Dereje Hunduma PGY1

RICKETS

 is a metabolic bone disease caused by

 A defect in the mineralization of osteoid matrix

 Subnormal osteoid production

 Excessive rate of de-ossification

 known as osteomalacia if it occurs after physeal

closure
 Cont…

 Rickets is a disease of growing bone that occurs in children

(before fusion of epiphysis)

 Cartilage and osteoid continues to expand the growth plate

that fails to mineralize

 The growth plate thickens, widens and increases in

circumference of metaphysis
Cont…

 Nutritional rickets due to low calcium and/or vitamin D intake

is the most common

 Calcipenic rickets or phosphopenic rickets

 Rickets associated with vitamin D deficiency usually occurs

between 6 months and 2 years of age.

 In adolescents, rickets may be related to low calcium status,

vitamin D deficiency, both, or phosphorus deficiency
Bone composition
Vitamin D Synthesis

Upregulated by PTH and

Hypophosphatemia
PTH in Ca Homeostasis
Vitamin D and PTH Pathway

Large
t
reserve fa
it D bl e
V lu cid
so e a
l
Bi
Regulation of Ca and phosphorus metabolism
Causes of Vit D Deficiency

 Vitamin D deficiency  Renal disease

• Reduced dietary intake – MC • Glomerular failure

• Reduced amount of sunlight • Renal osteodystrophy.

• Pigmented skin  Antiepileptic drugs favor

formation of hepatic
 Malabsorption
enzyme, which prevents
• Celiac disease
conversion of calciferol
• Hepatic osteodystrophy
 Pathophysiology

 Vitamin D and PTH play an important role in

calcium homeostasis

 Disruption of calcium/phosphate homeostasis

 Poor calcification of cartilage matrix of

growing long bones

 occurs at zone of provisional calcification

 Leads to increased physeal width and cortical

thinning/bowing
 Cont…
 Widened growth plate is due to
continued hypertrophy of cartilage cells

 Capillaries grow from metaphysis to

epiphysis via tunnels in the zone of
provisional calcification

 Growth of capillaries destroys the

cartilaginous cells in zone of
hypertrophy, thereby limiting the growth
of epiphyseal plate
 Cont…
 Metaphysis is soft >>> absent
mineralization

 Epiphysis is pushed into metaphysis with

axial pressure >> cupping

 Metaphysis widens under axial pressure

and defective modeling of bone >> flaring

 Irregular calcification >> fraying of

metaphysis - “trees on plateau top”
CLINICAL FEATURES

Head

• Craniotabes—softening of cranial bones

• Frontal bossing

• Delayed dentition and tooth caries

• Delayed closure of fontanel

• Craniosynostosis
Clinical features

Chest

 Rachitic rosary

 Harrison’s groove

 Pectus carinatum (pigeon chest)

Clinical features

Spine

• Scoliosis (uncommon)

• Kyphosis (rachitic cat back)

