The Clinical Utility of Bone Turnover Markers in Postmenopausal Women with Osteoporosis

Postmenopausal osteoporosis is characterised by increased bone turnover, a negative balance (where bone resorption exceeds bone formation), reduced BMD and increased fracture risk. Diagnosis is based on assessment of BMD measured by DXA. The development of specific and sensitive bone turnover markers such as PINP and CTX are widely used in clinical studies. The overall aim of this thesis was to investigate the clinical utility of BTMs in a population based study and in clinical trials of licenced antiresorptive treatments. Postmenopausal and premenopausal women were recruited and whole blood, serum and urine samples were collected. Several diseases and treatments were identified that influenced bone turnover markers in older women and these needed to be excluded for establishing healthy reference intervals. In postmenopausal osteoporosis the negative balance between bone resorption and formation may be associated with the low BMD, bone loss and increased vertebral and non-vertebral fracture risk. Antiresorptive treatments inhibit bone resorption in the short-term by having direct action on mature osteoclasts. There was also a later effect mediated by a reduction in the population of circulating osteoclast precursors. With bisphosphonate treatments bone balance is positive relative to healthy premenopausal women. The clinical utility of sclerostin remains unclear but it does appear to be related to bone resorption and bone formation and levels of which are reduced with raloxifene treatment. Bone turnover markers provide additional information to BMD assessments about bone remodelling. The combined assessment of bone turnover and bone balance may help identify patients at risk of bone loss and fracture. These findings can be used to investigate the mechanisms of actions of current and future treatments that are being developed in order to identify the most suitable for patients with postmenopausal osteoporosis.