Beta-2-agonists are effective in reducing airway narrowing in asthma and protecting against stimuli that produce bronchoconstriction. The combination of long-acting beta agonists (LABA) and inhaled corticosteroids (ICS) has become the most commonly used asthma controller medication class in the United States, but unfortunately, even when LABAs are added to ICS and used regularly, 58-81% of patients with asthma fail to achieve total control. Regular use of beta-agonists, both short and long-acting, reduces the ability of these agents to protect against the airway narrowing that occurs in asthma in response to bronchoconstrictor stimuli. We refer to this reduced effect as loss of bronchoprotection. In this proof of concept trial we aim to determine if alendronate, which diminishes beta-2 adrenergic receptor internalization, can reduce the loss of bronchoprotection that occurs with regular use of LABAs, even when used in combination with ICS.

Inclusion Criteria:

• Clinical history consistent with moderate asthma for >1 year
• Asthma is controlled with ICS, with an FP dose ≤ 1000mcg/day and >100mcg/day (or equivalent)
• Able to perform reproducible spirometry according to ATS criteria
• Baseline FEV1 ≥ 50% of predicted and ≥1L.
• If FEV1 <80%, a minimum 12% increase in FEV1 post-bronchodilator or a MCh PC20 ≤ 8 mg/mL
• If FEV1 ≥80%, a MCh PC20 ≤ 8 mg/mL
• Salmeterol protected MCh ≤ 16 mg/mL

Exclusion Criteria:

• Uncontrolled asthma, as suggested by an ACT score <18 while on high-dose ICS (FP daily dose >500mcg or equivalent)
• Non-ICS controller medication or LABA use within 4 weeks of study entry.
• Contraindications to use of bisphosphonates: history of intolerance to bisphosphonates, history of esophageal ulcers, history of hematemesis, uncontrolled gastro-esophageal reflux disease, inability to stay erect for 30 minutes after oral drug, history of osteonecrosis of the jaw, dental extraction or root canal in prior 8 weeks, or anticipated during the study
• Calculated GFR of less than 35 mL/min
• History of smoking (cigarettes, cigars, pipes, marijuana or any other substances) within the past 1 year, or > 10 pack-years total if ≥ 18 years of age
• Systemic corticosteroid treatment for any condition within 4 weeks of enrollment at Visit 1, history of significant asthma exacerbation requiring systemic corticosteroids within 4 weeks of Visit 1 or more than five courses of systemic corticosteroids in the past year, history of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure within the last 2 years
• History of a respiratory tract infection within 4 weeks of Visit 1
• Receiving hyposensitization therapy other than an established maintenance regimen defined as a continuous regimen for ≥ 3 months prior to enrollment

8 weeks