Invited Speakers Lead Lecture 75 Proceedings of the 23rd IPVS Congress, Cancun, Mexico – June 8-11, 2014 Nutritionally induced cellular signals that affect skeletal integrity in swine TD Crenshaw, L Rortvedt-Amundson Department of Animal Sciences at the University of Wisconsin-Madison. Introduction Insights into skeletal integrity gained from an accidental omission of vitamin D. A recent escalation in lameness and mortality issues in the U.S. swine industry (Madson et al., 2012) were attributed to hypovitaminosis D. An explanation for the abrupt increase in clinical cases of vitamin D deficiency in commercial swine is not apparent. The swine industry has alleviated some of these issues by modifications in vitamin D supplements, but problems still persist (Arnold et al., 2014). Although the number of cases has subsided, the issues spurred interest and questions about bone composition and methods used to accurately assess skeletal integrity. Necropsy reports that describe fractures, callous ribs, and “rubbery” bones may reflect extreme conditions of a nutrient deficiency. More definitive descriptors are needed as guidelines to establish a balance between nutrient inputs required for animal well-being and the environmental issues that often pressure nutrient formulation strategies. This review will provide a brief overview of basic principles involved in bone composition, the impact of dietary nutrients on bone composition, and a critical assessment of methods used to quantify bone integrity in clinical and research settings as presented earlier (Crenshaw et al., 2013). Additional background will be provided to assess the potential for identification of nutrient-induced cellular signals that may provide diagnostic indicators of physiological perturbations that lead to failures in skeletal integrity in swine. Specific cellular signals involved in vitamin D and bone homeostasis have not been clearly elucidated for pigs, which leads to speculative recommendations (Crenshaw et al., 2014). Our recent research interest in vitamin D and skeletal abnormalities was stimulated by an accidental omission of vitamin D from a premix fed to our research herd. Efforts to explain the symptoms induced has led us to explore new pathways recently discovered. A better understanding of the signaling pathways by which vitamin D alters endochondral ossification will enhance development of treatments to prevent lameness and bone related disorders in pigs. Bone composition and integrity Diagnosis of clinical symptoms in nutrient based problems. Before discussing the major nutrient induced signals involved in endochondral ossification, a brief overview of bone composition and methods used to diagnose bone will be summarized from a recent review (Crenshaw et al., 2013). This review provided a foundation for use in diagnosis of nutrient-induced skeletal integrity issues in swine. Bone tissue composition. The water and fat content of bone varies with age, type of bone, and nutrient inputs. Therefore, the mineral content expressed as a percentage of the dry, fat-free weight is a better descriptor of the extent to which the organic matrix has become saturated with mineral (Crenshaw, 2001). On a dry, fat-free basis, approximately 56% of the entire skeleton is ash. The percent ash varies from 62 to 72% in cortical bone from mature sows (Crenshaw et al., 2013) to 44 to 46% in bones from young pigs that are mostly trabecular such as ribs or vertebrae. Thus, selection of a single bone sample and animal age are critical determinants for comparison if percentage ash is used for diagnostic assessment of mineral adequacy. However, over a range in percent ash, the Ca and P content of bone remains constant. The inorganic ash contains Ca (38 to 40%) and P (17 to 19%) in a 2.1:1 ratio. If Ca and P values deviate from these values, then the analytical methods should be questioned. The amount of ash may change in response to diet, but the Ca and P composition of the ash remains constant. Bone strength. Bone integrity (soundness) is affected by both the organic and inorganic materials that compose the tissue. Bone tissue is a composite material which requires synthesis of an organic matrix by osteoblast cells that are eventually embedded in an extra-cellular matrix. The matrix is composed primarily of collagen fibrils arranged in helical strands with proteoglycan polymers inter-dispersed within the matrix. With time, hydroxyapaptite-like [(Ca 3 (PO 4 ) 2 ) 3 ·Ca(OH) 2 ] mineral crystals form within the collagen helical matrix. Systemic hormones and localized growth factors stimulate osteoblast proliferation and differentiation with consequences on the rate and accumulation of the organic matrix. However, the actions do not act directly stimulate mineral crystal formation. Attempts to increase mineralization by over-supplementation of diets will down-regulate homeostatic mechanisms and decrease the efficiency of nutrient use. The combination of the organic matrix and mineral crystals define the material strength properties of bone. The combination of collagen fibers, which contribute primarily tensile (resistance to stretching) properties, and mineral crystals, which contribute primarily compressive (resistance to compression) properties produces an anisotropic material with properties that cannot be explained by the summation of the individual components. Normal loads imposed on a bone are not singularly a tensile or compressive force. Rather, most forces imposed on live animals