Fracture at the isthmus of a class II amalgam restoration most commonly occurs due to inadequate depth of the isthmus, which leads to a thinner, unsupported amalgam section. This insufficient bulk compromises the mechanical strength and resistance of the restoration against occlusal forces. A properly prepared isthmus with adequate depth ensures optimal amalgam thickness, enhancing durability and minimizing fracture risk. Maintaining proper cavity dimensions is critical to withstand functional stresses and prevent restoration failure.

Reference: Sturdevant's Art and Science of Operative Dentistry, 7th Edition.