Reid, IBolland, MBillington, Emma2017-10-022017http://hdl.handle.net/2292/35833Background Osteoporosis and fragility fractures affect a large proportion of the population and have significant health and economic consequences. This thesis addresses several emerging questions regarding bone metabolism and the entity of osteoporosis, specifically: 1. How is bone mineral homeostasis related to energy metabolism and cardiovascular health? 2. By what mechanisms do certain disease states and medications contribute to the development of secondary osteoporosis? 3. Why do different tools used to estimate fracture risk sometimes give discordant results for the same patient, and how should these be addressed in clinical practice? 4. How can we better understand the side effect profiles of osteoporosis treatments, and develop strategies to mitigate adverse effects? Methods Six studies are described herein: 1. An analysis of relationships between circulating parathyroid hormone (PTH), cardiometabolic risk factors, and bone mineral density (BMD) in healthy men 2. An assessment of associations between phosphate and adiposity in three cohorts, and between fibroblast growth factor 23 (FGF23) and weight in a fourth cohort 3. A meta-analysis of randomized controlled trials (RCTs) assessing the effects of thiazolidinedione (TZD) medications on BMD and bone turnover 4. An assessment of the effects of patient characteristics on absolute fracture risk estimates generated by the FRAX and Garvan fracture risk calculators 5. A crossover RCT evaluating the acute effects of calcium supplementation on blood pressure in postmenopausal women 6. A RCT assessing the effect of oral dexamethasone on prevention of the acute phase response (APR) following administration of zoledronic acid Results & Conclusions Results and their implications are summarized as follows: 1. PTH was positively associated with markers of cardiometabolic risk, including measures of adiposity and coronary artery calcification, but not with BMD. Adiposity may represent a cause of secondary hyperparathyroidism. 2. Serum phosphate was inversely associated with adiposity, independent of PTH. FGF23 and body weight were correlated, suggesting that FGF23 may mediate the relationship between phosphate and adiposity. 3. TZDs were associated with modest declines in BMD with no reversal after discontinuation. Avoidance of TZDs in those at high fracture risk may be prudent. 4. Estimates of fracture risk were higher, on average, with Garvan than FRAX. However, using a 3% ten-year hip fracture risk as a treatment threshold, the calculators were in agreement in 75% of cases. It is reassuring that the calculators often agree, but important to recognize that each incorporates different risk factors. 5. Supplementation with calcium as citrate resulted in attenuation of normal diurnal reductions in systolic blood pressure compared to placebo. Calcium supplements may work via this mechanism to increase cardiovascular risk. 6. Compared to placebo, a single dose of oral dexamethasone did not reduce the likelihood or severity of APR following zoledronic acid infusion. A higher dose or longer dosing interval may be required.Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htmhttp://creativecommons.org/licenses/by-nc-sa/3.0/nz/ThesisCopyright: The authorhttp://purl.org/eprint/accessRights/OpenAccessQ112200723