Using biochemical markers of bone turnover in clinical practice
ABSTRACTBiochemical markers of bone turnover provide clinically useful evidence of the normal and pathologic processes that reflect bone cell activity in the skeleton. Understanding the behavior of markers of bone formation and bone resorption should aid in managing patients with a variety of skeletal disorders.
KEY POINTS
- Biomarkers of bone formation and resorption reflect the overall osteoblastic and osteoclastic activity in the skeleton and in some situations may serve as surrogates for histologic examination of bone.
- Biomarkers of bone turnover can be used to document the effects of therapeutic agents in some patients with osteoporosis and possibly reduce the need for frequent bone density testing.
- In cancer patients with bone metastases, biomarkers of bone resorption provide evidence of the efficacy of antiresorptive therapy. The baseline levels also have prognostic value: patients with the highest levels have the worst prognosis.
In cancer
Bone metastases are a common complication in cancer patients. They are classified as osteolytic, osteoblastic, or mixed on the basis of radiographic features. Biochemical markers of bone turnover have proven useful in assessing the magnitude of the metastases, the response to therapy, and even the prognosis for survival.87
Osteolytic metastases, which are common in breast cancer, are associated with increases in bone resorption markers, and after treatment with intravenous bisphosphonates the levels can decrease nearly 70%.88,89
Patients with higher levels of urinary NTx had a higher risk of skeletal complications and disease progression than patients with low levels across multiple tumor groups, including multiple myeloma.87
In osteoblastic metastases. Prostate cancer patients, who typically have predominantly osteoblastic lesions, have elevations of serum total alkaline phosphatase activity and other markers of bone formation.90 In addition, they have elevated bone resorption markers. Urinary NTx decreased markedly but serum bone-specific alkaline phosphatase decreased only slightly after treatment with intravenous zoledronic acid (Zometa),91 whereas androgen ablation therapy has inconsistent effects on bone turnover.92,93 High levels of these markers again predict poor prognosis.93,94
In hormone-suppression therapy. Two of the most successful cancer therapies, aromatase inhibitors for breast cancer95 and androgen ablation for prostate cancer,96 accelerate bone loss through marked suppression of gonadal steroids. Bone resorption and formation markers increase and bone loss ensues, with resorption exceeding formation. Estrogen suppression appears mainly responsible in both sexes, since raloxifene prevents bone loss in prostate cancer patients.97
Bisphosphonates are highly effective in preventing bone loss in either sex.98–100 A single infusion of zoledronic acid in androgen-ablated prostate cancer patients can prevent bone loss for at least 1 year.100
In Paget disease of bone
Paget disease of bone evolves over many years, from an early osteolytic phase to dominance of secondary osteoblastic activity. In patients with extensive polyostotic disease, bone resorption and formation marker levels may be higher than in almost any other skeletal disorder. An exception is serum osteocalcin,101 which once again usually does not accurately reflect the rate of bone formation.
Bisphosphonates, given orally or intravenously, produce an early decrease in bone resorption followed by a fall in bone formation.102 In clinical practice it appears adequate to use the least expensive test, serum total alkaline phosphatase activity, to assess disease activity and the response to therapy.103
Acknowledgments: Grant support to FRS from the Edythe and Eli Broad Foundation and Lois Rosen. Grant support to DRE from the National Institutes of Health (NIAMS: AR37318, AR36794).
