Rickets

Rickets

is defined as the failure

of osteoid to calcify in a growing
person or animal.
Defective mineralization of
cartilage taking place in the
epiphyseal growth plate, leading
to widening of the long ends of
bones, growth retardation, and
skeletal deformities in children
Osteomalacia: disorder of
mineralization of newly formed
matrix in adults

History of Rickets and vitamin D

1600

- In the mid 1600s, rickets

is first described.
1918 - Edward Mellanby induces
rickets in dogs and then cures the
disease by feeding the animals
cod-liver oil.
1919 - K. Huldschinsky cures
children of rickets using
artificially produced ultraviolet
light.

History

1936 - Windaus deduces the chemical structure

of vitamin D3 produced in the skin (now known
as cholecalciferol) and identifies the
structure of its parent molecule, 7dehydrocholesterol.
1968 - Hector F. DeLuca and colleagues identify
25-hydroxyvitamin D3.
1970, the existence of a second active
metabolite produced from 1 alfha D is reported
by Anthony W. Norman, and coworkers.
1971 - Three research groups identify the
chemical/molecular structure of the final
active form of vitamin D as 1,25dihydroxyvitamin D3, which is soon reclassified
as a hormone controlling calcium metabolism.

Incidence and High Risk Group

for Rickets
Those at higher risk for developing rickets
include:
Dark-skinned children
Breast-fed infants whom or there mothers
are not exposed to sunlight
Individuals on vegetarian or vegan diets
who do not drink milk
Lactose intolerant individuals
Living in an inner-city area also is a
risk factor for rickets because of the
presence of smog.
(extremely pale skin that burns rather than
tans) have a decreased risk for rickets
due to their greater production of vitamin
D in sunlight.

Pathogenesis

 Defective

mineralization of
cartilage taking
place in the
epiphyseal growth
plate, leading to
widening of the
long ends of
bones, growth
retardation, and
skeletal
deformities in
children

Causes of calcipeonic
rickets
1- vitamin D deficiency.
2- defect of 1-alph
hydroxylase.
3- dietary ca deficiency.
4- chronic R F.

Radiological findings:
Widening

of the epiphyseal plate.

Broadning, cupping & fraying.
Shafts of long bones are osteopnic &
the cortex become thin.
The trabecular pattern is reduced &
becomes coarse.
Fractures & deformities.
Periosteal elevation.
Psudofracture.

CLINICAL MANIFESTATIONS
Skeletal findings:
Skull:
delay

closure of the
fontanelles
wide suture.
parietal & frontal bossing.
craniotabes.

Thorax:
1-enlargement of the
costochondral
junction.
2- development of
harrison sulcus.
3- pectus carinatum.

Extremities:

1- increase
width of
epiphyseal
line at the
distal
forearm &
knee.
2- swelling.
3- genovarum.
4-genuvulgum.
5- wind swept.

Spine
1- scoliosis.
2-kyphosis.

In more advanced cases

Thinning of the cortex.
Radiolucent transfer bands.
Green stick fractures.
Deformities.

Extra skeletal finding

1- dental hypoplasia .
2- dental abscesses.
3- hypotonia.
4-seizure.
5- acquire infection.

6- increase sweating.
7- tetany.
8- cataract.
9- Calcification of the Basal
Ganglia
10- extra pyramidal disorder.
11- malnutrition.

Laboratory Findings

ALP increase.
Serum phosphorus will be low
Serum calcium low / normal
Serum concentration of the PTH
increased
TRP .
Serum 25-OH vit D
1,25-OH2 vit D .

Vitamin D Deficiency
Rickets

Vitamin D deficiency
Rickets
Vitamin deficiency rarely occurs
in newborns, but symptoms most
commonly develop bet 4 & 8mon.
The main reasons for inadequate vit
D supply in infants are
prolonged breast feeding without
vit D supplementation &
concomitant avoidance of sun
exposure .

Dark

skin is an additional
risk factor for developing
rickets in breast feed
infants.

Laboratory finding:
Serum calcium normal | low.
Serum phosphate always low.
Serum ALP elevated.
Serum 25-OH vit D
low.
Serum concentration of the PTH
increased
A generalized aminoaciduria occurs from
the parathyroid activity; aminoaciduria
does not occur in familial
hypophosphatemia rickets (FHR).

