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This version published online on February 19, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-1413
A more recent version of this article appeared on May 1, 2008
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Submitted on June 25, 2007
Accepted on February 12, 2008

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

Giampiero I Baroncelli*, Abdullah Bereket, Mohamed El Kholy, Laura Audì, Yasar Cesur, Behzat Ozkan, Mona Rashad, Monica Fernández-Cancio, Yoseph Weisman, Giuseppe Saggese, and Ze'ev Hochberg

Department of Pediatrics, University of Pisa, Pisa, Italy (G.I.B., G.S); Department of Pediatrics, Division of Pediatric Endocrinology, Marmara University School of Medicine, Istanbul, Turkey (A.B.); Department of Pediatrics, Ain Shams University, Cairo, Egypt (M.E., M.R.); Pediatric Endocrinology Research Unit, Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain (L.A., M.F.-C.); Department of Pediatrics, Division of Pediatric Endocrinology, Yuzuncu Yil University, School of Medicine, Van, Turkey (Y.C.); Department of Pediatrics, Division of Pediatric Endocrinology, Ataturk University, School of Medicine, Erzurum, Turkey (B.O.); Dana Children's Hospital and Tel Aviv University, Israel (Y.W.); and Meyer Children's Hospital and Technion - Israel Institute of Technology, Haifa, Israel (Z.H.)

* To whom correspondence should be addressed. E-mail: g.baroncelli{at}med.unipi.it.

Context: The Middle East has a high incidence of rickets and it is also common in Europe-dwelling children of Middle Eastern origin.

Obiective: To explore the mechanisms leading to rickets in children of the Middle East.

Design and Setting: We conducted a prospective study in 98 rachitic and 50 controls (age 6 mo – 4 yr) from university and community outpatient hospitals in Egypt and Turkey.

Main outcome measures: We collected epidemiological, maternal, nutritional, radiographic, and biochemical parameters, markers of bone turnover, and vitamin D receptor gene polymorphisms.

Results: Epidemiological factors had a key role in pursue of rickets; Egyptian and Turkish patients had lower (P < 0.01) dietary calcium intake than controls and the recommended dietary intakes (RDI), and serum 25-hydroxyvitamin D [25(OH)D] levels were reduced in patients, the difference with controls being significant (P < 0.001) only in Turkey, although rickets was more severe in Egypt as determined by the X-ray score (P < 0.05). In Turkey, the F VDR allele frequency was significantly (P < 0.05) increased in patients. The BB VDR genotype was associated with lower serum 25(OH)D levels in both patients and controls, and with severity of rickets.

Conclusions: In Turkey most patients had vitamin D deficiency, whereas in Egypt they had mostly calcium insufficiency combined with vitamin D deficiency. In this environ, VDR genotypes may predispose to rickets by increased frequency of the F allele. The unique environs and genetic predisposition have to be accounted for in the design of preventive measures, rather than using European or American RDI for calcium and vitamin D.


Key words: Calcium insufficiency • suboptimal calcium intake • vitamin D deficiency • vitamin D receptor polymorphisms







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