This document summarizes rickets, a disease characterized by softening and weakening of bones in children due to a lack of vitamin D or calcium and phosphate. It discusses calcium, phosphate, and vitamin D metabolism and how deficiencies can lead to inadequate mineralization of bone. Symptoms include bone pain, deformities like bowed legs, and fractures. Diagnosis involves biochemical testing showing low calcium, phosphate, and vitamin D levels as well as characteristic findings on x-rays of bones. Treatment is supplementation to correct nutritional deficiencies.

1. Rickets
DR.KUMAR SUPRASHANT
DNB
HINDU RAO HOSPITAL AND NDMC MEDICAL COLLEGE

2. CALCIUM METABOLISM
Increase in calcium starts in 3rd trimester reaches a nadir in adulthood and then
declines at the rate of 1-2 % per year
Total body calcium- 1-2 kg , of which 99% lies in skeleton
Intracellular content – less (100 nmol /lt)
Extracellular content – 1000 times more (2.2- 2.6 mmol/lt ---- 8. 5 -10.5 mg/dl)
leading to a steep extracellular to intracellular gradient
50 % ionized 50% unionized
( active form and major regulator) (bound to albumin, Igs,
sulphate,phosphate ,
citrate)
Ionized calcium maintain calcium homeostasis by regulating PTH secretion
and 1,25 D production
In gut – absorbed in distal duodenum & proximal jejunum- paracellular
pathway( non saturable ) trans cellular pathway(vit D dependent).
Absorption favored by acidic PH,absence of chelators , presence of bile
which reduces formation of calcium fatty soaps and increase availability of
fat soluble Vit D.

3. EXCRETION- mainly by kidney- reabsorbed 65% in PCT concomitant with
Nacl absorption(passive) ; 20% in thick asc loh (passive) dependent on
level of ionized calcium through a protein paracellin 1; 10% in DCT
(actively) PTH, vit D dependent by using ca2+ATPase,ca2+ na+ exchanger.
Absorption decreased by high conc. Of Na+ in urine , increased by PTH and
Vit D.
Normally over 95 % of filtered calcium is reabsorbed
Fecal excretion is dependent on dietary intake and comes into significance in
renal diseases

4. PHOSPHOROUS METABOLISM
 Total body content- 600 mg ( 85% in bones)
 Intracellular & extracellular contents are almost equal( 1-2 mmol/l, 2.5 -4.5
mg/dl)reabsorbed in
 65% of phosphate can be reabsorbed in absence of vitamin D, in its
presence increases to 90%
 90% of phosphate is reabsorbed in proximal tubules( Na+Phosphate
cotransporter)
 Phosphate reabsorption has a Tm(2 -6 mg per minute)
 Reabsorption control- vit D increases, PTH & FGF 23 decreases
 For diagnosis best to use Basal fasting levels

5. VIT D METABOLISM
 Major dietary source – D2 (calciferol)- produced from ergosterol
 Formed in body – D3( cholecalciferol) produced from 7-
dehydrocholesterol
 U.V radiation of 230-313 nm required for conversion of ergo & dehydroch.
to D2 & D3
 D2 absorbed in upper 2/3 rd part of intestine – goes to lymphatics (aided by
bile salt) & D3 endogenous synthesized form, both binds to globulin and
reaches liver- hydroxylation occours form 25 OH Vit D ( 25 OH
ergocalciferol & 25 OH cholecalciferol/calcifediol)
 25 OH Vit D is major circulating form- 0.03% free, rest bound to vit D
binding protein(mainly) and albumin.
 25 OH Vit D goes to kidney for second hydroxylation by 1α hydroxylase in
PCT to 1,25 OH Vit D( calcitriol)
 Other places of 1 α hydroxylase – keratinocytes, trophoblast of placenta,
macrophages of granuloma and lymphoma.

