rickets as a disease

1. RICKETS
Sylvester
Kmtc chuka

2. Background
 Normal bone growth and mineralization
require adequate availability of Ca and
phosphate.
 Disease of growing bone that is unique
to children and adolescents
 Due to failure of osteoid to calcify in a
growing person
 Deficient bone mineralization can result
in rickets and/or osteomalacia

3. ..
Rickets: Changes caused by deficient
mineralization at the growth plate
Osteomalacia: Impaired mineralization of
the bone matrix
 Usually occur together as long as the
growth plates are open
 Only osteomalacia occurs after the
growth plates have fused

4. ..
 Vit D deficiency – commonest cause
of rickets
 Less commonly, a dietary deficiency of
Ca or phosphorus may also produce
rickets
 Vit D-3 (cholecalciferol) is formed in the
skin from a derivative of cholesterol
under the stimulus of UV light
 UV light or cod liver oil was the only
significant source of vit D until early in
the 20th C

5. ..
 Natural nutritional sources of vit D are
limited primarily to fatty, ocean-going
fish
 Human milk contains little vit D,
generally less than 20-40 IU/L
 Breastfed infants at risk esp those who
receive no oral supplementation and
with darkly pigmented skin – melanin
blocks penetration of UV light

6. Requirements
 Commonly measured in micrograms
(mcg)
 International Units (IU) is the unit of
measurement that appears on food
labels
 200 IU is equivalent to 5mcg (1mcg = 40
IU)

7. Epidemiology
 In Africa, deficiency of Ca, phosphorus,
or both in the diet may lead to rickets,
especially in societies were corn is
predominant in the diet
 Kenya:
-6.6% in preschoolers (1-4yrs)
-Risk factors:
1. Weaning under 1yr
2. Use of cereal-based, unfortified foods
3. Negligible cow or goat milk consumption
4. Being kept indoors when mothers were
working in the fields
Charlotte Grantz Neumann and Nimrod O Bwibo

8. ..
 In the developed world, Vit D deficiency
rickets does not occur in formula-fed
infants because formula and milk sold
contain 400 IU of vit D/L
 Nearly all cases occur in breastfed
infants with dark skin who receive no Vit
D supplementation
 Patients with chronic malabsorption
syndromes

9. ..
 Race: Individuals with dark skin are at
increased risk for vit D deficiency
rickets
 Sex: No sexual predilection is noted
 Age: By definition, rickets is observed
only in growing children, although the
effects may be observed later in life

10. Ossification
 Process of bone formation, in which
connective tissues, such as cartilage are
turned to bone or bone-like tissue
 Bone-forming cells(osteoblasts) deposit a
matrix of collagen
 The tissue is invaginated with blood vessels -
bring minerals and deposit it in the ossifying
tissue
 Ca, Mg and phosphate ions, chemically
combine and harden within the matrix into
hydroxyapatite

11. ..
 The combination of hard mineral and
flexible collagen makes bone harder
than cartilage without being brittle
 Bone formation is a dynamic process,
with osteoblasts depositing minerals,
and osteoclasts removing bone
 This process, termed bone remodeling
continues throughout life

12. Etiology
VITAMIN D DISORDERS
◦ Nutritional deficiency
◦ Secondary deficiency
Malabsorption
◦ Vitamin D–dependent rickets type 1
◦ Vitamin D–dependent rickets type 2
◦ Chronic renal failure

13. ..
CALCIUM DEFICIENCY
 Low intake
Diet
Premature infants (rickets of prematurity)
 Malabsorption
Primary disease
Dietary inhibitors of calcium absorption
PHOSPHORUS DEFICIENCY
 Inadequate intake
Rickets of prematurity
Aluminum-containing antacids

14. ..
 Anticonvulsant drugs (eg phenobarbital,
phenytoin) accelerate metabolism of
calcidiol, which may lead to insufficiency
and rickets, particularly in children who
are kept indoors in institutions
 Aluminum-containing antacids interfere
with the absorption of phosphate
 Transplacental transport of vit D, mostly
25-D, provides enough vitamin for the
1st 2mo of life unless there is severe
maternal def

