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Humans & animal utilize only vitamin D3 &
they can produce it inside their bodies from
Cholesterol is converted to 7-dehydro-
cholesterol (7DC), which is a precursor of
Exposure to the ultraviolet rays in the
sunlight convert 7DC to cholecalciferol.
Vitamin D3 is metabolically inactive until it is
hydroxylated in the kidney & the liver to the
active form 1,25 Dihydroxycholecalciferol.
1,25 DHC acts as a hormone rather than a
vitamin, endocrine & paracrine properties.
Vitamin D: The Sunshine Vitamin
Not always essential
Body can make it if
exposed to enough
Made from cholesterol in
Formation of Vitamin D
Skin (UV light)
7-dehydro cholesterol Vitamin D3
Ergosterol Vitamin D2
25-Hydroxy vitamin D3
Storage form of vitamin (~3 months storage in liver)
OH-group added by 1-hydroxylase
1,25-dihydroxy vitamin D3
Active form of vitamin D, a “steroid hormone”
OH-group added by 24-hydroxylase
24,25-dihydroxy vitamin D3
Inactive form of vitamin D, ready for excretion
•Calcium metabolism: vitamin D enhances ca
absorption in the gut & renal tubules.
•Cell differentiation: particularly of collagen
& skin epithelium
•Immunity: important for Cell Mediated
Immunity & coordination of the immune
Vitamin D - Functions
Calcium absorption (small intestine)
Calcium resorption (bone and kidney)
Maintain blood calcium levels
Phosphorus absorption (small intestine)
Regulation of gene expression
GROUPS AT RISK
•Kidney failure patients
•Patients with chronic liver disease
•Fat malabsorption disorders
•Genetic types of rickets
•Patients on anticonvulsant drugs
Parathyroid Hormone (PTH)
Calcium-sensor protein in the thyroid gland
Detects low plasma calcium concentrations
Effects of parathyroid hormone
Urine / kidneys
Increases calcium reabsorption
Increases phosphorus excretion
Stimulates 1-hydroxylase activity in the kidneys
25-OH D 1,25-(OH)2 D
PTH required for resorption of Ca from bone
Activates a calcium pump on the osteocytic
P in urine Decalcification of old bone
P in blood Ca in blood normal or low slightly
Ca, P product
Low secretion of PTH
Failure of decalcification of bone
Low serum Ca level
Vitamin D deficiency
•Deficiency of vitamin D leads to:
Rickets in small children.
RICKETS : Defective mineralization of growing
bone before epiphyseal fusion
RENAL OSTEODYSTROPHY : Alteration in
skeletal growth & remodelling in CRF
OSTEOMALACIA : Defective mineralization of
bone after epiphyseal fusion
OSREOPOROSIS : Proportionate loss of bone
volume & minerals
OSTEOPENIA OF PREMATURITY : Post natal
inadequate bone mineralization in preterm babies
NUTRITIONAL VITAMIN D
Most common cause globely
Etiology –poor intake - Neonate
-Infant -on formula diet
-on breast milk
- inadequate cutaneous synthesis
NUTRITIONAL VITAMIN D
The clinical features are typical of rickets
with a significant minority presenting with
symptoms of hypocalcemia
prolonged laryngospasm occasionally
these children have an increased risk of pneumonia
and muscle weakness, adding to a delay in motor .
CONGENITAL VITAMIN D
severe maternal vitamin D deficiency during
Maternal risk factors
poor dietary intake of vitamin D,
lack of adequate sun exposure
closely spaced pregnancies
intrauterine growth retardation
decreased bone ossification,
classic rachitic changes
SECONDARY VITAMIN D
inadequate absorption -cholestatic liver disease,
-defects in bile acid
- cystic fibrosis
- other causes of pancreatic
dysfunction, celiac disease, and
-after intestinal resection
decreased hydroxylation in the liver,-insufficient enzyme
activity more than
increased degradation - medications, by inducing the P450 system,-
-anticonvulsants, such as
phenobarbital or phenytoin;
isoniazid and rifampin
RICKETS, TYPE 1.
autosomal recessive disorder,
mutations in the gene encoding renal 1α-
preventing conversion of 25-D into 1,25-D.
present during the 1st 2 yr of life
classic features of rickets including
They have normal levels of 25-D, but low levels of
1,25-D (see Table 48-4
RICKETS, TYPE 2.
mutations in the gene encoding the vitamin D receptor,
Levels of 1,25-D are extremely elevated
autosomal recessive disorder
Most patients present during infancy, although less
severely affected patients may not be diagnosed until
Less severe disease is associated with a partially
functional vitamin D receptor.
