Rickets in Childhood

ABSTRACT

Bone accretion is a two-stage process, with the osteoblasts laying down osteoid, which is then mineralized. Mineralization of osteoid requires vitamin D to be available in its active form (1,25(OH)₂D); in addition, mineralization also requires normal levels of serum calcium, phosphorus, and alkaline phosphate. Deficiencies of any of these will result in defective mineralization of bone, in which the mineral-osteoid ratio is reduced (a qualitative abnormality). In the juvenile skeleton deficiencies particularly affect enchondral ossification at the growth plates, giving the characteristic clinical and radiological features of rickets. The bone may be soft, leading to deformity. In this article the causes of rickets in childhood are reviewed, together with the clinical and radiological features and strategies for prevention and treatment.

Rickets - vitamin D deficiency - XLH

REFERENCES

• 1 Fraser D R, Kodicek E. Unique biosynthesis by kidney of a biologically active vitamin D metabolite.  Nature . 1970;  228 764-766
• 2 Johnson J A, Kumar R. Renal and intestinal calcium transport: roles of vitamin D and vitamin D dependent binding proteins.  Semin Nephrol . 1994;  14 119-128
• 3 Lian J B, Stein G S. Vitamin D regulation of osteoblast growth and differentiation. In: Berdanier CD, Hargrove JL, eds. Nutrition and Gene Expression Boca Raton, FL: CRC Press 1993: 391-429
• 4 Agarwal K S, Mughal M Z, Upadhyay P. The impact of atmospheric pollution on vitamin D status of infants and toddlers in Delhi, India.  Arch Dis Child . 2002;  87 111-113
• 5 Clemens T L, Adams J S, Henderson S L, Holick M F. Increased skin pigmentation reduces the capacity of skin to synthesize vitamin D3.  Lancet . 1982;  1 74-76
• 6 Dunnigan M G, Glekin B M, Henderson J B. Prevention of rickets in Asian children: assessment of the Glasgow campaign.  BMJ . 1985;  291 239-242
• 7 Mughal M Z, Salama H, Greenaway T, Laing I, Mawer E B. Florid rickets associated with prolonged breast feeding without vitamin D supplementation.  BMJ . 1999;  318 39-40
• 8 Specker B L, Tsang R C, Hollis B W. Effect of race and diet on human-milk vitamin D and 25-hydroxyvitamin D.  Am J Dis Child . 1985;  139 1134-1137
• 9 Carvalho N F, Kenney R D, Carrington P H, Hall D E. Severe nutritional deficiencies in toddlers resulting from health food milk alternatives.  Pediatrics . 2001;  107 E46
• 10 Binet A, Kooh S W. Persistence of vitamin D-deficiency rickets in Toronto in the 1990s.  Can J Public Health . 1996;  87 227-230
• 11 Department of Health. Nutrition and Bone Health: With Particular Reference to Calcium and Vitamin D. Report on Health and Social Subjects No 49. London: Her Majesty's Stationary Office; 1998
• 12 Matsuoka L Y, Ide L, Wortsman J, MacLaughlin J A, Holick M F. Sunscreens suppress cutaneous vitamin D3 synthesis.  J Clin Endocrinol Metab . 1987;  64 1165-1168
• 13 Specker B L, Valaris B, Hertzberg V. Sunshine exposure and serum 25-hydroxyvitamin D concentration in exclusively breast-fed infants.  J Pediatr . 1985;  107 372-376
• 14 Prader A, Illig R, Heierli E. Eine besondere form der primaren vitamin D resistenten rachitis mit hypocalcamie und autosomal-dominantem erbgany: die heridtare pseudo-mangel rachitis.  Helv Paediatr Acta . 1961;  16 452-468
• 15 Malloy P J, Pike J W, Feldman D. The vitamin D receptor and the syndrome of hereditary 1,25-dihydroxyvitamin D-resistant rickets.  Endocr Rev . 1999;  20 156-188
• 16 Balsan S, Garabedian M, Larchet M. Long-term nocturnal calcium infusions can cure rickets and promote normal mineralisation in hereditary resistance to 1,25-dihydroxyvitamin D.  J Clin Invest . 1986;  77 1661-1666
• 17 Oginni L M, Worsfold M, Oyelami O A. Etiology of rickets in Nigerian children.  J Pediatr . 1996;  128 692-694
• 18 Pettifor J M, Ross F P, Travers R, Glorieux F H, DeLuca H F. Dietary calcium deficiency: a syndrome associated with bone deformities and elevated serum 1,25-dihydroxyvitamin concentrations.  Metab Bone Dis Rel Res . 1981;  2 301-306
• 19 The HYP Consortium. A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets.  Nature Genetics . 1995;  11 130-136
• 20 Rowe P S. The role of the PHEX gene (PEX) in families with X-linked hypophosphatemic rickets.  Curr Opin Nephrol Hypertens . 1998;  7 367-376
• 21 Walton R J, Bijovet O LM. Nomograms for derivation of renal threshold phosphate concentration.  Lancet . 1975;  II 309-310
• 22 White K E, Evans W E, O'Riordan J L. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23.  Nat Genet . 2000;  26 345-348
• 23 Tieder M, Modai D, Samuel R. Hereditary hypophosphatemic rickets with hypercalciuria.  N Engl J Med . 1985;  312 611-617
• 24 Olivares J L, Ramos F J, Carapeto F J, Bueno M. Epidermal nevus syndrome and hypophosphatemia: description of a patient with central nervous system anomalies and review of the literature.  Eur J Pediatr . 1999;  158 103-107
• 25 Shimada T, Mizutani S, Muto T. Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia.  Proc Natl Acad Sci USA . 2001;  98 6500-6505