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Flavia Prodam

Divisione di Pediatria, Dipartimento di Scienze della Salute Endocrinologia, Dipartimento di Medicina Traslazionale

Università del Piemonte Orientale «A. Avogadro»

Novara

CONSENSUS VITAMINA D

CARENZA: TRA RANGE ED EPIDEMIOLOGIA

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FISIOLOGIA

 CUT-OFF

 PREVALENZA

 FATTORI DI RISCHIO

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1,25 OH2 vitamina D3:

forma attiva

vitamina D3 / colecalciferolo

Metabolismo della

VITAMINA D

25OH vitamina D3 E’ la principale sorgente

Origine steroidea

(4)

1,25 OH2 vitamina D3:

forma attiva

vitamina D3 / colecalciferolo

Metabolismo della

VITAMINA D

25OH vitamina D3

E’ la principale sorgente Origine

steroidea

(5)

Deficit grave Deficit Insufficienza Sufficienza

Canad Ped Soc - < 10 ng/ml 10-29 ng/ml ≥ 30 ng/ml

LWPES < 5 ng/ml 5-14 ng/ml 15-19 ng/ml ≥ 20 ng/ml

IOM - < 20 ng/ml - ≥ 20 ng/ml

ES - < 20 ng/ml 20-29 ng/ml ≥ 30 ng/ml

SIOMMMS - < 20 ng/ml 20-29 ng/ml ≥ 30 ng/ml

Brit Paed Adol

Bone Group - < 10 ng/ml 10-19 ng/ml ≥ 20 ng/ml

Francia - < 20 ng/ml - ≥ 20 ng/ml

Spagna - < 20 ng/ml - ≥ 20 ng/ml

Svizzera < 10 ng/ml < 20 ng/ml - ≥ 20 ng/ml

ESPGHAN < 10 ng/ml < 20 ng/ml - ≥ 20 ng/ml

Europa Centrale - < 20 ng/ml 20-29 ng/ml ≥ 30 ng/ml

Soc Adol Health

Med - < 20 ng/ml 20-29 ng/ml ≥ 30 ng/ml

Oceania < 5 ng/ml 5-11 ng/ml 12-19 ng/ml ≥ 20 ng/ml

AAP - < 20 ng/ml - ≥ 20 ng/ml

(6)

Lips P et al. Best Pract res Clin Endocrinol Metab 2001 Kuchuk NO et al J Clin Endocrinol Metab 2009

50 nmol/l 20 ng/ml

(7)

BACKGROUND:

Calcium absorption is generally considered to be impaired under conditions of vitamin D deficiency, but the vitamin D status that fully normalizes absorption is not known for humans.

OBJECTIVE:

To quantify calcium absorption at two levels of vitamin D repletion, using pharmacokinetic methods and commercially marketed calcium supplements.

DESIGN:

Two experiments performed in the spring of the year, one year apart. In the first, in which participants were pretreated with 25-hydroxyvitamin D (25OHD), mean serum 25OHD concentration was 86.5

nmol/L; and in the other, with no pretreatment, mean serum concentration was 50.2 nmol/L. Participants received 500 mg oral calcium loads as a part of a standard low calcium breakfast. A low calcium lunch was provided at mid-day. Blood was obtained fasting and at frequent intervals for 10 to 12 hours thereafter.

METHODS:

Relative calcium absorption at the two 25OHD concentrations was estimated from the area under the curve (AUC) for the load-induced increment in serum total calcium.

RESULTS:

AUC(9) (+/- SEM), was 3.63 mg hr/dL +/- 0.234 in participants pretreated with 25OHD and 2.20 +/- 0.240 in those not pretreated (P < 0.001). In brief, absorption was 65% higher at serum 25OHD levels averaging 86.5 nmol/L than at levels averaging 50 nmol/L (both values within the nominal reference range for this analyte).

CONCLUSIONS:

Despite the fact that the mean serum 25OHD level in the experiment without supplementation was within the current reference ranges,

calcium absorptive performance at 50 nmol/L was significantly reduced relative to that at a mean

25OHD level of 86 nmol/L.

Thus, individuals with serum 25-hydroxyvitamin D levels at the low end of the current reference ranges may not be getting the full benefit from their calcium intake.

We conclude that the lower end of the current reference range is set too low.

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IOM e ES

Nessuna evidenza per 25OHD >30 ng/ml 2.5% dei pazienti con 25OHD < 20 ng/ml

Studi bioptici sulle fratture di femore: 0-37%

Priemel M et al. JBMR 2009 Lips P. Endocr Rev 2001

(9)

Chapuy et al, Osteoporos Int, 1997

40 ng/mL

JAMA Pediatrics, 2014

< 6 anni di età

(10)

Hill KM et al J Nutr 2010

Stadio puberale Età

Sesso Etnia

Località di valutazione (dieta, introito di calcio, geografia)

(11)

Abrams SA et al JCEM 2005 Abrams SA et al JCEM 2009

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25-OH-D, ng/ml

P T H ,p g /m l

Vierucci F, et al Eur J Ped 2013

Nessun caso di iperPTH II nei soggetti

con

25-OH-D >30 ng/ml

(14)

We propose > 30 ng/ml as “sufficient”, 20-30 ng/ml as “insufficient”

and < 20 ng/ml as “deficient” 25-OH-D levels .

