The 33-year-old attacking midfielder, who had a sensational past season (33 matches, 12 goals, 11 assists) and was recalled to the Spanish national team, injured his fibula yesterday during a friendly against Malaga, his former club.
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He will miss around three months of match action.
Real Betis announced: "Isco Alarcón, Real Betis Balompié player, was injured in the last pre-season friendly against Malaga CF. After medical examinations, he has suffered a new, non-displaced fracture of the left fibula.
"This is a new traumatic injury that is not related to the previous process, which has been resolved. The player will undergo treatment in the coming weeks, and his return will depend on the evolution of his condition."