This document provides an overview of rickets presented by Lyudmyla Olexandrivna Rakovska from the Department of Pediatrics at V.N. Karazin Kharkiv National University. The 10-point plan discusses the definition, etiology, pathogenesis, classification, clinical manifestations, laboratory/radiological findings, differential diagnosis, treatment and prevention of rickets. Key points include that rickets is caused by vitamin D deficiency impairing bone mineralization, especially in children under 2 years old. Symptoms involve soft, deformed bones and skeletal abnormalities. Treatment focuses on vitamin D supplementation through either low daily doses or high single doses.

1. The Department
of Pediatrics
V.N. Karazin
Kharkiv
National
University

2. RICKETS
Assistant of the Department of Pediatrics
Lyudmyla Olexandrivna Rakovska

3. The plan of the lecture:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Definition and types of Rickets
Metabolism of Vitamin D, Ca, and P
Etiology of Rickets
Pathogenesis of Rickets
Classification of Rickets
Clinical manifestations of Rickets
Laboratory and radiological findings
Differential diagnosis
Treatment and Prevention of Rickets
Hypervitaminosis D: pathogenesis,
clinical features, diagnosis, differential
diagnosis, treatment

4. Rickets (Rachitis)

is a metabolic disease of
growing bone that is unique
to children (especially of first
2 years) and adolescents. It
is caused by a failure of
osteoid to calcify in a growing
person.

5. Rickets

characterized by a failure of
bone tissue to be properly
mineralized, especially by
imperfect calcification, typically
resulting in soft bones and
skeletal deformities.

6. “English disease” is another
name of Rickets
old English
word wrick,
(wrickken)
means "to
twist”.
 The Greek word
"rachitis"
(ῥαχίτης,
meaning “to
bend”


7. Types of Rickets
Nutritional Rickets or vitamin
D-deficiency Rickets
Vitamin D-dependent Rickets


•
•


Type I
Type II
Vitamin D-resistant Rickets
(“looks like Rickets”)
Secondary Rickets

8. ETIOLOGY

Main cause of Rickets is
vitamin D deficiency

9. VITAMIN

Vitamin D is a
fat-soluble
vitamin. It is
often called the
"sunshine"
vitamin

10. Role of vitamin D
calcium homeostasis
absorption of Ca and P
in the small intestine
reabsorption Ca and P
in the renal tubule
normal mineralization of
bone

11. Vitamin D
D3
cholecalciferol
D2
ergocalciferol

12. Vitamin D Metabolism
( Adapted from Lucas et al.)
2009;10:e590-e599
©2009 by American Academy of Pediatrics
Taylor S N et al. Neoreviews

13. Pathophysiology

14. Vitamin D and Health
Results of vitamin D deficiency:
 rickets in children
 osteomalacia in adults
 fractures in adults and older adults
 cancers (breast, prostate, colon)
 autoimmune diseases
 infectious diseases
 type I diabetes mellitus and other

15. PATHOGENESIS
Causes of vitamin D deficiency
1. Disorders associated with Vitamin D
synthesis
•
•
Deficiency in cutaneously synthesized
vitamin D
Lack of dietary intake
2. Disorders associated with Vitamin D
absorbtion
3. Chronic diseases of the liver or kidney
4. Hereditary (congenital) anomalies
of metabolism of Vitamin D, Ca, P.

16. Sun Exposure

20 to 30 minutes
of sun
(especially
between the
hours of 10:00
am and 3:00
pm) three or
four times a
week ensure
enough vitamin
D in people.

17. Causes of vitamin D deficiency
cutaneously synthesized
Cance
r???

18. Lack of
dietary Intake

19. Vitamin D malabsorption
problems
celiac sprue,
 short bowel syndrome,
 cystic fibrosis


20. Medications are associated
with vitamin D deficiency
Steroids
 Antiepileptic (anticonvulsants) drugs:
Phenobarbital and Phenytoin
(brand name Dilantin®)
 Orlistat (brand names Xenical® and
alliTM) and the cholesterol-lowering
drug Cholestyramine (brand names
Questran®, LoCholest®, and
Prevalite®)


21. Secondary Rickets
Chronic liver diseases
 End-stage renal diseases (renal
osteodystrophy)


22. Hereditary (congenital)
anomalies of metabolism of
Vitamin D, Ca and P

Vit D-dependent rickets of I type
(pseudovitamin D-deficiency rickets) - defect
in the gene coding of renal 1-alpha-hydroxylase.
Autosomal recessive desease.


