History

Fact Explanation
Enlargement of wrists and ankles [1] Due to widening of the distal end of the metaphysis as a result of thickening of the growth plate due to decreased calcification [2]
Bowing of distal radius and ulna (coxa vera) [1], [3] The posterior bowing of the distal tibia and deformities of the forearms are more commonly seen in infants [1]
Lateral bowing of femur and tibia (genu valgum and varum) [1], [3] Varus deformity is seen in a toddler who's just started to walk where as valgus deformity is seen in an older child. [1]
Windswept deformity (valgus deformity of one leg and varus deformity of the other) [1], [3] This is seen in an older child with weight bearing [1]
Leg pain and fractures [2], [3] Due to decreased bone mineralization [2]
Muscle weakness (especially proximal) [2], [3] Due to decreased muscle tone owing to reduced calcium level [1]
Delayed motor milestones [1] , [3] Due to decreased muscle tone owing to reduced calcium level [1]
Delayed dentition; caries [2], [3] Hypoplasia of the dental enamel is a typical finding of rickets due to hypocalcaemia whereas dental abscesses occur more often in phosphotaemic rickets [1]
Seizures [2], [3] Due to hypocalcaemia [2]
Tetany [2], [3] Due to hypocalcaemia [2]
Stridor due to laryngeal spasm [2], [3] Due to hypocalcaemia [2]
Respiratory infections [2], [3] Softening of the ribs impairs air movement and predisposes patients to atelectasis or collapse of alveoli which increases the risk of pneumonia [2]
Failure to thrive [2] Children with rickets are prone to recurrent infections and associated nutritional deficiency [1]
Alopecia [2] This is seen in vitamin D–dependent rickets type 2 [2]
References
  1. SAHAY M, SAHAY R. Renal rickets-practical approach. Indian J Endocrinol Metab [online]. 2013;17(Suppl1):S35-S44 [viewed on 21st April]. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830358/
  2. GREENBAUM, Larry A. Rickets and hypervitaminosis D. In KLIGEMAN, Robert M, BEHRMAN, Richard E, JENSON, Hal B and STANTON, Bonita F. Nelson textbook of Paediatrics. 18th ed. Philadelphia: Saunders Elsevier, 2007
  3. HOLICK MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest[online]. 2006;116(8):2062-72 viewed on 22nd April. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1523417/

Examination

Fact Explanation
Enlargement of wrists and ankles [1] Due to widening of the distal end of the metaphysis as a result of thickening of the growth plate due to decreased calcification [2]
Bowing of distal radius and ulna (coxa vera) [1], [5] The posterior bowing of the distal tibia and deformities of the forearms are more commonly seen in infants [1]
Lateral bowing of femur and tibia (genu valgum and varum) [1], [5] Varus deformity is seen in a toddler who's just started to walk where as valgus deformity is seen in an older child. [1]
Windswept deformity (valgus deformity of one leg and varus deformity of the other) [1] This is seen in an older child with weight bearing [1]
Deformities of the back: scoliosis, kyphosis, lordosis [2] Due to skeletal changes [2]
Craniotabes [2] ,[5] This is due to softening of the cranial bones, which can be detected by applying pressure at the occiput or over the parietal bones. The sensation is similar to the feel of pressing into a table tennis ball and then releasing.[2]
Parietal and frontal bossing with caput quadratum [1], [5] Due to skeletal changes [2]
Delayed fontanelle closure [2], [5] Due to skeletal changes [2]
Craniosynostosis [2] Due to skeletal changes [2]
Rachitic rosary [2], [5] This is widening of the costochondral junctions results in a rachitic rosary; this feels like the beads of a rosary when felt along the costochondral junctions. [2]
Harrison groove [2], [5] The horizontal depression along the lower anterior chest and this groove occurs due to pulling of the softened ribs by the diaphragm during inspiration [2]
pigeon-breast deformity/Pectus carinatum [2], [5] Due to skeletal changes [2]
Short stature [3] Due to failure to thrive and growth failure [3]
Protuding abdomen/ Pot belly [1], [2] Due to muscle hypotonia [1]
Dental manifestations: dentin defects, large pulp chambers, enlarged pulp horns, hypoplastic enamel, dental abscesses. [4], [5] Hypoplasia of the dental enamel is a typical finding of hypocalcaemic rickets, whereas dental abscesses occur more often in hypophosphataemic rickets. [1]
Pallor [5] Due to associated hypochromic anaemia or rarely with Von Jacksch–Luzet syndrome in which there's severe anamia and clinical features similar to chronic myeloid leukemia [5]
Hepato splenomegaly [5] As a result of extra medullary hemopoiesis [5]
References
  1. SAHAY M, SAHAY R. Renal rickets-practical approach. Indian J Endocrinol Metab [online]. 2013;17(Suppl1):S35-S44 [viewed on 21st April]. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830358/
  2. GREENBAUM, Larry A. Rickets and hypervitaminosis D. In KLIGEMAN, Robert M, BEHRMAN, Richard E, JENSON, Hal B and STANTON, Bonita F. Nelson textbook of Paediatrics. 18th ed. Philadelphia: Saunders Elsevier, 2007
  3. LISSAUER, Tom. CLAYDEN, Graham. Illustrated textbook of Paediatrics. 3rd ed. London: Mosby Elsevier, 2007
  4. SOUZA AP, KOBAYASHI TY, LOURENCO NETO N, SILVA SM, MACHADO MA, OLIVIERA TM. Dental manifestations of patient with vitamin D-resistant rickets. J Appl Oral Sci [online]. 2013;21(6):601-6 [viewed on 21st April]. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891287/
  5. HOLICK MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest[online]. 2006;116(8):2062-72 viewed on 22nd April. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1523417/

