PAEDIATRICS — CLINICAL NOTES

Nutritional Rickets &

Vitamin D De!ciency
Comprehensive notes for MBBS & MD Paediatrics) examinations

Ghai Essential Paediatrics 9e Nelson Textbook 21e IAP Guidelines 2023

CONTENTS

01 Definition & Introduction 02 Vitamin D Metabolism

03 Aetiology & Risk Factors 04 Classification
05 Pathophysiology 06 Clinical Features
07 Investigations & Staging 08 Radiological Features
09 Differential Diagnosis 10 Treatment
11 Prevention & IAP Guidelines 12 Complications & Prognosis
13 High-Yield Points

01
De!nition & Introduction

DEFINITION

Nutritional Rickets is a disorder of impaired bone mineralisation in growing

children due to deficiency of Vitamin D, calcium, or phosphorus, leading to failure
of mineralisation of osteoid matrix at the growth plate.

VITAMIN D DEFICIENCY — DEFINITION IAP 2023

 Deficiency: Serum 25OH Vitamin D < 12 ng/mL 30 nmol/L
Insufficiency: 1220 ng/mL 3050 nmol/L
Sufficiency: > 20 ng/mL 50 nmol/L
Toxicity: > 150 ng/mL 375 nmol/L

Epidemiology: Remains a major public health problem in South Asia, Middle East, and
Africa. In India, prevalence of Vitamin D deficiency is 5090% in various population
groups. Ghai 9e

KEY TERMINOLOGY

Rickets — affects growing children (open growth plates); disorder at

epiphysis/growth plate
Osteomalacia — same process in adults (fused growth plates); generalised
bone softening
Craniotabes — earliest sign; ping-pong ball sensation on skull

Rachitic rosary — beading at costochondral junctions

02
Vitamin D Metabolism

METABOLIC PATHWAY EXAM ESSENTIAL

 Skin: UVB  7-dehydrocholesterol → Cholecalciferol Vit D₃ (or dietary

Ergocalciferol D₂)
 Liver: 25-hydroxylase → 25OH D₃ Calcidiol) — storage & measurement form

 Kidney: 1α-hydroxylase → 1,25OH₂D₃ Calcitriol) — active form

 Target organs: Intestine (↑Ca absorption), Bone (mineralisation), Kidney (↑Ca
& P reabsorption)

Regulation
 Factor Effect on 1α- Net Result
hydroxylase

↓ Serum Ca²⁺ → ↑ PTH ↑ Stimulates ↑ Calcitriol → ↑ Ca

absorption

↓ Serum Phosphorus → ↓ ↑ Stimulates ↑ Calcitriol

FGF23

↑ FGF23 (from osteocytes) ↓ Inhibits ↓ Calcitriol, ↑ urinary P

loss

↑ Calcitriol (feedback) ↓ Inhibits Self-regulation

Growth hormone, Prolactin ↑ Stimulates ↑ Calcitriol

(pregnancy/lactation)

DAILY REQUIREMENTS IAP 2023

Infants 012 months): 400 IU/day

Children 1 year to adults: 600 IU/day
Pregnancy & lactation: 600800 IU/day
Safe upper limit children: 20004000 IU/day

03
Aetiology & Risk Factors

VITAMIN D DEFICIENCY CAUSES CALCIUM-DEFICIENCY CAUSES

Inadequate sun exposure (indoor Low dietary calcium (cereal-

lifestyle, dark skin, cloudy based diets, low dairy)
regions) Malabsorption syndromes
Exclusively breastfed infants High phytate diet (binds Ca)
(breast milk Vit D 25 IU/L —
Calcium-deficiency rickets is
inadequate)
distinct — normal Vit D levels
Dietary deficiency (vegetarian
Common in Nigeria, South
diet, no fish/eggs)
 Malabsorption (celiac, Crohn's, Africa, Bangladesh
cystic fibrosis, cholestatic liver Normal 25OH D but ↑ PTH, ↓
disease) Ca, low dietary Ca intake
Drugs: Phenytoin,
phenobarbitone (↑ catabolism of
Vit D
Prematurity (inadequate stores)

Maternal Vit D deficiency

(congenital/late neonatal rickets)