• Accentuation of lumbar lordosis

 Clinical features
Limbs and Joints

• Bone pain and tenderness

• Coxa vara

• Genu valgum or varum

• Windswept deformity

• Bowing of tibia, femur, radius and ulna

• Widening of wrist, elbow, knee and ankle

• Rachitic saber shins

• Double malleoli sign

Clinical features

Nonosseous manifestation

 Failure to thrive

 Protuberant abdomen

 Apathy, listlessness and irritability

 Proximal muscle weakness

 Ligament laxity

 Tetany, seizures, recurrent pneumonia and dilated cardiomyopathy

Lab investigations
Histology

 Disordered and elongated zone of proliferation

 Poorly defined zone of provisional calcification

 Widened osteoid seams

 "swiss cheese" trabeculae

 Abnormally arranged collagen fibers

 Run perpendicular to Haversian canals

 Radiography

 Abnormalities are evident before biochemical and

histological abnormalities

 Physeal widening

 Metaphyseal cupping

 Decreased bone density

 Looser's zones/Pseudofracture on the

compression side of bone
Types of Rickets
 NUTRITIONAL DEFICIENCY OF VITAMIN D

 Globally, vitamin D deficiency remains the MC cause of

rickets

 Poor intake and inadequate cutaneous synthesis

 Breast milk – low vitamin D

 Transplacental (25- Vitamin D) - provides enough

vitamin D for the first 2 months of life

 Presents at 6 months - 3 years of age

 Treatment

Prevention

 Sun light exposure

 Vitamin D supplementation – Diet or Drug

 Oily fish, cod liver oil, liver and organ meats,

and egg yolk

 Calcium supplementation
IAP recommendations for supplementation of Vitamin D
Treatment

 Stoss therapy: 300,000–600,000 IU of vitamin D po or IM 2–

4 doses over 1 day

 Alternate therapy: High dose vitamin D, with doses ranging

from 2,000–5,000 IU/day over 4–6 weeks

 Followed by daily vitamin D intake of 400 IU/day

 Symptomatic hypocalcemia (20 mg/kg of calcium chloride or

100 mg/kg of calcium gluconate IV
 Treatment

 corrective surgery (multilevel osteotomy)

Vitamin D-resistant (familial hypophosphatemia)

 The most common form of heritable rickets

 Presents at 1-2 years of age

 Caused by the inability of renal tubules to absorb

phosphate

GFR is normal

Vitamin D3 response is impaired

 Genetics

 X-linked dominant

 most common form

 renal phosphate absorption decreased and renal 25-(OH)-1α-

hydroxylase activity suppressed

 Autosomal dominant

 Autosomal recessive

 leads to impaired osteocyte maturation and bone mineralization

 Rx : Phosphate replacement,
VITAMIN D-DEPENDENT RICKETS TYPE 1

 Pseudovitamin D deficiency

 Genetic disorder with an autosomal recessive mode of

inheritance

 1α-hydroxylase gene mutation >> Reduction in Vit D

hydroxylation (25-D into calcitriol)

 Hypotonia, muscle weakness, growth failure, hypocalcemic

seizures, joint pain/deformity, fractures in early infancy
 Treatment
 Long-term treatment with calcitriol

 Initial doses are 0.25–2 μg/day, with lower doses - rickets healed

 Adequate calcium supplementation

 The dose of calcitriol is adjusted to

 Maintain a low normal serum Ca level

 Normal serum P level

 High normal serum PTH level

 Target of less than 4mg/kg/day

 VITAMIN D-DEPENDENT RICKETS TYPE 2

 An autosomal recessive disorder

 Vit D receptor (VDR) gene mutation - prevent a normal physiologic

response to calcitriol - of end-organ resistance

 Severe Disease – Early presentation

 Less severe – late presentation, partially functional VDR

 Calcitriol extremely elevated

 hypotonia, muscle weakness, growth failure, hypocalcemic seizures,

growth retardation, bone pain, severe dental caries or dental hypoplasia
 Treatment

 A 3–6 month trial of high dose of vitamin D2, 25-D or

calcitriol and oral calcium

 The initial dose of calcitriol should be 2 μg/day. Oral

calcium doses range from 1,000–3,000 mg/day

 Non-responders - long-term intravenous calcium

 Patients not responding to vitamin D are difficult to

treat
 Findings of healing rickets

 The earliest finding is the reappearance of the provisional zone

of calcification, which gradually thickens into a transverse band

 Re-calcification of the spongiosa in the metaphysis

– A dense line appears at the end of metaphysis

– Epiphyseal shadow is clearly defined

– The end of shaft and epiphysis become clearly differentiated

– Finally, the bone appears to be normal

 Lab parameters

 Levels of Ca and P are normalized in 6−10 days by

this therapy.

 It takes 1−2 months for PTH to reach normal level.

 It may take 3 months for the normal serum ALP levels

to be restored and the radiological findings of rickets
to disappear
References
Thank you!!