6.  1 α hydroxylase – induced by PTH , hyphophosphatemia
repressed by ↑ ca2+; 1,25 D; FGF 23
 Action- acts through nuclear receptor- ↑ ca2+ reabsorption in gut, resorption
of bone( receptors present on osteoblast which activate RANK ligand
expression which promotes osteoclast activity), reabsorption of calcium in
renal tubels , antiproliferative effect on parathyroid.
 For diagnosis 25 OH D is most appropriate ( bcoz its pool is large enough
to form sufficient 1,25 D even in deficient state so measuring 1,25 D can be
fallacious).
 Sufficient levels - > 50 nmol/lt(>20 ng/ ml)
 <37 nmol/lt(15 ng/ml) deficient

8. Adequate supplies of vitamin
D3 can be synthesized with
sufficient exposure to solar
ultraviolet B radiation
Melanin, clothing or
sunscreens that absorb UVB
will reduce cutaneous
production of vitamin D3

11. PARATHORMONE
 ↑ ca2+ flow from bone to blood
 ↓ Renal clearance of calcium
 ↑ intestinal absorption of calcium by activating vit D
 In kidney-In Proximal tubule- inhibit phosphate reabsorption, activate renal
1 α hydroxylase
In Distal tubules- ↑ calcium absorption
also inhibit bicarbonate reabsorption
 Bones- acute- causes resorption
chronic- causes increase in both osteoblastic and osteoclastic activity
continuous- ↑ osteoclastic activity
intermittent- ↑ bone formation
 Receptors are present on osteoblast which release cytokines to activate
osteoclast.

12. RICKETS & OSTEOMALACIA
 These are different expression of the same disease.
 Lack of available calcium and phosphorus ( or both)
for mineralization of newly formed osteoid .
 Called as English disease
Rickets-
 Occur in children
 Before fusion of epiphysis
 Leads to softening of bone & deformity
Osteomalacia- occur in adult
- softening of bone

13. GROUPS AT RISK
• Infants
• Elderly
• Dark skinned
• Covered women
• Kidney failure patients
• Patients with chronic liver disease
• Fat malabsorption disorders
• Genetic types of rickets
• Patients on anticonvulsant drugs

14. PATHOPHYSIOLOGY
 Metabolic abnormality- ↓ vitamin D- ↓ ca2+ - feedback ↑ in PTH – lead
to overall increase calcium absorption , phosphate loss , increase
mobilization of ca2+ and po43- from bone – overall negative balance of
ca2+ & po43- for mineralization of bone.
 Epiphysial plate abnormality
RESTING- cells sparse rounded randomly arranged
PROLIFERATIVE- cells regular flattened & arranged in column site of
DNA synthesis & mitotic activity and growth in length of plate
MATURATION- columnar arrangement becomes large & more rounded,
contain glycogen→ lowermost part k/a ZONE OF HYPERTROPHY –
cells have ↑ lacunae shrunken nuclei, vascular buds grows from
metaphysis at the base of column towards lacunae whereas bars of
cartilage which are highly calcified lies in b/w columns – this entire
region k/a ZONE OF PROVISIONAL CALCIFICATION.
ZONE OF PRIMARY SPONGIOSA – lower in metaphysis calcified bars
surrounded by osteoblast which produce seams of osteoid around bars.

16. CHANGES IN GROWTH PLATE
 Resting & proliferative zones are normal
 Maturation zones column of cells largely
elongated as irregular tongue of cartilage
sometimes extending to metaphysis→
increased height of cartilagenous plate as well
as width.
 Hypertrophic zones column of bars cannot be
identified properly

17. CAUSES OF CHANGES
 Normally in hypertrophic zone vascular
ingrowth occours from metaphysis towards
tunnels formed by calcified cartilage which
destroys the basilar cells of hypertrophic layer
along with intervening cartilage.
 IN RICKETS- calcified tunnels not formed-
vascular in growth does not occour so basilar
layer cannot be destroyed leading to increased
proliferation without destruction.

19.  CUPPING- normally epiphyseal plate growth push against
calcified lower zones, so opposite pressure from both sides
leads to push of epiphyseal nucleus farther from metaphysis
along the axis of bone leading to longitudinal growth.
 IN RICKETS- cartilage softened--calcified zone & metaphysis
collapse and spread under applied external force & intrinsic
growth force.
 BIOCHEMICAL- resting and proliferative zone are normal
with normal DNA synthesis , zone of maturation is selectively
targeted along with zone of hypertrophy – respiratory paralysis
& shift from aerobic to anaerobic & HMP shunt, ↓ high energy
phosphate molecules→ ↓ RNA, protein , glycogen,
proteoglycan, polysaccharide leading to maturation arrest.But
no change in lysosomal activity.