High-Risk Groups

Risk Group Reason

Exclusively breastfed infants Breast milk insufficient in Vit D

Dark-skinned children ↓ UVB absorption, ↓ Vit D synthesis

Premature infants ↓ Bone mineral stores, ↓ 25OH D

Twins, closely spaced siblings Maternal depletion

Infants born to Vit D deficient mothers Low placental transfer

Children with fat malabsorption Fat-soluble vitamin deficiency

Anticonvulsant therapy Enzyme induction → ↑ Vit D catabolism

Children in purdah/veiled cultures No sun exposure

04
Classi!cation of Rickets

25
1,25
Type Cause Ca P PTH OH ALP
OH D
D
 Vit D Deficiency ↓ Vit D ↓ ↓ ↑ ↓↓ ↓/N ↑
Rickets intake/sunlight

Calcium- ↓ Dietary Ca ↓ N/ ↑↑ N/ ↑↑ ↑
Deficiency ↑ ↑
Rickets

VDDR Type I 1α-hydroxylase ↓ ↓ ↑ N ↓↓ ↑

PDDR deficiency AR

VDDR Type II VDR mutation ↓ ↓ ↑ N ↑↑↑ ↑

HVDRR AR; alopecia

XLH PHEX mutation; N ↓↓ N N N/↓ ↑

Phosphopenic) ↑ FGF23

Fanconi Renal tubular N ↓↓ ↑ N N/↓ ↑

Syndrome defects

Renal CKD; ↓ 1α- ↓ ↑ ↑↑ N ↓↓ ↑

Osteodystrophy hydroxylase

VDDR  Vitamin D Dependent Rickets; XLH  X-linked Hypophosphataemia; HVDRR  Hereditary Vit D
Resistant Rickets; AR = autosomal recessive

05
Pathophysiology

CORE MECHANISM

↓ Vit D → ↓ Intestinal Ca & P absorption → ↓ Serum Ca → ↑ PTH (secondary

hyperparathyroidism) → ↑ Bone resorption, ↑ Urinary P loss, ↓ Urinary Ca loss →
Unmineralised osteoid accumulation at growth plate → Widened, frayed, cupped
metaphysis

Sequence of Events
 Phase 1 Biochemical): ↓ 25OH D → ↓ gut Ca absorption → hypocalcaemia → ↑ PTH
→ normocalcaemia maintained; ↑ ALP
 Phase 2 Radiological): Continued ↓ Ca/P → growth plate changes on X-ray; ↑ ALP
markedly
 Phase 3 Clinical): Overt bony deformities, muscle weakness, tetany

PTH EFFECTS (SECONDARY GROWTH PLATE PATHOLOGY

HYPERPARATHYROIDISM)
Zone of provisional calcification
↑ Bone resorption → ↑ serum — absent/irregular
Ca (compensatory)
Hypertrophic zone — widened
↑ Renal phosphate excretion → (cells can't mineralise →
hypophosphataemia → ↓ accumulate)
mineralisation
Metaphysis — frayed, cupped,
↑ 1,25OH D synthesis (partial widened
compensation)
Periosteum — undermineralised
↑ Alkaline phosphatase → soft bones → deformities
(osteoblast activity)

06
Clinical Features

⚠ AGE OF PRESENTATION

Craniotabes: 36 months (skull not yet mineralised)

Rachitic rosary, Harrison's sulcus: 612 months
Long bone deformities, genu varum/valgum: After weight-bearing, 12 years
Hypocalcaemic tetany/seizures: Any age; especially 36 months and
adolescent growth spurts

A. Skeletal Manifestations

Sign Description Site

Craniotabes Ping-pong ball sensation on occipital/parietal Skull

bones; earliest sign; NOT if at vertex (normal
 in neonates)

Frontal bossing Square head (caput quadratum); prominent Skull

forehead

Delayed fontanelle Anterior fontanelle open beyond 18 months Skull

closure

Delayed dentition Defective enamel, dental caries Teeth

Rachitic rosary Palpable/visible beading at costochondral Chest

junctions (bilaterally symmetric)

Harrison's sulcus Horizontal depression along lower chest wall Chest

(attachment of soft diaphragm)

Pigeon/chicken Pectus carinatum (protruding sternum) Chest

chest

Genu varum Bow legs — pre-walking toddlers Lower

limbs

Genu valgum Knock knees — after 2 years Lower

limbs

Coxa vara Reduced neck-shaft angle → waddling gait Hip

Triradiate pelvis Distorted pelvis → obstructed labour in girls Pelvis

Metaphyseal Broadening at wrists, ankles Wrist/Ankle

widening

Green-stick Pathological fractures from soft bones Long

fractures bones

Scoliosis/kyphosis Spinal deformity Spine

B. Non-Skeletal Manifestations Nelson 21e

NEUROMUSCULAR OTHER SYSTEMS

Hypotonia — "floppy baby", Growth: Short stature, growth

delayed motor milestones failure
Proximal muscle weakness Respiratory: Recurrent LRTI (soft
 (difficulty climbing stairs) chest → poor respiratory
Hypocalcaemic tetany: mechanics + immune
Trousseau's sign, Chvostek's dysfunction)

sign Immune: ↑ susceptibility to

Hypocalcaemic seizures infections Vit D's role in innate
(neonatal, grand mal) immunity)

