Reduced serum 25-hydroxyvitamin D concentration and disordered mineral metabolism in patients with cystic fibrosis

doi:10.1016/S0022-3476(79)80346-7

The Journal of Pediatrics

Volume 94, Issue 1, January 1979, Pages 38-42

https://doi.org/10.1016/S0022-3476(79)80346-7 Get rights and content

Vitamin D and mineral metabolism were studied in 21 adolescents and young adults with cystic fibrosisand the results were compared to those in 21 matched controls. All CF patients had been maintained on standard multivitamin supplements in combination with pancreatic enzyme replacement. Despite this supplementation, relative to control subjects the CF patients had a 36% reduction in serum 25-hydroxyvitamin D concentration, a slight but significant reduction in serum calcium concentration, evidence of calcium malabsorption with secondary hyperparathyroidism, and a 14% decrease in bone mass measured by the photon absorption technique. Currently accepted modes of pancreatic enzyme replacement and vitamin D supplementation are often inadequate to maintain normal mineral homeostasis in CF patients; additional measurements may be required to reduce the risk of clinically significant osteopenia concomitant with prolonged survival in CF.

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Cited by (115)

A Clinician's guide to vitamin D supplementation for patients with cystic fibrosis
2021, Journal of Clinical and Translational Endocrinology
Citation Excerpt :
Many patients with cystic fibrosis are underweight, and the decreased body fat may store less vitamin D than in those with healthy body weight [13]. Additionally, poor hepatic 25-hydroxylation of vitamin D and accelerated enterohepatic dumping can decrease overall vitamin D stores [10,14]. Patients with CF may have decreased storage of vitamin D because of decreased levels of vitamin D binding protein, which is the main carrier in circulation and helps recover 25-hydroxyvitamin D excreted in urine [15].
Vitamin D deficiency is common in the general population, and even more so in patients with cystic fibrosis. Deficiency is exacerbated in cystic fibrosis patients because of a myriad of causes including malabsorption, decreased fat mass, reduced 25-hydroxylation of vitamin D, reduced exposure to sunlight, decreased vitamin D binding protein, and exposure to drugs that increase catabolism. In turn, vitamin D deficiency can contribute to poor bone health. Additionally, it may contribute to pulmonary decline in the form of worsening pulmonary function, increased colonization with pathogens, and increased pulmonary exacerbation. Because vitamin D deficiency is correlated with negative clinical effects in multiple organ systems of patients with cystic fibrosis, it is important to screen for and treat deficiency in these patients. The Cystic Fibrosis Foundation has issued guidelines for the treatment of vitamin D deficiency, targeting serum levels of 25-hydroxyvitamin D of at least 30 ng/ml. The guidelines offer age-specific escalating dose regimens depending on serum vitamin D levels, with monitoring at 12- week intervals after changing therapy. They address the literature on alternative vitamin D sources, such as UV lamps, ideal formulations (cholecalciferol in preference to ergocalciferol), and optimal vehicles of administration. Despite these detailed recommendations, most centers are still unable to achieve in-target serum vitamin D levels for many of their patients. Future research examining ideal treatment regimens to achieve serum targets and maximize clinical effects are needed. Moreover, it is unknown whether vitamin D sufficiency will be easier to achieve on new triple therapy cystic fibrosis drug combinations, and how these drugs will contribute to vitamin D-related clinical outcomes.
Circulating biomarkers of antioxidant status and oxidative stress in people with cystic fibrosis: A systematic review and meta-analysis
2020, Redox Biology
Citation Excerpt :
Whilst GSH was studied in blood neutrophils (n = 2) [40,52] and erythrocytes (n = 2) [39,51] by 4 eligible trials, a meta-analysis was not possible for either biomarker as mean ± SD was not computable for 2 trials as medians and interquartile ranges were reported [39,40]. The concentration of albumin in the plasma or serum was significantly lower in people with clinically-stable CF compared to the non-CF controls (SMD -0.98, 95% CI -1.68 to −0.27, p < 0.01, I2 86%, 6 trials) [45–50]. The concentration of protein thiol groups in plasma or serum were not significantly different between people with clinically-stable CF and non-CF controls (SMD -0.35, 95% CI -0.90 to 0.20, p = 0.22, I2 0%, 2 trials) [53,54].