Vit D-dependent rickets of II type
(hereditary 1-alfa, 25-dihydroxyvitamin Dresistent rickets) - mutation exists in the
vitamin D receptors (VDR). Autosomal recessive
desease.
Vit D-resistent rickets (familial
hypophosphatemic rickets) - mutations of the
phosphate-regulating gene on the X chromosome

23. Classification of Rickets
Degree
Period of disease
Initial
Height (manifest)
Mild
(“Florid rickets”)
(I)
Moderate Reconvalescenction
(reparation)
(II)
Residual symptoms
Severe
(permanent
(III)
changes)
Course
Acute
Subacute
Recurring

24. CLINICAL MANIFESTATIONS
I. Findings specific to the bone
tissue in rickets
 Symptoms of osteomalacia:
 Symptoms of hyperplasia of
osteoid tissue
 Symptoms of hypoplasia of
osseous tissue
II. Findings not specific to the
bone tissue in rickets

25. Findings specific to the bone tissue
Symptoms of osteomalacia:
сraniotabes
 softening of the big fontanel's
edges
 softening of ribs
 kyphosis
 bowing in the legs


26. Findings specific to the bone tissue
Symptoms of hyperplasia of
osteoid tissue:
increase of frontal and occipital
tubers (frontal bossing, “caput
quadratum”)
 costohondral prominence ("rachitic
rosary")
 chest deformities (Harrison’s groove
and pigeon breast)


27. Findings specific to the bone tissue
Symptoms of hypoplasia of
osseous tissue:
delayed fontanel closure
 delayed teething
 enamel hypoplasia
 costal or lower extremity fractures
(particularly greenstick fractures)
 lag of growth of tubular bones in
length in severe cases.


28. Findings not specific to the
bone tissue in rickets:
occipital alopecia
 muscular hypotonia
 constipation,
 hypocalcemic convulsions,
 anemia,
 increased risk for respiratory
infections.
 growth retardation and low
height−for−age (rachitic dwarfism).


29. 


In acute course of rickets symptoms of
osteomalacia prevail, in subacute –
symptoms of hyperplasia of osteoid tissue.
Skeletal deformities become obvious in
stage II and worsen in stage III.
Initial period is starting from 2-3 month of
life, lasts from 2-3 weeks to 2-3 months.
In breast-fed infants whose mothers have
osteomalacia, rickets may develop before
2 mo.
Florid rickets appears toward the end of
the 1st and during the 2nd year of life.
Later in childhood, manifest vitamin D
deficient rickets is rare.

30. PHYSICAL EXAMINATION: Head
Craniotabes (areas
of thinning and
softening of bones of
the skull) manifests
early in infants older
than 2−3 months.
It detected by pressing
firmly over the
occiput or posterior
parietal bones. A
ping-pong-ball
sensation will be felt.


31. PHYSICAL EXAMINATION: Head

frontal bossing which give the head a
boxlike or "square headed" appearance
(caput quadratum)

32. PHYSICAL EXAMINATION:
Chest

knobby
deformities
«rachitic rosary»
(“rosary beads”)
along the
costochondral
junctions

33. PHYSICAL EXAMINATION: Chest
The weakened ribs pulled by muscles also
produce flaring over the diaphragm, which
is known as Harrison groove.

34. PHYSICAL EXAMINATION: Chest

pigeon-breast
deformity

35. PHYSICAL EXAMINATION:
Extremities

enlargement thickening of the wrists

36. PHYSICAL EXAMINATION:
Extremities

enlargement
thickening of the
ankles

37. Вowing in the legs

38. Genu varum

bowlegs or “O“−type leg deformity
occurs when the femoral
intercondylar distance exceeds 5 cm

39. Genu varum

40. Genu valgum

knock-knees or
“X“−type leg
deformity

41. PHYSICAL EXAMINATION:
Spine


kyphos

43. PHYSICAL EXAMINATION:
non specific symptoms
Muscular hypotonia
Generalized muscular hypotonia
 "floppy baby syndrome" or "slinky
baby" (such that the baby is floppy
or slinky-like)


44. PHYSICAL EXAMINATION:
non specific symptoms
Neurologic abnormalities
 observed in all cases and revealed at
initial period of disease as irritability,
interrupted sleep, sweating.

45. PHYSICAL EXAMINATION:
non specific symptoms
Occipital alopecia
 Increased sweating, particularly
around the head, may also be
present as non specific symptom. It
leads to occipital alopecia and occurs
in 30%.

