This document provides an overview of rickets, including: - It is a disorder of defective bone mineralization caused by vitamin D deficiency that disturbs calcium and phosphorus homeostasis. - Those at risk include children with dark skin and those exclusively breastfed without vitamin D supplementation. - Vitamin D is synthesized in the body from sun exposure and obtained through diet. A deficiency can be caused by inadequate intake or absorption. - Symptoms include bone deformities, muscle weakness, and fractures. Diagnosis involves blood tests showing low vitamin D and elevated alkaline phosphatase. Treatment is vitamin D supplementation.

1. RICKETS
Presenter : Dr. Gowtham singh
Moderater : Dr. Aakash tomar
Dr. Bejoy

2. INRODUCTION:
• Rickets is a disorder of defective mineralization of the growing
skeleton (before epiphyseal closure), the pediatric counterpart of
osteomalacia(adult form of rickets).
• There is a deficiency of vitamin D that disturbs the calcium and
phosphorus homeostasis and produces the characteristic
manifestations.
• To understand the disorder, it is necessary to understand the
metabolism of calcium and vitamin D in the body.

3. POLPULATION AT RISK
• Children with dark skin (increased melanin)
• Exclusively breastfed for past 06months of age (since breast milk is
poor in vitamin D)
• No vit-D supplementation

4. METABOLISM OF CALCIUM
PHOSPHOROUS AND VITAMIN D
• Vitamin D is synthesized primarily in the body (90%) from 7-
dehydrocholesterol present in the epidermis upon exposure to
sunlight.
• while small amounts (10%) are added by the dietary sources (vitamin
D3 or cholecalciferol from animal sources and vitamin D2 or
ergocalciferol from plant sources).

6. HOMEOSTASIS of calcium and
phosphorous

7. CAUSES OF VIT D DEFICIENCY

8. PATHOPHYSIOLOGY OF RICKETS
• The prime pathology in rickets is inadequate mineralization or
calcification of physis (growth plates) in growing bones due to
deficiency of vitamin D.
• Hence, the zone of provisional calcification is inadequately
mineralized and bony trabeculae become weak.
• Under increasing stresses of body weight, the physis gets deformed,
leading to defective growth and bony deformities.

10. SIGN & SYMPTOMS
• Nutritional rickets generally manifests in infants and preschool children.
Generalized features are failure to thrive, muscle weakness, listlessness and
lethargy.
• The child may present with tetany (positive Trousseau or Chvostek sign) or
convulsions because of hypocalcemia.
• Pathological fractures may result due to weak bones.
• Once the patient starts walking, bony deformities may develop like bow
legs (genu varum, most common), knock knees (genu valgum, occurs in
older children), windswept deformity of the legs (varum at one knee and
valgum at the other).

11. Some other classical clinical features are:
• Frontal bossing (thickening of frontal bone), usually evident after the age of
6 months
• Delayed closure of fontanel
• Craniotabes (usually first manifestation): Refers to soft skull bones that can
be pressed like a ping-pong ball
• Delayed dentition
• Broadening of ankle, wrist and knee joints: Due to deformed physis
• Enlarged costochondral junctions (rickets rosary Due to subluxation of the
physis
• Indentation over the lower chest at attachment of diaphragm (Harrison's
sulcus)
• Pot belly: Due to abdominal muscle hypotonia
• Pigeon chest (pectus carinatum}: Refers to a protruding sternum

13. PARADOX OF RICKETS
• As the rickets becomes more severe and the child becomes more
sick,the changes in the epiphyseal plate become milder and may
actually disappear if the patient lives long enough.
• This paradoxical behavior is d/t the fact that rickets, by definition,is a
disease of growth.
• If the patient becomes chronically ill with respiratory,cardiac or renal
diseases , growth is inhibited on a hypoproteinemic or nutritional
basis and the epiphyseal manifestations of rickets fade.

14. RADILOGICAL
FEATURES
• There may be delayed appearance of the
epiphysis.
• The physis is widened due to non-
mineralized osteoid that accumulates in
the area.
• There is no zone of calcification due to
defective mineralization and the area is
filled by irregularly arranged cartilage cells,
so the metaphyseal margins touching the
growth plate look irregular and frayed.
• Due to weight-bearing stresses, the
metaphysis becomes cup-shaped and
splayed (flat and wide). Generalized
osteopenia may be visible and the cortex
may thin out.
• Deformities of bones may be visible in the
later stages.