50–70% of children - alopecia, -more severe
CHRONIC RENAL FAILURE
decreased activity of 1α-hydroxylase in the kidney,
hyperphosphatemia as a result of decreased renal
Along with inadequate calcium absorption and
secondary hyperparathyroidism, the rickets may
be worsened by the metabolic acidosis of chronic
In addition, failure to thrive and growth
retardation may be accentuated because of the
direct effect of chronic renal failure on the growth
-rare ,severe anorexia
-long-term use of aluminum-
humoral mediator that decreases renal
tubular reabsorption of phosphate and therefore decreases
decreases the activity of renal 1α-hydroxylase,
Fibroblast growth factor-23 (FGF-23) is the
most well characterized phosphatonin
X-linked hypophosphatemic rickets (XLH)
most common, with a prevalence of 1/20,000.
The defective gene is on the X chromosome, but
female carriers are affected, so it is an X-linked
. PHosphate-regulating gene with homology to
Endopeptidases on the X chromosom –PHEX gene
role in inactivating a phosphatonin or phosphatonins.
FGF-23 may be the target phosphatonin.
These patients have rickets, but abnormalities of
the lower extremities and poor growth are the
Delayed dentition and tooth abscesses are also
Some patients have hypophosphatemia and short
stature without clinically evident bone disease.
mutation in the gene encoding FGF-23.
The mutation prevents degradation of FGF-23 by
proteases, leading to increased levels of this
hypophosphatemia, and inhibition of the 1α-
hydroxylase in the kidney, causing a decrease in
RICKETS WITH HYPERCALCiuRIA.
The primary problem is a renal phosphate leak
that causes hypophosphatemia,
which then stimulates production of 1,25-D.
The high level of 1,25-D increases intestinal
absorption of calcium, suppressing PTH.
Hypercalciuria ensues due to the high absorption
of calcium and the low level of PTH, which
normally decreases renal excretion of calcium
McCune-Albright syndrome , an entity that includes
the triad of polyostotic fibrous dysplasia,
hyperpigmented macules, and polyendocrinopathy
epidermal nevus syndrome, sporadic disorder consisting of
congential epidermal nevi associated with anomalies of
other organ systems, especially the skeleton and central
Rickets due to phosphate wasting is an extremely rare
complication in children with neurofibromatosis
Fanconi syndrome is secondary to generalized dysfunction of the
renal proximal tubules
There are renal losses of phosphate, amino acids, bicarbonate,
glucose, urate, and other molecules that are normally reabsorbed
in the proximal tubule.
hypophosphatemia -- phosphate losses
proximal renal tubular acidosis -- bicarbonate losses.
The findings of aminoaciduria, glucosuria, and a low serum uric
acid level are helpful diagnostically.
genetic disorder –cystinosis
Secondary to –heavy metal exposure
-drug toxicity ,(ifosfamide, valproate,
X-linked disorder ,,,,male
mutations in the gene encoding a chloride
channel that is expressed in the kidney.
hematuria, nephrolithiasis, nephrocalcinosis, ric
kets, and chronic renal failure.
Almost all patients have low molecular weight
proteinuria and hypercalciuria
. Rickets occurs in approximately 25% of
patients, and it responds to oral phosphorus
Aetiological classification –
enal causes –
Familial hypophosphataemic rickets
Renal tubular acidosis
Secondary - cystinosis, wilsons disease,lowe
Vitamin D dependent type 1 rickets
Vitamin D dependent type 2 rickets
Enlargement of long bones around wrists and ankles
Bow legs, knock knees, anterior curving of legs
Coxa vara and green stick fractures
Deformities of spine, pelvis and leg – rachitic
Lower extremities are extensively involved in Familial
Upper limb more involved than lower limbs in
difficulty walking due to a combination of
failure to thrive and symptomatic hypocalcemia (
Extra – skeletal manifestations
SEIZURES AND TETANY –
Secondary to hypocalcemia in Vit D deficiency rickets
and VDDR type 1
HYPOTONIA AND DELAYED MOTOR DEVELOPMENT
In rickets developing during infancy.
PROTUBERANT ABDOMEN, BONE PAIN, WADDLING
GAIT AND FATIGUE.