46. 
rachitic rosary (62.1%),
craniotabes (49%), occipital
alopecia (31.4%) and
enlargement of the wrists
(27.1%) were the four most
common physical examination
findings for the age group 0−6
months

47. TETANY (SPASMOPHILIA)

disease of infants, resulting from
disturbances of Ca metabolism and
characterized by the development of
tonetic and tonoclonic convulsions.

48. Most frequent symptoms and
signs of latent Tetany
Chvostek’s sign;
 Trousseau’s symptom;
 Maslov’s symptom;
 Erb’s symptom;
 Lust’s sign


49. Most frequent symptoms and
signs of Manifest Tetany
Laryngospasm
 Carpopedal spasm
 General tonic convulsions

Convulsive spasm of a heart
muscle leading to child’s death is
possible!!!

51. 
In a patient suspected to have
rickets based on clinical findings,
the diagnosis is confirmed by
biochemical and radiological
findings.

52. LABORATORY FINDINGS
Obligatory serum measurements :
 Calcium
 Phosphorus
(N)
 Alkaline phosphatase
(N)
Additional:
 25-hydroxy vitamin D
 Parathyroid hormone

Sulkovich’s test of urine

53. Calcidiol
(25-hydroxy
vitamin D)
PTH

54. Serum 25(OH)D (calcidiol)
vitamin D deficiency-insufficiecy
Normal
≥50 nmol/L
(≥20 ng/mL)
0
25
50
** 1 nmol/L = 0.4 ng/mL
75
potential
adverse
effects
>125 nmol/L
(>50 ng/mL)
125 nmol/L

55. Sulkovich’s test
This test gives approximate
presentation about Ca content in
blood from is presents in urine.
 Assessment of result:
“+” – normal level
“++, ++++” – hypercalcaemia and
hypercalciuria


56. RADIOLOGICAL FINDINGS

57. RADIOLOGICAL FINDINGS

58. 

Rickets leads to
cupping and to a
brush−like
appearance of the
epiphyseal ends on
radiograms.
Radiographs of the
knee of a 3.6-yearold girl with
hypophosphatemia
depict severe
fraying of the
metaphysis.
N
Active Rickets recovery

59. RADIOLOGICAL FINDINGS

Anteroposterior and lateral radiographs of
the wrist demonstrates cupping and
fraying of the metaphyseal region.

60. RADIOLOGICAL FINDINGS


Rosary beads of
rickets
curved back

61. DIFFERENTIAL DIAGNOSIS



Vitamin
Vitamin
Vitamin
D ̶ deficient rickets
D ̶ dependent rickets (types I and II)
D-resistent Rickets (“looks like Rickets”):
• Hereditary X-linked hypophosphatemic rickets with
hypocalciuria
• Familial hypophosphatrmic
• Phosphat-diabetes
• Achondrodroplasia
• Fanconi syndrome (De Toni-Debre-Fanconi desease) (types
I and II)





Pseudohypoparathyroidism
Renal tubular acidosis
Cystinosis
Tyrosinemia
Secondary Rickets (renal, gastrointestinal, tumorassociated, medications, malabsortion syndromes et
all)

62. Familial
hypophosphatemic
Low stature in the
family, dental
deformities,
orthopaedic
abnormalities, and
consanguineous
marriage indicated
for hereditary
hypophosphatemic
rickets

63. Renal osteodystrofy

Chronic renal
failure IV st,
prolonged of
haemodyalis

64. 
Achondrodroplasia

65. Differential diagnosis tetany

includes hyperthermic convulsions,
complicated pneumonia, meningitis,
viral diseases. In hypoparathyroidism
which is very rare in babies,
hypocalcemia and
hyperphosphatemia are usual.
Eclamptic form is necessary to
differentiate from epilepsy.

66. TREATMENT
Common measures
in rickets
treatment
irrespective of its
form are the
following:
 adequate feeding,
regimen and
walks;
 massage and
physical training

67. Ergocalciferol is a form of vitamin
D, also called vitamin D2.

It is marketed under various names
including Deltalin (Eli Lilly and Company),
Drisdol (Sanofi-Synthelabo) and Calcidol
(Patrin Pharma).