15. • LOOSER’S ZONES : these are
transverse bands of
unmineralized osteoid, which
typically appear in the aspect
the proximal femur and at the
posterior aspect of ribs
• They are also described as
pseudofractures / milkman’s
line (in adults they can progress
to true fractures).

16. TYPES OF RICKETS & LAB FINDINGS
1) NUTRITIONAL RICKETS
• This is the most common variety in developing countries.
• The recommended daily intake of vitamin D is 400 IU for infants, 600 IU from 1
year to 70 years of age, and 800 IU for those over 70.
• Inability to take these recommended levels leads to dietary deficiency of
vitamin D, so active vitamin D [l,25(0H)2 D] levels are low.
• This leads to inability to absorb calcium and phosphorus.
• PTH is elevated in response to hypocalcemia, corrects the serum calcium, so
calcium levels are normal to low while phosphate levels may be low to normal.
Alkaline phosphatase (ALP) is elevated.
• Cut-off value for vitamin D deficiency: Most investigators have used different
cut-off levels to define vitamin D deficiency .
• Most commonly used cut-off value to define vitamin D deficiency is 25(0H)-
vitamin D less than 20 ng/mL, insufficiency as 20- 29 ng/mL and sufficiency as
more than or equal to 30 ng/ mL. Severe deficiency is defined as a level less
than 5 ng/mL.

17. 2) Vitamin D-dependent Rickets (VDDR)
VDDR-1:
• It is an autosomal recessive disorder due to deficiency of 1-alpha-hydroxylase
renal enzyme.
• It is necessary for the formation of the active metabolite of vitamin D which is not
formed in adequate amount [ 1,25( OH- vitamin D levels low].
• This leads to inability to absorb calcium and phosphorus and levels of both
minerals are low in serum.
• PTH is elevated in response to hypocalcemia.
• ALP is also elevated.
• To differentiate it from nutritional rickets, levels of 25(0H)-vitamin D and
l,25(0H)2 -vitamin are measured. In nutritional variety, both will be low while in
vitamin D-dependent rickets (VDDR) type I, the levels of 25( OH)-vitamin D will be
increased while the active form [l,25(0H)2-vitamin D] will be markedly decreased.
The rachitic features appear early with renal tubular dysfunction.

18. VDDR-2:
• It is vitamin D receptor insensitivity disease due to mutation of VDR
gene.
• End organs are insensitive to l,25(0H)2 -vitamin D, so calcium and
phosphorus cannot be absorbed leading to low levels.
• PTH will be elevated in response to hypocalcemia.
• To differentiate it from VDDR-1, vitamin D metabolite levels are used.
Here, both 25(0H)-vitamin D and l,25(0H)2 -vitamin D would be
elevated to increase calcium absorption as there is no problem in the
metabolic pathway.
• Alopecia is present in association with the rachitic features.

19. 3) Vitamin D-Resistant Rickets (Renal Tubular Rickets)
• This is also known as familial hypophosphatemic rickets.
• Here, the basic abnormality is renal tubules' inability to retain
phosphate. Large amounts of phosphorus are excreted in the urine,
leading to hypophosphatemia
• the calcium levels are however normal.
• Defective mineralization results as both calcium and phosphorus are
needed for mineralization. Since calcium levels are normal, PTH is not
stimulated and its blood levels remain unchanged, so would be the
case with vitamin D metabolites as the metabolic pathway is not
affected. Alkaline phosphatase is elevated.
• The diagnosis is established by documenting a low urinary pH and
decreased urinary calcium and increased levels of urinary
phosphates.

20. • Rachitic features in this type appear early, just after infancy.
• Children lag behind in growth have severely deformed bones, but no
myopathy and no hypocalcemia.
• This situation can occur in renal tubular defects like Fanconi anemia
and renal tubular acidosis where there is a problem with the kidney
to reabsorb phosphorus. In acidosis, the body has to excrete fixed
base, i.e. bicarbonate and calcium phosphate are excreted along.

21. 4) X-linked hypophosphatemic rickets
• It is a genetic disorder with dominant inheritance characterized by
mutations in the phosphate-regulating gene (PHEX gene-having
homology to endopeptidases) present on chromosome X.
• This leads to excessive urinary excretion of phosphate by restricting
the ability of proximal renal tubular brush border to reabsorb
phosphorus and calcium.