Carpopedal spasm, Haematological: Anaemia

laryngospasm (nutritional + iron deficiency

often coexist)
Cardiovascular: Dilated
cardiomyopathy (rare but
reported)

RAC HI TI S
R Rosary (rachitic) + Respiratory infections

A ALP ↑ + Anaemia

C Craniotabes + Caput quadratum

H Harrison's sulcus + Hypocalcaemia signs

I Increased fontanelle (delayed closure)

T Tetany + Trousseau/Chvostek

I Impaired growth + long bone deformities

S Sweating (head sweating — early symptom)

07
Investigations & Biochemical Staging

Essential Investigations

Test Finding in Nutritional Rickets Note

Serum 25OH 12 ng/mL (deficiency) Best test for Vit D status;
Vitamin D storage form

Serum Ca Normal to ↓ 2.02.1 mmol/L Maintained by PTH; late to fall

Serum ↓ 3.5 mg/dL in infants, 2.5 Key mineralisation deficit

Phosphorus mg/dL in older)

Alkaline ↑↑ (often 500 IU/L; can be Best correlate of disease

Phosphatase 1000 activity; not normal values
ALP

PTH (intact) ↑↑ Secondary

hyperparathyroidism

1,25OH D Normal or ↑ (elevated PTH Not useful for screening

Calcitriol) stimulates 1α-hydroxylase)

Urinary Ca/Cr ↓ 0.1 Renal Ca conservation

ratio

TmP/GFR Normal (vs. ↓ in phosphopenic Distinguishes from XLH

rickets)

X-ray wrist & See Section 8 Most diagnostic imaging

knee

CBC Anaemia (often iron deficiency —

coexists)

Thacher Radiological Scoring System Ghai 9e

Feature Score 0 Score 0.5 Score 1

Metaphyseal density Normal Slight ↓ Marked ↓

Zone of provisional calcification Sharp Partially absent Absent

Metaphyseal margin Smooth Slightly irregular Frayed

Metaphyseal concavity Convex Flat Cupped

Epiphyseal plate width Normal Slightly widened Widened

Total score (each wrist + each knee = 4 sites × max 10  40 Score 1.5/10 per site =
radiological rickets; severity proportional to score

Biochemical Staging Fraser's Staging / Ghai adaptation

25
Stage Ca P PTH ALP X-ray Clinical
OH D

Stage ↓ N ↑ ↑ ↓↓ Normal Craniotabes,

I sweating

Stage N ↓ ↑↑ ↑↑ ↓↓ Radiological Rachitic

II (compensated) changes rosary,
widened
metaphyses

Stage ↓↓ ↓↓ ↑↑↑ ↑↑↑ ↓↓↓ Severe Deformities,

III changes tetany,
fractures

08
Radiological Features

PREFERRED X-RAY: WRIST PA VIEW (DISTAL RADIUS/ULNA)

Most active growth plates are at wrist and knee — changes are earliest and most
prominent here.

X-ray Features (in order of appearance)

ACTIVE/EARLY RICKETS ADVANCED RICKETS

Widening of epiphyseal plate Generalised osteopenia (↓ bone

(growth plate) density)

Fraying of metaphyseal margin Bowing deformities —

(paintbrush/brush-border tibia/femur
 appearance) Green-stick/pathological
Cupping of metaphysis fractures
(concave, saucer-shaped) Looser's zones
Loss of zone of provisional (pseudofractures) — more in
calcification osteomalacia

Haziness/loss of density of Spine: codfish vertebrae

metaphysis (biconcave)

Epiphysis — irregular, small, Skull: hair-on-end pattern (less

delayed appearance common)

Healing Rickets (after treatment)

First sign of healing: appearance of dense line of provisional calcification (within 24
weeks)
Gradual decrease in width of epiphyseal plate

Remineralisation of metaphysis
ALP falls as healing progresses (may initially rise briefly — "healing flare")
Bony deformities can correct spontaneously in young children 2 yrs