Eur J Pediatr 2015

(15)

Consensus VD SIPPS 2015

(16)

Saggese G et al. Eur J Ped 2015 Consensus VD SIPPS 2015

(17)

Consensus VD SIPPS 2015

54,8%

67,5%

55,6%

77,6%

75,6-97,9%

71,7-81,1%

79,5-82,8%

88,7%

75%

74,8-89,7%

(18)

Consensus VD SIPPS 2015

Stagione del prelievo, esposizione solare, uso di filtri solari Età

Etnia BMI

Circonferenza vita, circonferenza fianchi

Età gestazionale, peso alla nascita, stagione di nascita Profilassi materna durante la gravidanza

(19)

«Vitamin D winter»

Holick, New Engl J Med, 2007.

Fattori geografici/ambientali

Latitudine: minore è la latitudine, maggiore è la sintesi di vitamina D

Stagione: minima o nulla sintesi di vitamina D nel periodo invernale

Ora del giorno: massima sintesi di vitamina D intorno alle ore 12.00

Altitudine: maggiore è l’altitudine, maggiore è la sintesi cutanea di vitamina D

Inquinamento atmosferico

(20)
(21)

Fattori individuali

Colore della pelle: gli individui di pelle scura necessitano di un tempo 5-10 volte più lungo di esposizione solare rispetto agli

individui di pelle chiara per raggiungere gli stessi valori di vitamina D

Superficie corporea esposta al sole

Filtri solari: SPF 8 ↓ sintesi del 92.5%, SPF 15 ↓ sintesi del 99%

Età: ↓ 7-deidrocolesterolo cutaneo

BMI: Tessuto adiposo = sede corporea principale di deposito della vitamina D → ridotta disponibilità di vitamina D nei soggetti obesi.

Holick, New Engl J Med, 2007.

(22)

Nel giovane adulto è stato calcolato che in primavera,

estate ed autunno è sufficiente l’esposizione delle braccia e delle gambe, due volte alla settimana, per 5-15 minuti, tra le ore 10:00 e le 15:00, per ottenere valori di 25(OH)D in grado di prevenire un deficit di vitamina D nei fototipi cutanei II e III.

Holick, Am J Clin Nutr, 2004.

(23)

• Pediatricians should inform parents on the risks related to UVR exposition.

• Children’s outdoor activities should be planned to minimize peak- intensity midday sun (10AM to 4PM). Infants younger than 6 months should be kept out of direct sunlight.

• Shade, clothing and broad rimmed hats are the best sun protection measures for infants. Sunscreens should be applied to areas of the skin not protected by clothing (SPF > 15, applied every 2 hrs).

Pediatrics 2012

(24)

In northern USA (45°N)

minimum recommended daily dose of vitamin D3 (600 IU/day) is made by skin type II, III, and IV children only during the summer

optimal dose of ≥ 1,200 IU/day is not made during any season, regardless of skin type, except by a small subset of skin type II children during the summer

Everyday outdoor exposure for children with skin type III and skin type IV rarely provides their minimum vitamin D3 needs (~ 600 IU/day), and children with skin type V may never meet their

minimum daily vitamin D needs

Godar DE et al. Environmental Health Perspectives 2012 24

(25)

Cadario F et al PlosOne 2015

(26)

Vierucci F, et al Eur J Ped 2013

(27)

Holmund S et al, PlosOne 2013

(28)

Vierucci F, et al It J Pediatr 2014

(29)

Bellone S, et al J Endocrinol Invest 2014

Pacifico L, et al Eur J Endocrinol 2011

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Gianni Bona Simonetta Bellone Francesco Cadario

Antonella Petri Valentina Agarla Matteo Castagno

Cristina Fiorito Giulia Genoni Enza Giglione Agostina Marolda

Alice Monzani Roberta Ricotti

Silvia Savastio Sara Zanetta

Gianluca Aimaretti Paolo Marzullo Loredana Pagano

Grazia Mauri Chantal Ponziani

Arianna Busti Marina Caputo

Chiara Mele Maria Teresa Samà

Marco Zavattaro

Endocrinologia, Università del Piemonte

Orientale, Novara, Italia Divisione di Pediatria

Università del Piemonte Orientale,

Novara, Italia

Gillian Walker Stefania Moia Marilisa De Feudis

Marta Roccio

Lab. di Pediatria

Riferimenti

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