22. 5) Renal Osteodystrophy
• It is seen in children who have a chronic renal disease that leads to
renal failure.
• The problem begins with a damaged renal glamorous inability to
excrete phosphorus leading to hyperphosphatemia.
• Because of kidney failure, less of l,25(0H-vitamin D is produced
which eventually leads to hypocalcemia.
• This stimulates PTH and causes secondary hyperparathyroidism.
Increased PTH resorbes calcium from bone in heavy amount, leading
to osteitis fibrosa cystica (multiple cysts in the bone).
• Spine radiograph may show alternate bands of sclerosis and lysis
referred to as the rugger jersey spine

23. • Ectopic calcification can occur due to high phosphate levels.
• Prolonged stimulation of PTH secretion leads to hyperplasia of the
parathyroid glands.
• Parathyroid gland becomes autonomous and insensitive to changes in
calcium, phosphate and vitamin D.
• This causes hypercalcemia and known as tertiary hyperparathyroidism.
• Labs are High serum phosphate level, markedly raised PTH levels and
decreased active vitamin D levels with low urinary calcium and
phosphorus, in the presence of other features of renal failure are
enough to establish the diagnosis.

24. Summary of lab findings in different
types of rickets

26. TREATMENT OF RICKETS
• Nutritional rickets may be treated gradually over several months with daily
dose regimen or with a radical approach using high-dose regimens.
• Single-day dose (Stoss therapy) of 15,000 mcg (or 600,000 IU) of vitamin D
is the commonly used highdose regimen. The single-day therapy is easy to
administer and has better compliance.
• The single day high-dose can be given orally or intramuscularly.
• With single day high-dose therapy, radiographic healing becomes visible in
6- 10 days. Single day high-dose therapy is followed by a daily based
maintenance dose of vitamin D.
• Another high-dose regimen is 50,000 IU of vitamin D weekly for 8 weeks
orally followed by a daily maintenance dose.
• High-dose vitamin D may be repeated (after 3 months) if poor compliance
persists.

28. • Calcium intake should be maintained at approximately 1,000 mg/ day (30-75
mg/kg of elemental calcium per day in three divided doses).
• The patient is also advised to take diet rich in calcium-containing foods like fish
oil, egg yolk
• Estimation of serum calcium, phosphorus and serum alkaline phosphatase levels
is recommended 1 month after initiation of therapy.
• To monitor the effect of treatment, ALP levels and 24-hours urinary calcium can
be used, but the best sign to comment on healing in rickets is healing of the
growth plate on X-rays.
• 24 hours urinary excretion of calcium should be in the range of 100-250 mg/24
hours. Lower value indicates persistent vitamin D deficiency.
• Treatment is continued until 24 hours urinary calcium and ALP return to normal.
• Radiological healing is usually evident after 1 month. Usually it takes 1-2 months
for serum 25(0H)-vitamin D levels to normalize and 3-6 months for ALP to return
to normal. In later stages of healing as mineralization proceeds in the provisional
zone of calcification, a white line appears on X-rays, next to the metaphysic,
called the white line of Frankel.

29. • Radiological healing is usually evident after 1 month.
• Usually it takes 1-2 months for serum 25(0H)-vitamin D levels to
normalize and 3-6 months for ALP to return to normal.
• In later stages of healing as mineralization proceeds in the provisional
zone of calcification, a white line appears on X-rays, next to the
metaphysic, called the white line of Frankel.

30. • In VDDR type I, active form of vitamin (calcitriol) has to be given since
1-hydroxylation is defective.
• VDDR type II has end organ insensitivity and requires very large doses
of vitamin D.
• Vitamin D-resistant rickets is treated by treating the underlying
problem along with phosphate administration to correct
hypophosphatemia in association with calcium supplementation.
• Treatment of renal osteodystrophy involves serum phosphate
reduction (dietaiy restriction, use of phosphate binders, calcium salts
and dialysis), use of vitamin D analog and renal replacement therapy.
• Sodium bicarbonate is used to correct acidosis. Cinacalcet, a calcium
receptor sensitiser (calcimimetic) that inhibits PTH release is usually
used in patients on dialysis with advanced disease.
• Parathyroidectomy may be required for tertiaiy hyperparathyroidism.

31. APPROACH TO RICKETS