic cascade. TNF-α inhibitors (anti-TNF) are also being studied for their impact on inflammatory pathways. However, their capacity to preserve bone mechanical/mineral integrity in allergic airway inflammation (AAI) remains unclear. This study compared the efficacy of anti-TNF, FP, and anti-IgE monotherapies and an FP/anti-IgE combination in mitigating AAI-induced deficits in bone mechanical/mineral integrity in an ovalbumin (OVA)-induced chronic murine AAI model. Fifty-six male BALB/c mice (8-10 weeks old; 22-24 g) were randomly assigned to control, AAI (OVA-sensitized/challenged), and five treatment cohorts: FP (2000 μg), low-/high-dose anti-IgE (aIgE-L/aIgE-H; 100/200 μg), anti-TNF (aTNF; 6.25 mg/kg-bw), and FP/aIgE-H combination. Following an 8-week protocol, three-point bending and inductively coupled plasma-mass spectrometry (ICP-MS) were used to assess bone mechanical properties and physicochemical characteristics of the mineral phase (calcium (Ca) and phosphorus (P) levels; stoichiometric Ca/P ratio), respectively. Analyses showed that aIgE-L and FP monotherapies failed to mitigate AAI-induced bone changes. aTNF and aIgE-H monotherapies provided comparable protection of cross-sectional properties, rigidity, energy-to-fracture, elastic modulus, and yield/ultimate moments; however, aIgE-H was more efficacious in preserving Ca and P levels and the stoichiometric Ca/P ratio. The FP/aIgE-H combination demonstrated the greatest efficacy in preventing mechanical deterioration and preserving mineral integrity, suggesting it as the optimal strategy for maintaining skeletal health in the management of type 2-driven AAI.