Abnormal Bone Turnover in Cystic Fibrosis Adults

Abstract

Cystic fibrosis (CF) patients often have low bone mineral density (BMD) and may suffer from fractures and kyphosis. The pathogenesis of low BMD in CF is multifactorial. To study bone metabolism, we collected fasting serum and urine from 50 clinically stable CF adults (mean age 28 years) and 53 matched controls to measure markers of bone formation and bone resorption. The CF subjects had moderate lung disease (FEV1: 46.1 +/- 18.6% predicted) and malnutrition (BMI: 20.0 +/- 3.3 kg/m2). Only 3 subjects had normal BMD. CF subjects had higher urinary N-telopeptides of type I collagen (81.0 +/- 60.0 vs 49.0 +/- 24.2 nm BCE/mmol creatinine, p = 0.0006) and free deoxypyridinoline (7.3 +/- 5.0 vs 5.3 +/- 1.9 nM/mM, p = 0.004) levels than controls. Serum osteocalcin levels were similar in the two groups, a result confirmed by two immunoassays that recognize different epitopes on osteocalcin. Serum bone-specific alkaline phosphatase levels were elevated in CF patients (32.0 +/- 11.3 vs 21.8 +/- 7.0 U/l, p < 0.0001), but were much more closely associated with serum total alkaline phosphatase levels (r = 0.51, p = 0.001) than with age or gender. Parathyroid hormone levels were elevated (p = 0.007) and 25-hydroxyvitamin D levels were depressed (p = 0.0002) in the CF patients in comparison with controls. These results indicate that adults with CF have increased bone resorption with little change in bone formation. Medications that decrease bone resorption or improve calcium homeostasis may be effective therapies for CF bone disease.

Reduced bone density in cystic fibrosis: F508 mutation is an independent risk factor

“…A longitudinal study of BMD in CF patients concluded that both reduced bone accretion and accelerated bone loss contribute to the reduced BMD [8]. Elevated levels of bone turnover markers, including serum osteocalcin, urinary N-telopeptide and bonespecific alkaline phosphatase, have been reported in CF patients [5,6,9,10], and it has been suggested that, in CF, there is an imbalance between bone formation and bone resorption in favour of resorption [11,12]. An association between reduced 25-hydroxyvitamin D levels and reduced BMD has been reported in CF patients [7].…”

The importance of monitoring bone metabolism markers and vitamin D in adult patients with cystic fibrosis

“…Было определено значительное изменение костного обмена -повы шение процессов резорбции при малой трансформа ции со стороны формирования костной ткани, что отражалось в выраженном увеличении β CrossLaps и нормальных или несколько сниженных показате лях остеокальцина. Схожие результаты были получе ны в других исследованиях у больных МВ [3,[7][8][9][10][11]. Это свидетельствует о дисбалансе и асимметричнос ти костного обмена с превалированием костной ре зорбции.…”

Cystic Fibrosis

“…A single study reported increasing levels of 25(OH)D post-lung transplant [ 47 ] . A lung transplant removes the effect of chronic infection and in fl ammation, though it does not change the pancreatic insuf fi ciency status or in fl uence of CFTR on other cellular function.…”

“…Neither of these studies used matched controls. PTH is frequently observed to be higher than reference ranges, though it has not been associated with BMD in any study to date [ 12,15,23,26,43,[47][48][49][50][51][52] . Many of these studies are limited by the fact that they used local reference ranges to determine whether PTH results are normal.…”