How useful are measures of BMD and bone turnover?

Measurements of bone mineral density (BMD) and biochemical markers of bone turnover are useful in the diagnosis and management of osteoporosis, as well as in research relating to the pathogenesis and treatment of the disease. Recent challenges to the utility of these measures have resulted in some confusion among both researchers and clinicians. BMD accounts for the great majority of bone strength and is the current gold standard for the diagnosis of osteoporosis, as well as for prediction of fracture risk. Although bone turnover increases sharply after menopause, biochemical markers of bone turnover have limited usefulness in fracture risk prediction. Persistently elevated bone turnover throughout the menopause is associated with structural decrements, but these cannot be measured routinely and non-invasively. In research applications, both BMD and markers of bone turnover are used to identify candidate agents in preclinical and clinical studies. In addition, head-to-head comparisons of treatments utilize these measures, because fracture endpoint trials would need to be extraordinarily large and complex. Analyses that have suggested that change in BMD or bone turnover 'explains' little of change in fracture risk with treatment appear to be flawed. Although neither can perfectly predict fracture, they are our current best alternatives.