Biochemical markers of bone turnover are influenced by recently sustained fracture

Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences, Malmö, Lund University, Sweden.
Bone (Impact Factor: 3.97). 05/2005; 36(5):786-92. DOI: 10.1016/j.bone.2005.02.009
Source: PubMed


In striving to refine the clinical utility of different markers of bone metabolism, we should take into account numerous confounders, many of which are well known, such as sampling time, fasting status, and bone density. One further confounder may be ongoing fracture healing and/or post-fracture immobilization, which at least theoretically should impose an increased bone formation and resorption. Since both recent fracture and high bone turnover are independent predictors for new fracture, we thought it of importance to define the potential influence of such fracture on markers of bone turnover. From a population-based cohort of 1604 women, all 75 years old (the OPRA-study), 1024 women attended a clinical examination. The bone metabolism was assessed in serum, by three markers of bone formation [bone-specific alkaline phosphatase (S-Bone ALP), intact and N-Mid osteocalcin (S-Total OC), and total carboxylated osteocalcin (S-cOC)], two markers of bone resorption [C-terminal cross-linked telopeptides of type I collagen (S-CTX) and tartrate-resistant acid phosphatase type 5b (S-TRACP5b)], and in urine by one marker of bone resorption [deoxypyridinoline/creatinine (U-DPD/crea)] and two putative markers of bone resorption [urinary osteocalcins (U-OC/crea)]. Current physical activity and retrospective fracture data were recorded by questionnaires. The fracture data, for the entire cohort of 1604 women, were validated with radiographic referrals and reports, saved since the beginning of the last century. All data provided, except date of occurrence of retrospectively sustained fracture, were thus obtained cross-sectionally and in all women at the age of 75. Fracture had ever been sustained by 727 of the entire cohort (n = 1604), and by 523 of the attending women (n = 1024). All markers were marginally higher (significant only for U-DPD/crea, P = 0.027) in women who had ever sustained fracture, compared to women without fracture. In women with recent retrospective fracture (since 2 years) (n = 100), the levels of all markers, except the two S-OCs, were significantly higher (r = 0.20-0.33, P = 0.049-0.001) the more recently the fracture had been sustained. Women with low current physical activity had elevated levels of U-DPD/crea (P < 0.001) and one U-OC (P = 0.014), while the other markers were unaffected.

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Available from: Kaisa Ivaska, Dec 04, 2014
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    • "When the women who had sustained fractures within two years prior to the study were compared to the others, women with recent fracture had higher level of bone formation markers and higher level of TSU of 99mTc-MDP. This is in line with our previous findings that bone formation markers remains elevated up to 1–2 years after fracture [34,35]. Only one out of eight women had visible focal uptake on the scintigram, on the site of prior fracture. "
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    ABSTRACT: Skeletal uptake of 99mTc labelled methylene diphosphonate (99mTc-MDP) is used for producing images of pathological bone uptake due to its incorporation to the sites of active bone turnover. This study was done to validate bone turnover markers using total skeletal uptake (TSU) of 99mTc-MDP. 22 postmenopausal women (52-80 years) volunteered to participate. Scintigraphy was performed by injecting 520 MBq of 99mTc-MDP and taking whole body images after 3 minutes, and 5 hours. TSU was calculated from these two images by taking into account the urinary loss and soft tissue uptake. Bone turnover markers used were bone specific alkaline phosphatase (S-Bone ALP), three different assays for serum osteocalcin (OC), tartrate resistant acid phosphatase 5b (S-TRACP5b), serum C-terminal cross-linked telopeptides of type I collagen (S-CTX-I) and three assays for urinary osteocalcin (U-OC). The median TSU of 99mTc-MDP was 23% of the administered activity. All bone turnover markers were significantly correlated with TSU with r-values from 0.52 (p = 0.013) to 0.90 (p < 0.001). The two resorption markers had numerically higher correlations (S-TRACP5b r = 0.90, S-CTX-I r = 0.80) than the formation markers (S-Total OC r = 0.72, S-Bone ALP r = 0.66), but the difference was not statistically significant. TSU did not correlate with age, weight, body mass index or bone mineral density. In conclusion, bone turnover markers are strongly correlated with total skeletal uptake of 99mTc-MDP. There were no significant differences in correlations for bone formation and resorption markers. This should be due to the coupling between formation and resorption.
    Full-text · Article · Apr 2009 · BMC Medical Physics
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    ABSTRACT: Bone metabolism can be assessed by measuring bone turnover markers in serum or urine. Bone turnover markers are substances released from bone during bone turnover. They can be skeletal tissue proteins, collagen fragments, peptides, or enzymes released from bone cells. Bone turnover markers are extensively used in research applications but also as tools for the management of skeletal disorders in clinical practice. Osteoporosis-related applications may include assessment of response to, or deciding on osteoporosis therapy; identification of individuals with increased bone loss, and prediction of risk for fragility fractures. Advancements in the development of assays to measure bone markers has made the measurements available also for clinical practice. The possibility to use them in various aspects of clinical practice has been tested in the recent years and given promising results. Monitoring the efficacy of bone-active drugs is currently the most promising application for bone turnover markers. Some markers, particularly resorption markers may also be useful in identifying individuals who are at high risk for bone loss and future fracture. In this article we discuss some potential applications of currently available bone turnover markers in postmenopausal osteoporosis.
    Full-text · Article · Mar 2009 · Clinical Reviews in Bone and Mineral Metabolism
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