DR SREEKRISHNA R

PG RESIDENT IN PAEDIATRICS

MGM MEDICAL COLLEGE INDORE

DISEASE OF GROWING BONE DUE TO

UNMINERALIZED MATRIX AT THE

GROWTH PLATES

AND OCCURS IN CHILDREN ONLY

BEFORE FUSION OF EPIPHYSES

CALCIUM AND PHOSPHATE

Constitutes the crystalline component of bone

Deficiency leads to disease ( Rickets and/or osteomalacia)

RICKETS:

Deficient mineralization at growth plate

OSTEOMALACIA:

impaired mineralization of the bone matrix.

Open plates: Occur in Osteomalacia and rickets.

Closed plates: Happens in osteomalacia only!

What is Rickets ?

Impaired Apoptosis of Terminally Differentiated Chondrocytes in the Growth Plate

Responsible for Clinical & Radiological Signs of Rickets

What is Rickets ?

Disease of the growing child

Impaired mineralisation of the growth plate & osteoid

Low serum phosphate is fundamental to pathogenesis of rickets

Normal Growth Plate Rachitic Growth Plate

Apoptosis of

Hypertrophic

Chondrocytes

caused by

PHOSPHATE ions

HYPOPHOSPHATEMIA

No Apoptosis of

Hypertrophic

Chondrocytes

VITAMIN D DISORDERS(most

common)

CALCIUM DEFICIENCY

PHOSPHORUS DEFICIENCY

RENAL LOSSES

VITAMIN D DISORDERS CALCIUM DEFICIENCY

Nutritional

Secondary Malabsorption

Vitamin D–dependent rickets type 1

Vitamin D–dependent rickets type 2

Chronic renal failure

LOW INTAKE

Diet

Premature infants (rickets of

prematurity

MALABSORPTION

Primary disease

Dietary inhibitors of calcium

absorption

PHOSPHORUS DEFICIENCY RENAL LOSSES

INADEQUATE INTAKE

Premature infants

Aluminum-containing

antacids

X-linked dom hypophosphatemic

Autosomal dominant

hypophosphatemic

Autosomal recessive

hypophosphatemic

Hereditary hypophosphatemic

rickets with hypercalciuria

Overproduction of phosphatonin

Fanconi syndrome

Dent disease

Distal renal tubular acidosis

GENERAL

- Failure to thrive

- Listlessness

- Protruding abdomen

- Muscle weakness (especially proximal)

- Fractures

- Craniotabes

- Frontal bossing

- Delayed fontanel closure

- Delayed dentition; caries

- Craniosynostosis

CHEST

- Rachitic rosary

- Harrison groove

- Respiratory infections and atelectasis

Tetany

Seizures

Stridor due to laryngeal spasm

Frontal bossing Rachitic rosary

Knock knee deformity

(genu valgum) Bowleg deformity

(genu varum)

A teenage male with rickets.

Note deformities of legs (bow legs)

and compromised height.

Fraying

Cupping

Widening of the distal end of the metaphysis

Rachitic rosary

Coarse trabeculation of the diaphysis

Generalized rarefaction

MOST COMMON CAUSE OF RICKETS

PEOPLE AT RISK

Children age 6 to 24 months old

Dark skinned people

Premature babies

Exclusively breast-fed babies

Source: -Fish, liver and oil,

- Human milk (30-40 IU/L)

- Exposure to sun light

Vitamin D requirement:

< 1 yr- 400IU/day

>1 yr- 600IU/day

PTH

High secretion

P in urine Decalcification of old bone

P in blood Ca in blood normal or low

Ca, P product

Rickets

LABORATORY FINDINGS Hypocalcemia or nornmal calcium

Hypophosphatemia

“ 25-D levels low” Variation in 1,25-D levels (low, normal, or high)

1,25-D is only low when there is severe vitamin D deficiency.

Metabolic acidosis secondary to PTH-induced renal bicarbonate wasting.

Generalized aminoaciduria.

HISTORY OF POOR VITAMIN D INTAKE.

RISK FACTORS FOR DECREASED CUTANEOUS SYNTHESIS

RADIOGRAPHIC CHANGES CONSISTENT WITH RICKETS

TYPICAL LABORATORY FINDINGS.

A NORMAL PTH LEVEL ALMOST NEVER OCCURS WITH VITAMIN D DEFICIENCY AND

SUGGESTS A PRIMARY PHOSPHATE DISORDER.