09
Differential Diagnosis

Condition Key Differentiating Feature

Physiological Resolves by 1824 months; no biochemical changes; no X

bowing ray rachitic features

X-linked Normal Vit D, persistent hypophosphataemia, FHH mutation,

Hypophosphataemia X-linked dominant, short stature, responds only to
XLH phosphate + calcitriol (not Vit D alone)

VDDR Type I PDDR Normal 25OH D, ↓↓ 1,25OH D, responds to calcitriol, AR

VDDR Type II Normal 25OH D, ↑↑↑ 1,25OH D, alopecia, doesn't

HVDRR respond to Vit D
 Renal tubular Hyperchloraemic metabolic acidosis, ↑ urinary pH, Fanconi
acidosis syndrome features

Hypophosphatasia ↓ ALP (not ↑), ALPL gene mutation, neonatal form lethal

Blount's disease Tibia vara — unilateral, obese, no biochemical changes,

proximal medial tibial beaking on X-ray

Scurvy Vitamin C deficiency; subperiosteal haemorrhage Pelkan

spurs), Trümmerfeld zone; no rickets changes per se

Osteogenesis Blue sclerae, frequent fractures, family history, normal ALP

imperfecta

Metaphyseal Normal biochemistry; specific X-ray patterns Schmid type)

chondrodysplasia

10
Treatment

⚠ EMERGENCY: HYPOCALCAEMIC TETANY/SEIZURES

IV Calcium Gluconate 10% 12 mL/kg (max 10 mL) slow IV over 10 min with
cardiac monitoring
Then oral calcium supplementation
Do NOT give Vitamin D until calcium is stabilised Vit D → ↑ bone
mineralisation → may worsen hypocalcaemia acutely)

Trousseau's/Chvostek's signs without overt tetany — oral Ca first, then add Vit
D

A. Vitamin D Supplementation IAP Guidelines 2023

STOSS (SINGLE DOSE) THERAPY DAILY DOSE THERAPY

Preferred when compliance is 1 year: 2,000 IU/day × 3

concern months
 1 month: 50,000 IU single oral 112 years: 3,0006,000 IU/day
dose × 3 months
112 months: 1,00,000 IU oral 12 years: 6,000 IU/day × 3
112 years: 3,00,000 IU oral months

12 years: 6,00,000 IU oral Then maintenance: 6001000

IU/day
Followed by maintenance 400
600 IU/day

B. Calcium Supplementation Ghai 9e; IAP

CALCIUM

Elemental calcium: 3075 mg/kg/day in 3 divided doses × 3 months (along

with Vit D
Calcium carbonate: 40% elemental Ca
Calcium gluconate: 9% elemental Ca (used IV in emergencies)
Essential to give calcium along with Vit D to prevent "hungry bone" syndrome

C. Treatment Monitoring

Parameter When to Check Expected Response

Serum Ca, P, 46 weeks after Ca & P normalise; ALP begins to fall
ALP treatment

X-ray wrist 48 weeks Dense line of provisional calcification

PTH 3 months Normalises

25OH D 3 months Should reach 20 ng/mL

Bony 612 months Spontaneous correction 2 yrs; surgical if

deformities persists 4 yrs

D. Surgical Treatment
Considered if deformities persist after age 4 years with complete biochemical healing
Corrective osteotomy for severe genu varum/valgum
 Stapling of growth plates — in XLH

E. Treatment of Speci!c Types

Type Treatment

VDDR Type I PDDR Calcitriol 0.252 µg/day (lifelong) + Calcium

VDDR Type II High-dose Calcitriol; IV Ca infusions; some respond to

HVDRR massive doses

X-linked Phosphate supplements + Calcitriol; Burosumab (anti-FGF

Hypophosphataemia 23 antibody) — newer

Renal Calcitriol + treat CKD; dialysis/transplant

Osteodystrophy

Calcium-deficiency Calcium supplementation (primary); Vit D if also deficient

rickets

11
Prevention & IAP Guidelines

IAP GUIDELINES 2023  VITAMIN D SUPPLEMENTATION

All breastfed infants: 400 IU/day from within first few days of life (regardless of
maternal Vit D status)
Formula-fed infants: If consuming 1L/day formula → supplement 400 IU/day
Continuation: At least until 1 year; can continue up to 2 years
Older children: 600 IU/day if inadequate sun exposure or dietary intake
Preterm infants: 400800 IU/day after full feeds; up to 1000 IU/day in VLBW
Pregnant women: 600800 IU/day throughout pregnancy
Universal supplementation preferred over screening in resource-limited
settings
Sunlight Recommendations IAP 2023