68. Cholecalciferol is a form of vitamin
D, also called vitamin D3 or calciol

69. 1. Low dosage and long−term
vitamin D therapy (gradual method)







1000− 10 000 IU/day (125-250 mcg) for
2−3 months
Vitamin D can be given according to the
infant’s age as follows:
1000 IU/day for infants < 1 month of age,
1000-5000 IU/ day for children 1-12 mon.
5000-10 000 IU/day for children > 12 mon.
If hypocalcemia is seen the initial dose of vit
D must be doubled.
Afterwards, it is recommended to give
maintenance therapy of 400 IU/ day.

70. 


Because this method requires daily
treatment, success depends on
compliance.
Levels of Ca and P are normalized in 6−10
days by this therapy, while it takes 1−2
months for PTH to reach normal levels.
Depending on the severity of the disease,
it may take 3 months for the normal
serum ALP levels to be restored and the
radiological findings of rickets to
disappear.
In this treatment model, lack of
compliance is an important cause of lack
of response

71. 2. Stoss therapy
(single-day therapy)
For patients who are suspected to
have poor compliance, a high dose of
vitamin D can be given orally or
intramuscularly as a single dose of
100 000−600 000 IU after the first
month of life.
 This dose is usually divided into 4 or
6 oral doses. An intramuscular
injection is also available.


72. Stoss therapy
(single-day therapy)
Administration of 150 000−300 000 units
of vitamin D and 600 000 units (15,000
mcg) in severe rickets is an effective and
safe method of treatment.
 Vitamin D (cholecalciferol) is well stored
in the body and is gradually released over
many weeks. This treatment evokes a
rapid clinical response, resulting in
biochemical recovery in a few days and
radiological recovery in 10−15 days.


73. 
The single-day therapy avoids
problems with compliance and may
be helpful in differentiating
nutritional rickets from familial
hypophosphatemia rickets (FHR). In
nutritional rickets, the phosphorus
level rises in 96 hours and
radiographic healing is visible in 6-7
days. Neither happens with FHR.

74. Ca therapy

Ca administration
becomes
necessary when
clinical signs of
tetany or
convulsions are
present.

75. Emergency care of tetany



10% Ca gluconate (1−2 ml/kg, or 0,3-0,5
mgkg 3 times a day) IV and slowly while
monitoring ECG (bradicardia, arrhythmia).
In convulsions it is necessary to inject i.v.
seduxen (0.1 ml/kg or 0,5 mgkg of 0,5%
solution), MgSO4 (0,2-0.5 ml/kg of 25%
solution), sodium oxybutirate (0.5 ml/kg
or 50-120 mgkg of 20% solution),
oxygen inhalations.
In laryngospasm it is necessary to create a
dominant focus of excitement in the brain
(irritation of nasal mucosa, skin with a
prick, tap).

76. Ca levels should then be maintained
with oral Ca supplements.
 Infants with latent tetany may
respond orally calcium gluconate
(5%) or calcium chloride (1-2%) – 1
teaspoonful x 3 times a day.
 Restriction of cow milk because of
great quantity of phosphates.
 After 3-4 days – vit D 2-4 000 twice
a day is prescribed.


77. Orthopedic correction

If severe
deformities have
occurred,
orthopedic
correction may be
required after
healing. Most of
the deformities
correct with
growth.

78. Pharmacologic Therapy
of D ̶ resistant rickets
familial hypophosphatemic rickets

The usual vitamin D preparations are not
useful for treatment in this disorder,
because they lack significant 1-alphahydroxylase activity. Original treatment
protocols advocated vitamin D at levels of
25,000-50,000 U/d (at the lower limit of
toxic dosage). Amiloride and
hydrochlorothiazide are administered to
enhance calcium reabsorption and to
reduce the risk of nephrocalcinosis.

79. Result of treatment of familial
hypophosphatemic rickets

80. PREVENTION
Postnatal
Antenatal
nonspecific
nonspecific
specific
specific
specific
specific
nonspecific
nonspecific
nonspecific
nonspecific
specific
specific
specific
specific

81. Physiological method to prevent
vitamin D insufficiency/deficiency

To educate society, sufficiently
exposed to sunlight mothers and
infants and rational feeding
(balanced diet rich in Ca and vitamin
D), individual care, gymnastics,
massage.

82. 

Natural nutritional
sources of vitamin D are
limited primarily to
fatty, ocean-going fish.
The fortification of milk
with vitamin D
beginning in the 1930s
has made rickets a rare
disease in the United
States. Thus, the
disorder is rarely seen
today in countries
where "fortified" milk is
available.
Dietary Intake

83. Specific methods of prevent of
vitamin D-deficiency Rickets (VDR)


Supplementation vitamin D
for mother and child.
Today, vitamin D
prophylaxis means not only
prevention of clinical
rickets (VDD) but also
maintenance of optimal
serum 25 (OH)D level in
order to prevent vitamin D
insufficiency.