20. HISTOLOGICAL FEATURES
 Thinned cortex, ↑ porosity , ↓ density
 Irregular haversian system
 Trabecular bone is thin & porous with diminished
total no of trabeculae.
 Trabeculae shows osteoid seams (thin layer of
mineralized bone surrounded by unmineralized
osteoid synthesized in preparation of mineralization
but cannot be done due to deficiency). Osteoid seams
are cardinal features but not pathognomic, width &
total no of osteoid seams is a good index of severity of
disease.

21.  Osteoid seams generally in relation to 1
trabeculae but in one or more bones due to
very poor mineralization contain very large
ribbion like radiolucent area of osteoid seams
k/a looser’s zone/ umbauzons/ milkman
pseudofracture (VIRTUALLY DIAGNOSTIC
of osteomalacic syndrome)

22. PARADOX OF RICKETS
 As the rickets become more severe and patient
become systemically more sicker with greater
abberation of biochemical abnormality the
changes in growth plate become less severe or
even disappear( if child survives) bcoz rickets
is a disease of growing bones with severe
systemic illness growth is suppressed due to
decreased nutrition & hypoprotenemia&
epiphyseal manifestation of rickets fade away
as they are directly related to rapidity of
growth.

23. CLINICAL FEATURES
AGE OF PRESENTATION
 VITAMIN D DEFICIENCY RICKETS –
6 to 18 months.
 NON NUTRITIONAL RICKETS
Beyond this age group.

24.  Stereotyped can rarely diffrentiate one form
from other, infants & young children with
florid rickets manifest by 6 months of age.
 Failure to thrive
 Listless, apathic , irritable, hypotonic,
underweight, anemic, ligamentous laxity,
sweating of face and forehead, hypocalcemic
features

25. Head
 craniotabes(soft skull)
 frontal bossing
 Widening of suture,
persistent fontanelae
 Delayed dentition, caries,
enamel hypoplasia
 Caput quadratum/ hot cross bun
skull( cruciate pattern in skull
due to widened sutures &
thickening around sutures)

26. Chest
 Rachitic rosary
 Flattening of hemithorax
 Harrison groove
 Pigeon chest
 Respiratory infection and
atelectasis

28.  Protuberant abdomen

29. Widening of wrist, knee and ankle due to physeal over
growth

30. Deformity
 Toddlers: Bowed
legs
(genu varum)

31. Deformity
 Older children: Knock-
knees
(genu valgum)

32. Deformity
 windswept knees

33.  Rachitic cat back- thoracic khyphosis,
lumbar lordosis, scoliosis, waddling gait
 Rachitic saber shin, coxa vara
 String of pearl deformity- enlarged ends of
phalanx and metacarpals with constricted
joints
 Hypotonia
 Pathological #- especially greenstick
 Tetany, PEM
 Bone pain or tenderness

34. Clinical evaluation
 Dietary history
 Maternal risk factors
 Drugs
 GI disease
 Renal disease

35. Diagnosis
 History & physical examination finding
 Biochemical study
 Radiographic abnormality
 Special etiology confirmed with lab. test

36. Biochemical findings
 Calcium - n/↑/↓, rarely fall below 7.5 to 8 mg/dl
 Urinary calcium-↓ usually less than 3 mg/ kg / 24 hr(
below normal level of 5 mg / kg / 24 hr in children),
in adults on dietary intake of 750 to 1000 mg / day if
urinary excretion less than 200 mg/day – significant.
 Fecal calcium - ↑ depends on dietary intake

37.  Phosphate- ↓ in all cases(b/w 1- 3.5 mg/dl) except
renal osteodystrophy - ↑ due to inadequate filteration
from kidney. Best to measure basal fasting levels as
dependent on time of day, GH levels
 Urinary phosphate- ↑ due to decreased tubular
reabsorption of phosphate but may be dependent on
dietary intake as well as serum levels( if high serum
conc. Excretion may be upto 300- 1000 mg/day, if low
serum conc.clearnce may be low despite ↓
reabsorption.

