Bone physiology and biochemical markers of bone turnover
- Harold N Rosen, MD
Harold N Rosen, MD
- Associate Professor in Medicine
- Harvard Medical School
In adults, bone is constantly being remodeled, first being torn down (bone resorption) and then being rebuilt (bone formation) [1,2]. The resorption and reformation of bone is important for repair of microfractures and to allow modification of structure in response to stress and other biomechanical forces. Bone formation is normally tightly coupled to bone resorption, so that bone mass does not change. Bone diseases occur when formation and resorption are uncoupled. (See "Normal skeletal development and regulation of bone formation and resorption".)
Changes in the rate of bone turnover are an important determinant of bone disease and, therefore, measurements that correlate with the rate of turnover provide important information in assessing patients with bone disease. In the past, the best way to measure bone turnover was to perform a bone biopsy after double-labeling with tetracycline [1,3]. This technique permits measurement of the rates of bone formation and bone resorption, and the fractions of bone surface at which active resorption and formation are ongoing. However, the complexity and expense of this procedure make it unsuitable for routine clinical practice.
As an alternative, several assays are currently available that measure bone turnover markers (BTMs) (table 1). These assays measure collagen breakdown products and other molecules released from osteoclasts and osteoblasts during the process of bone resorption and formation. Although the development of better assays has improved the ability of BTMs to reflect the rate of bone turnover, biologic and laboratory variability have confounded their widespread use in clinical practice.
This topic will review bone physiology and the measurement of BTMs. The clinical utility of BTMs is reviewed separately. (See "Use of biochemical markers of bone turnover in osteoporosis" and "Investigational biologic markers in the diagnosis and assessment of rheumatoid arthritis" and "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma".)
The steps involved in bone formation and resorption are described briefly here and in detail separately. (See "Normal skeletal development and regulation of bone formation and resorption".)
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- BONE REMODELING
- Bone resorption
- Bone formation
- MARKERS OF BONE TURNOVER
- Assay variability
- Biologic variability
- Practical aspects of measurement
- VALIDATION OF MARKERS OF BONE TURNOVER
- Correlation of markers with histomorphometry and calcium kinetics
- Elevation of markers in conditions characterized by increased bone turnover
- Decline in markers after antiresorptive therapy
- SUMMARY AND RECOMMENDATIONS