Failure of alphacalcidol (1α-hydroxyvitamin D3) in treating nutritional rickets and the biochemical response to ergocalciferol

doi:10.1016/j.jsbmb.2010.03.075

The Journal of Steroid Biochemistry and Molecular Biology

Volume 121, Issues 1–2, July 2010, Pages 273-276

https://doi.org/10.1016/j.jsbmb.2010.03.075 Get rights and content

Abstract

It has been previously documented that alphacalcidol (1α-hydroxyvitamin D₃) is inefficient in healing rickets, partly because it results in a suboptimal rise in 1,25-dihydroxyvitamin D (1,25-(OH)₂D) and partly because it fails to replenish the store of 25-hydroxyvitamin D (25-OHD). However, very few studies have actually documented this outcome. The aim was to document biochemically the response to alphacalcidol and subsequently the change in response to ergocalciferol. This study was conducted at our institution from January 2005 till December 2008. We included all patients referred to our clinic with active rickets after a failed course of alphacalcidol. At baseline the median (IQR) for PTH l7.1 (4.5–35.3) pmol/L, 25-OHD 29.0 (18–66.2) nmol/L, 1,25-(OH)₂D 205 (158.2–311.2) pmol/L and ALP 676 (462.5–1101.7) IU/L. After 3 months treatment with ergocalciferol the concentrations changed markedly with biochemical healing: PTH 4.5 (3.9–7.5), 25-OHD 143.5 (101.5–206.5), 1,25-(OH)₂D 277 (221.0–572.7), ALP 369 (302.2–438.0). The results confirm the biochemical and physiological basis for using ergocalciferol (or cholecalciferol) in nutritional rickets. Unfortunately these forms are not readily available in many geographic areas. This supply problem together with marketing strategies forces physicians to make an incorrect choice of medication. Treatment with ergocalciferol was either with intramuscular stosstherapy or drops for 3 months. The former ensures compliance and is associated with higher 25-OHD and 1,25-(OH)₂D concentrations.

Introduction

Rickets remains prevalent in the Middle East despite a favorable latitude as well as abundant sunshine [1]. It is estimated that rickets in this region may be a hundredfold more common than in its western counterparts [1]. Recent studies have described cohorts of rachitic children within the United Arab Emirates [2], [3]. A number of factors may account for the prevalence of vitamin D deficiency in this region, including the urbanization umbrella [4]. In addition, the Mediterranean region remains the epicenter of many cases of resistant rickets as well, possibly related to genetic predisposition and consanguinity [5], [6]. Alphacalcidol's popularity in this region may in part relate to its well-known use in resistant forms of rickets. This is despite both a recent Cochrane analysis as well as a consensus statement of the American Academy of Pediatricians advocating vitamin D and calcium in the treatment and prevention of nutritional rickets [7], [8].

There have been clear proscriptions against the use of alphacalcidol in nutritional rickets [9], [10]. Firstly, it does not replenish the vitamin D stores and has a short half life, and secondly it fails to cause a supraphysiological increase in the 1,25-(OH)₂D [9], [11], [12]. The evidence documenting the failure of alphacalcidol or other vitamin D analogs is sparse [13]. There is also sparse evidence to the contrary supporting its use, and alphacalcidol has been used successfully in vitro [14] as well as in vivo [4], [15], [16] in nutritional rickets. The continued use of alphacalcidol rests on its market penetration in areas where resistant rickets is frequent, its availability in suspension form which is convenient for children and its availability to physicians. These conditions are not always met with ergocalciferol or cholecalciferol [10].

The aim of this study was to examine the plasma concentration of the major vitamin D metabolites of patients with nutritional rickets who failed to heal with alphacalcidol and their subsequent biochemical response to ergocalciferol. The secondary aim was to compare the biochemical response between ergocalciferol given orally versus stosstherapy.

Section snippets

Methods

This study was a retrospective audit of children with nutritional rickets who were referred to our hospital, Sheikh Khalifa Medical City (SKMC), a tertiary level 500 bed hospital in Abu Dhabi (24°N 28), which is the capital city of United Arab Emirates. The inclusion criteria were patients who met the definition of rickets (radiologically and biochemically) and who were on current therapy with alphacalcidol. All patients were referred to our clinic from peripheral clinics or physicians in

Results

A total of 10 patients participated in this study. Their age range (2.5–97.5th percentile) was 11–39 months. Rapid healing (within 3 months) followed the introduction of therapeutic doses of ergocalciferol (either oral or stosstherapy). All were of Arab lineage except one patient from Southern Africa. Baseline characteristics are shown in Table 1. At the time of referral to our hospital the milk intake in six patients was provided exclusively by breastfeeding, even though all children were on

Discussion

This study demonstrates the biochemical resolution in a group of rachitic patients who failed to improve with alphacalcidol. The patients who were subsequently treated with ergocalciferol all attained biochemical and radiological healing. This is the first case series highlighting the failure of alphacalcidol in nutritional rickets. The mean age of the patients is older than earlier cohorts described in this region [2], [3], reflecting their delayed presentation to our institution.

The peak

Conflict of interest

None.

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^☆: Special issue selected article from the 14th Vitamin D Workshop held at Brugge, Belgium on October 4–8, 2009.

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Failure of alphacalcidol (1α-hydroxyvitamin D3) in treating nutritional rickets and the biochemical response to ergocalciferol☆

Abstract

Introduction

Section snippets

Methods

Results

Discussion

Conflict of interest

J. Pediatr.

The Lancet

J. Pediatr.

J. Nutr.

J. Pediatr.

Lancet

J. Steroid Biochem. Mol. Biol.

Vitamin D deficiency in the Middle East and its health consequences for children and adults

Clin. Rev. Bone Miner. Metab.

Nutritional rickets and z scores for height in the United Arab Emirates: to D or not to D?

Pediatr. Int.

Adolescent rickets in Saudi Arabia: a rich and sunny country

J. Pediatr. Endocrinol. Metab.

Rickets in the Middle East: role of environment and genetic predisposition

J. Clin. Endocrinol. Metab.

Genetic diversity among the Arabs

Commun. Genet.

Failure of alphacalcidol (1α-hydroxyvitamin D₃) in treating nutritional rickets and the biochemical response to ergocalciferol☆