TREATMENT 2 strategies

STOSS THERAPY,(300,000-600,000 IU of vitamin D

are administered orally or intramuscularly as 2-4

doses over 1 day)

DAILY THERAPY

2,000-5,000 IU/day over 4-6 wk

EITHER STRATEGY SHOULD BE FOLLOWED BY DAILY VITAMIN D

INTAKE OF 400 IU/DAY IF <1 YR OLD OR 600 IU/DAY IF >1 YR

ENSURE THAT CHILDREN RECEIVE ADEQUATE DIETARY CALCIUM

AND PHOSPHORUS

Rare occurs in severe maternal vitamin D

deficiency during pregnancy

Risk factor in mother

POOR DIETARY INTAKE OF VITAMIN D.

LACK OF ADEQUATE SUN EXPOSURE.

CLOSELY SPACED PREGNANCIES.

CLINICAL FEATURES

symptomatic hypocalcemia, tetany

intrauterine growth retardation

decreased bone ossification

classic rachitic changes.

TREATMENT

vitamin D supplementation

adequate intake of calcium and phosphorus

PREVENTION

Use of prenatal vitamins containing vitamin D

ETIOLOGY INADEQUATE ABSORPTION

DECREASED HYDROXYLATION IN THE LIVER

INCREASED DEGRADATION

Occurs Secondary to liver and GI diseases

CHOLESTATIC LIVER DISEASE,

DEFECTS IN BILE ACID METABOLISM

CYSTIC FIBROSIS

PANCREATIC DYSFUNCTION,

CELIAC DISEASE

CROHN DISEASE.

INTESTINAL LYMPHANGIECTASIA AND AFTER INTESTINAL RESECTION.

=Degradation of vitamin D

Phenobarbitone and phenytoin cytochrome P450

inducers

TREATMENT High doses of vitamin D. 50mcg/day or 5-

7mcg/kg/day.

Alternatively, may be treated with 1,25-D

Stoss therapy

Is an autosomal recessive disorder

Etiology

Due to mutations in the gene encoding renal 1α-

hydroxylase

Prevents conversion of 25-D into 1,25-D

Presentation

during the 1st 2 yr of life

classic features of rickets

symptomatic hypocalcemia

LAB FINDINGS Normal levels of 25-D

low levels of 1,25-D

high PTH

low serum phosphorus levels

Treatment long-term 1,25-D (calcitriol) with 0.25-2 g/day.

ensure adequate intake of calcium.

Monitor periodic urinary calcium excretion, (<4 mg/kg/day).

Excessive dosing can cause hypercalciuria & nephrocalcinosis.

Is an autosomal recessive disorder

Etiology

mutations in the gene encoding the vitamin D

receptor

prevents a normal physiologic response to 1,25-D

Most cases present during infancy.

50-70% of children have alopecia.

less commonly Epidermal cysts is seen

LAB FINDINGS

1,25-D are extremely elevated

TREATMENT HIGH DOSES OF VITAMIN D2, 25-D OR 1,25-D

(2 G/DAY- AS HIGH AS 50-60 G/DAY.)

CALCIUM 1,000-3,000 MG/DAY

3-6 MO TRIAL OF HIGH-DOSE VITAMIN D AND ORAL

CALCIUM

INTRAVENOUS CALCIUM WHO DO NOT RESPOND TO ORAL.

There is decreased activity of 1α-hydroxylase in the kidney.

leading to diminished production of 1,25-d

patients have “hyperphosphatemia” due to decreased renal excretion.

TREATMENT

therapy with calcitriol

leads adequate absorption of calcium

directly suppresses the parathyroid gland.

ETIOLOGY

Rickets occurs secondary to inadequate dietary calcium <200 mg/day.

Children who receive parentral nutrition without adequate calcium

Early weaning from milk and milk produts

Malabsorption of calcium can occur in CELIAC DISEASE,

INTESTINAL ABETALIPOPROTEINEMIA,

SMALL BOWEL RESECTION

Diagnosis Lab findings include increased levels of alkaline

phosphatase, PTH, and 1,25-D

Calcium levels may be normal or low

Decreased urinary excretion of calcium

Low phosphorus levels due to renal wasting of

phosphate

In coexisting nutritional vitamin D deficiency, have

low 25-D levels

provide adequate calcium, dietary supplement

(doses of 700 [1-3 yr age]m/k/d

1000 (4-8)

1300(>8)

vitamin d supplementation

discouraging early cessation of breast-feeding.

increasing dietary sources of calcium.

RICKETS IN VERY LOW BIRTHWEIGHT INFANTS

PATHOGENESIS 80% TRANSFER OF CALCIUM AND PHOSPHORUS

OCCURS DURING THE 3RD TRIMESTER.

PREMATURE BIRTH INTERRUPTS THIS PROCESS.

MOST CASES OF RICKETS OCCUR IN INFANTS WITH A

BIRTHWEIGHT <1,000G

RISK FACTORS LOW BIRTHWEIGHT & YOUNGER GESTATIONAL AGE.

