Investigating the pathogenesis of catastrophic humeral fractures in dairy heifers in New Zealand : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University, Palmerston North, New Zealand

Catastrophic outbreaks of spontaneous humeral fractures in dairy heifers in New Zealand have given rise to animal welfare problems and resulted in significant economic losses to the New Zealand dairy industry. Preliminary small sample size studies have identified potential causes and/or factors associated with the occurrence of humeral fractures including periods of protein-calorie malnutrition, increased osteoclastic bone resorption related to lactation, and low liver and/or serum copper concentration (suggestive of periods of copper deficiency). Nevertheless, outbreaks of humeral fractures still occur throughout New Zealand with devastating consequences. Therefore, the main objective of this thesis was to investigate the likely causes and/or major risk factors associated with the occurrence of spontaneous humeral fractures in dairy heifers in New Zealand and propose a likely pathogenesis of the condition. For this, a large cohort of bone samples (humerus and ribs), as well as liver and blood/serum samples were collected from 2-year-old dairy heifers that suffered spontaneous humeral fracture post calving (affected heifers) for comparison with age-matched post-calving heifers with no bone fractures (control heifers). Blood/serum samples, used for the determination of biochemical profile in affected heifers, showed increased B -hydroxybutyrate and decreased creatinine concentration indicative of negative energy balance and/or periods of undernutrition. Bone samples were used for gross, histologic, histomorphometric, Raman and Fourier transform infrared spectroscopic analysis as well as for the measurement of the collagen and collagen crosslink content in bones from affected heifers compared with control heifers. Histologically affected humeri had osteoporosis (reduction in trabecular volume with abnormal trabecular architecture, thicker growth plates with abnormal architecture, increased resorption in the distal humerus, and a thinner cortex with increased and abnor