38.  Better to measure % tubular reabsorption- <
85% significant, < 60% abnormal
 Po43- creatinine clearance, max tubular
reabsorption, exogenous phosphate load
handling- done to diagnose hyperPTH
 Alk. Phophatase - ↑(> 15 – 50 bodansky unit)
 Bone biopsy
 Hb, ESR
 Other specefic tests

40. DISORD
ER
Ca2+ Po4
3- PTH 25 D 1,25D Alk.ph Urine
ca2+
Urine
po4
3-
Vit D def N/↓ ↓ ↑ ↓ ↓/N/↑ ↑ ↓ ↑
Ca2+ def N/↓ ↓ ↑ N ↑ ↑ ↓ ↑
Po4
3- def N ↓ N/↓ N ↑ ↑ ↑ ↓
VDDR 1 N/↓ ↓ ↑ N ↓ ↑ ↓ ↑
VDDR 2 N/↓ ↓ ↑ N ↑↑ ↑ ↓ ↑
VDRR N ↓ N N ↓ ↑ ↓ ↑
HHRH N ↓ N/↓ N ↓ ↑ ↑ ↑
RTA N ↓↓ N N ↓ ↑ ↑/↓ ↑
CRF N/↓ ↑ ↑ N ↓ ↑ N/↓ ↓

41. ETIOLOGICAL CLASSN & DIAGNOSIS
 Dietary deficiency
 Vit D def.
Decreaserd vit D - ↓ calcium -secondary hyperPTH- causes
phosphaturia & ↑ 1α hydroxylase: 1,25 D can be↑/N
(compensatory increase bcoz still 25 D pool is enough to
produce 1,25 D or ↓(in severe def of 25 D)
Metabolic acidosis – PTH induced HCO3- loss
DISO
RDER
Ca2+ Po4
3- PTH 25 D 1,25D Alk.ph Urine
ca2+
Urine
po4
3-
Vit D
def
N/↓ ↓ ↑ ↓ ↓/N/↑ ↑ ↓ ↑

42. CALCIUM DEFICIENCY
Calcium chelators- phytate, oxalate , fatty acid( forms
insoluble soap with calcium) excessive phosphate
(forms insoluble salt with calcium)
DISO
RDER
Ca2+ Po4
3- PTH 25 D 1,25D Alk.ph Urine
ca2+
Urine
po4
3-
Ca2+
def
N/↓ ↓ ↑ N ↑ ↑ ↓ ↑

43. Phosphate def.
Rare (bcoz almost all food are sufficient enough in
phosphate)
DISO
RDER
Ca2+ Po4
3- PTH 25 D 1,25D Alk.ph Urine
ca2+
Urine
po4
3-
Po4
3-
def
N ↓ N/↓ N ↑ ↑ ↑ ↓

44.  Absorptive defect- can be gastric( post surgery) biliary
( bile salts are required for proper emulsification of fat
soluble vit D) enteric ( malabsorption syndromes)

45. VDDR TYPE 1
 Defect in 1 α hydroxylase
1,25 D is decreased in spite of hypophosphatemia & ↑
PTH
DISO
RDER
Ca2+ Po4
3- PTH 25 D 1,25D Alk.ph Urine
ca2+
Urine
po4
3-
VDDR
1
N/↓ ↓ ↑ N ↓ ↑ ↓ ↑

46. VDDR TYPE 2
 Defect in Vit D receptors
1,25 D ↑↑
DISO
RDER
Ca2+ Po4
3- PTH 25 D 1,25D Alk.ph Urine
ca2+
Urine
po4
3-
VDDR
2
N/↓ ↓ ↑ N ↑↑ ↑ ↓ ↑

47. RENAL TUBULAR RICKETS
 Spectrum of renal tubular abnormalities causing
hypophosphatemic rickets having resistance to vit D
to varied extent
Pathophysiology –
 ↑ phosphate clearance due to ↓ reabsorption
 Failure to produce H+ ions & and its substitution with
fixed base in distal tubules
 Failure of conversion of 25 OH D to 1, 25 OH D
Two theories has been given for pathogenesis –
1)Renal tubular deficit is primarily genetic due to which vit
D cannot cause phosphate reabsorption whereas ca2+
absorption is normal in gut.

