Presentation on theme: "Dr Salah Mansy Consultant Paediatrician Conquest Hospital"— Presentation transcript:
1Dr Salah Mansy Consultant Paediatrician Conquest Hospital Vitamin D metabolismDr Salah MansyConsultant PaediatricianConquest Hospital
2Objectives Understand physiology and pathophysiology of vitamin D Clinical presentations of vit D deficiency/insufficiencyPrevention and treatment of vit D deficiency/insufficiencyThoughts for the future
3Human skeletonProtein matrix: osteoid (90%), osteocalcin and other proteinscalcium phosphate, calcium carbonate, sodium, magnesium, and citrateDynamic
4DefinitionsRickets: only in growing children. Poor mineralisation before fusion of the epiphyses.Osteomalacia: poor mineralization at all ages.All patients with rickets have osteomalacia, but not all patients with osteomalacia have ricketsOsteoporosis: poor mineralization and loss of bone volume
5EpidemiologyA disease of 19th and 20th century in northern Europe and the United StatesResurgence of vitamin D deficiency in UKRecent prevalence data in UK children is lackingAdult study46.6% of white adults are vit D deficient. Am J Clin Nutr 2007;85:860-8One in 8 white, 1 in 4 African Caribbean, 1 in 3 Asian adults are vit D deficient. Ann Clin Biochem 2006; 43:468-73
6Risk factors Exclusively breast fed Multiple short interval pregnanciesVegetarian (or other non-fish eating) dietLack of sunlight exposureCultural influence on dressSedentary indoors lifestyleSunscreen useFear of cancerPigmented skinObesityMalabsorption, short bowl or cholestatic liver diseaseUse of anticonvulsants, rifampicin, cholestyramin, glucocorticoids or highly active antiretroviral treatment (HAART)
7Sources Ultraviolet B sunlight exposure 90% of supply Oily fish Cod liver oilsInfant formula milk (400 IU/L)some breakfast cereals, breads and margarineBreast milk: low (12–60 IU/L)Egg yolk (20 IU)Mushrooms (small quantities)
8Table 2: Recommended Dietary Allowances (RDAs) for Vitamin D  AgeMaleFemalePregnancyLactation0–12 months*400 IU (10 mcg)1–13 years600 IU (15 mcg)14–18 years19–50 years51–70 years>70 years800 IU (20 mcg)* Adequate Intake (AI)
9The metabolic pathway of vitamin D, indicating its conversion to the hormone 1,25(OH)2D3 and to 24,25(OH)2D3. Vitamin D2 (ergosterol), of plant origin, appears to undergo similar metabolic steps.
10Physiology1,25-D:Intestine: marked increase in calcium absorption, less significant increase in phosphorus absorption ( most dietary phosphorus absorption is vitamin D–independent)Bone resorptionPTH secretion suppression (negative feedback loop)Kidney: inhibits its own synthesis and increases the synthesis of inactive metabolites25-D is the standard method for determining a patient's vitamin D status because there is little regulation of the liver hydroxylation step.
11PhysiologyParathyroid hormone (PTH) and vitamin D are the principal regulators of calcium homeostasisCalcitonin and PTH-related peptide (PTHrP) are important primarily in the fetus.Phosphate homeostasis is regulated by the kidneys because intestinal phosphate absorption is nearly complete and renal excretion determines the serum level
12Causes of Rickets Vitamin D deficiency Calcium deficiency Nutritional vitamin D deficiencyCongenital vitamin D deficiencySecondary vitamin D deficiency Malabsorption Increased degradation Decreased liver 25-hydroxylaseVitamin D–dependent rickets type 1Vitamin D–dependent rickets type 2Chronic renal failureCalcium deficiencyIntakeAbsorptionRickets of prematurityPhosphate deficiencyRenal diseasesRenal tubular acidosis
13Diagnosis: HistoryHistory of poor growth, delayed walking, waddling gait, dental caries, pneumonia, and hypocalcaemia symptomsDecrease dietary intakeDecrease skin synthesis: clothing, skin pigmentation, sun screen, seasonMalabsorption due to liver or intestinal diseaseRenal diseaseDrugs e.g. Phenobarbital, phenytoin, aluminium-containing antacids, rifampicin, cholestyramin, glucocorticoids or highly active antiretroviral treatment (HAART)Maternal risk factors for nutritional vitamin D deficiencyFamily history of genetic disorders, leg deformities, difficulties with walking, or unexplained short stature , unexplained sibling death (Cystinosis)
14Clinical features: General Failure to thrive Listlessness Protruding abdomen Muscle weakness (especially proximal) Fractures
15Clinical features: Head Craniotabes Frontal bossing Delayed fontanelle closure Delayed dentition; caries Alopecia (vitamin D–dependent rickets type 2)
16Clinical features: Chest Rachitic rosary Harrison groove Respiratory infections and atelectasis
17Clinical features: Extremities Leg painEnlargement of wrists and ankles Valgus or varus deformities Coxa vara Anterior bowing of the tibia and femur Windswept deformity (combination of valgus deformity of 1 leg with varus deformity of the other leg)
18Clinical features: Back Scoliosis Kyphosis Lordosis
19Clinical features: Hypocalcaemia symptoms Tetany Stridor due to laryngeal spasmSeizures Stebbing C, Mansy S, Kanabar D (2002) The first reported presentation of rickets with metabolic seizures. Hospital Medicine 63:
20(A) a normal child(B) a child with rickets: metaphyseal fraying and cupping of the distal radius and ulna.
