Acute Effects of Fracture on Bone Markers and Vitamin K

¹ Department of Orthopedic Surgery, Hamamatsu University School of Medicine, 3600 Handa, Hamamatsu 431-31, Japan,
² Department of Orthopaedic Surgery, Iwata Municipal General Hospital, Iwata 438, Japan
^a Author for correspondence. Fax 53-435-2296; e-mail taka1m{at}akiha.hama-med.ac.jp.

To the Editor:

New biochemical markers provide useful information in the diagnosis and monitoring of metabolic bone disease and in the prediction of fracture risk. Vitamin K has become increasingly of interest in this field because of its role as a cofactor in the carboxylation of osteocalcin ((1)). Because hip fractures generally occur in severely osteoporotic patients, biochemical markers of bone metabolism and vitamin K have been studied extensively in patients with hip fractures. However, it is not clear whether a fracture itself affects the concentrations of biochemical markers of bone metabolism or, if so, how soon after or for how long after the fractures. The ideal way to study this is to obtain samples before a fracture. This is not feasible, however, because it requires a huge amount of sampling and a long follow-up. A secondary way is to do successive sampling immediately after a fracture to observe whether values change.

We studied 28 women with hip fracture, ages 64–94 years (mean age, 80.3 years). Their fractures were caused by low-energy trauma, such as a fall. They were immediately taken to an emergency room at a hospital. Serum and urine were collected from them on 3 successive days immediately after admission to the hospital (termed day 0). Most patients had surgery on day 2 after the sampling of that day. All had been ambulatory before the fracture. Exclusion criteria were: hip fractures resulting from severe trauma, admission to the hospital >24 h after the onset of fracture, blood transfusions or surgical procedures during the period of sample collection, past and present illnesses related to bone metabolism, and increased concentrations of serum creatinine. No subjects had been treated for osteoporosis, and none received medications before or during the study that might have affected calcium metabolism. Informed consent was obtained from all participants. The procedures followed were in accordance with the principles of the Declaration of Helsinki in 1975, as revised in 1983.

Serum osteocalcin was measured by RIA with a Yamasa osteocalcin kit with the use of polyclonal antibodies. Intra- and interassay CVs were <15%. Pyridinoline and deoxypyridinoline in urine were measured by HPLC after hydrolysis according to an automated analysis described by Pratt et al. ((2)). Before hydrolysis, urinary creatinine content was measured. The values of urinary Pyr and Dpyr were expressed per mol of urinary creatinine. The intra- and interassay CVs were <10%. Vitamin K₁, menaquinone 4 (MK4), and menaquinone 7 (MK7) were measured by HPLC. The method is based on a hydrogen gas-saturated mobile phase with fluorescent detection after postcolumn reduction by a platinum oxide catalyst column ((3)). The detection limits with 1 mL of plasma were 0.1 µg/L for vitamin K₁, MK-4, and MK-7. The CVs were <5%. Urinary -carboxyglutamic acid was measured by HPLC. An aliquot of the urine was chromatographed on an anion-exchange column with a silica-based microparticulate support, and the amino acids of the eluate were detected fluorometrically by postcolumn derivatization with o-phthalaldehyde ((4)). The CV was 6.3%. The statistical significance of differences was determined with nonparametric statistics using a Wilcoxon signed-rank test. P values of <0.05 were considered significant.

Alkaline phosphatase and osteocalcin did not change significantly during the 3 days (Table 1 ). Pyr and Dpyr slightly but significantly increased on the third day (P <0.05). Vitamin K₁ and MK7 showed a 20–30% reduction, but this was not significant. Because MK4 was detected in only one patient, the data are not shown. Although the reduction of urinary -carboxyglutamic acid was slight, its decrease on the third day was significant (P <0.05). Thus biochemical markers of bone turnover were not affected for at least 48 h after fracture.

Most previous publications on longitudinal changes of biochemical markers of bone turnover after fractures have focused on the changes over a period of months. Few reports have looked for acute changes after fracture. Although a report of osteocalcin measurements within 22 h of hip fracture ((5)) described a slight but significant correlation between osteocalcin and the time after fracture, the study was cross-sectional. This is the first report to investigate acute successive changes of vitamin K and biochemical markers of bone turnover in patients with hip fractures. Because proteins that require vitamin K were involved in blood coagulation, it was expected that vitamin K would be consumed in the process of a large fracture such as in the hip. However, the results in this study indicate that concentrations of vitamin K were not affected by fractures in its acute phase. Bone formation markers did not change during the acute phase of hip fracture. Bone resorption markers increased on the third day. Biochemical markers of bone turnover were not affected for at least 48 h after fracture. Therefore, the values of those measurements during the first 48 h after fracture appear to reflect bone metabolism uninfluenced by the hip fracture itself.

References

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