Increased whole body hydroxyproline production as assessed by a new stable isotope technique is associated with hip and spine bone mineral loss in cystic fibrosis.

BACKGROUND & AIMS: Bone mineral loss, reduced lung function and impaired nutritional status are frequently present in children with Cystic Fibrosis (CF). Blood concentrations and urinary excretion of hydroxyproline (OH-PRO) have been used as markers of bone mineral status and lung function in CF.

OBJECTIVE

To examine whether whole body hydroxyproline production, as assessed by a new stable isotope methodology, is increased in pediatric patients with CF and associated with bone mineral loss, lung function decline and impaired nutritional status.

DESIGN

In a cross-sectional study in 15 pediatric patients with CF and 17 healthy young control subjects, whole body hydroxyproline production (Wb OH-PRO) was assessed in the postabsorptive state by primed-constant and continuous infusion of the stable isotope 2-D-OH-PRO for 3 h. Bone mineral density (BMD) of whole body, hip and spin, and body composition (fat mass and fat-free mass) were determined by dual-energy X-ray Absorptiometry (DXA). Plasma isotopic enrichments and OH-PRO concentrations were measured by LC/MS/MS.

RESULTS

Higher values for WbOH-PRO production and plasma OH-PRO concentrations were found in pediatric CF patients than in the healthy young subjects (p < 0.001). WbOH-PRO production was significantly correlated with plasma OH-PRO concentrations in the CF (r: 0.70, p = 0.007) but not in the healthy group. WbOH-PRO production in CF was associated with low BMD values in hip (r = -0.61, p = 0.02) and spine (r = -0.59, p = 0.02) but not with whole body BMD, lung function or body composition.

CONCLUSION

A new stable isotope approach revealed enhanced levels of whole body hydroxyproline production rate in pediatric patients with CF, indicative of enhanced whole body collagen breakdown. Increased levels for whole body hydroxyproline production in CF were associated with severe bone mineral loss in hip and spine but not with lung function decline or impaired nutritional status. Registration ClinicalTrials.gov = NCT01172301.