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We investigated the combined impact of two prevalent risk factors: mechanical loading and genetically abnormal cartilage tissue properties. We used cyclic tibial compression to simulate mechanical loading in the cho\/+ (<jats:italic>Col11a1<\/jats:italic> haploinsufficient) mouse, which has abnormal collagen fibrils in cartilage due to a point mutation in the <jats:italic>Col11a1<\/jats:italic> gene. We hypothesized that the mutant collagen would not alter phenotypic bone properties and that cho\/+ mice, which develop early onset OA, would develop enhanced load\u2010induced cartilage damage compared to their littermates. To test our hypotheses, we applied cyclic compression to the left tibiae of 6\u2010month\u2010old cho\/+ male mice and wild\u2010type (WT) littermates for 1, 2, and 6 weeks at moderate (4.5\u2009N) and high (9.0\u2009N) peak load magnitudes. We then characterized load\u2010induced cartilage and bone changes by histology, microcomputed tomography, and immunohistochemistry. Prior to loading, cho\/+ mice had less dense, thinner cortical bone compared to WT littermates. In addition, in loaded and non\u2010loaded limbs, cho\/+ mice had thicker cartilage. With high loads, cho\/+ mice experienced less load\u2010induced cartilage damage at all time points and displayed decreased matrix metalloproteinase (MMP)\u201013 levels compared to WT littermates. The thinner, less dense cortical bone and thicker cartilage were unexpected and may have contributed to the reduced severity of load\u2010induced cartilage damage in cho\/+ mice. Furthermore, the spontaneous proteoglycan loss resulting from the mutant collagen XI was not additive to cartilage damage from mechanical loading, suggesting that these risk factors act through independent pathways. \u00a9 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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