Reference intervals in Danish children and adolescents for bone turnover markers carboxy-terminal cross-linked telopeptide of type I collagen (ß-CTX), pro-collagen type I N-terminal propeptide (PINP), osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP).

PURPOSE: Bone turnover markers (BTM) are gaining ground in clinical practice but to fully use their potential there is a need for establishing valid reference intervals (RI). Consequently, the purpose of the study was to establish general RI as well as suggested clinical RI for carboxy-terminal cross-linked telopeptide of type I collagen (ß-CTX), pro-collagen type I N-terminal propeptide (PINP), osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP) in children and adolescents. METHOD: BTM were measured on Danish children and adolescents participating in the CHAMPS-study DK. A total of 762 participants were included (8-18 years, 50.4% girls) contributing a total of 1410 study visits. The RI was calculated based on 2-years age spans. Participants with biochemical signs of metabolic bone disease were excluded. RESULTS: The differences in RI between age groups clearly reflect changes in growth with an initial increase in BTM, greatest in boys, and a subsequent decrease most pronounced in girls. ß-CTX and PINP are markers most affected by these changes, compared to OC and bone ALP. The suggested clinical 95% RI included participants with vitamin D insufficiency but no biochemical signs of metabolic bone disease which did not markedly alter the RI. CONCLUSION: RI for ß-CTX, PINP, OC and bone ALP varies with age and sex. ß-CTX and PINP which reflect bone resorption and formation processes are mostly affected by these changes. We suggest a set of clinically applicable 95% RI for the four BTM to heighten the usefulness and generalizability of the RI.

Effects of age and sex on osteocalcin and bone-specific alkaline phosphatase-reference intervals and confounders for two bone formation markers.

Bone formation markers bone-specific alkaline phosphatase and osteocalcin are used in many clinical situations. Therefore, we calculated reference intervals for the two markers and investigated how they are influenced by several factors including sex and age. Furthermore, we established clinically relevant reference intervals for the two markers. OBJECTIVE: The bone turnover markers (BTMs), bone-specific alkaline phosphatase (bone ALP), and osteocalcin (OC), are frequently measured formation markers. The purpose of this study was to establish reference intervals (RIs) for the two BTMs in a general adult Danish population. METHODS: Bone ALP and OC were measured on the iSYS (IDS Plc) automatic analyzer in samples from the Danish Health2006 5-year follow-up study on serum from 2308 participants (54% women, age range 24-76). Participants with self-reported diagnosis of osteoporosis or receiving hormonal replacement were excluded from analyses while participants on hormonal contraceptives were included. RESULTS: The geometric mean and 95%RI for bone ALP were 13.9 µg/L (7.6-25.6) for men and 13.8 µg/L (7.0-27.4) for women, while for OC 16.0 µg/L (7.5-34.4) for men and 18.6 µg/L (8.1-42.9) for women. Levels of bone ALP increased with increasing age (ß 1.004, p < 0.001), while female sex had no effect. OC levels decreased with increasing age (ß 0.998, p = 0.009) and increased with female sex (ß 1.104, p < 0.001). Based on our findings, we propose for bone ALP and OC three clinical RIs for men based on age and three clinical RI for women based on age and menopausal status. CONCLUSION: The RI for bone ALP and OC varies with age and sex and the BTMs are influenced differently by the two factors. Consequently, the need for establishing valid RIs is of great importance before the full potential of BTM can be used in clinical practice.

Bone mass development is sensitive to insulin resistance in adolescent boys.

PURPOSE: Insulin resistance may exert a negative influence on bone mass in childhood and adolescence. The objective was to assess the association between insulin resistance and total body less head (TBLH) bone mineral content (BMC) and to investigate whether body composition, physical activity or osteocalcin levels may influence this association. METHODS: A longitudinal study with follow-up over more than 6 years was performed and included 562 apparently healthy participants with a mean age of 9.6 years at baseline. Participants underwent DXA scanning at baseline. At the two follow-ups, participants had performed another DXA scanning, had blood samples taken for fasting insulin, glucose and osteocalcin and had physical activity measured with an accelerometer. HOMA-IR was calculated as an index of insulin resistance. RESULTS: HOMA-IR was negatively associated with TBLH BMC in boys at follow-ups (ß = -31.4, p < 0.001) after adjustment for maturity, height, bone area, and baseline level of TBLH BMC. The negative association remained almost unchanged after further adjustments for body composition and physical activity. No association between HOMA-IR and TBLH BMC was found in girls. CONCLUSION: Insulin resistance may be detrimental for bone development through puberty in boys independent of body composition and the level of physical activity.

Bone Mass Development in Childhood and Its Association with Physical Activity and Vitamin D Levels. The CHAMPS-Study DK.

This longitudinal study examined associations of bone mass with physical activity and vitamin D level over more than 6 years through puberty. A total of 663 participants (320 boys) with mean age 9.6 years at baseline (10-17 years at follow-up), underwent dual energy X-ray absorptiometry, anthropometry and blood samples for vitamin D at least twice during the study period (with three possible time-points). Physical activity was assessed using accelerometers at follow-up. A positive association was found between percent time spent at vigorous physical activity and total-body less head bone mineral content (ß = 5.8, p = 0.002). The magnitude of this association increased with maturational development; thus physical activity may have a greater influence on bone mass in the more mature participants. The vitamin D levels were also positively associated with bone mass. A high degree of tracking was observed with changes in anthropometric Z scores predictive of deviation from tracking. No environmental factor predicted deviation from tracking.

S100A8/A9 (Calprotectin), Interleukin-6, and C-Reactive Protein in Obesity and Diabetes before and after Roux-en-Y Gastric Bypass Surgery.

BACKGROUND: In obesity, which is a major contributor to insulin resistance and diabetes, the circulating level of S100A8/A9 (calprotectin) is elevated and declines after Roux-en-Y gastric bypass surgery (RYGB). However, studies on S100A8/A9 and the pathophysiological mechanisms in insulin resistance and diabetes are few and contradictory. METHODS: We studied 48 subjects who underwent RYGB, comprising a non-diabetic control group and two diabetic groups in whom diabetes either regressed or persisted, 6-12 months post-surgically. S100A8/A9, interleukin 6 (IL-6) as well as other inflammatory and diabetes-related markers were measured pre- and post-surgically. RESULTS: Significant and similar decreases of BMI were found in all groups. S100A8/A9 and IL-6 decreased significantly in the group with diabetes remission and in the control group, but not in the group with persistent diabetes. The relative changes in S100A8/A9 and IL-6 correlated significantly (r = 0.905, p = 0.005) only in the group with persistent diabetes. In contrast, leukocyte count and C-reactive protein correlated significantly to S100A8/A9 only in the control group. CONCLUSION: Our study is suggestive of S100A8/A9 and IL-6 being related to a persistent diabetes status post-surgically and of different pathophysiological mechanisms being involved in the post-surgical changes in the three groups, despite similar decreases in BMI.