Rickets In Children

Basics Of Orthopaedics

Bone: The structure of a bone is divided into two parts:

1. Proteinaceous Part
   • 90% is composed of osteoid (which consists of various proteins, collagen fibrils, phospholipids, and various amorphous proteins). Vitamin C is essential for the formation of osteoid, which is affected in patients with scurvy. 
   • Other proteins like osteocalcin and osteopontin also form the protein part.
   • Osteoids have a microfibrillar structure. There are gaps in between the fibers where the deposition of mineral parts takes place, forming a compact structure of the bone. 
2. Mineral Part
   • For conditions like rickets, where there is a vitamin D deficiency, the mineral part is affected. The mineral part is composed of crystals of calcium and phosphorus organized in the form of hydroxyapatites. Hydroxyapatites are found in the core of the bone rather than the superficial surface. 
   • Hydroxyapatite is a poorly crystalline substance and allows cross-linking. 
   • Octacal phosphate and amorphous calcium phosphate crystals are formed on the surface. 
   • The nature of the protein is part, and the mineral part forms together a compact bone structure.

Metabolism Of Vitamin D

• Vitamin D forms in the human body when sunlight falls on the skin. 7- dehydrocholesterol of the skin is converted into Vitamin D 3. UVB rays are responsible for the formation of vitamin D3. 
• The 25-hydroxylase enzyme present in the liver converts vitamin D3 into 25 (OH) Vit D3, which usually has a long life and is carried by binding protein. 
• In the kidneys, 1 alpha-hydroxylase leads to the formation of 1, 25 DHCC, the active form of vitamin D. The parathyroid hormone and FGH 23 tend to influence this step.
• 1, 25 DHCC acts on the gut, the bones, and the kidneys. Meat and fish in the diet are rich sources of vitamin D3. 
• The aim of active vitamin D3 (1, 25 DHCC) Is to increase the serum calcium level. It acts on the intestine and increases the absorption of calcium (by increasing calbindin expression) and phosphorus.
• It produces increased reabsorption of calcium in the kidneys. It decreases the reabsorption of phosphorus. 
• It activates osteoclasts in the bones. It releases calcium and phosphorus into the bloodstream and balances their ratio, allowing mineralization to proceed in an organized manner.

Parathyroid Hormone Normal Action

• When there is a primary fall in calcium levels, the thyroid gland will produce more PTH hormone. This will act on the kidney and bone directly and on the small intestine indirectly. This will lead to increased calcium and phosphate absorption in the small intestine, increased calcium reabsorption, and decreased potassium reabsorption. The opposite is effectively seen in the case of Kidneys. There will be a net increase in serum calcium levels. The normal range of serum calcium will be restored. 
• The opposite happens in patients with hypercalcemia. 

Role Of FGF 23

• This is produced by the bone cells (osteocytes and osteoclasts). 
• When dietary phosphate loading, elevated 1,25-DHCC, and chronic phosphate retention occur, bone cells start producing large amounts of FGF-23.  

Key Points To Understand

• In normal individuals, FGF-23 directly inhibits PTH secretion. 
• In CKD patients, both PTH and FGF-23 levels may be high, implying resistance of PTH to FGF-23. 

Rickets and related terms

• Rickets is a syndrome that arises due to defective mineralization of growing long bones. It occurs only in children. 
• Osteomalacia is produced in adults, in which case there is the mineralization of long bones.
• Osteoporosis refers to the reduction of bone volume. Both the osteoid and mineral parts are reduced.

Pathophysiology of Rickets

Metaphysis

• Growth plate zones

• Zone 1 consists of the resting or quiescent zone. 
• Zone 2 consists of a growth or proliferation zone. 
• Zone 3 is the hypertrophic zone, where the cells become larger and more compact.
• Zone 4 is the calcification zone. Cells are necrotic due to the presence of phosphate. The deposition of calcium and phosphorus leads to mineralization.
  • In rickets, zone 4 is the zone that is affected the maximum.
• Zone 5 is the zone of ossification.

Causes of Rickets

A. Vitamin D Disorders

These consist of the following:

• Nutritional vitamin D deficiency is the most common cause.
• Congenital vitamin D deficiency.
• Secondary vitamin D deficiency.
• Malabsorption of Vitamin D.
• Increased degradation.
• Decreased liver 25-hydroxylase.
• Vitamin D-dependent rickets types 1 and 2. 