SUN EXPOSURE

Adequate: 30 min/week of full body sun exposure (diaper only) OR 2 hr/week

(face and hands only) for infants

Best time: 10 AM  3 PM UVB index 3

Not recommended as primary prevention strategy due to skin cancer risk —
supplementation preferred

Sunscreen SPF 15 blocks 99% UVB synthesis

Glass blocks UVB completely

Dietary Sources of Vitamin D

Food Source Vit D Content IU per 100g)

Cod liver oil 10,000 IU/100mL

Salmon (cooked) 6001000 IU

Tuna (canned) 235 IU

Egg yolk 4050 IU/egg

Fortified milk India 100 IU/100mL

Breast milk 25 IU/L (inadequate)

Mushrooms UV-exposed) Variable 400 IU

12
Complications & Prognosis

ACUTE COMPLICATIONS LONG-TERM COMPLICATIONS

Hypocalcaemic tetany & Permanent skeletal deformities if

seizures untreated
 Laryngospasm — life- Short stature
threatening Obstructed labour (pelvic
Pathological fractures deformity in girls)
Respiratory failure (soft chest Dental enamel defects, early
wall) caries
Cardiac arrhythmias Increased susceptibility to TB,
(hypocalcaemia) pneumonia
Dilated cardiomyopathy Osteoporosis in adulthood

Prognosis

PROGNOSIS

Excellent if diagnosed and treated early

Biochemical normalisation: 34 weeks
Radiological healing: 68 weeks
Bony deformities 2 years — good spontaneous correction with treatment

Deformities 4 years after biochemical cure — may need surgical correction

Hereditary forms VDDR, XLH — lifelong treatment required

13
High-Yield Points for Exams

MUST-KNOW FACTS — MBBS/MD

Best test for Vit D status: Serum 25OH Vitamin D (not 1,25OH D
Active form of Vit D 1,25OH₂D₃ Calcitriol)

Earliest clinical sign of rickets: Craniotabes 36 months)

Earliest biochemical change: ↓ 25OH D, then ↑ PTH, then ↑ ALP
Best marker of rickets activity: Serum ALP (proportional to severity)

Earliest radiological sign of healing: Dense line of provisional calcification

Most common radiological site examined: Wrist PA view — distal radius &
 ulna)
Do NOT start Vit D in acute hypocalcaemic tetany — treat Ca first
Rachitic rosary vs. Scorbutic rosary: Rachitic — costochondral junction
beading, sharp; Scorbutic — more lateral, tender, irregular
Physiological bowing — resolves by 18 months, bilateral symmetric, no
biochemistry changes
XLH — X-linked dominant (father→all daughters, mother→50% sons &
daughters); doesn't respond to Vit D alone
VDDR Type II — alopecia is pathognomonic; ↑↑↑ 1,25OH D
IAP 2023 — 400 IU/day from first few days of life for all breastfed infants
Stoss therapy — preferred when compliance is an issue; single large oral dose
Vitamin D toxicity: Hypercalcaemia, hypercalciuria, metastatic calcification,
nephrocalcinosis; treat with IV fluids, steroids, bisphosphonates

Classic Exam Questions

Question Theme Answer

Earliest sign of rickets Craniotabes (skull softening, 36 months)

Earliest healing sign on X-ray Dense line of provisional calcification

Best screening test for Vit D Serum 25OH Vitamin D

Active metabolite of Vit D 1,25OH₂D₃ synthesised in kidney

Rickets with ↑ 1,25OH D VDDR Type II HVDRR + Calcium-deficiency

rickets

Rickets + alopecia VDDR Type II VDR mutation)

Rickets not responding to Vit D XLH, VDDR Type II, Calcium-deficiency rickets,
Renal tubular disorders

Emergency treatment of tetany IV Calcium Gluconate 10%  12 mL/kg slow IV

Rickets + normal Vit D + ↑ PTH Calcium-deficiency rickets

+ low dietary Ca

IAP recommended Vit D for 400 IU/day from first few days
 breastfed infant

When to consider surgery for After 4 years of age with complete biochemical
deformities healing

Pseudo-Vit D deficiency rickets VDDR Type I  1α-hydroxylase deficiency;

PDDR responds to calcitriol

W R IST
X-ray features of active rickets at wrist

W Widening of growth plate

R Ragged/frayed metaphyseal margins

I Irregular epiphysis

S Saucer/Cupped metaphysis

T Translucency (↓ density of metaphysis)

Compiled from Ghai Essential Paediatrics 9e · Nelson Textbook of Pediatrics

21e · IAP Guidelines 2023 | For educational use only