Serum 25(OH)D is associated with an altered bone turnover marker response after a hip fracture

Abstract

C-terminal telopeptide of type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) are bone turnover markers (BTMs) that are promising surrogate measures of fracture healing; however, it is unknown if their response is affected by other bone healing metabolites. Since 70% of fracture patients are reported to have insufficient serum vitamin D, we sought to determine if serum 25(OH)D levels are associated with differential changes in CTX and P1NP concentrations after hip fracture. This prospective cohort included hip fracture patients 65 years of age or older admitted to one of eight Baltimore-area hospitals. Serum samples were collected at baseline, 2-, 6-, and 12-month post-fracture. A mixed-effects repeated-measures analysis was used to determine the longitudinal association between vitamin D deficiency (25(OH)D < 20 ng/ml) and CTX and P1NP. Baseline lab values were obtained for 296 participants (mean age, 80.8 years; 51% male; 55% 25(OH)D < 20 ng/ml). During the acute fracture healing period P1NP concentrations increased by 14% (95%CI: 7-21%, p < 0.01) while CTX levels did not change (p = 0.07). Both CTX and P1NP decreased below baseline at 6 and 12 months. CTX levels were higher in participants with baseline 25(OH)D < 20 ng/ml (p = 0.01). There was no association between 25(OH)D < 20 ng/ml and P1NP levels over the study duration (p = 0.33). Data from this large, longitudinal cohort support claims that CTX and P1NP concentrations change during fracture healing; however, the differential response of CTX among vitamin D deficient patients highlights important questions for its utility as a reliable surrogate marker of fracture healing. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Keywords: CTX; P1NP; bone turnover markers; hip fracture; vitamin D.

Figure 1.

Flow diagram.

Figure 2.

Change in CTX (A) and P1NP (B) relative to baseline in the full cohort. Each time point is represented as the mean serum level relative to baseline with standard error. Time is coded as a continuous variable based on months from injury.

Figure 3.

Change in CTX (A) and P1NP (B) relative to baseline and stratified by baseline serum 25(OH)D level of 20ng/ml. Each time point is represented as the mean serum level relative to baseline with standard error. Time is coded as a continuous variable based on months from injury. Time, serum 25(OH)D, and the interaction between time and serum 25(OH)D are included as fixed effects with serum CTX (A) and P1NP (B) levels as dependent variables.

Figure 4.

Change in CTX (A) and P1NP (B) relative to baseline and stratified by baseline serum 25(OH)D level of 30ng/ml. Each time point is represented as the mean serum level relative to baseline with standard error. Time is coded as a continuous variable based on months from injury. Time, serum 25(OH)D, and the interaction between time and serum 25(OH)D are included as fixed effects with serum CTX (A) and P1NP (B) levels as dependent variables.