In older children presenting with rickets
Extra – Skeletal manifestations.
Features of primary problems
Features of hepatic disease
acidotic breathing or failure to thrive.
Radiologists detect in X ray chest film taken for a
different reason in a child.
BASIC INVESTIGATIONS TO CONFIRM RICKETS
Serum Ca, P and SAP
X rays of ends of long bones at knees or wrists
CLASSICAL RADIOLOGICAL CHANGES
Disappearance of provisional zone of calcification
Widening, fraying, cupping of the distal ends of shaft.
most easily visualized on posteroanterior
radiographs of the wrist ,knee ,chest
Decreased calcification leads to thickening of the
The edge of the metaphysis loses its sharp
border, which is described as fraying.
In addition, the edge of the metaphysis changes
from a convex or flat surface to a more concave
surface. This is termed cupping,
and is most easily seen at the distal ends of the
radius, ulna, and fibula. 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
Second level investigations
Blood urea, creatinine, electrolytes, ABG
Tubular reabsorption of phosphate( Trp)
Urine analysis for specific
gravity, glucose, protein, aminoacids, potass
ium and calcium.
LFT, malabsorption and IEM studies
Tertiary level investigations
Estimation of vitamin D metabolites to
differentiate VDDR type 1 from type 2
Receptor vitamin D interaction – in vitro
study to assess VDDR type 2
Bone mineral content
VIT D LEVEL IN SERUM -
25 (OH) D3 level ng/ml
DEFICIENT < 10
INSUFFICIENT 10 - 20
OPTIMAL 20 - 60
HIGH 60 - 90
Practical approach to child with
Level 1. Is it true rickets or rickets like states ?
Do preliminary investigations –
Serum calcium, phosphate, SAP
Have a close look at the x rays
Consider the following conditions –
Level 1 – is it true rickets or rickets
like states ?
Radiological signs similar to rickets. But growth plate
are not wide with differential involvement of bones in a
Eg. Femur shows changes but tibia is normal.
Levels of serum Ca, P and SAP normal.
Clinical signs or rickets are present but x rays show tongue
like radiolucency projecting from growth plate into
metaphysis whereas in rickets growth plate is uniformly
SAP levels are low but S. ca, P Levels are normal.
Diagnosis -- Hypophasphatasia
Practical approach to rickets
Level 2 – is it nutritional or non nutritional ?
Look for clues in the history or examination-
chronic renal disease
Level 1.. Is it nutritional or non
nutritional? Useful clues
Jaundice - hepatobiliary disease
Cataract - galactosemia, wilsons
Positive family history - metabolic disease,
Mental retardation, seizures -
Galactosemia, drug induced rickets in primary
Alopecia - VDDR type 2.
Level 2.. Is it nutritional or non
In the absence of clues –
Presume and treat it as vit D deficiency rickets. Give
vitamin D2 (inj. arachitol) 600000 units 2 doses at two
to three weeks interval . Improvement occurs in
Healing is indicated by the presence of provisional
zone of calcification.
Non healing favours a non nutritional cause.
Level 2.. Is it nutritional or non
Features of non nutritional causes
Presentation before six months or after two years of
Associated failure to thrive
Positive family history
Obvious clues mentioned earlier
Failure of vitamin D therapy
Level 3. if it is non nutritional and lack any
obvious clues it could be either due to GI
or renal cause
Recurrent diarrhea, oily stools.
Recurrent abdominal pain and distension.
Multiple vitamin and mineral deficiencies.
Diagonosis - Malabsorption with rickets.
If it is non nutritional and lack any obvious
clues it could be either due to GI or renal
Raised serum billirubin, low serum albumin and
prolonged prothrombin time.
Diagnosis - Hepatic rickets
Level 3.. If it is non nutritional and lack any
obvious clues it could be either due to GI
or renal cause
Failure to thrive, rec. vomiting, lethargy, acidotic
Hypertension, anemia with or without edema.
Positive findings in urine analysis.
Abnormalities in electrolytes, blood urea and
Renal abnormalities in ultrasound abdomen.
Diagnosis –Renal rickets.
Level 4.. If it is rickets due to renal causes what
is the underlying renal problem that led to
Depends on the clinical features of chronic renal
failure and on laboratory investigations.
Do urine analysis..
blood for electrolytes, urea and creatinine.
blood gas analysis.
ultrasonography of abdomen.
