Rickets guidance: part II-management

Pediatr Nephrol. 2022 Oct;37(10):2289-2302. doi: 10.1007/s00467-022-05505-5. Epub 2022 Mar 29.

Abstract

Here, we discuss the management of different forms of rickets, including new therapeutic approaches based on recent guidelines. Management includes close monitoring of growth, the degree of leg bowing, bone pain, serum phosphate, calcium, alkaline phosphatase as a surrogate marker of osteoblast activity and thus degree of rickets, parathyroid hormone, 25-hydroxyvitamin D3, and calciuria. An adequate calcium intake and normal 25-hydroxyvitamin D3 levels should be assured in all patients. Children with calcipenic rickets require the supplementation or pharmacological treatment with native or active vitamin D depending on the underlying pathophysiology. Treatment of phosphopenic rickets depends on the underlying pathophysiology. Fibroblast-growth factor 23 (FGF23)-associated hypophosphatemic rickets was historically treated with frequent doses of oral phosphate salts in combination with active vitamin D, whereas tumor-induced osteomalacia (TIO) should primarily undergo tumor resection, if possible. Burosumab, a fully humanized FGF23-antibody, was recently approved for treatment of X-linked hypophosphatemia (XLH) and TIO and shown to be superior for treatment of XLH compared to conventional treatment. Forms of hypophosphatemic rickets independent of FGF23 due to genetic defects of renal tubular phosphate reabsorption are treated with oral phosphate only, since they are associated with excessive 1,25-dihydroxyvitamin D production. Finally, forms of hypophosphatemic rickets caused by Fanconi syndrome, such as nephropathic cystinosis and Dent disease require disease-specific treatment in addition to phosphate supplements and active vitamin D. Adjustment of medication should be done with consideration of treatment-associated side effects, including diarrhea, gastrointestinal discomfort, hypercalciuria, secondary hyperparathyroidism, and development of nephrocalcinosis or nephrolithiasis.

Keywords: Burosumab; Fanconi syndrome; Fibroblast growth factor 23; Management; Nephrocalcinosis; Nutritional rickets; Phosphate; Rickets; Vitamin D; Vitamin D-dependent rickets; X-linked hypophosphatemia.

MeSH terms

  • Calcium / therapeutic use
  • Child
  • Familial Hypophosphatemic Rickets* / drug therapy
  • Familial Hypophosphatemic Rickets* / genetics
  • Fanconi Syndrome*
  • Fibroblast Growth Factors
  • Humans
  • Osteomalacia
  • Paraneoplastic Syndromes
  • Phosphates
  • Rickets* / drug therapy
  • Rickets* / etiology
  • Rickets, Hypophosphatemic* / drug therapy
  • Rickets, Hypophosphatemic* / etiology
  • Vitamin D / therapeutic use

Substances

  • Phosphates
  • Vitamin D
  • Fibroblast Growth Factors
  • Calcium

Supplementary concepts

  • Oncogenic osteomalacia