para>Ca, calcium; Phos, phosphorus; Alk phos, alkaline phosphatase; iPTH, intact parathyroid hormone; 25-(OH)D, 25-vitamin D; 1,25-(OH)2D, 1,25-dvitamin D; Ca/Cr, calcium/creatinine ratio; TRP, tubular reabsorption of phosphorus ([1 " ô (U phos â Ś P Cr/U Cr â Ś S Phos)] â Ś 100, normal 85 " ô95%); N, normal; AD, autosomal dominant; AR, autosomal recessive
Risk Factors
- Infants born to vitamin D " ôdeficient mothers
- Low birth weight and/or prematurity
- Breastfeeding without vitamin D supplementation
- Poor nutrition
- Increased skin pigmentation
- Higher latitudes and winter months
- Use of sunscreens
- Malabsorption
- Renal tubulopathies
Diagnosis
History
- Inadequate nutrition
- Prolonged breastfeeding without vitamin D supplementation
- Low dietary calcium intake
- Strict vegan diet without adequate calcium
- Premature infants taking unfortified formula
- Parenteral hyperalimentation
- Low levels of sunlight exposure
- Symptoms of malabsorption:
- Steatorrhea, abdominal pain, weight loss
- Symptoms of renal tubular dysfunction:
- Nephrolithiasis, polyuria
- Bone pain
- Delayed gross motor development
- Generalized muscular weakness
- Irritability
- Fractures following minimal trauma
- Dental abscesses
- Anticonvulsant use
- Family history of rickets
Physical Exam
- Growth deceleration
- Widening at the wrists, knees, and/or ankles
- Bowing of the extremities (varus or valgus deformities)
- Skull abnormalities
- Anterior fontanelle widening and/or delayed closure
- Frontal bossing
- Craniotabes (softening of the skull)
- Chest deformities
- Prominent costochondral junctions ( "rachitic rosary " Ł)
- Pectus carinatum
- Horizontal groove along the lower ribs ( "Harrison groove " Ł)
- Scoliosis
- Hypotonia
- Waddling gait
Diagnostic Tests & Interpretation
Initial Lab
- 25-vitamin D
- Major circulating form, and most sensitive indicator of vitamin D stores
- Sometimes reported as D2 (plant derived) and D3 (animal derived) forms
- D2 + D3 = total available 25-vitamin D
- Serum calcium, phosphorous (make sure age-appropriate norms for phosphorus are used by lab), and alkaline phosphatase
- Intact parathyroid hormone
- Urine calcium, creatinine, and urinalysis
- If rarer forms of rickets being considered: 1,25-vitamin D, urine phosphorus
Imaging
- Radiographic findings:
- Widening, cupping, and/or fraying of the growth plates
- Expansion of anterior ribs at the costochondral junctions
- Bowing of the long bones
- Osteopenia
- Knee or wrist films may be used diagnostically, and to monitor treatment response
Differential Diagnosis
- See Table 1 for ways to differentiate forms of rickets.
- Metaphyseal chondrodysplasia
- Blount disease
- Chronic recurrent multifocal osteomyelitis
- Neurofibromatosis type 1
- Renal osteodystrophy (combines features of rickets, osteomalacia, secondary hyperparathyroidism, and osteoporosis)
Treatment
General Measures
Treatment depends on the underlying etiology. é á
Additional Therapies
- Treatment of vitamin D deficiency: high dose repletion with cholecalciferol (D3) or ergocalciferol (D2) over 8 " ô12 weeks (goal total of ~200,000 " ô400,000 IU)
- Infants and children <5 years of age: 2,000 IU daily
- Children 5 years of age " ôadult: 4,000 " ô5,000 IU daily, or 14,000 to 50,000 IU weekly
- Following repletion, transition to daily maintenance dose (see "Table 2 " Ł).
é á
Table 2Dietary reference intake for calcium and vitamin DView LargeTable 2Dietary reference intake for calcium and vitamin DCalciumVitamin DAgeEstimated Average Requirement (mg/day)Recommended Dietary Allowance (mg/day)Upper Level Intake (mg/day)Estimated Average Requirement (IU/day)Recommended Dietary Allowance (IU/day)Upper Level Intake (IU/day)0 " ô6 months2002001,0004004001,0006 " ô12 months2602601,5004004001,5001 " ô3 years5007002,5004006002,5004 " ô8 years8001,0002,5004006003,0009 " ô18 years1,1001,3003,0004006004,00019 " ô30 years8001,0002,5004006004,000Adapted from Ross é áC, Abrams é áS, Aloia é áJ, et al. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press; 2011.
