Sonia A Talwar, MD; Chief Editor: George T Griffing, MD

The field of bone turnover markers has developed considerably in the past decade. Biochemical monitoring of bone metabolism depends upon measurement of enzymes and proteins released during bone formation and of degradation products produced during bone resorption. Various biochemical markers are now available that allow a specific and sensitive assessment of the rate of bone formation and bone resorption of the skeleton. Although these markers are not recommended for use in diagnosis of osteoporosis yet, they appear to be useful for the individual monitoring of osteoporotic patients treated with antiresorptive agents.

Prediction of bone loss with biochemical bone markers. Adapted from Ross PD, Knowlton W. Rapid bone loss is associated with increased levels of biochemical markers. (DPD stands for deoxypyridinoline.) J Bone Miner Res 1998 Feb; 13(2): 297-302.

A summary list of bone formation markers is as follows:

Serum total alkaline phosphatase

Serum bone–specific alkaline phosphatase

Serum osteocalcin

Serum type 1 procollagen (C-terminal/N-terminal): C1NP or P1NP

A summary list of bone resorption markers is as follows:

Urinary hydroxyproline

Urinary total pyridinoline (PYD)

Urinary free deoxypyridinoline (DPD)

Urinary collagen type 1 cross-linked N-telopeptide (NTX)

Urinary or serum collagen type 1 cross-linked C-telopeptide (CTX)

Bone sialoprotein (BSP)

Tartrate-resistant acid phosphatase 5b

Such markers can also be useful in selected cases to improve the assessment of individual fracture risk when bone mineral density (BMD) measurement by itself does not provide a clear answer. The combined use of BMD measurement and bone markers is likely to improve the assessment of the risk of fractures in those cases.

Diagnosis of osteoporosis is not based on evaluation of bone markers, and bone mineral density (BMD) assessment is still the criterion standard for evaluation and diagnosis. However, mean values for markers of bone turnover are higher in osteoporosis patients than in the matched controls. In various studies, the mean urinary excretion of DPD is 20-100% higher in patients with osteoporosis than in healthy subjects. In another study, an inverse relationship between the quartile of urinary collagen type 1 cross-linked N-telopeptide (NTX) excretion and mean BMD exists, but these results are not consistent. Moreover, values of healthy subjects and patients with osteoporosis overlap substantially. Therefore, measurement of bone markers is not recommended to make a diagnosis of osteoporosis.

For other discussions on osteoporosis, see the overview topics Osteoporosis and Pediatric Osteoporosis, as well as the articles Osteoporosis in Solid Organ Transplantation and Nonoperative Treatment of Osteoporotic Compression Fractures.