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PE12.3 | Vitamin D — SDL Guide

Learning Objectives

• Describe the causes of Vitamin D deficiency in children including nutritional, environmental and metabolic factors
• Identify the clinical features of nutritional rickets including skeletal deformities, systemic signs and complications
• Classify rickets and distinguish nutritional from metabolic subtypes
• Interpret the biochemical and radiological findings in active rickets
• Prescribe the correct treatment for nutritional rickets (stoss therapy and daily therapy) and state the prophylaxis dose
• Recognise the clinical features and management of Vitamin D toxicity (hypervitaminosis D)

INSTRUCTIONS

Nutritional rickets remains a common paediatric problem in India, with both Vitamin D deficiency and dietary calcium deficiency contributing to the burden. The disease causes painful, disfiguring skeletal deformities and, in infants, dangerous hypocalcaemic seizures. Treatment is highly effective when initiated early, and the disease is entirely preventable with simple supplementation from birth. This module covers the disease arc — clinical presentation, pathophysiology, diagnosis, and management — equipping you to recognise, treat, and prevent rickets in clinical practice.

References

• Ghai Essential Pediatrics, 9th ed., Ch 9 (Vitamins and Minerals — Vitamin D) (textbook)
• Nelson Textbook of Pediatrics, 21st ed., Ch 63 (Vitamin D Deficiency and Rickets) (textbook)
• IAP Consensus Statement on Vitamin D Deficiency in Childhood and Adolescence (2017) (guideline)
• WHO/UNICEF Technical Note on Nutritional Rickets: Summary of Deliberations (2016) (guideline)

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Version 2.0 | NMC CBUC 2024

Clinical Presentation of Rickets

Nutritional rickets typically presents in children between 6 months and 3 years of age — the period of most rapid skeletal growth when the demand for mineralisation is highest. The disease presents with a characteristic combination of skeletal deformities, systemic features of hypocalcaemia, and signs of delayed development. The clinical picture varies depending on the child's age and which part of the skeleton is growing most rapidly at the time: skull changes predominate in early infancy, chest deformities in the first year, and lower-limb bowing becomes prominent once the child begins to bear weight. This age-related variation means that the same diagnosis may present very differently in a 3-month-old infant (craniotabes, hypocalcaemic seizures) compared to an 18-month-old toddler (genu varum, wrist widening). A systematic head-to-toe examination is essential to capture the full spectrum.

Skeletal manifestations are the most recognisable features and vary with the region of skeleton most actively growing at the time of deficiency:

Skull and head:
• Craniotabes: softening of the occipital and parietal bones, felt as a 'ping-pong ball' on pressing; earliest sign in infants <6 months (also seen in premature infants without rickets — not pathognomonic alone)
• Frontal bossing: prominence of the frontal and parietal bones due to excessive osteoid
• Delayed fontanelle closure: anterior fontanelle remains open beyond 18 months
• Delayed dentition

Chest:
• Rachitic rosary: beading at the costochondral junctions (soft, palpable, non-tender beads)
• Harrison's sulcus: horizontal depression at the line of diaphragmatic attachment — due to softened rib cage being pulled inward by the diaphragm
• Pigeon chest (pectus carinatum) or bell-shaped chest

Limbs:
• Widening of wrists and ankles: metaphyseal expansion — a very useful clinical sign, easy to elicit
• Genu varum (bow legs) in walking children (lower limb weight-bearing forces curve the soft bones)
• Genu valgum (knock knees) — less common, seen more in older children
• Coxa vara — bowing at the hip

Spine:
• Kyphoscoliosis in older children

Systemic features reflect hypocalcaemia:
• Hypocalcaemic seizures — the most dangerous complication; can be the presenting feature in infants; tetany (Chvostek's and Trousseau's signs positive)
• Laryngospasm — stridor from hypocalcaemic laryngeal spasm; may mimic croup
• Muscle hypotonia — causes delayed motor milestones (sitting, standing, walking)
• Irritability and poor feeding
• Recurrent infections — Vitamin D has immunomodulatory functions
• Growth retardation — both height and weight affected in chronic disease

Clinical Features and Pathophysiology of Nutritional Rickets

Pathophysiology and Aetiology of Vitamin D Deficiency

Understanding the metabolism of Vitamin D illuminates both its multiple causes and the rationale for treatment. Vitamin D exists in two dietary forms: Vitamin D3 (cholecalciferol), synthesised in the skin from 7-dehydrocholesterol under the influence of UV-B radiation (wavelength 290–315 nm), and Vitamin D2 (ergocalciferol), derived from fungal and plant sources. Vitamin D is not biologically active in either of these forms — it must be converted in two sequential steps, first in the liver and then in the kidney, before it can regulate calcium and phosphate homeostasis. This two-step activation means that disease at either step (liver disease, renal disease) can produce clinical Vitamin D deficiency even when dietary intake and sun exposure are adequate, and explains why renal failure causes secondary hyperparathyroidism and metabolic bone disease. In nutritional rickets, the problem lies upstream — inadequate substrate entering the metabolic pathway — rather than in the conversion enzymes themselves. Both forms undergo two sequential hydroxylation steps before becoming biologically active:

