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.

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.

[Stiff baby syndrome is a rare cause of neonatal hypertonicity]. / Stiff baby syndrome er en sjælden årsag til neonatal hypertonicitet.

Stiff baby syndrome (hyperekplexia) is a rare genetic disorder. The condition can easily be misdiagnosed as epilepsy or severe sepsis because of hypertonicity and seizure-like episodes and has an increased risk of severe apnoea and sudden infant death. Tapping of the nasal bridge inducing a startle response is the clinical hallmark. We report cases of two sisters born with stiff baby syndrome with hypertonicity, exaggerated startle reaction and cyanosis. The syndrome has a good prognosis if treated with clonazepam and both cases were developmental normal after one year.