48. 2) Either defect in hydroxylation of vitamin D or end
organ insensitivity to vitamin D( primary lesion is
calcium deficiency leads to increase in PTH which
causes phosphate wastage)
PHOSPHATONIN
A humoral mediator that decreases –
 Renal tubular reabsorption of phosphate
 Decreases hydroxylation of vitamin D

49. Decreased reabsorption of po43- due to phosphatonin
cause hypophosphatemia which should ↑ 1α
hydroxylase activity(1α hydroxylase activity
increased by PTH & ↓ po43- ) but phosphatonin ↓ the
activity of 1α hydroxylase also so in these conditions
rather than increase, a decrease occours in the the
level of 1,25,OH D.
FGF-23– well known phosphatonin

50. Renal tubular rickets can be broadly divided into 3
catogeries
A. Proximal tubular lesions
B. Distal tubular lesions
C. Proximal and distal tubular lesions
General biochemical picture
With some specific findings acc. to disease
DISO
RDER
Ca2+ Po4
3- PTH 25 D 1,25D Alk.ph Urine
ca2+
Urine
po4
3-
VDRR N ↓ N N ↓ ↑ ↓ ↑

51. PROXIMAL TUBULAR LESIONS
 4 TYPES
1)Classical Vit D resistant rickets( hypophosphatemic
rickets/ phosphate diuresis)- Commonest form
X linked HPOPHOSPHATEMIC RICKETS- primary
mode of inheritance X linked dominant. Defective
PHEX(phosphate regulating gene with homologies to endopeptidase on x
chromosome) gene which is required to inactivate FGF23.
In presence of defective PHEX there is ↑ FGF 23
leading to abnormality.

52. ADHR- mutation in FGF23 which prevents degradation
of FGF23 by proteases.
ARHR- mutation in dentin matrix protein 1 which
results increase in FGF-23.
May be recognized at about 3 months milder forms at
about 2-3 years, sometimes hypophosphatemia may
be only finding. Unlike deficiency rickets hypotonia
& other systemic findings are less & overt
manifestations are mainly confined to skeletal systems

53. X ray- features of rickets, metaphyseal lines shows sclerotic
lines at irregular intervals, In adults looser zones are less
common.
% tubular reabsorption of phosphate is 40- 70%.
Most striking feature is failure to respond toVit D even
massive doses

54. 2)VDRR WITH GLYCOSURIA- hypophosphatemic
rickets with glycosuria without diabetes or pancreatic
disease.
3) PROXIMAL FANCONI SYNDROME- phosphate,
glucose & AA wastage. Serum AA is normal. The
disease is more florid than above two but less
refractory to treatment with Vit D.
4) Rare type which manifest in adulthood & PTH action
on tubules is cause of defect rather than primary
tubular defect.

55. PROXIMAL AND DISTAL TUBULAR LESIONS
features common to syndromes in this group
Aminoaciduria with normal serum AA,Dehydration,
alkaline urine(bicarbonate loss)
acidosis,hyperchloremia, hyponatremia,
hypokalemia
1)Proximal and distal fanconi syndrome-
Due to anatomical defect in renal tubules
Autosomal recessive, less refractory to treatment
May be secondary to multiple myeloma or toxic drug
reaction
Epiphyseal plate several centimeter in height.

56. 2) lignac fanconi syndrome(cystinosis)
Metabolic abnormality as above with cystine deposition
throughout soft tissue( doubly refractile crystal on slit
lamp examination). Disease difficult to treat & patient
rarely survives beyond ten years of age despite
adequate treatment.
3) Occulocerebral syndrome/ lowe’s syndrome
Features of rickets, undescended testes, CNS
abnormality- MR, hypotonia ,dyskinetic movements,
nystagmus, megalocornea, glaucoma, mixture of
glomerular(rbc, wbc cast) PT & DT lesion- gives above
metabolic abnormality.less refractory to treatment.