UNSUPPLEMENTED BREAST MILK AND STANDARD INFANT

FORMULA DO NOT CONTAIN ENOUGH CALCIUM AND

PHOSPHORUS

CHOLESTATIC JAUNDICE IN PRETERM

PROLONGED USE OF PARENTERAL NUTRITION

MEDICATIONS SUCH AS DIURETICS AND CORTICOSTEROIDS

OCCURS 1-4 MO AFTER BIRTH

INFANTS CAN HAVE NONTRAUMATIC FRACTURES OF

LEGS, ARMS, AND RIBS.

RACHITIC RESPIRATORY DISTRESS USUALLY

DEVELOPS >5 WK AFTER BIRTH

FRONTAL BOSSING, RACHITIC ROSARY,

CRANIOTABES, AND WIDENED WRISTS AND ANKLES.

LONG TERM EFFECT IS ENAMEL HYPOPLASIA

Serum phosphorus level is low

Normal levels of 25-D

1,25-D are high

Hypercalciuria indicates that phosphorus is the limiting nutrient for bone mineralization

Alkaline phosphatase levels are often elevated

WEEKLY MEASUREMENTS OF CALCIUM, PHOSPHORUS, AND ALKALINE PHOSPHATASE.

X-RAY FOR RICKETS AT 6-8 WK OF AGE

PREVENTION ADEQUATE AMOUNTS OF CALCIUM, PHOSPHORUS, AND

VITAMIN D

EARLY TRANSITION TO ENTERAL FEEDINGS

HUMAN MILK FORTIFIED WITH CALCIUM AND PHOSPHORUS OR PRETERM INFANT FORMULA, WITH HIGH CONCENTRATIONS

PHOSPHORUS DEFICIENCY RENAL LOSSES

INADEQUATE INTAKE

Premature infants

Aluminum-containing

antacids

X-linked dom hypophosphatemic

Autosomal dominant

hypophosphatemic

Autosomal recessive

hypophosphatemic

Hereditary hypophosphatemic

rickets with hypercalciuria

Overproduction of phosphatonin

Fanconi syndrome

Dent disease

Distal renal tubular acidosis

PHOSPHATONIN HUMORAL MEDIATOR THAT DECREASES RENAL

TUBULAR REABSORPTION OF PHOSPHATE

DECREASES THE ACTIVITY OF RENAL 1Α-

HYDROXYLASE

INCREASED LEVELS OF PHOSPHATONIN CAUSE

MANY OF THE PHOSPHATE-WASTING DISEASES

X LINKED DOM

HYPOPHOSH

RICKETS

AUTSO

DOM

HYPOPH

OS

RICKETS

AUTO

RECESSI

HYPOPH

OS

RICKETS

HEREDI HYPOPHOS RICK

WITH HYPER CALCIURIA

MOST COMMON GENET

DISORDER CAUSING

HYPOPHOSPHA

LESS

COMMON

RARE RARE AUTO DOM

PHEX GENE MUTATION FG 23 GENE

MUTA

MUTA

DENTIN MATRIX

PROTEIN

MUTATION IN SOD –PHOS CO

TRANSPORTER IN PROX TUBULE

PREDOM LOWER EXTREMITY

INVOLVEMENT

MAY BE SHORT STATURE ONLY

RACHITIC LEG ABNORM

BONE PAIN,MUSLE WEAKNESS

DISPROPOR DECREASE IN LENGTH OF

LOWER EXTRE

FAMILY HISTORY OF RENAL STONE

WITH HYPERCALCIURIA

HYPO PHOSP

INCREASED ALP

LOW TO NOR 1 25

NOR PTH

SIMILAR TO

XLP

SIMILAR TO

XLP

HYPO PHOS

INCRE ALP

INCREASED 1,25 D

LOW PTH

PHOSP (1-3 G/D) DIV DOSES

1 ,25 D

SIMILAR IN

XLP

SIMILAR IN XLP PHOSP ()1-2.5 G) DIVIDED DOSES

Tumor-induced osteomalacia

McCune-Albright syndrome.

Epidermal nevus syndrome.

Neurofibromatosis

Above all produses phospate deficency can

lead to rickets. But more common in adults

IT IS SECONDARY TO GENERALIZED DYSFUNCTION OF THE PROXIMAL RENAL TUBULE.

THERE IS LOSS OF PHOSPHATE, AMINO ACIDS, BICARBONATE, GLUCOSE, URATE.