Treatment:
Vitamin

D 5000 IU | day.
CA intake should be maintained at 1000
mg|day.
This regime should lead to the
resolution of biochemical & radiological
abnormalities within 3 monnth.
Reappearance of urinary ca excretion
shows that the bodys vit D & ca stores
have been refilled.
If the pt has no detectable calciurea
after 3 month of treatment , contiuation
of the same Rx regimen for another 3mon
is advisable.

Alternative Recommended
regiems
An

alternative and recommended

therapy is to administer the vitamin
D in a single day, usually divided
into 4 or 6 oral doses dose with
15,000 mcg (600,000 U) of vitamin D
In this method Vitamin D is well stored
in the body and released gradually
over many weeks and problem of
compliance can be solved by this way
An intramuscular injection also is
available and recommended
Laurence Finberg, MD, Clinical Professor, Department of
Pediatrics, University of California at San Francisco and

Monitoring:
In nutritional rickets, the phosphate
level rises in 96 hours and
radiographic healing is visible in 67 days (differentiating point with
FHR)
Serum ca, ph, ALP
urinary ca | creatinine ratio should
be measured 4 wks after start of
therapy.
Also repeated after 3mon of therapy &
radiographs should be obtained.

American Academy of pediatrics

recommends that vit D
supplementation (200IU | day) be
provided to:
All breast fed infants unless
they are receiving at least
500 ml of vit D fortified
milk | day.
Supplementation should start in
the 1st 2mon of life.
1)

2) All non breast fed infants who

are ingesting less than 500 ml
of vitD fortified milk | day.
3) Children & adolescent who do
not ingest at least 500 ml , &
do not get regular sunlight
exposure & do not take a
multivitamin supplement that
contains at least 200 IU of vit
D.

How Much Sun Exposure

Necessary??
Sensible

sun exposure
(usually 510 min of exposure of the
arms and legs or the hands, arms,
and face, 2 or 3 times per week)
In one study as little as 20 min/d
of ultraviolet light to the face of
a light-skinned baby is sufficient;

CALCIPEONIC RICKETS
Pseudo vitamin D deficiency
Or
Vitamin D Dependent type 1
Rickets
Or
1 alpha hydroxylase
deficiency

Skin
dihydrotachysterol
Ultraviolet light

cholecalciferol Vitamin D3

calcidiol
Hydroxylation in liver
25 hydroxycholecalciferol

Hydroxylation in kidney

calcitriol

kidney

1-25
Hydroxy
Active metabolite
cholecalciferol

PTH
Facilitate hydroxylation

Ergosterol
Vitamin D2

Pseudo vitamin D
deficiency:
It

is AR disorder cause by
defective conversion of
calcidiol to calcitriol.
The gene encoding the enzyme
that is responsible for the
conversion has been mapped to
chromosome 12q14.
The biochemical findings are
normal serum level of calcidiol
& low calcitriol.

Treatment:
Replacement

therapy with
calcitriol, an off-labeled use of
this drug.
Wt < 10 kg (1 microgram | day)
Wt > 10 Kg (2 microgram | day)
Rx is continued until the bone is
healed.
There after the maintenance dose
varies bet 0.25 to 8 microgram |
day.

Monitoring
Closed

supervision is needed during the

initial phase of Rx includes physical
examination & biochemical evaluation every
2 to 3 wks.

Radiographs

should show clear improvement

after 4 wks of therapy & repeated after
3mon.

During

administration of maintenance
therapy , pts evaluated at 3mon
intervals , hand x-ray performed once|year
to check for appearance of ricketic
changes.

Vitamin D Resistant
Rickets
Or

Vitamin D Dependent Rickets

type 2

or
hereditary vit D
resistant

 Known

as hereditary vit D
resistant receptor.
It is a very rare form of rickets.
Reflecting the type of mutation
within the vit D receptor & the
amount of residual vit D receptor
activity.
It is AR disorder caused by the
mutation in the gene encoding the
vit D receptor.& the defect in the
Receptor interferes with binding of
hormone R complex to DNA threby
preventing calcitriol action.