B. Calcium Deficiency

• Low intake in the diet. 
• Premature infants (rickets of prematurity).
• Malabsorption of nutrients. 
• Dietary inhibitors of calcium absorption. 

C. Phosphorous Deficiency

• Inadequate intake. 
• Premature infants (rickets of prematurity).
• Aluminium-containing antacids. 

D. Increased Renal Losses

• X-linked hypophosphatemia rickets. 
• AD and AR forms of hypophosphatemia rickets. 
• Hereditary hypophosphatemia rickets with hypercalciuria. 
• Overproduction of fibroblast growth factor-23.
• Tumor-induced rickets.
• McCune-Albright syndrome. 
• Epidermal nevus syndrome.
• Neurofibromatosis.
• Fanconi syndrome.
• Dent disease.
• Distal renal tubular acidosis. 

Risk Factors for Nutritional Rickets

Maternal Factors

In very young infants, rickets caused by nutritional deficiency are usually the maternal deficiency that is seen in the child. The maternal factors that can lead to risk include the following.

1. Vitamin D Deficiency

• Dark skin pigmentation is seen to have a greater chance of vitamin D deficiency.
• When the body is fully covered in clothing, it is exposed to less sunlight, which can lead to vitamin D deficiency.
• High latitude.
• Indoor living or disability.
• Low vitamin D-based diet.

2. Calcium Deficiency

This is usually related to malnutrition and poverty. 

• Infant and Childhood factors
  • Lack of infant supplementation.
  • Prolonged breastfeeding beyond 6 months without complementary feeds.
  • Dark skin pigmentation in the child.
  • Lack of sunlight exposure.
  • Low vitamin D or calcium in the diet.
  • Poverty.
  • Malabsorption.
  • Protein-energy malnutrition.
  • Drugs like phenobarbitone and phenytoin. 

Also Read: Pathophysiology Of Malnutrition 

Clinical Features of Rickets

First Sign

Craniotabes or ping pong ball-like sensation on the skull of the child, which is seen mostly at 6 months of age. When pressure is applied, there is a depression in the skull, but when the pressure is removed, the skull pops back to its normal place. Craniotabes are to be checked away from the suture lines (parietal-temporal region or the temporal, occipital region).

Signs Noticed in 6 Months to 1 Year

• Frontal bossing: It is the excessive prominence of the frontal bones. It can be checked by drawing a Vertical line from the bridge of the nose. If a significant part of the skull is projecting to thefront of this line, this condition is called frontal bossing. 
• Rachitic rosary: It is the costochondral prominence in the ribs; round, smooth,  and non-tender rosary or bead-like ribs.
• Harrison sulcus: It is the horizontal prominence in the anterior part of the thorax corresponding to the attachment of the diaphragm.  
• Craniosynostosis: It is the premature fusion of these sutures of the skull.
• Widened wrists: The deformity of the wrist at 8 or above 8 months of age.

• There is delayed dentition. 
• No incisors by 10 months of age and no molars by 18 months of age.
• Delayed closure of anterior fontanelle. 
• Double malleoli.
• Bowing of legs (Genu Varum) or knock knee (Genu Valgum). 
• Windswept deformity. 
• Anterior bowing of tibia and femur.
• VERTEBRAL ANOMALIES
  • Scoliosis 
  • Kyphosis
  • Lordosis

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Clinical features of Rickets

• General Features
  • Failure to thrive and listlessness.
  • Protruding abdomen or pot belly.
  • Viceroptosis (sinking of the abdominal, internal organs below their natural position).
  • Proximal muscle weakness.
  • Pathological fracture.
  • Hypocalcaemia dilated cardiomyopathy (MCQ). 
  • Raised ICP and seizures. 
  • Stridor due to laryngeal spasms. 
  • Pectus carinatum (Pigeon-shaped chest). 

Radiology

• Most commonly done radiographic imaging: PA view of the wrist joint.
• It is often said that in cases of rickets that are caused by vitamin D deficiency, the best x-ray that can be performed is that of the wrists. 
• The first change noticed is the loss of the normal provisional zone of calcification. 
• Fraying: It is the indistinct or irregular margins. (These come before cupping or splaying).
• Cupping: Concavity in the metaphysis. Chronologically, fraying comes before cupping. 
• Splaying: There is whitening of metaphyseal ends laterally. 
• Osteopenia can develop, which can produce generalized rarefaction. 
• Trabeculation of the diaphysis.