23X-rays of the knees in a 7 yr old girl with distal renal tubular acidosis and rickets. A, At initial presentation, there is widening of the growth plate and metaphyseal fraying. B, Dramatic improvement after 4 mo of therapy with alkali.
24a two-year old rickets sufferer, with a marked genu varum, (bowing of the femurs) and decreased bone opacity, suggesting poor bone mineralization
25VDDR: vitamin D–dependent rickets XLH: X-linked hypophosphatemic ricketsADHR: autosomal dominant hypophosphatemic ricketsHHRH: hereditary hypophosphatemic rickets with hypercalicuriaPi: phosphorusRD: relatively decreased (because it should be increased given the concurrent hypophosphatemia
26Consequences of untreated vitamin D deficiency Skeletal complicationsMusculoskeletal pain particularly in adolescence. Arch Dis Child 2011;96:694-6Reduced whole body bone mineral content and bone mass even at 9 years of age. Lancet 2006; 367:36-43Hypertension, hyperglycaemia and metabolic syndrome in adolescents. Pediatrics 2009 Aug 3Type 1 diabetes, multiple sclerosis, malignancy and schizophrenia. Pediatrics 2008;122:Cardiomyopathy (3 deaths in the last 10 years in UK). Heart 2008;94:581-4
27Threshold for intervention for vit D deficiency 25-hydroxyvitamin D level reliably determine vit D status. Nutr Rev 2008;66:S153-64<25 nmol/l = severe deficiency = treat25-50 nmol/l = insufficiency = supplementation51-75 nmol/l = sufficiency = lifestyle advice>250 nmol/l = excess = stop treatmentArch Dis Child 2011,96:
28Prevention of vit D deficiency in UK Huge economic burden and preventive strategies are cost effective. Prog Biophys Mol Biol 2009;99:104-13Healthy Start schemeFree vit D to economically disadvantaged children and young mothersRestrictive qualification criterion for supplementsOnly children under 4Only mothers with a very limited incomeAsylum seekers are not entitledInconsistent dissemination of message regarding supplementation to pregnant womenPoor availability of supplements
29Prevention of vit D deficiency in UK Recommendations for vit D supplementation have not generally been implemented. Update on Vitamin D. Position Statement by the Scientific Advisory Committee on NutricianBetter targeting of health resources to antenatal care, pregnant mothers and at risk childrenExtending the range of food fortified with vit DClarification of the risk associated with UV radiation against the risk of deficient vit D synthesis
30Vit D preparations Ergocalciferol (yeast derived D2) Oily solution 3000 IU/ mlTablets IU or IUTablets calcium 400 mg and vitamin D 400 IUParenteral IU/ mlColecalciferol (fish or lanoline derived D3)Dalvit 400 IU/ 0.6 mlAbidec 400 IU / 0.6mlHealthy Start vitamin drops 300 IU/ 5dropsTablets IUAlfacalcidol (one Alpha Hydroxycolecalciferol)Oral/IV in persistent cases, renal, cholestatic liver disease
31Treatment of deficiency < 6months: 3000 IU daily for 8-12 weeks> 6 months: 6000 IU daily for 8-12 weeks> 1 year: 300,000–600,000 IU orally or intramuscularly as 2–4 doses over 1 dayAdequate dietary calcium and phosphorusDaily vitamin D intake of 400 IU/day
32Treatment of insufficiency < 6 months: IU daily> 6 months IU daily
33Unanswered questionsWould eradication of vitamin D insufficiency in the UK reduce cancer incidence and improve cancer outcome?Does poor vitamin D status cause obesity, or is it a consequence of obesity?Are individuals genetically susceptible to vitamin D insufficiency or toxicity?How much does vitamin D insufficiency contributes to north/south health inequalities?
35Summary points Vitamin D insufficiency is common in UK Vitamin D deficiency presentation is different in different age groupVitamin D deficiency is easy to treatVitamin D is linked to other health problems e.g. cardiovascular, DM type 2 etc.Vitamin D insufficiency is preventable however robust measures are not yet in place