Elevated levels of serum alkaline phosphatase reflect increased osteoblast activity. The newly available bone-specific serum alkaline phosphatase assays have not provided more information, except in patients with concomitant liver disease. Serum levels of the carboxyl-terminal portion of human type I procollagen have been shown, by histomorphometry, to be correlated with trabecular bone formation. Serum osteocalcin has been shown to be less useful than serum alkaline phosphatase and is associated with unpredictable changes in Paget's disease. There are no urinary markers for new bone formation.
Bone resorption generates several collagen breakdown products, which are excreted in the urine.
Previously, the most commonly measured urinary marker was hydroxyproline, corrected for 24 hours and milligrams of creatinine excreted. The newer pyridinium cross-link markers, however, are remarkably reproducible and primarily directly related to bone collagen resorption, particularly in active disease states. Improved assays of urinary pyridinium cross-links are in development, and those currently available have been approved for diagnostic use in the United States.