THERE IS HYPOPHOSPHATEMIA DUE TO PHOSPHATE LOSSES, LEADS TO RICKETS

PROXIMAL RENAL TUBULAR ACIDOSIS DUE TO BICARBONATE LOSSES LEADS TO BONE DISSOLUTION

FTT IS A CONSEQUENCE OF BOTH RICKETS AND RTA.

o USUALLY MANIFESTS WITH FAILURE TO THRIVE

METABOLIC ACIDOSIS WITH AN INABILITY TO ACIDIFY

URINE

HYPERCALCIURIA AND NEPHROCALCINOSIS ARE TYPICALLY

PRESENT..

RICKETS IS VARIABLE, AND IT RESPONDS TO ALKALI

THERAPY

DISORDER Ca Pi PTH 25-

OHD

1,25-

(OH)2D

ALK

PHOS

URINE

Ca

URINE

Pi

Vitamin D

deficiency

N,

↓

↓ ↑ ↓ ↓, N, ↑ ↑ ↓ ↑

VDDR, type 1 N,

↓

↓ ↑ N ↓ ↑ ↓ ↑

VDDR, type 2 N,

↓

↓ ↑ N ↑↑ ↑ ↓ ↑

Chronic Renal

Failure

N,

↓

↑ ↑ N ↓ ↑ N, ↓ ↓

Dietary Pi

deficiency

N ↓ N, ↓ N ↑ ↑ ↑ ↓

XLH N ↓ N N RD ↑ ↓ ↑

ADHR N ↓ N N RD ↑ ↓ ↑

HHRH N ↓ N, ↓ N RD ↑ ↑ ↑

Tumor-induced

rickets

N ↓ N N RD ↑ ↓ ↑

Fanconi

syndrome

N ↓ N N RD or ↑ ↑ ↓ or ↑ ↑

Dietary Ca

deficiency

N,

↓

↓ ↑ N ↑ ↑ ↓ ↑

DIET HISTORY- VIT D DEF

CUTANEOUS SUN EXPOSURE:CULTURE,CLOTHING

MATERNAL RISK FACTOR FOR VIT D

MALABSORPTION:GI SYMPT, LIVER DISEASE

CHILD ON ANTICONVULSANT,AL ANTACID

RENAL DISEASE:CRF,POLYURIA-FANCONI

FAMILY HISTORY OF SHORT STATURE,BONE DISEASE,UNEXPLAINED DEATH OF SIBLING(CYSTINOSIS, FANCONI)

ALOPECIA-VIT D DEPENDENT RICKETS TYPE 2

Rickets

Heals Does not heal

Nutritional rickets Refractory rickets

s.Urea,Creat-High

Azotemic rickets

sUrea,Creat-Normal

PseudoHypopathyroidism

Acidosis

RTA

- Type 1

- Type 2

VitaminD resistant

Hypophosphatemic

- XLH

- ADHR

- ARHR

- HHR Hypercalciuria

Vitamin D disorder

-VitD malabsorption

- Liver disease

- Vit.DDR Type I

- Vit.DDR Type II

Stoss therapy

Xray,Ca,Po4,Alk.P,U

rea, Creat,ABG

Phosp N or Low Phosp- High

Chronic Renal Failure

Renal osteodystrophy

Non Azotemic rickets

Hypocalcemia Normocalcemia

Dietary Calcium deficiency

Aminoaciduria

Fanconi

Syndrome

MANY CASES OF RICKETS ARE NUTRITIONAL AND RESPOND TO VITAMIN D

THERAPY

.

A SINGLE DOSE OF 6 LAKH IU INTRAMUSCULAR (IM) IS THE MOST PRACTICAL WAY

TO TREAT NUTRITIONAL RICKETS ALONG WITH CALCIUM.

IN CASE OF NONRESPONSE, THE RENAL CAUSES SHOULD BE CONSIDERED.

A NORMAL SERUM CREATININE EXCLUDES RENAL OSTEODYSTROPHY.

THE PRESENCE OF ACIDOSIS POINTS TOWARDS RTA.

HYPERCALCIURIA OCCURS DUE TO BONE RESORPTION AS A RESULT OF CHRONIC

ACIDOSIS AND DECREASED RENAL TUBULAR REABSORPTION OF CALCIUM.

FURTHER DIFFERENTIATION BETWEEN TYPES 1 AND 2 IS BY URINE PH.

THE ABSENCE OF ACIDOSIS INDICATES EITHER HYPOPHOSPHATEMIC RICKETS OR

VDDR.

HYPOPHOSPHATEMIC RICKETS SHOWS RENAL PHOSPHATE WASTING.

VDDR CAN BE IDENTIFIED BY MEASURING SERUM VITAMIN D.

References

Nelson textbook of pediatrics

Bagga textbook pedia Nephrology

Sperling pediatrics Endocrinology.