84. 
The daily maintenance dose of
vitamin D varies by age. It has
been reported that the dose of
prophylactic vitamin D should be
between 400 and 1000 IU/day to
maintain the serum 25(OH)D at
optimum levels (50-75 nmol/L).

85. 

The 2003 American Academy of
Pediatrics (AAP) vitamin D guidelines
recommended a minimal vitamin D dose of
200 IU/day due to evidence demonstrating
that this dose would maintain serum
25(OH)D concentrations greater than 27.5
nmol/L.
The 2008 AAP guidelines recommend an
increased minimum supplementation of
400 IU/day to ensure serum 25(OH)D
values greater than 50 nmol/L to avoid
vitamin D-deficient rickets. AAP report
recommends 400 IU/day for all infants,
children, and adolescents, with initiation of
the supplementation in the “first few days”
after birth.

86. The Endocrine Society
recommends (2011) :




The Endocrine Society, along with the Canadian Society
of Endocrinology and Metabolism and the National
Osteoporosis Foundation, published a clinical practice
guideline in 2011 titled "Evaluation, Treatment and
Prevention of Vitamin D Deficiency."
400 IU (10 mcg) for children aged 0-1
year
600 IU/day (15 mcg) for children aged 118 years
1500-2000 IU for all men and women
older than 18 years, including lactating
and pregnant women whose infants are
not ingesting vitamin D.

87. 
Also with a perspective to prevent
early rickets, it is recommended that
vitamin D at a dose of 2000 IU/day
should be administered during the
last trimester of pregnancy to
mothers with poor exposure to
sunlight due to various reasons and
who are at high risk of Vitamin D
deficiency.

88. 
Ergocalciferol and Cholecalciferol
are used for specific prevent of
rickets. Use of total 2-5 daily
doses in one intake
(correspondingly every 2-5
days).

89. Prophylactic course of vitamin D
may be interrupted by UV
irradiation.
 Specific prevention isn’t carried
out in the children receiving
formula feeding.


90. 
Families with inherited rickets may
seek genetic counseling.

91. HYPERVITAMINOSIS D

Hypervitaminosis D is a condition
result from toxic action of vitamin D
and is characterized with intoxication
of different degree, affection of
organs and systems and
development of hypercalcemia.

92. HYPERVITAMINOSIS D
10,000 - 40,000 IU/day

93. Pathogenesis

direct toxic action upon cellular
membranes, metabolism, and
consequences of hypercalcemia.

94. Classification of
Hypervitaminosis D
Course
Form
Acute
(as
Nervous
neurotoxicosis
Gastroor
toxicosis intestinal
with
Renal
dehydration of
Cardio1-3 degree)
vascular
Chronic
Period
Clinical
manifestations
Residual
signs

95. Symptoms of vitamin D
poisoning include:
Dehydration (polyuria, vomiting)
 Decreased appetite (anorexia)
 Irritability
 Constipation
 Fatigue
 Muscle weakness


96. 
An excess of vitamin D causes
abnormally high blood concentrations
of calcium (hypercalcemia), which
can cause overcalcification of the
bones, soft tissues, heart and
kidneys.

97. Laboratory findings:





A serum 25(OH)D concentration >500
nmol/L (>200 ng/mL)
hypercalcemia, hypophosphatemia.
hypomagnesemia, hypokalemia,
increased levels of cholesterin ;
metabolic acidosis.
Blood: leucocytosis;
Urine: increase of calcium, Sulkowitch's
test is positive (++++);

98. Treatment



To cancel immediately vit D, and limited
quntety of cow milk (that is rich in calcium).
Intensive detoxicative therapy:
i.v. injections of albumin, 5% solution of
glucose with Ringer’s solution, cocarboxylase,
vit C, prednisolone (1-2mg/kg), vit A (5-10000
IU/day), vit E, furosemid (1 mg/kg 3 times/d),
thyreocalcitonin (75-150 U i.m. every day), 3%
solution of ammonium chloride (1 teaspoonful 3
times a day), almagel, chlolestiramine (0.5
g/kg 3 times/day),Trilon B 50 mg/kg 2-3
times/d orally, in severe cases –i.v. are used.