Vitamin D alternative

A nice case showing superiority of calcifediol daily over cholecalciferol weekly in supplementing vitamin D levels and improving hypocalcemia, hyperparathyroidism and bone mineralization in someone with malabsorptive bariatric surgery (biliopancreatic diversion).

Chronic malabsorption can cause malnutrition, leading to poor liver function and reduced ability to hydroxylate vitamin D3 to D3-25OH, subsequently inducing calcium metabolic derangements and lower bone density.

Calcifediol – a preformed D3-25OH and an easier absorbed (due to an extra hydroxy group) form of vitamin D – bypasses the need for hepatic conversion of D3 to D3-25, and helped the index patient achieve impressive outcomes in 2-6 months.

Findings suggest using calcifediol in persons with refractory hypovitaminosis D and hypocalcemia in the setting of advanced gastrointestinal malabsorption.

GT


Also see:

Vitamin D supplementation in hypoparathroidism

 

 


J. of the Endocrine Society

Case Report

July 2017

Vitamin D deficiency following malabsorptive bariatric surgery can lead to osteomalacia. We report a patient with severe vitamin D deficiency following malabsorptive bariatric surgery successfully treated with calcifediol but not cholecalciferol.

A 40-year-old woman, submitted to biliopancreatic diversion 20 years before and chronically treated with 50,000 IU cholecalciferol weekly, was admitted to our Endocrine Unit because of severe lower back pain, muscle weakness, and generalized muscular hypotrophy, associated with hypocalcemia and elevated PTH levels.

Initial evaluation revealed low serum albumin, low albumin-corrected serum calcium (cCa++7.36 mg/dL), high serum PTH (240 pg/mL), bone-specific alkaline phosphatase (125 μg/L) and 1,25-dihydroxyvitamin D (112 pg/mL) concentrations, undetectable serum 25-hydroxyvitamin D (<7 ng/mL), and evidence of reduced liver function. Bone mineral density was markedly low.

Normocalcemia was initially restored with intravenous albumin and calcium gluconate. Treatment with calcitriol (0.5 μg three times daily) and oral calcium carbonate (1000 mg daily) was simultaneously started and cholecalciferol was replaced with calcifediol [125 μg (5000 IU) daily)]. During follow-up the calcifediol dose was progressively tapered to 25 μg (1000 IU) daily and the calcitriol dose was progressively reduced and finally withdrawn.

Serum albumin and other biochemical parameters normalized, bone mineral density significantly increased, and the patient’s clinical conditions progressively improved, with a substantial recovery of autonomy. Serum vitamin D binding protein at the last observation was in the normal range.

Our data suggest that calcifediol might be more efficacious than cholecalciferol for prevention and treatment of vitamin D deficiency in patients treated by malabsorptive bariatric surgery.


More from the publication:

Severe obesity is frequently associated with vitamin D deficiency. The prevalence of vitamin D deficiency in patients who undergo bariatric surgery is dependent on the type of procedure performed. Malabsorptive interventions involve bypassing a large part of the small intestine, so that fat absorption is confined to the more distal sections. Such interventions, despite being associated with a greater weight loss compared with nonmalabsorptive procedures, are even associated with a higher frequency of postoperative vitamin D deficiency, osteomalacia, as well as a high risk of hypocalcemia and fragility fractures. Currently there is no clear consensus on the modality and the doses of vitamin D supplementation in patients previously submitted to bariatric surgery.

Vitamin D deficiency is very common in obese patients and its origin is multifactorial. Sequestration and dilution of vitamin D in the adipose tissue, reduced sun exposure, and the influence of the inflammatory status related to obesity on vitamin D metabolism are advocated as the main determinants of the low vitamin D status among these patients. The current guidelines of the US Endocrine Society recommend for obese subjects a vitamin D intake twofold to threefold higher than for healthy, normal-weight adults.

Bariatric surgery for morbid obesity, particularly malabsorptive procedures such as biliopancreatic diversion, is a well-known cause of severe vitamin D deficiency. Indeed, despite the substantial weight loss following surgery and the use of vitamin D supplements in large doses, data show that hypovitaminosis D persists and sometimes even worsens thereby. The American Association of Clinical Endocrinologists, the Obesity Society, and the American Society for Metabolic and Bariatric Surgery recommend the use of at least 3000 IU daily of cholecalciferol in all patients following bariatric surgery, and the use of larger doses (up to 50,000 IU daily) in patients with severe malabsosorption states.

Several mechanisms may contribute to the low serum 25(OH)D levels in our patient, including malnutrition and its consequences, and malabsorption. Malnutrition may cause impaired liver function, which may be associated with decreased levels of DBP and albumin and, in severe cases, inability to hydroxylase vitamin D. As a matter of fact, at initial observation serum albumin, as well as other serum parameters, revealed an impaired liver function, which improved during the follow-up. 

It is well known that chronic malabsorption of liposoluble substances, such as cholecalciferol, may occur following biliopancreatic diversion. Pharmacokinetic studies in healthy subjects have shown that oral calcifediol supplementation is 2-3 fold more potent in rising serum 25(OH)D concentration than cholecalciferol. Moreover, it is well known that malabsorption of colecalciferol and, to a lower extent, of calcifediol occurs after gastrectomy, in celiac diseases and other small bowel diseases. Based on these considerations, we tested the hypothesis that calcifediol, a more polar, water-soluble vitamin D metabolite that does not require hepatic 25-hydroxylation, might be more effective than cholecalciferol in restoring a normal vitamin D status. As a matter of fact, this treatment resulted in a rapid, progressive, and stable normalization of serum levels of 25(OH)D and biochemical parameters of calcium phosphate metabolism, marked improvement of BMD, and resolution of the clinical symptoms. The large increase of BMD over the 8-month period is likely related to the improvement of vitamin D status and mineralization of unmineralized matrix.

No evidence-based guidelines for vitamin D supplementation after malabsorptive bariatric surgery are available and no clinical trial on the use of calcifediol in this setting has been performed, as yet.

In summary, the use of calcifediol rather than cholecalciferol, and the improvement of the nutritional status, have contributed to the attainment of normal serum levels of 25(OH)D in our patient. Based on our observation, we suggest that calcifediol should be considered as an alternative to cholecalciferol in patients after malabsoptive bariatric surgery, a condition in which lipid malabsorption and impaired liver function are present.