Oxidative stress may play an important role in the pathophysiology of cystic fibrosis (CF). This review aimed to quantify CF-related redox imbalances.
Systematic searches of the Medline, CINAHL, CENTRAL and PsycINFO databases were conducted. Mean content of blood biomarkers from people with clinically-stable CF and non-CF controls were used to calculate the standardized mean difference (SMD) and 95% confidence intervals (95% CI).
Forty-nine studies were eligible for this review including a total of 1792 people with CF and 1675 controls. Meta-analysis revealed that protein carbonyls (SMD: 1.13, 95% CI: 0.48 to 1.77), total F₂-isoprostane 8-iso-prostaglandin F_2α (SMD: 0.64, 95% CI: 0.23 to 1.05) and malondialdehyde (SMD: 1.34, 95% CI: 0.30 to 2.39) were significantly higher, and vitamins A (SMD: −0.66, 95% CI -1.14 to −0.17) and E (SMD: −0.74, 95% CI: −1.28 to −0.20), β-carotene (SMD: −1.80, 95% CI: −2.92 to −0.67), lutein (SMD: −1.52, 95% CI: −1.83 to −1.20) and albumin (SMD: −0.98, 95% CI: −1.68 to −0.27) were significantly lower in the plasma or serum of people with CF versus controls.
This systematic review and meta-analysis found good evidence for reduced antioxidant capacity and elevated oxidative stress in people with clinically-stable CF.
Effect of high dose vitamin D3 therapy on serum vitamin D3 levels in vitamin D insufficient adults with cystic fibrosis
2018, Clinical Nutrition ESPEN
The effect of a high dose oral cholecalciferol repletion strategy in Vitamin D insufficient adults with CF is still unknown. Therefore, we assessed the effectiveness of our current approach, giving oral vitamin D3 supplementation at a dose of 10,000 IU from Monday to Friday for a total of 50,000 IU D3 weekly in vitamin D insufficient adult with CF.
We performed a retrospective chart review of all 59 adult CF patients between the ages of 17 and 64 years routinely followed at the CF Adult Program of Winnipeg Health Sciences Centre. Through consultation with the endocrinologist, our clinic vitamin D repletion protocol for treating CF adult patients who have serum 25-hydroxyvitamin D (25-OHD) < 30 ng/ml (<75 nmol/L) was to prescribe vitamin D3 10,000 IU orally from Monday to Friday (or the weekly equivalent of 50,000 IU) for 12 weeks in addition to their regular CF vitamin that supplied from 800 to 2000 IU vitamin D3 daily. Cholecalciferol was conveniently administered orally as either one capsule (oil-based) 10,000 IU or one tablet (powder-based) 10,000 IU. All patients were instructed to obtain follow-up serum 25-OHD levels post completion of treatment.
Of the 59 adult patients at our CF Clinic, 35 patients (59%) had below optimal serum 25-OHD levels. Of the 35 patients identified, 10 patients with insufficient serum 25-OHD levels between 10 and 30 ng/ml (25–75 nmol/L) fulfilled the inclusion criteria. A significant increase in serum 25-OHD levels was observed (P < 0.01) from mean value of 21.6 ± 5.9 ng/ml (54.1 ± 14.8 nmol/L) at baseline to 31.7 ± 9.1 ng/ml (79.3 ± 22.8 nmol/L) ≥ 2 months post intervention. The current treatment approach was successful in treating Vitamin D insufficiency in 70% of the patients with low 25-OHD levels.
The results of this study demonstrate that a large number of adults attending Winnipeg Health Sciences Centre CF Clinic have serum 25-OHD levels below 30 ng/ml (75 nmol/L). This supports the need for dedicated and individualized approach to manage this condition. High dose therapy of vitamin D3, although a more aggressive treatment approach, may result in achieving optimal levels of serum 25-OHD in adults with CF.
Adults with cystic fibrosis have deficits in bone structure and strength at the distal tibia despite similar size and measuring standard and relative sites
2018, Bone
Individuals with cystic fibrosis (CF) have lower bone mineral density (BMD) by DXA and are at higher risk of fracture than healthy controls. However, the 2-dimensional measurement of areal BMD (aBMD) provided by DXA is influenced by bone size and the true extent of the bone deficit is unclear. Our objective was to use high-resolution peripheral quantitative computed tomography (HR-pQCT) and individual trabecula segmentation (ITS) analysis to compare volumetric BMD (vBMD), microarchitecture and estimated strength at the distal radius and tibia in 26 young adults with CF and 26 controls matched for age, gender, and race. To assess the effect of limb length and minimize the confounding effects of size on HR-pQCT outcomes, we scanned participants at both the standard fixed HR-pQCT