Affected

children appear
normal at birth but develop
rickets within the 1st 2year
of life.
Alopecia in 2\3 of cases &
is a marker of D severity.
Rx (2 microgram| day of
calcitriol) & 1000mg of ca.

Monitoring
Should

be evaluated initially at least

once | day.
If not respond , dosage of calcitriol
increased gradually to reach serum
concentration of up to 100 times the
normal mean.
Repeated 3-4 months of Rx.

Calcium deficiency
Insufficient

ca intake rather than

primary vitamin D def is the main
causative factor.
Most the children had normal serum
calcidiol (25OH D)& high serum
calcitriol ( 1,25-OH vit D conc.)
indicating adequate intake of
vitamin D .
Those pts respond to Rx with ca
alone or combined with vitamin D .
Rx with 1000 mg of ca & maintenance
of vit D 400IU\day.

What Other Causes??

MCQ
CP child with seizure
disorder having good
nutrition and care by
parents
Presented with fractures
what will be the
possibility?

Child abuse
Vitamin D deficiency

Drugs.Anticonvulsant

therapy can be the reason

Other causes of vit D

deficiency
1- diminished absorption by
gastrectomy.
2- celiac disease.
3- malabsoption.
4- extensive bowel surgery.
5- IBD.
6- cystic fibrosis.

Phosphopenic rickets

Definition
Rickets caused by phosphate
deficiency.
Causes:
1- inadequate nutrition.
2- increase renal loss.

Classifications:
Nutrition

Parentral

nutrition.

Prematurity.

Increase renal
loss:
familial

hypophosphatemia
.
Renal tubular
acidosis.
Fanconi syndrome.
Oncogenesis.

Rickets of Prematurity
1)

Increase risk in premature babies

with birth weight < 1,500kg with
breast feeding.
BPD and chronic lung
disease

2) Pt develop rickets even if the

vitamin D intake adequate.

Diagnosis
History
Physical

examination usually
reveals few or no sign of rickets
except for craiotabes.
lab studies show:
low P with normal ca serum.
Decrease P in urine with increase
ca.
x-ray with severe
osteopenia with
typical metaphyseal fracture of
rickets & fractures rib.

Prevention
1- daily intake of (10-15 mg)
vitaminD in 1st wk of life.
2- elemental ca (50-60 mg | kg |
day)
3- inorganic phosphorus (30-40mg
| kg| day)

Familial hypophosphatemic
The

kidneys fail to reabsorb

sufficient phosphate,
leading to low levels of serum
phosphate
.Defect in the proximal tubule
reabsorption
This usually begins after age
6-10 months.

Incidence
1|20-25,ooo .

Clinical features
1- Usually occurs between end of
the 1st year to 3 years.
2- slow growth & deformities in
lower extremities.
3- Poor dental development &
tooth abscesses.

Clinical findings
Similar

to those of nutritional
rickets, but without proximal
myopathy.
have high bone density.
infantile skull defects are not
apparent as hypophosphatemia is
usually clinically evident at a later
age.
calcium levels normal,
NO tetany nor secondary
hyperparathyroidism

How to differentiate
it from calcipeonic
rickets ??

Investigations

1234-

low serum phosphate.

normal calcium.
normal PTH
1,25-(OH )2 D in low normal

Treatment
In

Older children Oral elemental

phosphate to provide 1-3 g PO per day
in 5 divided doses
In Young children 0.2-1 gm/ day
Calcitriol (1 25 hydroxy vitamin D)
0.5-1.5 mcg/d PO.

(Calcitriol prevents increases in

parathyroid hormone caused by
phosphate therapy)

Treatment:
Vit D (20-60 ng|kg|d)
2) Phosphate (0.2- 1 g|d) in
young children
(1-4 g|d) in older children.
3) Minor serum ca, p, ALP &
urine excretion of ca to avoid
nephrocalcinosis)
1)

Monitoring
Calcitriol

dose may produce

hypercalcemia and renal damage.
The calcium-creatinine (mg/mg) ratio
in urine must be monitored closely
at first, and then every 3-6 months
to avoid renal complications
Elevated phosphate intake may
produce secondary
hyperparathyroidism

Differential DX
1- Fanconi syndrome
2- Renal tubular acidosis
3-Oncogenic Rickets