Bone Mass and Vitamin D Deficiency in Adults with Advanced Cystic Fibrosis Lung Disease

Abstract

Osteoporosis and fractures are increasingly recognized in children and adults with cystic fibrosis. To investigate the prevalence and pathogenesis of osteoporosis and low bone mass in adults with advanced pulmonary disease due to cystic fibrosis, we examined the relationships between bone mineral density (BMD), anthropomorphic variables, pulmonary status, glucocorticoid therapy, and vitamin D concentrations. BMD of the lumbar spine, hip, and proximal radius was measured by dual energy X-ray absorptiometry in 30 white adults (16 women), age 30 +/- 2 yr (mean +/- SEM). Compared with a normal control population, the patients had significantly reduced BMD at the lumbar spine (17 +/- 3%), total hip and femoral neck (24 +/- 3% and 20 +/- 4%, respectively). The radius was significantly less demineralized (4 +/- 2%; p <= 0.003) than the other sites. Moreover, only 21% of patients with cystic fibrosis had normal BMD (T score > -1.0) at the lumbar spine, 23% at the hip sites, and 39% at the radius. Age, weight, and body mass index (BMI) were most strongly correlated with bone mass, whereas glucocorticoid therapy and pulmonary function were not predictive. Despite oral vitamin D (400 to 800 IU daily), the mean serum 25-hydroxyvitamin D (25-OHD) concentration was at the low end of the normal range (16 +/- 2 ng/ml; normal 10 to 52 ng/ml); 8 of 20 patients (40%) had frankly low (<= 10 ng/ml) levels. BMD was significantly lower in patients with low 25-OHD concentrations at the lumbar spine (0.774 +/- 0.02 versus 0.913 +/- 0.04 g/cm2; p = 0.01) and total hip (0.648 +/- 0.04 versus 0.811 +/- 0.04 g/cm2; p = 0.01). Vertebral fractures were present in 19% of subjects and 41% had a confirmed history of previous fracture. In summary, osteoporosis, low bone mass, and fractures are common in adults with advanced cystic fibrosis lung disease. Despite oral supplements, vitamin D deficiency is also common and is associated with more severe demineralization at the lumbar spine and hip. We conclude that the widespread practice of oral supplementation with 400 to 800 units of vitamin D is ineffective in maintaining normal vitamin D stores in many patients with cystic fibrosis. To ensure adequacy of vitamin D stores, measurement of serum 25-OHD should be included in the routine management of patients with cystic fibrosis.

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

“…A prevalence of vitamin D deficiency of 38% seen among the current participants is the exact prevalence noted by Haworth et al [34], and participants in that study were also receiving vitamin D supplementation. While previous studies have shown that vitamin D status is a predictor of bone mass in these patients [12,47], our data replicate those of two previous studies [6,9] in showing that this variable was not predictive.…”

“…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.…”

Sunlight is an important determinant of vitamin D serum concentrations in cystic fibrosis

“…As a natural consequence, all nutritional guidelines insist on preventing this deficiency by means of a daily oral supplement (Borowitz et al, 2002;Sinaasappel et al, 2002;Aris et al, 2005). Data on serum concentrations of 25-OH cholecalciferol (25 (OH) D) in CF are, however, not unequivocal, as they have been reported as too low by some authors (Donovan et al, 1998;Mortensen et al, 2000;Rovner et al, 2007), whereas others disagree (Buntain et al, 2004;Chavasse et al, 2004). Moreover, the failure of oral supplement treatments is common and has been widely published (Donovan et al, 1998;Boyle et al, 2005;Green et al, 2008;Green et al, 2010).…”

Failure of High-Dose Ergocalciferol to Correct Vitamin D Deficiency in Adults with Cystic Fibrosis

“…With this increase in survival, there has also been growing recognition of health issues unique to the adult population with CF (2). One of these issues is bone health, because studies using dual-energy x-ray absorptiometry measurements of bone density have determined that, despite their young age, approximately 20 to 25% of adults with CF have osteoporosis and another 40% have osteopenia (3)(4)(5). The etiology of this bone disease is multifactorial, with contributors including fat malabsorption (resulting in vitamin D malabsorption and abnormal calcium metabolism) (6)(7)(8), glucocorticoid therapy (9, 10), poor nutritional status (11), inadequate gonadal hormones (10,12), and elevated circulating cytokines (13).…”

“…The etiology of this bone disease is multifactorial, with contributors including fat malabsorption (resulting in vitamin D malabsorption and abnormal calcium metabolism) (6)(7)(8), glucocorticoid therapy (9, 10), poor nutritional status (11), inadequate gonadal hormones (10,12), and elevated circulating cytokines (13). Recognition of this increased risk of osteoporosis in CF has led to greater efforts to optimize vitamin D status and calcium absorption (4,14). The overall prevalence of vitamin D deficiency in adults with CF is strikingly high, with as many as 50 to 60% having 25-hydroxyvitamin D (25-OHD) levels below 20 ng/ml (5,15).…”