Biochemical Markers of Bone Turnover

Abstract

While radiographic approaches such as dual-energy X-ray absorptiometry (DXA) remain a primary diagnostic modality to assess for osteoporosis and fracture risk, radiographic methods have several limitations. Radiographic methods tend to respond relatively slowly to disease processes or therapeutics that influence bone metabolism, and there is commonly an interest in assessing therapeutic or disease-mediated impact on bone before radiographic changes are detectable. Moreover, it has become apparent that radiographic measures of total bone mass only capture a portion of fracture risk, thus spurring interest in complimentary alternative approaches such as serum or urine biomarkers that reflect the dynamics of bone turnover (hereafter, bone turnover markers, BTMs). Ultimately, bone mass reflects the balance in activity between bone formation by osteoblasts versus bone resorption by osteoclasts. Accordingly, BTMs can also be mapped to these cell types. Generally, anabolic markers reflect either characteristic proteins secreted by osteoblasts, such as bone-specific alkaline phosphatase (BSAP), or matrix protein fragments thereof that are released into circulation when the organic matrix of bone is secreted. The most widely utilized markers of bone resorption all tend to be fragments of matrix proteins that are released into circulation during the course of controlled proteolysis that accompanies bone resorption. Here we will first profile the bone turnover markers with the widest clinical utilization, reviewing the composition of each of these markers and how they relate to bone physiology. Next we will consider how both pre-analytic variation and differences in analytic methods pose challenges to the clinical use of BTMs. Lastly, we will review evidence supporting the use of BTMs for a variety of clinical applications.