57. 4)superglycine syndrome- hypophosphatemic rickets
withhyperglycinuria

58. RENAL TUBULAR ACIDOSIS
Two types-
Type 1- distal tubular lesion
Type 2- proximal tubular lesion
Hyponatremic hypokalemic hyperchloremic normal
anion gap metabolic acidosis with alkaline urine in
type 1 and acidic urine in type 2 with dehydration
Cause of bone lesion – excretion of calcium as fixed base
DISO
RDER
Ca2+ Po4
3- PTH 25 D 1,25D Alk.ph Urine
ca2+
Urine
po4
3-
RTA N ↓↓ N N ↓ ↑ ↑/↓ ↑

59. Causes chronic hypocalcemia and secondary hyperPTH
which cause bicarbonate loss and mobilization of
calcium from bone due to acidosis. Intestinal
absorption of calcium is decreased due to decreased
formation of 1,25 D.
Nephrocalcinosis due to chronic hypercalciuria and
decreased citrate excretion in urine
All combined proximal and distal tubular lesion is
somewhat associated with RTA.

60. HEREDITARY HYPOPHOSPHATEMIC RICKETS
WITH HYPERCALCIURIA
Mutation of Na+ po43- cotransporter in proximal tubules
phosphate leaks out- hypophosphatemia- ↑ 1,25 Vit D
- ↑ calcium absorption- ↓ PTH – causes hypercalciuria
DISO
RDER
Ca2+ Po4
3- PTH 25 D 1,25D Alk.ph Urine
ca2+
Urine
po4
3-
HHRH N ↓ N/↓ N ↓ ↑ ↑ ↑

61. RENAL OSTEODRYSTROPHY
Chronic glomerular disease resulting in renal
insufficiency, azotemia & acidosis has profound effect
on skeletal system which include rickets, osteomalacia
osteitis fibrosa cystica, osteoporosis, osteosclerosis &
metastatic calcification.
Reduction in renal mass leads to poor conversion of 25
D to 1,25 D→ poor absorption of calcium from gut.
DISO
RDER
Ca2+ Po4
3- PTH 25 D 1,25D Alk.ph Urine
ca2+
Urine
po4
3-
CRF N/↓ ↑ ↑ N ↓ ↑ N/↓ ↓

62. Renal excretion of calcium N/↓ probably reflecting the
↓ glomerular flow and contraction of extracellular
pool( <60 mg/24 hr)
Fecal excretion of calcium ↑ due to decreased transport
across gut wall.
Serum calcium levels are often N/ ↓ but marked
hypocalcemia is unusual, since uremic patient is
acidotic & hypoalbumenic – both contribute to
increase in % of total calcium in the ionized form so
hypocalcemic tetany is a rare finding although total
calcium is less.

63. Po43- levels are raised caused by decreased glomerular
filtration.
PTH levels are raised due to feedback stimulus from
hypocalcemia & hyperphosphatemia
Urinary phosphate loss is increased presumably bcoz of ↑
PTH levels.
Metabolic changes results in classical osteitis fibrosa cystica
by favoring the formation of labile calcium carbonate at
the expense of more stable calcium apatite.
Osteosclerosis- Theories
 Exaggerated response of bone during healing phase with
excessive amount of osteoid being laid down &
mineralized

64.  In uremic osteodystrophy a factor elaborated by PTH
acts to increase bone formation rather than decreasing
it.
 Can be bcoz of sporadic period of excessive treatment
with ca2+ , Vit D or both
Soft tissue calcification
metastatic calcification usually results from ↑ conc. of
ca2+ & po43- more than solubility product of CaHPo4
favored by acidosis, prolonged bed rest.
C/F
Unless the child is severe ill classical features of rickets are
present, craniotabes & frontal bossing are less common