15. Pathophysiology
 Cutaneous synthesis - the most important
source of Vit D, depends on the conversion of 7-
dehydrochlesterol to cholecalciferol by UV
radiation from the sun
 Undergoes a 2 step hydroxylation - 1st at position
25 in the liver → calcidiol (25-
hydroxycholecalciferol)
 Circulates in the plasma as the most abundant of
the vit D metabolites - good indicator of overall vit
D status
 2nd in the kidney at the 1 position → the active
metabolite calcitriol (1,25-
dihydroxycholecalciferol) – facilitated by PTH

16. ..
 Calcitriol acts at 3 known sites to
tightly regulate Ca metabolism:
1. Promotes absorption of Ca and
phosphorus from the intestines
2. Increases reabsorption of phosphate in
the kidney
3. Acts on bone to release Ca and
phosphate

17. ..
 These actions increase the
concentrations of Ca and phosphorus
in ECF
↓
Calcification of osteoid, primarily at the
metaphyseal growing ends of bones
but also throughout all osteoid in the
skeleton
 In vit D deficiency → hypocalcaemia
→ excess PTH → renal phosphorus
loss → ↓deposition of Ca in the bone

18. ..
 Early in the course of rickets, the Ca
concentration in the serum
decreases
 After the parathyroid response, the
Ca concentration usually returns to
normal, though phosphorus levels
remain low
 ↑ALP- produced by overactive
osteoblasts

19. Clinical Features
General
 Failure to thrive
 Listlessness-spiritless mood
 Protruding abdomen
 Muscle weakness (especially proximal)
 Fractures
Head
 Craniotabes
 Frontal bossing
 Delayed fontanelle closure
 Delayed dentition; caries

20. ..
Chest
 Rachitic rosary
 Harrison groove
 Respiratory infections and atelectasis
Back
 Scoliosis
 Kyphosis
 Lordosis

21. ..
Extremities
 Enlargement of wrists and ankles
 Valgus or varus deformities
 Windswept deformity
 Anterior bowing of the tibia and femur
 Coxa vara
 Leg pain
Hypocalcemic Symptoms
 Tetany
 Seizures
 Stridor due to laryngeal spasm

22. ..
 The site and type of deformity of the
extremities depend upon the age of the child
and the weight-bearing patterns in the limbs
 Deformities of the forearms and posterior
bowing of the distal tibia more common in
infants
 Exaggeration of the normal physiological
bowing of the legs (genu varum) is a
characteristic finding in the toddler who has
started to walk
 In the older child, valgus deformities of the
legs or a windswept deformity may be
apparent

23. ..
 Hypocalcemic rickets can affect the
musculoskeletal system with decreased
muscle tone, leading to delayed
achievement of motor milestones
 Hypocalcemic seizures are a frequent
presenting sign in the first year of life
 Children with hypocalcemic rickets also are
particularly prone to acquiring infectious
diseases
 Increased sweating is a common finding
in young infants with hypocalcemic
rickets and may be caused by bone pain

24. Varus

25. valgus

26. Windswept

27. Wrist jt widening

28. Rosary

29. Scoliosis

30. Leg deformity

31. Diagnosis
 Based on the combination of:
1. History of poor Vit D intake and risk
factors for decreased cutaneous
synthesis
2. Consistent radiographic changes and
3. Typical laboratory findings

32. ..
Laboratory Studies
 ALP markedly increased - Excellent
marker of activity of disease because it
participates in the mineralization of bone
and growth plate cartilage
 ↓ Ca early in the disease course; often
within the reference range at the time of
diagnosis as PTH levels increase
 ↓Calcidiol (25-hydroxy vit D) - levels
reflects the amount of vit D stores in the
body

33. ..
 ↑PTH
 Calcitriol levels maybe normal or
elevated because of increased
parathyroid activity
 The phosphorus level is invariably
low for age

34. ..
Radiographic findings
 Changes best visualized at the growth plate
of rapidly growing bones - the distal ulna and
the metaphyses above and below the knee
joint
 Decreased calcification leads to thickening of
the growth plate
 The edge of the metaphysis loses its sharp
border – fraying
 The metaphysis changes from a convex or
flat surface to a more concave surface –
cupping

