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

Abstract

Survival has steadily improved in cystic fibrosis (CF) over the last few decades, with the median survival age now older than 33 years, and over 40% of all individuals with CF older than 18 years (1). 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 (3-5). The etiology of this bone disease is multifactorial, with contributors including fat malabsorption (resulting in vitamin D malabsorption and abnormal calcium metabolism) (6-8), 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). Data demonstrating that serum 25-OHD levels need to exceed 30 ng/ml to prevent a rise in serum parathyroid hormone (16) suggest that the prevalence of vitamin D deficiency in CF may be even higher.Because of the growing concern about bone disease in CF, the U.S. Cystic Fibrosis Foundation (CFF) convened a panel of experts to develop consensus treatment guidelines to optimize CF bone health, and these recommendations were recently published (17). The guidelines contained several specific recommendations regarding vitamin D. First, greater attention to maintaining adequate serum 25-OHD levels should occur, with levels being checked annually in the late fall with the goal of maintaining serum 25-OHD between 30 and 60 ng/ml (75-150 nmol/L). Second, all individuals with CF who are older than 1 year should receive 800 IU/day of oral ergocalciferol (vitamin D 2 ). Failure of this supplementation to maintain serum 25-OHD levels above 30 ng/ml should lead to aggressive repletion with high-dose oral ergocalciferol. The guidelines recommended a stepped approach for repletion, with an initial regimen of 50,000 IU/week of oral ergocalciferol for 8 weeks. Failure of this regimen to raise serum 25-OHD to over 30 ng/ml should lead to a second course of oral ergocalciferol with 50,000 IU/twice weekly for 8 weeks. Persistence of serum 25-OHD levels below 30 ng/ml despite these supplemental regimens should result in consideration of alternative modes of therapy, such as calcitriol or phototherapy. This treatment protocol was developed on the basis of data in individuals without CF, but was recognized as a "first step" in addressing the clear need for more aggressive vitamin D therapy in individuals with CF. Conference leaders stated a need for CF-specific data in the future on which to determine optimal dosing rec...

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

“…It is therefore to be expected that at least as many people with CF will also have 25 (OH) D serum concentrations under the recommended values. Just as it occurs in healthy people, the percentages of 25 (OH) D serum concentrations below 20 ng/ml observed in CF patients can vary considerably from one study to another because of disparity in disease severity, Sunlight determines vitamin D concentration in CF E Robberecht et al age, geographical location and season (Buntain et al, 2004;Gronowitz et al, 2004;Boyle et al, 2005;Rovner et al, 2007). In this study the difference between the percentages of 25 (OH) D serum concentrations below 20 ng/ml in the 4 successive years amounted to 58% exclusively because of sunshine variations.…”

“…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). Holding fat malabsorption solely responsible for vitamin D deficiency overlooks the importance of the dermal supply, which in healthy people determines up to 85% of 25 (OH) D concentrations in conditions of sunshine (Heaney et al, 2003).…”

Treatment of vitamin D deficiency with UV light in patients with malabsorption syndromes: a case series

“…The cause for decreased bone density in CF is multifactorial; however, due to the inability to absorb fat soluble vitamins, vitamin D insufficiency is a major contributing factor (8) (10). The CF consensus guidelines for bone health suggest the use of UV lamps in subjects who fail to achieve optimal vitamin D status; however, no standard protocols have been established (8).…”

Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37

“…Vitamin D is a steroid hormone classically linked to bone and calcium metabolism and supposedly involved in the regulation of innate immune responses. Despite routine oral supplementation with vitamin D, more than 90% of CF patients are presented with insufficient serum vitamin D levels (<30 ng·mL −1 ) [10,11]. Epidemiological studies show an inverse association of vitamin D levels in the serum and infections of the upper [12,13] and lower [14,15] respiratory tract.…”