Differential Diagnoses

Fact Explanation
Hypophosphatasia [1] This is a rare genetic disorder of alkaline phosphatase activity. Similar to rickets, it is characterized by bone demineralization but, serum alkaline phosphatase activity is very low in hypophosphatasia [1]
Jansen syndrome [1] This is a rare autosomal dominant form of short-limbed dwarfism in which infants present with metaphyseal chondroplasia [1]
Skeletal dysplasia: achondroplasia, pseudoachondroplasia, metaphyseal chondrodysplasia) [1] This causes bilateral, symmetric bowed legs. Radiographic features can be similar to those of rickets but serum inorganic phosphorus and PTH concentrations usually are normal in children with skeletal dysplasia in contrast to rickets. [1]
Osteogenesis imperfecta [2] Osteogenesis imperfecta or brittle bone disease is a generalized disorder of connective tissue and causes skeletal dysplasia hence bowed legs [2]
Blount's disease [2] This is also known as infantile Tiba Vara, an uncommon condition predominantly seen in Afro Caribbean children, where there is breaking of the proximal medial tibial epiphysis in x ray [2]
Physiological bowing [2] It's common in children and toddlers up to age 3 [2]
References
  1. SAHAY M, SAHAY R. Renal rickets-practical approach. Indian J Endocrinol Metab [online]. 2013;17(Suppl1):S35-S44 [viewed on 21st April]. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830358/
  2. LISSAUER, Tom. CLAYDEN, Graham. Illustrated textbook of Paediatrics. 3rd ed. London: Mosby Elsevier, 2007

Investigations - for Diagnosis

Fact Explanation
X-ray of the distal ends of the radius, ulna, and fibula (wrists, knee and ankles) [1] Decreased calcification leads to thickening of the growth plate and the edge of the metaphysis loses its sharp border,this is described as "fraying". Also the edge of the metaphysis changes from a convex surface to a concave surface, this process is is termed 'cupping'. There is also widening of the distal end of the metaphysis, coarse trabeculation of the diaphysis, pathological fractures and Looser's zones (also known as Milkman's pseudofractures ). [1], [2]
Serum calcium and phosphorus [2] To identify causes of rickets which include conditions that lead to hypocalcemia and/or hypophosphatemia as a result of decreased intake; malabsorption; and/or increased excretion of calcium, phosphate, or vitamin D [1]
Serum Alkaline phosphatase [2] To identify causes of rickets which include conditions that lead to hypocalcemia and/or hypophosphatemia [1]
Serum Parathyroid hormone (PTH) level [2] To identify causes of rickets which include conditions that lead to hypocalcemia and/or hypophosphatemia [1]
Serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D3 level [2] To identify causes of rickets which include conditions that lead to hypocalcemia and/or hypophosphatemia [1]
Serum Creatinine and electrolytes [2] To identify whether there's any renal impairment which gives rise to renal rickets [2]
Urinalysis [2] This is useful for detecting the glycosuria and aminoaciduria (positive dipstick for protein) seen with Fanconi syndrome [2]
Urinary excretion of calcium (24 hr collection for calcium or calcium-creatinine ratio) [2] This is helpful if hereditary hypophosphatemic rickets with hypercalciuria or Fanconi syndrome is suspected [2]
Other fat-soluble vitamins (A, E, and K) or indirect assessment of deficiency (prothrombin time for vitamin K deficiency) [2] This is appropriate if malabsorption is suspected [2]
Arterial blood gas analysis and urinary pH [1] To identify any renal tubular acidosis( RTA). All types of RTA present with a normal anion gap (hyperchloremic) metabolic acidosis and the degree of acidosis varies with the type of RTA. For example, In distal (type 1) RTA,there is hydrogen ion retention and fall of plasma bicarbonate and the urine pH is 5.5 or higher. In proximal (type 2) RTA, whenever the plasma bicarbonate is above threshold, that is, 15 mEq/l there is loss of bicarbonate hence acidosis [1]
References
  1. SAHAY M, SAHAY R. Renal rickets-practical approach. Indian J Endocrinol Metab [online]. 2013;17(Suppl1):S35-S44 [viewed on 21st April]. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830358/
  2. GREENBAUM, Larry A. Rickets and hypervitaminosis D. In KLIGEMAN, Robert M, BEHRMAN, Richard E, JENSON, Hal B and STANTON, Bonita F. Nelson textbook of Paediatrics. 18th ed. Philadelphia: Saunders Elsevier, 2007

