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

Vitamin D and Fracture Healing: An Ongoing Puzzle

“…In addition, even though some case reports appear promising, the ambiguity of these results, along with inconsistent findings from animal studies and cellular investigations suggests a need for more comprehensive higher level research, and novel study designs. At the same time, recommendations for what vitamin D intakes should be for both therapeutic fracture healing as well as what levels are unsafe for fracture repair should be especially examined, along with prospective changes in bone turnover markers to ensure that a viable treatment for some is not overlooked as outlined by Bryson et al [113] , Maier [121] , Bouillion et al [122] , Stewart et al [123] and Larsen and Shmal [124] .…”

Bone turnover markers as surrogates of fracture healing after intramedullary fixation of tibia and femur fractures

“…Nonunion after fracture results in high burdens to patients and healthcare systems, and early identification continues to be a challenge. 1 Bone turnover markers (BTMs) have been demonstrated to follow distinct trends following several fracture types, [2][3][4][5][6][7] and limited evidence suggests that differential levels of BTMs are seen in patients with delayed healing. 1,[8][9][10][11] While BTMs are an appealing potential early marker of delayed healing, inadequate evidence exists to support using BTMs as surrogate markers of fracture healing.…”

“…28,29 Similarly, serum 25(OH)D levels have been observed to be inversely correlated with CTX and P1NP in several studies, albeit with some heterogeneity of results. 7,[30][31][32][33] However, few studies investigating the relationship between vitamin D and BTMs were from fracture patients, and these studies consisted of low-energy fractures without fracture healing outcomes. 7,[34][35][36][37] Given this unclear relationship between CTX and P1NP, fracture healing, and vitamin D, we aimed to explore five questions: 1) do BTM values change in the 12 weeks after a tibial or femoral shaft fracture?…”

“…7,[30][31][32][33] However, few studies investigating the relationship between vitamin D and BTMs were from fracture patients, and these studies consisted of low-energy fractures without fracture healing outcomes. 7,[34][35][36][37] Given this unclear relationship between CTX and P1NP, fracture healing, and vitamin D, we aimed to explore five questions: 1) do BTM values change in the 12 weeks after a tibial or femoral shaft fracture? ; 2) does an association exist between baseline serum 25(OH)D levels and BTM response?…”

Correlation between Serum Bone Turnover Markers and Estimated Glomerular Filtration Rate in Chinese Patients with Diabetes

“…Bone turnover markers (BTMs) are markers to reflect bone metabolism, such as 25-hydroxyvitamin D (25(OH)D), osteocalcin (OC), procollagen type 1 intact N-terminal propeptide (P1NP), and β -carboxy-terminal cross-linking telopeptide of type I collagen ( β -CTX). BTMs indicate dynamics of bone turnover and correlate with osteoporosis and fracture [ 8 , 9 ]. A meta-analysis has shown markers of both bone formation and bone resorption are decreased in patients with diabetes, suggesting diabetes mellitus is a state of impaired bone metabolism [ 10 ].…”