35. ..
 There is widening of the distal end of
the metaphysis, corresponding to the
clinical observation of thickened wrists
and ankles, as well as the rachitic
rosary
 Other radiologic features include
coarse trabeculation of the diaphysis
and generalized
rarefaction(osteomalacia)

36. widening, cupping, and fraying of the
distal radius and ulna metaphyses

37. Osteomalacia with
pseudofractures

38. Treatment
 Gradually over several months or in a
single-day dose
 Single day dose: 15,000 mcg
(600,000 U)
divided into 4 or 6 oral doses, IM
injection available
 Vit D is well stored in the body and is
gradually released over many weeks

39. ..
 In nutritional rickets, the phosphorous
level rises in 96 hrs and radiographic
healing is visible in 6-7 days with
single day dose
 Gradual approach: 125-250 mcg (5000-
10,000 U) daily for 2-3mo until healing is
well established and the ALP
concentration is approaching the
reference range - success depends on
compliance
 If severe deformities have occurred,
orthopedic correction may be required,
most of the deformities correct with

40. Prevention
 Adequate UV light for at least 20 min/d to the
face of a light-skinned baby - longer for darker
children
 10 mcg (400 IU) PO daily and an adequate
dietary supply of calcium and phosphorus
 Human milk contains little vit D and too little
phosphorus for babies who weigh <1500g – need
special supplementation if breast milk is their
primary dietary source
 Vit D supplement from the 1st week of life for
susceptible infants who are breastfed is safe
and effective

41. RICKETS OF PREMATURITY
 80% of the transfer of Ca and phosphorus from
mother to fetus occurs during the 3rd trimester
 Most cases in infants with a birthweight <1,000 g.
Presents 1–4 mo after birth
 Breast milk and standard infant formula do not
contain enough Ca and phosphorus for the needs
of a premature infant
 Nontraumatic fractures, esp of the legs, arms, and
ribs; most fractures are not suspected clinically
 Fractures and softening of the ribs lead to
decreased chest compliance → respiratory distress

42. ..
 Poor linear growth
 Frontal bossing, rachitic rosary, craniotabes, and
widened wrists and ankles
 Most infants have no clinical manifestations, with
the diagnosis based on radiographic and laboratory
findings
 Provision of adequate amounts of Ca, phosphorus,
and vit D significantly decreases the risk of rickets
of prematurity
 Increased mineral feedings should continue until
the infant weighs 3–3.5 kg
 400 IU/day of vit D via formula and vitamin
supplements

43. CONGENITAL VITAMIN D DEFICIENCY
 Rare
 Due to severe maternal vit D deficiency
during pregnancy
 Risk factors: poor dietary intake, lack of
adequate sun exposure, and closely
spaced pregnancies
 Newborns may have symptomatic
hypocalcaemia, IUGR, decreased bone
ossification, along with classic rachitic
changes

44. VITAMIN D–DEPENDENT RICKETS, TYPE 1
 Autosomal recessive
 Mutations in the gene encoding renal 1α-
hydroxylase, preventing conversion of 25-D
into 1,25-D
 Normally presents during the 1st 2 yr of life
with any of the classic features of rickets
 Normal levels of 25-D, but low levels of 1,25-
D
 Responds to long-term treatment with 1,25-D
(calcitriol) 0.25–2 μg/day

45. VITAMIN D–DEPENDENT RICKETS, TYPE 2
 Autosomal recessive
 Mutations in the gene encoding the vit D receptor,
preventing a normal physiologic response to 1,25-D
 Levels of 1,25-D are extremely elevated
 Most patients present during infancy
 50–70% of children have associated alopecia;
epidermal cysts are a less common manifestation
 May respond to extremely high doses of vit D2, 25-D, or
1,25-D. Treatment of patients who do not respond is
difficult

46. CHRONIC RENAL FAILURE
 ↓ activity of 1α-hydroxylase in the kidney →
diminished production of 1,25-D
 Hyperphosphatemia as a result of decreased renal
excretion
 The rickets is worsened by the metabolic acidosis
of CRF
 Therapy by calcitriol (does not require 1-
hydroxylation by the kidney)
 Because hyperphosphatemia stimulates PTH
secretion, dietary phosphorus restriction and oral
phosphate binders always required