effect. Neuromuscular disorders, such as muscular dystrophy, may reduce bone mass by limiting a child’s activity and thus decreasing muscle loading forces that strengthen bone. Chronic inflammatory diseases, such as Crohn disease or juvenile idiopathic arthritis, may accelerate bone resorption due to inflammatory cytokines produced in the disease process. Childhood malignancy, particularly leukemia, can compromise bone health. And endocrine disorders such as diabetes mellitus, hyperthyroidism, primary hyperparathyroidism and glucocorticoid excess are associated with reduced bone mass (see figure 1).


Deficiencies of calcium and vitamin D


may be especially relevant to children in Middle Eastern populations. The primary source of vitamin D is the skin. High-energy UVB light, principally


from sunlight, penetrates the epidermis and photochemically cleaves 7-dehydrocholesterol to produce previtamin D3


. Previtamin D3 then undergoes a


thermally induced isomerization to vitamin D3


continues for many hours. (cholecalciferol) that takes two to three


days to reach completion. Therefore, after a single sunlight exposure, cutaneous synthesis of vitamin D3


It is not possible to generate too much vitamin D3 in the skin, as prolonged


sunlight exposure activates a mechanism that converts excess previtamin D3


and vitamin D3 to biologically inert products.


Vitamin D can also be obtained from the diet, from plant sources as ergocalciferol (vitamin D2


), and from animal sources as 38 www.lifesciencesmagazines.com


cholecalciferol (vitamin D3


). Dietary and


endogenously-produced vitamin D can be stored in fat for later use. To become metabolically active, vitamin D must undergo two biochemical modifications. Vitamin D first undergoes 25-hydroxylation in the liver by the cytochrome p450 enzyme CYP2R1 to form 25(OH)D. Subsequently, 25(OH)D3


is directed to


the kidney where it is either converted to 24,25-dihydroxyvitamin D3


(an inactive


derivative) or to 1,25-dihydroxyvitamin D3 (calcitriol, the active hormone). Activation


to calcitriol requires hydroxylation by a 1α-hydroxylase enzyme (CYP27B1) that is tightly regulated and is the rate-limiting step in the bioactivation of vitamin D: parathyroid hormone increases production of calcitriol by stimulating CYP27B1 activity while FGF23 decreases CYP27B1 activity. Dietary intake of vitamin D is


inadequate in many parts of the world, and therefore daily requirements for vitamin D depend upon cutaneous synthesis and sunlight exposure. Dark skin, use of UV sunblockers or customs of dress that largely cover the skin can reduce cutaneous absorption of UVB light and thereby prevent adequate synthesis of vitamin D to meet daily or long-term requirements.


«Later in life the loss of bone tissue exceeds the rate of bone replacement»


RETHINKING BONE STRENGTH Traditionally, in considering bone strength, clinicians have focused on bone density, reflected in bone quantity and mineralization. The NIH Consensus Conference added an emphasis on bone quality, comprising bone geometry, micro-architecture, turnover, micro- damage repair and mineralization. Among children and adolescents, clinicians need to pay special attention to athletes and dancers who may compromise bone quality by overtraining, by sustaining injuries in contact sports, or by consuming inappropriate diets that result in calorie deprivation. Another factor affecting bone quality is chronic undernourishment due to poverty and socio-economic factors. A history of recurrent fractures,


particularly low-impact or atraumatic fractures, should alert the clinician to carefully assess a child’s bone density (see figure 2).


QUANTITATIVE BONE ASSESSMENT Early attempts to measure bone density utilized plain skeletal radiography. However, bone demineralization becomes visibly apparent only after bone density loss exceeds 40%, making this test too insensitive for clinical use. More quantitative imaging technologies for assessing bone health have been developed, and currently used modalities include metacarpal morphometry, quantitative ultrasound, quantitative computed tomography (QCT),


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