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The Institute of Bone Health estimates approximately 40 percent of Caucasian women in the United States and 13 percent of men aged 50 years will experience at least one clinically apparent fragility fracture in their lifetime. An estimated 54 percent of post-menopausal Caucasian women are osteopenic and 30 percent are osteoporotic, and by the age of 80, 27 percent are osteopenic and 70 percent are osteoporotic.
Fractures resulting from this common condition are painful and lead to varying levels of disability. Osteoporosis today is a treatable condition, so proper and early identification of a decreasing bone mineral density is critical for treatment and lifestyle changes that allow patients a higher quality of life.
Bone Testing
Bone mineral density (BMD) tests using dual-energy X-ray absorptiometry (DXA) or other absorptiometry methods are the traditional method for monitoring bone density. Bone turnover biomarkers, however, are coming to light as ways of providing information to allow physicians to monitor response to treatment and assess whether a patient's condition is improving or worsening.
High performance liquid chromatography (HPLC), radioimmunoassay (RIA), enzyme-linked immunosorbent assays (ELISA) and automated immunoassays are available to assess serum and urine markers. Lab Tests Online (http://www.labtestsonline.org/) defines the following urine or blood tests for bone resorption and bone formation blood tests:
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C-telopeptide (C-terminal telopeptide of type 1 collagen [CTx]) is a peptide fragment from the carboxy terminal end of the protein matrix that aids in monitoring antiresorptive therapies, such as bisphosphonates and hormone replacement therapy, in postmenopausal women and people with osteopenia.
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N-telopeptide (N-terminal telopeptide of type 1 collagen [NTx]) is a peptide fragment from the amino terminal end of the protein matrix; it is recommended that the test be performed at baseline before starting osteoporosis therapy and again 3 to 6 months later.
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Deoxypyridinoline (DPD) is a collagen breakdown product with a ring structure.
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Pyridinium Crosslinks are a group of collagen breakdown products including DPD; used to monitor therapy response; not as specific for bone collagen as the telopeptides.
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Tartrate-resistant acid phosphatase (TRAP) 5b is produced by osteoclasts during bone resorption.
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Bone-specific alkaline phosphatase is an isoenzymes (types) of ALP associated with osteoblast cell function and thought to have a role in bone mineralization; it is recommended that the test be performed at baseline before starting osteoporosis therapy and again 3 to 6 months later; results may be affected by levels of liver ALP.
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Osteocalcin is a protein formed by osteoblasts and is part of the non-collagen portion of the new bone structure and helps predict the rate of bone loss in postmenopausal women and can serve as an indicator of the rate of bone remodeling.
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P1NP (Procollagen Type 1 N-Terminal Propeptide) also is formed by osteoblasts and reflects the rate of collagen and bone formation; may be ordered along with bone resorption marker such as C or N-telopeptide; most sensitive marker of bone formation and particularly useful for monitoring bone formation therapies and anti-resorptive therapies; it is recommended that the test be performed at baseline before starting osteoporosis therapy and again 3 to 6 months later.
 Bone Marker Challenges
In the AACC audioconference "Emerging Biomarkers of Bone Turnover: Gaining Ground in Osteoporosis Management," Serge Cremers, PharmD, PhD, assistant professor of Medical Sciences, Departments of Medicine and Pathology & Irving Institute for Clinical and Translational Research at Columbia University in New York City, explained bone turnover biomarkers have a bad reputation because they do show some variability. Recent years, however, have seen improvements in some of the assays and the use of these markers, minimizing variability to use them to monitor pharmacological treatment in osteoporosis.
A significant amount of analytical variability remains problematic, Dr. Cremers explained. Interlaboratory variability exists even when the same method is used, and available proficiency testing covers only some of the markers used. Also, preanalytical variances must be considered: Circadian variances and food intake may affect certain bone biomarkers, as well as menstrual status and exercise. Controlling for these variances-fasting before a test and testing at a similar point in the menstrual cycle will help ensure more reliable test results.
In that same audioconference, Stuart Silverman, MD, FACP FACR, clinical professor of Medicine at Cedars-Sinai/UCLA suggested an algorithm for the use of biochemical bone markers after diagnosis and during therapy. Use total P1NP/CTX to measure the baseline value for both anti-resorptive and anabolic therapies, he recommended. Assess P1NP/CTX again after 90 days, and if the patient is receiving anti-resorptive therapy and shows a significant decrease, or is receiving anabolic therapies and shows a significant increase, the therapy is effective and the therapeutic regimen should be maintained with continued monitoring.
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