1. Hepatic 25-hydroxylation: Vitamin D3/D2 is hydroxylated by hepatic CYP2R1 (25-hydroxylase) to form 25-hydroxyvitamin D [25(OH)D, calcidiol] — the principal circulating storage form, measured to assess Vitamin D status.
2. Renal 1-alpha-hydroxylation: 25(OH)D is converted in the proximal tubular cells of the kidney by CYP27B1 (1-alpha-hydroxylase) to 1,25-dihydroxyvitamin D [1,25(OH)2D, calcitriol] — the active hormone. This step is stimulated by PTH, hypophosphataemia, and hypocalcaemia; it is inhibited by fibroblast growth factor-23 (FGF-23) and by renal disease.

Calcitriol's actions:
• Increases intestinal absorption of calcium and phosphate (principal action)
• Stimulates renal calcium reabsorption
• Acts on osteoblasts to promote bone mineralisation
• Has immunomodulatory effects (reduces susceptibility to infections, autoimmune diseases)

Causes of nutritional Vitamin D deficiency rickets in India:
• Inadequate UV-B exposure: exclusive indoor living, air pollution reducing UV-B penetration, northern latitudes in winter, covering of the body (cultural dress practices, purdah)
• Exclusive breastfeeding without supplementation: breast milk contains very little Vitamin D (15–50 IU/L regardless of maternal status); an exclusively breastfed infant receives ~1–3 IU/kg/day — far below the 400 IU/day requirement
• Dark skin pigmentation: melanin reduces UV-B penetration; children with darker skin need more sun exposure to synthesise equivalent Vitamin D
• Prematurity: inadequate placental transfer and limited postnatal sun exposure
• Malabsorption syndromes: coeliac disease, cholestatic liver disease, short bowel syndrome impair absorption of fat-soluble vitamins
• Calcium deficiency (calcium-deficiency rickets): seen in parts of South India and sub-Saharan Africa where dietary calcium intake is extremely low despite adequate Vitamin D; the mechanism is secondary hyperparathyroidism driven by low calcium, resulting in phosphaturia and undermineralisation

Deficiency status (serum 25(OH)D):
• Deficiency: <20 ng/mL (<50 nmol/L)
• Insufficiency: 20–30 ng/mL
• Sufficient: >30 ng/mL

Vitamin D Metabolism and Deficiency Consequences

Diagnosis and Investigation of Rickets

The diagnosis of rickets is clinical and radiological, supported by characteristic biochemical findings. In the community setting, a confident clinical diagnosis can often be made on history and physical examination alone, with investigations confirming the severity and guiding treatment. A combination of skeletal signs (rachitic rosary, wrist widening, genu varum) in a child with known risk factors (exclusively breastfed without supplementation, limited sunlight exposure) is highly suggestive. However, investigations are essential for three reasons: to confirm the diagnosis when clinical signs are equivocal, to distinguish nutritional Vitamin D deficiency from metabolic subtypes (renal osteodystrophy, Vitamin D-dependent rickets, hereditary hypophosphataemic rickets), and to establish a baseline for monitoring treatment response. The biochemical profile of nutritional rickets has a characteristic pattern that reflects the downstream consequences of calcitriol deficiency on calcium-phosphate-PTH homeostasis. Understanding this pattern allows the clinician to both confirm the diagnosis and infer the underlying mechanism.

Biochemical profile in active nutritional rickets:

Investigation	Expected finding in active nutritional rickets
Serum calcium	Low or low-normal (7–8.5 mg/dL)
Serum phosphate	Low (renal phosphate wasting driven by PTH)
Serum ALP	Markedly elevated (hallmark — reflects osteoblastic activity)
Serum PTH	Elevated (secondary hyperparathyroidism)
Serum 25(OH)D	Low (<20 ng/mL in nutritional Vitamin D deficiency)
Serum 1,25(OH)2D	May be low or raised (PTH stimulates 1-alpha-hydroxylase)
Urinary calcium	Very low (hypocalciuria — calcium is being retained)

Radiological features — X-ray of wrist and knee (most informative):
The changes reflect failure of normal metaphyseal mineralisation:
• Cupping, fraying, and splaying of the metaphysis — the most characteristic sign; the normally sharp, straight metaphyseal edge becomes flared, irregular, and concave ('champagne glass' deformity)
• Widened growth plate — the zone of provisional calcification fails to mineralise
• Reduced bone density (osteopenia) — generalised thinning of cortices
• Delayed appearance of epiphyseal ossification centres
• In healing rickets: Looser's zones (pseudofractures) — translucent bands perpendicular to the bone cortex (more common in osteomalacia/adults)
• Codfish vertebrae (biconcave vertebral bodies) in severe spinal involvement

Wrist X-ray Changes and ALP Hallmark in Active Rickets