Ann Pediatr Endocrinol Metab.  2024 Oct;29(5):284-307. 10.6065/apem.2448044.022.

Diagnostic approach to rickets: an Endocrine Society of Bengal (ESB) consensus statement

• Roy A
• Chowdhury AS
• Ray A
• Baidya A
• Roychowdhury B
• Sarkar D
• Sanyal D
• Maisnam I
• Biswas K
• Pandit K
• Banerjee M
• Raychaudhuri M
• Sengupta N
• Chakraborty PP
• Mukhopadhyay P
• Raychaudhuri P
• Sahana PK
• Palui R
• Bhattacharjee R
• Mukhopadhyay S
• Mukhopadhyay S
• Ray S
• Goswami S
• Chowdhury S
• Pramanik S
• Swar SC
• Ghosh S
• Mondal S
• Das TC

• KMID: 2560464
• DOI: http://doi.org/10.6065/apem.2448044.022

Abstract

Rickets, one of the leading causes of bony deformities and short stature, can be calciopenic (inciting event is defective intestinal calcium absorption) or phosphopenic (inciting event is phosphaturia). Early diagnosis and timely treatment of rickets are crucial for correction of the limb deformities. Guidelines exist for nutritional rickets, but the diagnosis and management of the relatively uncommon forms of rickets are complex. This consensus aims to formulate a simplified diagnostic approach for rickets, especially in resource-limited settings. The consensus statement has been formulated by a 29-member committee from the Endocrine Society of Bengal. The process included forming a working group, conducting a literature review, identifying controversies, drafting, and discussion at a consensus meeting. Participants rated their agreement with the clinical practice points, and a 70% consensus was required. Input integration and further review led to the final consensus statements. Children with suspected rickets should initially be examined for distinctive skeletal deformities. The diagnosis of rickets should be confirmed with characteristic radiographic abnormalities. It is advisable to order tests for serum calcium, inorganic phosphorus (Pi), liver function, 25-hydroxyvitamin D (25OHD), parathyroid hormone, creatinine, and potassium in all patients with rickets. In cases of refractory rickets, it is also recommended that assessments be conducted for spot urine calcium, Pi, creatinine, and, blood gas analysis. In children with rickets and metabolic acidosis, tests for glycosuria, uricosuria, aminoaciduria, low molecular weight proteinuria, and albuminuria should be conducted. In children with resistant calciopenic rickets and sufficient serum 25OHD levels, serum 1,25(OH)2D concentration should be tested. 1,25(OH)2 D and fibroblast growth factor 23 estimation is useful for certain forms of phosphopenic rickets.

Keyword

Calciopenic rickets; Phosphopenic rickets; Resistant rickets; Nutritional rickets; Rickets mimickers

Figure

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  Fig. 1. Flow diagram for article selection for this consensus statement. COVID-19, coronavirus disease 2019.

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  Fig. 2. Mechanism of apoptosis of late hypertrophic chondrocytes. The numbers within the black solid circles denote factors contributing to enlarged growth plates in rickets.

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  Fig. 3. Radiological abnormalities in rickets. (A) Increased width of the zone of provisional calcification (bidirectional arrow). (B) Fraying of metaphysis. (C) Cupping (notched arrow) and splaying (arrow) of metaphysis with increased radiolucent gap between the epiphysis and metaphysis (bidirectional arrow). (D) Irregular margins of the epiphysis (arrow). (E) Thin cortices (arrow) and skeletal changes of secondary hyperparathyroidism (notched arrow) in calciopenic rickets. (F) Thick cortices (arrow) in phosphopenic rickets. (G) Healing lines (arrow) after adequate doses of oral cholecalciferol and calcium in nutritional rickets.

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  Fig. 4. Rickets mimickers. (A) Beaking of proximal tibial metaphyses in Blount’s disease (arrow). (B) metaphyseal irregularities (arrow) giving rise to a moth-eaten appearance in metaphyseal chondrodysplasia. (C) platyspondyly (arrow) in progressive pseudorheumatoid dysplasia. (D) characteristic radiological appearance of the hand in progressive pseudorheumatoid dysplasia. (E) mega os trigonum (arrow) in progressive pseudorheumatoid dysplasia. (F) anterior beaking of the vertebra (arrow) in mucopolysaccharidoses. (G) bullet-shaped metacarpals (arrow) and a V-shaped configuration between the distal ends of the radius and ulna (notched arrow) in mucopolysaccharidoses.

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  Fig. 5. Schematic diagram for measuring intercondylar and intermalleolar distances and the tibiofemoral angle.

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  Fig. 6. Appearance of healing lines following vitamin D supplementation in an adolescent with nutritional rickets due to VDD (A–C) and in a 4-year-old child with dRTA (D, E). (A) Typical radiological features of rickets at baseline. (B) Note the healing lines (white notched arrow) 12 weeks after the initiation of vitamin D therapy. (C) Complete radiological recovery 5 months after treatment initiation. (D, E) Healing lines (white notched arrows) following high-dose vitamin D therapy in a child with dRTA. VDD, vitamin D deficiency; dRTA, distal renal tubular acidosis.

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  Fig. 7. Diagnostic algorithm for children with rickets (◇PTH is often more than 100 pg/mL in CR and less than 100 pg/mL in PR; *other forms of rickets can have similar levels of 25OHD; #coexistent calcium deficiency or partially treated NR due to VDD; ^some patients with VDDR-1A might not have low 1,25(OH)2D levels; **can be considered in mutation-negative FGF23-dependent PR) (words in italics denote acceptable alternatives). 1,25(OH)2D,1,25-dihydroxyvitamin D; 25OHD, 25-hydroxyvitamin D; ABG, arterial blood gas; ALP, alkaline phosphatase; CKD, chronic kidney disease; CR, calciopenic rickets; dRTA, distal RTA; FGF23, fibroblast growth factor 23; FS, Fanconi syndrome; iCa, ionized calcium; LMW, low molecular weight; NR, nutritional rickets; PHPT, primary hyperparathyroidism; Pi, inorganic phosphorus; PR, phosphopenic rickets; PTH, parathyroid hormone; RM, rickets mimicker; RTA, renal tubular acidosis; TIO, tumor-induced osteomalacia; VBG, venous blood gas; VDD, vitamin D deficiency; VDDR, vitamin D dependent rickets.

Reference

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