Risedronate prevents exercise-induced hypercalcemia but not nausea or vomit in humans: a double-blind randomized controlled trial

Abstract

Abstract Background: Reportedly, nausea or vomiting after heavy exercise was associated with post-exercise increased blood calcium (Ca) levels, which was correlated with enhanced bone resorption. Methods: We conducted a randomized, double-blind, placebo-controlled trial, enrolling 104 healthy trained male members of the Japan Self-Defense Forces. Risedronate (17.5 mg) or placebo was prescribed 3 and 10 days before heavy exercise lasting approximately 5 hours. We estimated Ca levels immediately after the exercise using the correlation between blood Ca and time from the end of exercise. The primary outcome was the severity of nausea or vomiting assessed by a visual analog scale during or post-exercise. The secondary outcomes included clinical symptoms associated with heat illness, post-exercise serum total Ca (tCa), whole blood ionized Ca (iCa), and serum tartrate-resistant acid phosphatase 5b (TRACP-5b) levels. Results: The mean age and baseline estimated glomerular filtration rate (eGFR) were 26 years and 87 mL/min/1.73 m2, respectively. The exercise resulted in a 4.5% weight loss. The two groups were comparable in terms of the symptoms, including primary outcome, and post-exercise eGFR. However, post-exercise estimated tCa and TRACP-5b were significantly lower with risedronate. A similar result was observed for estimated iCa. The incidence of hypercalcemia (defined as an estimated tCa or iCa levels ≥ each median value of all subjects) and urinary Ca excretion were significantly lower with risedronate. A stronger treatment effect of risedronate on blood Ca levels was observed in participants who lost substantial bodyweight. Conclusion: Our strategy may help decrease the incidence of urinary stones often observed in marathon runners. Trial Registration Registered on www.umin.ac.jp (UMIN000032110)