Vomiting , lethargy, growth retardation
Hypertension, anemia, with or without edema.
Features of obstructive uropathy.
Raised blood urea, creatinine.. S. potassium may be high.
Abnormalities in USG, MCU and DMSA scan.
Diagnosis – Chronic renal failure - renal osteodystrophy.
Recurrent vomiting, diarrhoea with acidotic breathing.
Positive family history.
Metabolic acidosis with normal anion
gap, hypokalemia, and raised serum chloride
Normal blood urea and serum creatinine.
No proteinuria or glycosuria.
Diagnosis - Renal tubular acidosis.
Severe form of rickets with stunting and deformity.
Features mentioned in RTA.
Proteinura, glycosuria present.
Normal or slightly increased B.urea and S.creatinine.
Features of underlying causes such as cystinosis.
diagnosis. - Fanconi syndrome.
Lower limb deformity, stunted growth.
Often with family history.
Frequent dental abscess and early decay.
Low serum phosphate and low TRP.
Diagnosis – Familial hypophosphataemic
Level 5.. Child with rickets, no
clues so far, what else?
Often presenting in early infancy.
Improvement with vitamin D therapy and recurrence
of symptoms on discontinuation.
Diagnosis - vitamin D dependent rickets type1
Alopecia with or without any response to any form of
High serum levels of 1,25 dihydroxy vitamin D.
Diagnosis – vitamin D dependent rickets type2
1,25(OH)2 vit D level is high in contrast to VDDR type
1 where it is low.
Types of rickets and treatment
Vit D deficiency rickets –
1 alpha vit D3 or vit D2(arachitol) 6,00,000 IU every
two to three weeks IM 2 to 3 doses. (STOSS REGIMEN)
VDDR 1 –
1,25 vit D 0.25 to 1.0 mcg/day orally.
VDDR 2 –
1,25 vit D or 1 alpha Vit D 6 mcg/kg/day (total of 30 to
60 mcg orally) with calcium supplements.
Low phospharous diet [low phosphate formulas to
Phosphate binders to enhance fecal excretion –
calcium carbonate & calcium acetate, newer non-
calcium based binders – sevelamer [Aluminum based
binders should be avoided].
Vit. D therapy :
If 25 (OH) D levels are low treat with ergocalciferol.
If 25 (OH) D levels are normal but PTH is high, treat
with calcitriol or 1,25 (OH) D 0.01-0.05 mg/kg/24hr
Treating the cause
Eliminating heavy metal exposure, chelation
Discontinuation of toxic drug.
Cystemine in cystinosis.
Avoiding tyrosine in tyrosinemia.
Bicarbonate & phosphorous supplementation [to
correct acidosis and hypophosphatemia]
3-5 meq/kg/day of alkali in distal RTA
5-15 meq/kg/day of alkali in proximal RTA
K supplementation accoding to S.k level
RICKETS OF PREMATURITY
Calcium 100 mg/kg/day
Vit D according to daily requirement for 3 months
Replacement of po4 every 4 to 6 hourly
1 alpha Vit D
Rickets in wrist - uncalcified lower
ends of bones are
porous, ragged, and saucer-shaped
(A) Rickets in 3 month old infant
(B) Healing after 28
days of treatment
(C) After 41 days
B C of treatment
1. Pay much attention to the health care of
pregnant and lactating women, instruct
them to take adequate amount of vitamin
2. Advocate sunbathing
3.Advocate breast feeding, give
supplementary food on time
4. Vitamin D supplementation:
In prematures, twins and weak babies, give
Vitamin D 800IU per day,
For term babies and infants the demand of
Vitamin D is 400IU per day,
For those babies who can’t maintain a daily
supplementation, inject muscularly Vitamin
D3 10000-200000 IU.
5. Calcium supplementation:
0.5-1gm/day, for premature, weak babies and babies
fed mainly with cereal
Sources of Vitamin D
Sunlight is the most important source
Fish liver oil
Fish & sea food (herring & salmon)
Plants do not contain vitamin D3
Vitamin D - Sources
Not found naturally in many
Synthesized in body
Fluid milk products are
fortified with vitamin D
Difficult for vegetarians
Vitamin D Toxicity
Calcification of soft tissue
Lungs, heart, blood vessels
Hardening of arteries (calcification)
Normal is ~ 10 mg/dl
Excess blood calcium leads to stone formation in
Lack of appetite
Excessive thirst and urination