Fracture-induced changes in bone turnover: a potential confounder in the use of biochemical markers in osteoporosis.

To examine the short- and long-term bone metabolic effects of fracture assessed by biochemical markers, we utilized a clinical fracture model-proximal tibial osteotomy-and prospectively followed 14 patients. This model of an induced fracture of a major bone gives the advantage of assessing baseline levels prior to fracture. Follow-up occurred at 6-9 weeks, 4-7 months, 9-13 months, and 14-17 months after fracture. Serum was assayed for type 1 procollagen peptide (PICP), total alkaline phosphatase (ALP), and carboxy-terminal-telopeptide of type I collagen (ICTP), while deoxypyridinoline (Dpyr) was measured in urine. Serum osteocalcin (OC) was measured using two recently developed two-site immunofluorometric assays, which both measure full-length and fragmented forms of OC (OCtot), with one of the assays specifically detecting only the carboxylated form of OC (OCcxy). In addition, OC was measured in urine using the same assays as those used for serum. Serum OCtot increased to a peak at 4-7 months after fracture (P < 0.001) and a similar increase was seen for OCcxy (P < 0.05) and ALP (P < 0.01). Bone formation had returned to baseline after a year. Dpyr increased significantly, with a doubling at 6 weeks, while serum (S)-ICTP increased by 73% (P < 0.01 and P < 0.001). Urine OC increased to a maximum of 84% at 6 weeks. The initial percentage increase of bone resorption was greater than that of bone formation. We conclude that: (1) bone turnover as measured by biochemical markers is altered soon after fracture, (2) the major changes occur within 6 weeks to 6 months, but may persist for up to a year. (3) The initial increase in bone resorption exceeds the increase in bone formation, which may contribute to the enhanced bone loss after fracture. (4) The two novel urine OC assays show a similar pattern of change as established marks of bone resorption, which may indicate that they measure bone resorption. (5) Fracture-induced effects on bone turnover are significant and, thus, are potential confounders in the assessment of osteoporosis.