Ramona Quimby/WMG

Howie's older sister died between Ramona the Pest and Ramona the Brave.

In Ramona the Pest Howie's mother mentions that his older sister was sick and she was taking her temperature when Howie made a mess. However, it's obvious in the later books that Howie doesn't have an older sister. Maybe she died of her illness and Ramona's sympathy for Howie led to their new friendship. As for why she's not mentioned again, maybe it's too painful to talk or think about.

Howie's father is never mentioned. It's possible that the older sister was his stepsister, and Howie's mother was his father's second marriage. His parents divorced, and his stepsister is technically no longer his stepsister, or any kind of sister. The sister is mentioned in one of the early books, written back when people were less likely to make distinctions like "step" and "half" in reference to siblings, especially around small children, who were presumed not to understand.