Investigations - Followup

Fact Explanation
Serum calcium and phosphorus [1] The metabolic derangements should be normalized and failure of treatment should be considered if no biochemical response occurs after 3-5 months of treatment [1]
Serum alkaline phosphatase [1] To see the response to the treatment and the level should be normalized[1]
Serum creatinine [1] To see the response to the treatment and the level should be normalized[1]
Serum 1,25(OH)2 D [1] To see the response to the treatment and the level should be normalized[1]
Serum PTH [1] To see the response to the treatment and the level should be normalized[1]
Urinary calcium/creatinine ratio [1] To see the response to the treatment and the level should be normalized[1]
X-rays [1] X-rays should show improvement after 4 weeks of treatment. When the growth plates regain a normal appearance after 3 months, these should be repeated again. Hand x-rays are performed annually to check for the reappearance of any rachitic changes.[1]
References
  1. SAHAY M, SAHAY R. Renal rickets-practical approach. Indian J Endocrinol Metab [online]. 2013;17(Suppl1):S35-S44 [viewed on 21st April]. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830358

Management - General Measures

Fact Explanation
Dietary management [1], [2] Encouraging the proper intake of vitamin D and calcium in diet. Most children in developed countries, receive vitamin D from formula, fortified milk, or vitamin supplements. However, exact composition of the formula or milk is important as rickets has been observed in children given milk substitute products such as soy milk, which are deficient in vitamin D and/or minerals. [1], [2]
Adequate sunlight exposure [1], [2], [4] It is important to encourage children to spend more time outside, advice not to use too much sunscreen, and regarding covered clothing (especially if there's a cultural reason for increased covering of the skin). Controlled exposure to sunlight or UV radiation from a commercial lamp is another alternative [1], [2], [4]
Avoidance of using certain medication [1] The child's medication use is relevant because certain medications, such as the anticonvulsants phenobarbital and phenytoin, increase degradation of vitamin D, and aluminum-containing antacids interfere with the absorption of phosphate. [1]
Management of renal impairment [1] Renal impairment may cause rickets. [1]
Management of malabsorptive conditions [1] This could be the underlying cause for rickets. [1]
Pain relief for bone pain [3] Class I analgesics (acetaminophen, paracetamol, some NSAIDs) are good for pain relief. [3]
References
  1. GREENBAUM, Larry A. Rickets and hypervitaminosis D. In KLIGEMAN, Robert M, BEHRMAN, Richard E, JENSON, Hal B and STANTON, Bonita F. Nelson textbook of Paediatrics. 18th ed. Philadelphia: Saunders Elsevier, 2007
  2. SAHAY M, SAHAY R. Renal rickets-practical approach. Indian J Endocrinol Metab [online]. 2013;17(Suppl1):S35-S44 [viewed on 21st April]. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830358/
  3. LINGLART A, BIOSSE-DUPLAN M, BRIOT K, et al. Therapeutic management of hypophosphatemic rickets from infancy to adulthood. Endocr Connect [online]. 2014;3(1):R13-30 [viewed on 21st April]. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959730/
  4. HOLICK MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest[online]. 2006;116(8):2062-72 viewed on 22nd April. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1523417/