65. Bowing is common
Prone to epiphyseal separation & metaphyseal #
SCFE
Palpable arteries due to calcification
X ray-
Osteitis fibrosa cystica
Diffuse rarefaction of bone
Subperiosteal resorption of cortices particularly in small
bones of hand & feet
Brown tumors- are cystic areas in shaft of long & flat
bones
Compression # of vertebra

66. Osteosclerosis of spine – Rugger jersey spine
Vascular & soft tissue calcification visible on x-ray

67. OTHER CAUSES
 Tumor-induced rickets
 McCune-Albright syndrome
 Epidermal nevus syndrome
 Neurofibromatosis
 Associated with anticonvulsant therapy
DUE TO OVER
PRODUCTION OF
PHOSPHATONIN-

68. RADIOGRAPHIC FINDINGS

70. X-RAY – LOOSER ZONE

71. X-RAY – LOOSER ZONE

72. lateral indentation of the
acetabulam (trefoil pelvis)

73. RUGGER JERSEY SPINE

74. SECONDARY HYPERPARATHYROIDISM

75. Cortical
erosion
Pathological #
Brown tumor

76. Practical approach to child with rickets.
 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 –
Hypophosphatasia,
Metaphyseal dysplasia

77. Features
 Radiological signs similar to rickets. But growth plate
are not wide with differential involvement of bones in
a joint.
 Eg. Femur shows changes but tibia is normal.
 Levels of serum Ca, P and SAP normal.
 Diagnosis
Metaphysial dysplasia

78. Features
 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
wide.
 Very low level of Alk.ph.
 Normal level of ca2+ & po43-
 ↑ serum conc. & excretion of phosphoethanolamine
Diagnosis -- Hereditary Hypophasphatasia ( 0ccours
due to genetic error in synthesis of alkaline
phosphatase)

79. level 2 – is it nutritional or non nutritional ?
 Look for clues in the history or examination-
 prematurity
 neonatal cholestasis
 anticonvulsant therapy
 chronic renal disease

80.  Jaundice - hepatobiliary disease
metabolic disorders
 Cataract - galactosemia, wilsons
 Positive family history - metabolic disease,
RTA
 Mental retardation, seizures - Galactosemia,
drug induced rickets in primary CNS problem
 Alopecia - VDDR type 2.

81.  In the absence of clues –
Presume and treat it as vit D deficiency rickets. Give
vitamin D3 (calcitriol) 600000 units 2 doses at four
weeks interval . Improvement occurs in nutritional
rickets.
 Healing is indicated by the presence of provisional
zone of calcification.
 Non healing favours a non nutritional cause.

82. FEATURES OF NON NUTRITIONAL CAUSES
 Presentation before six months or after two years of
age
 Associated failure to thrive
 Positive family history
 Obvious clues
 Failure of vitamin D therapy

83. LEVEL 3. IF IT IS NON NUTRITIONALAND LACK ANY
OBVIOUS CLUES IT COULD BE EITHER DUE TO GI
OR RENAL CAUSE
Features
 Recurrent diarrhea, oily stools.
 Recurrent abdominal pain and distension.
 Anemia, hypoproteinemia.
 Multiple vitamin and mineral deficiencies.
 Diagonosis - Malabsorption with rickets.

84. Features
 Hepatobiliary findings.
 Raised serum bilirubin, low serum albumin and
prolonged prothrombin time.
Diagnosis - Hepatic rickets

85. Features
 Failure to thrive, rec. vomiting, lethargy, acidotic
breathing.
 Hypertension, anemia with or without edema.
 Positive findings in urine analysis.
 Abnormalities in electrolytes, blood urea and
creatinine.
 Renal abnormalities in ultrasound abdomen.
Diagnosis –Renal rickets.

86. LEVEL 4.. IF IT IS RICKETS DUE TO RENAL
CAUSES WHAT IS THE UNDERLYING RENAL
PROBLEM THAT LED TO RICKETS.?
 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.

87. Features…
 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.

88. Features…
 Recurrent vomiting, diarrhoea with acidotic breathing.
 Positive family history.
 Metabolic acidosis with normal anion gap,
hypokalemia, and hyperchloremia
 Normal blood urea and serum creatinine.
 No proteinuria or glycosuria.
Diagnosis - Renal tubular acidosis.