Investigations Performed on a Child with Rickets

• It is generally assumed that the child has nutritional rickets. First-line investigations are usually performed. 
• Serum levels of calcium, phosphorus, and alkali phosphatase. Calcium and phosphorus levels will be normal to low depending on the type of rickets. 
• Alkali phosphatase is high in all types of rickets.
• Serum PTH levels are also performed.
• A renal function test (serum creatinine) is also performed because chronic kidney disease can also lead to rickets. 
• Serum 25 (OH) Vitamin D levels (these are more sensitive markers for vitamin D deficiency). In early forms of rickets, parathyroid activity is increased, and the conversion into active Vitamin D is more. So, the vitamin D levels will be normal to high even if the patient has rickets. Serum 25 (OH) Vitamin D is a more sensitive marker. 
• Urine analysis.

Findings Suggestive of Vitamin D Deficiency Rickets

• Serum calcium levels are normal to low.
• Serum phosphate levels are low.
• Alkaline phosphatase levels are high.
• Serum PTH levels are high.
• Serum 25 (OH) D levels are found to be reduced. If they are less than 10 nanograms per ml, it is termed as a deficient condition. If they are below 20 nanograms per ml, it is termed as an insufficient condition.
• Rarely do these patients also develop generalized aminoaciduria. 
• Metabolic acidosis is caused due to PTH-induced renal bicarbonate wasting.

Treatment of Vitamin D-Deficient Rickets

A. Stoss Regimen/Stoss Therapy

• Vitamin D is given in the dosages 300000 to 600000 IV of Vitamin D3 given at a single day. The oral route is always preferred over the parenteral route. 
• Vitamin D3 is always preferred over D2 because it has a longer half-life. 
• Calcium is prescribed to the patient, which is to be taken through oral supplements. The dosage is 30 to 75 milligrams per kg per day. This is given for a period of 2 to 3 months.

B. The Newer Regimen

• The IAP 2017-18 guidelines followed in India are a typical example of the newer regimen.
• In this regimen, vitamin D is given at a smaller dose for a few months. The dose is administered based on the age of the patient.
• The patient is aged less than 1 year: 2000 IU of Vitamin D3 per day is prescribed for 3 months or beyond if the doctor feels necessary.
• The patient is 1 year old or above, 3000 to 6000 IU per day of Vitamin D3 is prescribed for at least three months.

C. Large Dose Regime 

• There is also an alternative regimen for when the doctor is not sure if the patient will continue taking the medication as has been prescribed by the doctor.
• Instead of prescribing daily dosage to any child who is above 3 months of age, 60000 IU of Vitamin D3 per week can be prescribed by the doctor. This treatment is to be carried out orally for the next 6 weeks.

D. Dosage of calcium

• For a child who is less than a year of age, 500 mg/day is given. 
• For a child who is at or above a year in age, 600-800 mg/day is prescribed.
• Calcium carbonate is effective and cheaper and is hence often considered to be a part of the treatment.
• Once the treatment has been administered, the preventive daily dose of Vitamin D3 must be started. If the child has enough milk or milk products, or other calcium-containing food in his diet, preventive doses are not required. Calcium supplementation becomes unnecessary. 
• But a preventive daily dose of Vitamin D3 for children who have just recovered after the treatment of vitamin D deficient rickets is mandatory. If the child is less than a year of age, the doors will be 400 IU per day. If the child is at or more than a year in age, 600 IU per day should be given. 

E. Vitamin D deficient Rickets with Hypocalcemia

• The treatment for such a patient includes IV calcium gluconate correction followed by oral calcium supplements tapered over 2 to 6 weeks. 
• Many patients may also benefit from oral or IV Calcitriol, which is given at a dosage of 0.05 micrograms/kg/day. 

Response to Therapy

• Usually, the radiological evidence of healing appears within 4 weeks. However, these findings are based on the Stoss regimen. Therefore, the next x-ray should be planned one month from the day the treatment was started.
• A healing line at the patient's wrists appears earlier.
• Radiological signs appear earlier than clinical signs and blood investigations because these take time.  
• If the patient does not respond to therapy, refractory rickets can be considered. In this case, a second line of investigations must be performed.

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