Management - Specific Treatments

Fact Explanation
Pharmacological management with Vitamin D for nutritional rickets [1], [2] Treatment for many forms of rickets include administration of vitamin D which could be given in a single day dose of 15,000 μg (600,000 U) or gradually over several months. The gradual dose is given until healing is well established indicated by x-rays and the alkaline phosphatase concentration becomes normal. Intramuscular injection is available as well. The cholecalciferol form is gradually released over weeks from the body stores. Both calcidiol and calcitriol are unsuitable for treatment since they have short half-lives. [1]
Bicarbonate therapy for proximal RTA [1] Treatment of proximal RTA includes 10-15 mEq/kg of bicarbonate per day to maintain a normal pH. Many bicarbonate preparations are available as Shohl's solution (citric acid and sodium citrate), Bicitra-K, Polycitra, and Potassium citrate solution. There are also Bicarbonate tablets and Bicarbonate powder. Other additional therapies include magnesium, carnitine, and thiazide diuretics which are given to reduce polyuria and vitamin D supplements [1]
Potassium citrate therapy for distal RTA [1] Treatment with alkali therapy usually improves both calcium and potassium balance in distal RTA, Also prevents stones and nephrocalcinosis. In contrast to the high alkali requirement in Proximal RTA, the daily bicarbonate requirement is only 1-2 mEq/kg per day [1]
oral administration of phosphate and calcitriol for hypophosphataemic rickets [1], [3] The treatment is indicated in symptomatic patients for bone pain or non-uniting fractures or those who are to undergo orthopedic surgery in next 3-6 months only. Treatment with Phosphate increases the plasma phosphate concentration, which in turn lowers the plasma ionized calcium, and plasma calcitriol concentration. And Hypocalcemia and low calcitriol causes secondary hyperparathyroidism which exacerbates the bone disease and increase urinary phosphate excretion. Therefore it's vital that Calcitriol is given along with oral phosphorus. Addition of a calcimimetic (cinacalcet) to the regimen may prevent secondary hyperparathyroidism. However, long-term studies in children with X Linked Hypophosphataemic rickets are necessary before calcimimetics can be generally recommended. Newer therapeutic strategies include neutralizing antibody to FGF23 are also suggested.[1]
Phosphorus supplementation without Calcitriol for hypophosphataemic rickets with hypercalciuria [1], [3] This is inherited in an autosomal recessive manner and is associated with high levels of vitamin D. These patients should be treated only with phosphorus supplementation. Calcitriol should not be used. [1]
Removal of tumour or treatment with octreotide when tumour can not be found for tumour induced osteomalacia [1], [3] Cinacalcet, which is a calcimimmetic may be useful. And the therapy is continued until the causative tumor is removed or indefinitely if tumor removal is not possible. Treatment with octreotide may be considered when the tumor cannot be found. [1]
Pharmacological management with calcitriol, for vitamin D dependent rickets type 1 and 2 along with Calcium for vitamin D dependent rickets type 2 or CKD stages 2 to 5 for the treatment of secondary hyperparathyroidism or for patients with severe vitamin D deficiency with severe symptomatic hypocalcemia, including seizure and tetany [1] , [2] Both are Autosomal recessive disorders which need treatment as described above. [1]
Orthopedic and surgical management [4] Physiotherapy is useful to prevent complete patellar dislocation and improve muscle fitness. Surgery during childhood is better avoided as it opens epiphyses and present a significant risk of recurrence. Therefore when necessary, surgery should be combined with adjusted doses of phosphate supplements and vitamin D analogs to prevent recurrence. Surgical options available are Bifocal femoral and tibiae metaphyseal–diaphyseal osteotomies, Osteosynthesis done by locking plates or intramedullary nails and external fixation [4]
References
  1. SAHAY M, SAHAY R. Renal rickets-practical approach. Indian J Endocrinol Metab [online]. 2013;17(Suppl1):S35-S44 [viewed on 21st April]. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830358/
  2. LEE JY,TY So , THACKRAY J. A Review on Vitamin D Deficiency Treatment in Pediatric Patients. J Pediatr Pharmacol Ther [online]. 2013;18(4):277-291 [viewed on 21st April]. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979050/
  3. JAGTAP VS, SARATHI V, LILA AR, BANDGAR T, MENON P, SHAH NS. Hypophosphatemic rickets. Indian J Endocrinol Metab [online]. 2012;16(2):177-82 [viewed on 21st April]. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313733/
  4. LINGLART A, BIOSSE-DUPLAN M, BRIOT K, et al. Therapeutic management of hypophosphatemic rickets from infancy to adulthood. Endocr Connect [online]. 2014;3(1):R13-30 [viewed on 21st April]. Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959730/