89. Features
 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.

90. Features
 Lower limb deformity, stunted growth.
 Often with family history.
 Frequent dental abscess and early decay.
 Low serum phosphate and low TRP.
 Reduced 1,25 D in soite of hypophosphatemia
Diagnosis – Familial hypophosphataemic
rickets(FHR).

91. LEVEL 5.. CHILD WITH RICKETS, NO CLUES SO
FAR, WHAT ELSE?
Features
 Often presenting in early infancy.
 Hypocalcemic tetany.
 Improvement with vitamin D therapy and recurrence
of symptoms on discontinuation.
Diagnosis - vitamin D dependent rickets type 1

92. Features
 Alopecia without any response to any form of vitamin
D
 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.)

93. TREATMENT
There is no simple regimen for treatment for such a
varied entity and even within each category the
treatment must be carefully tailored to meet the needs
of individual patient.
Generally treatment include combination of vit D , ca2+ ,
phosphate, alkalinizing solution
Orthopaedic measures may be required to correct
deformities that cannot be expected to improve with
growth.

94. Standard dosing
(A) Administer 1000–2000 IU of vitamin D3 orally per day until
radiographic improvement is seen, then switch to 400 IU per
day
(B) Administer 8000–16,000 IU of vitamin D3 orally per day
until
radiographic resolution, then switch to 400 IU per day
Stosstherapy
(C) Administer 600,000 IU of vitamin D3 orally in 6 doses
(100,000 IU/dose) every 2 hours over a 12-hr period, followed
by supplemental vitamin D3 (400 IU/day)
(D) Administer 150,000–300,000 orally as a single dose
(E) Administer 600,000 IU intramuscularly as a single dose, then
400 IU per day
Data from Levine and Carpenter,5 Shah and Finberg,6 Cesur et
al,7
and Lubani et al.8

95. Estimated daily requirement of Vit D
Children -200 to 400 IU
Adult- 100 to 400 IU
1 mg of vit D = 40,000 IU
1 µ gm = 40 IU
Amount of calcium that can be taken orally- 1 to 1.5gm/day.
If sufficient Vit D is administered upto 0.5 gm can be
absorbed. There is probably no role of I.V calcium to treat
rachitic syndrome except in emergency such as acute
hypocalcemic tetany or cardiac failure.
Alkalinizing solution – sodium bicarbonate, shohl’s solution

97. EVALUATION OF TREATMENT
 Serial mesurement of alkaline phosphatase
 Serial measurement of serum po43-
 serial roentgenographic examination shows
progressive healing
 when alk.ph, po43- return to normal range and x ray
shows progressive healing – treatment is adequate
 In addition if there are no side effects and growth is
adequate – treatment optimal
 Osteomalacia- repeated biopsies of iliac crest to
show improvement in mineralization.
 serial measurement of % tubular reabsorption of
po43-.

98. Radiological healing is evident at about 4 weeks of
therapy. If no healing is evident at 4 weeks of therapy
patient should be evaluated for refractory rickets.

99. IMP. TO DIAGNOSE POTENTIAL SIDE EFFECTS
Serial measurement of serum calcium and urinary calcium
excretion
Serum ca2+ > 11 mg/dl
Urinary ca2+ excretion > 250 mg/24 hr
Can lead to nephrocalcinosis and soft tissue calcification
Whereas urinary calcium <100 mg/dl – shows inadequate
treatment.

100. TOXICITY
• Hypervitaminosis D
 causes hypercalcemia, which manifest as:
Nausea, vomiting, ↓Appetite
Excessive thirst & polyuria
Severe itching
Joint & muscle pains
Disorientation & coma.
Soft tissue & vessel calcification

101. ORTHOPAEDIC MEASURES
 Deficiency rickets
 If t/t given earlier, deformity correct spontaneously

102.  Long standing case and Vit-D resistant rickets
 Mild deformity----------brace
(Mermaid splint for knock knee)
 If deformity is mark----osteotomy

103. WHO SHOULD BE TESTED FOR VIT D DEFICIENCY

105. HOW DO WE TREAT