Vitamin D deficiency and its treatment in cystic fibrosis

Abstract

Vitamin D deficiency is a common finding in individuals with cystic fibrosis (CF), despite routine supplementation. Hypovitaminosis D is often the result of fat malabsorption, but other contributors include increased latitude, poor nutritional intake, decreased sun exposure, impaired hydroxylation of vitamin D, and nonadherence to the prescribed vitamin D regimen. Vitamin D is critical for calcium homeostasis and optimal skeletal health, and vitamin D deficiency in CF can lead to skeletal complications of osteopenia and osteoporosis. Over time, our understanding of treatment regimens for vitamin D deficiency in CF has evolved, leading to recommendations for higher doses of vitamin D to achieve target levels of circulating 25-hydroxyvitamin D. There is also some evidence that vitamin D deficiency may have non-skeletal consequences such as an increase in pulmonary exacerbations. The exact mechanisms involved in the non-skeletal complications of vitamin D deficiency are not clearly understood, but may involve the innate immune system. Future clinical studies are needed to help address whether vitamin D has a role in CF beyond skeletal health.

Vitamin D intoxication in patients with cystic fibrosis: report of a single-center cohort

“…Repeat values for VD were available at 4 and 8 months for 10 out of 13 patients, revealing that only four patients had levels above 100 ng/mL after 4 months while none exceeded this value after 8 months. Finally, as nephrolithiasis 9 and nephrocalcinosis 10 are potential complications of VD intoxication, the yearly abdominal ultrasonography of the patients were assessed at the time of intoxication (median time-lapse from intoxication 0 days (0–56)) and at least 6 months after the event. Kidneys were evaluated in 10 out of 13 patients and none displayed compatible signs.…”

“…Circulating D 3 undergoes a first hydroxylation step in the liver by vitamin D 25-hydroxylase, yielding 25(OH)D before being hydroxylated in the kidney to 1,25(OH) 2 D, its effective form under normal conditions 3 . This metabolite is then capable of binding the vitamin D receptor (VDR) with a strong affinity, influencing the behaviour of cells implicated in bone turn-over, calcium-phosphate metabolism or immunity 9 . The first hydroxylation step is much less controlled than the second one, resulting in high 25(OH)D levels in case of D 3 overdose 3 while 1,25(OH) 2 D levels remain normal or are slightly elevated 11 .…”

Cystic fibrosis bone disease treatment: Current knowledge and future directions

“…Biological efficacy of this treatment should include monitoring of 25 (OH)D but also PTH, targeted to be within the normal range, as well as serum and urine calcium levels to help detect too high dosage. Vitamin D therapy in CF is described in more detail in 'Vitamin D' by Daley et al [115].…”

Puberty in cystic fibrosis

“…Delayed puberty and hypogonadism may be a factor to include when considering whether a specific patient with CF would benefit from treatment of osteopenia and in the interpretation of dual energy x-ray absorptiometry [47]. Further discussion of CF bone disease and vitamin D supplementation are discussed in separate articles in this issue [51].…”