Bone Demineralization in Cystic Fibrosis: Evidence of Imbalance between Bone Formation and Degradation

Abstract

Bone turnover, collagen metabolism, and bone mineral status were investigated in 59 patients with cystic fibrosis and in 72 sex and age-matched control subjects. In all patients and control subjects serum concentrations of osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and urinary values of cross-linked N-telopeptides of type I collagen (NTX), as well as total body bone mineral content (TBBM) were measured. Higher ICTP (microgram/L) and NTX (bone collagen equivalent/urinary creatinine (nmol/mmol) values were found in pre-pubertal, pubertal, and young adult patients than in control subjects (ICTP: 15.4 +/- 2.1 and 13.2 +/- 1.8, p < 0.001; 23.3 +/- 5.3 and 20.1 +/- 4.1, p < 0.02; 4.8 +/- 1.1 and 4.0 +/- 1.0, p < 0.05. respectively; NTX: 1047.5 +/- 528.6 and 227.8 +/- 71.8, p < 0.01; 997.8 +/- 391.7 and 376.3 +/- 91.0, p < 0.01; 993.2 +/- 398.0 and 73.9 +/- 28.5, p < 0.01, respectively). Lower OC and PICP levels (microgram/L) were showed in pubertal patients in comparison with control subjects (OC: 20.2 +/- 12.3 and 39.0 +/- 15.1, p < 0.01; PICP: 305.8 +/- 130.4 and 436.2 +/- 110.1, p < 0.02, respectively). Lower OC and higher PIIINP levels (microgram/L) were found in young adult patients than in control subjects (OC: 4.4 +/- 3.0 and 7.0 +/- 3.1, p < 0.05; PIIINP: 4.8 +/- 1.1 and 3.1 +/- 1.0, p < 0.001, respectively). TBBM (z score) was reduced in prepubertal, pubertal, and young adult patients (-0.8 +/- 0.4, -1.0 +/- 0.4, -1.1 +/- 0.5, respectively). Patients with cystic fibrosis have bone demineralization and imbalance between bone formation and degradation.

Vitamin K supplementation in cystic fibrosis

“…Several studies showed that vitamin K supplementation induced a decrease of serum u-OC and may alter other bone markers such as NTX and BAP. [5][6][7] Our data showed a similar tendency, with the most prominent changes in the vitamin Figure 1 Boxplot showing total osteocalcin (t-OC in black), undercarboxylated osteocalcin (u-OC in grey), and carboxylated osteocalcin (c-OC in white) for vitamin K supplementation in CF patients, compared to healthy controls. Vitamin K supplementation is shown in three different groups: CF no = no supplementation; CF low = ,0.25 mg/day; and CF high = >1 mg/day.…”

Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis

“…Previous studies have documented a decreased bone mineral content (BMC) in both children [3][4][5][6][7][8] and adults [1,6,9,10] with this disease as well as an increased fracture rate [10][11][12]. There is debate in the literature as to the mechanisms that mediate bone loss in patients with CF.…”

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].…”