measurement sites and at a subject-specific relative site that varied according to limb length. CF participants did not differ significantly in age, height, weight, or BMI from controls. Ulnar and tibial lengths were 9 mm shorter in CF patients, though differences were not significant. CF patients had significantly lower BMI-adjusted aBMD by DXA at the lumbar spine (8.9%, p < 0.01), total hip (11.5%, p < 0.01) and femoral neck (14.5%, p < 0.01), but not at the forearm. At the fixed radius site, thickness of trabecular plates and torsional stiffness were significantly lower in CF participants than controls. At the relative radius site, only torsional stiffness was significantly lower in CF participants. At the tibia, total, trabecular and cortical vBMD were significantly lower at both fixed and relative sites in CF participants, with fewer, more widely-spaced trabecular plates, lower trabecular connectivity, and lower axial and torsional stiffness. Our results confirm that aBMD is lower at the spine and hip in young adults with CF, independent of BMI and body size. We also conclude that vBMD and stiffness are lower at the weight-bearing tibia. The pathogenesis of these differences in bone density and strength at the tibia appear to be related to trabecular drop-out and reduced trabecular connectivity and to be independent of differences in limb length, as assessed by scanning participants at both standard and relative sites. We concluded that significant deficits in bone structure and strength persist in young adults with CF, despite advances in care that permit them to attain relatively normal height and weight.
Vitamin D deficiency is associated with pulmonary dysfunction in cystic fibrosis
2015, Journal of Cystic Fibrosis
Citation Excerpt :
Vitamin D deficiency in CF is common [1]. Deficiency of vitamin D is most commonly associated with poor bone health and is thought to contribute to the premature onset of osteopenia and osteoporosis commonly seen in CF [2,3]. Recently, vitamin D depletion has been associated with multiple other disease states in the general population, including hypertension, diabetes mellitus, cardiovascular disease, and cancer [4].
Vitamin D deficiency is common in CF. Whether vitamin D affects pulmonary function in CF is unknown.
Data were abstracted from clinically stable CF patients who had pulmonary function studies and serum 25-hydroxyvitamin D [25(OH)D, ng/ml] levels drawn within 2 months of each other. Findings were adjusted for multiple variables known to affect pulmonary function in CF.
Enrollees totaled 597. Overall mean 25(OH)D level was 29.6 ± 12.8 ng/ml (SD). Serum 25(OH)D levels showed a significant correlation with forced expiratory volume in 1 s (FEV₁) % predicted (r = 0.20, p < 0.0001) and forced vital capacity % predicted (r = 0.13, p = 0.0019). Multivariate analysis revealed that serum 25(OH)D remained an independent predictor of FEV₁ % predicted even after controlling for multiple other factors known to affect CF lung function.
Serum 25(OH)D levels are significantly associated with pulmonary function in CF. Further study is required to determine whether this association is causal.
Persistent Fat Malabsorption in Cystic Fibrosis
2015, Diet and Exercise in Cystic Fibrosis
Despite pancreas enzyme replacement therapy, intestinal fat absorption remains insufficient in most cystic fibrosis (CF) patients. We reviewed the potential causes of CF-related persistent intestinal fat malabsorption. Data are obtained from studies in patients and in CF experimental animal models. Based on the physiology of intestinal fat absorption, we discuss the pathology in CF conditions. The chapter covers CF-related alterations of intestinal pH and bicarbonate secretion, bile salt metabolism, and enterohepatic circulation and intestinal mucosal abnormalities.

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^†: Supported in part by National Institutes of Health Grants AMO7033, NS10262 and NIH Career Development Award NS70540.

^**: Cystic Fibrosis Foundation Fellowship Awardee.

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Original articleReduced serum 25-hydroxyvitamin D concentration and disordered mineral metabolism in patients with cystic fibrosis†

J Clin Nutr

J Pediatr

J Pediatr

Clin Endocrinol Metab

J Pediatr Surg

Cystic fibrosis presenting with severe hemorrhage due to vitamin K malabsorption: a report of three cases

Pediatrics

The pancreas

Research in cystic fibrosis (third of three parts)

N Engl J Med

Serum 25-hydroxycalciferol levels and bone mass in children on chronic anticonvulsant therapy