- Supplement with 30 " ô75 mg/kg elemental calcium divided t.i.d. to prevent hungry bone syndrome (hypocalcemia and hypophosphatemia during healing).
- Higher doses of vitamin D often required in patients with malabsorption, altered vitamin D metabolism, and/or obesity
- Optimal serum 25-vitamin D concentrations are controversial, however concentrations >20 ng/mL (50 nmol/L) sufficient to prevent rickets in otherwise healthy children.
Issues for Referral
- Consider endocrinology referral for infants, children with hypocalcemia, severe disease, suspected genetic forms of rickets, and/or lack of radiographic evidence of healing by 3 months.
- Nephrology referral for management of tubular dysfunction
- Orthopedic referral for patients with severe bowing
Inpatient Considerations
Admission Criteria
- Rickets can generally be managed in the outpatient setting, however inpatient admission may be considered if:
- Severe hypocalcemia with tetany or seizures
- Lack of response to therapy (suspected non-adherence)
Discharge Criteria
- Stable laboratory values
- Normalization in mental status and neurology exam improvement
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Monitor serum calcium, phosphorus, alkaline phosphatase, PTH, and spot urinary calcium/creatinine ratio every 2 " ô4 weeks. Note: Alkaline phosphatase may rise initially with treatment and then decrease gradually.
- Consider follow-up imaging after completion of high-dose vitamin D repletion.
- Patients who continue high-dose vitamin D for longer than prescribed may be at risk for hypercalcemia.
Patient Education
Ensure appropriate vitamin D and calcium intake to prevent recurrence (see "Table 2 " Ł). é á
Prognosis
- Rickets generally resolves with appropriate treatment.
- If radiographs and/or biochemical parameters not improving, consider the possibility of poor adherence, other forms of rickets, or alternative diagnoses.
Complications
- Failure to thrive, poor motor development
- Bowing and skeletal deformity
- Fractures
- Hypocalcemic tetany and seizures
Additional Reading
- Holick é áMF, Binkley é áNC, Bischoff-Ferrari é áHA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911 " ô1930. é á[View Abstract]
- Prentice é áA. Vitamin D deficiency: a global perspective. Nutr Rev. 2008;66(10)(Suppl 2):S153 " ôS64. é á[View Abstract]
- Ross é áC, Abrams é áS, Aloia é áJ, et al. Dietary reference intakes for calcium and vitamin D. Institute of Medicine Report Brief. 2010.
- Shaw é áNJ, Mughal é áMZ. Vitamin D and child health part 1 (skeletal aspects). Arch Dis Child. 2013;98(5):363 " ô367. é á[View Abstract]
- Weisberg é áP, Scanlon é áK, Li é áR, et al. Nutritional rickets among children in the United States: review of cases reported between 1986 and 2003. Am J Clin Nutr. 2004;80(6)(Suppl):1697S " ô1705S. é á[View Abstract]
Codes
ICD09
- 268.0 Rickets, active
- 268.9 Unspecified vitamin D deficiency
- 275.40 Unspecified disorder of calcium metabolism
ICD10
- E55.0 Rickets, active
- E55.9 Vitamin D deficiency, unspecified
- E58 Dietary calcium deficiency
SNOMED
- 41345002 Rickets (disorder)
- 34713006 Vitamin D deficiency (disorder)
- 238117007 Calcium deficiency (disorder)
- 82236004 Familial x-linked hypophosphatemic vitamin D refractory rickets (disorder)
FAQ
- Q: What is the best way to diagnose rickets?
- A: Laboratory evaluation and x-rays are the best ways to make the diagnosis. Radiographic findings are best seen at the distal radius and ulna, and/or the distal femur and proximal tibia.
- Q: What are the recommendations for vitamin D supplementation in infants and children?
- A: The American Academy of Pediatrics recommends the following:
- All breastfed infants should receive 400 IU daily.
- Nonbreastfed infants ingesting <500 mL/day of vitamin D " ôfortified formula or milk should receive 400 IU daily.
- Children who do not get regular sunlight exposure or do not consume at least 500 mL/day of vitamin D " ôfortified milk should receive 600 IU daily.
- Q: How is rickets/osteomalacia different from osteoporosis?
- A: Osteoporosis in children is defined by a combination of decreased bone mass coupled with fracture. Although bone density is reduced, bone matrix is generally normally mineralized. In rickets/osteomalacia, the primary defect is impaired mineralization of the underlying bone matrix. Osteoporosis and rickets/osteomalacia both result in an increased fracture risk; however, osteoporosis does not generally lead to growth plate and long bone deformities.