Nutritional Rickets

AUTHORS:
Drishti Tolani, MD¹ • Neha Bansal, MD² • Deepak Kamat, MD, PhD³

AFFILIATIONS:
¹Department of Pediatrics, Children’s Hospital of Michigan, Detroit, Michigan
²Division of Pediatric Cardiology, Children’s Hospital at Montefiore, Bronx, NY, USA
³Department of Pediatrics, University of Texas Health Science Center at San Antonio, Texas

CITATION:
Tolani D, Bansal N, Kamat D. Nutritional rickets. Consultant. 2020;60(6):e3. doi:10.25270/con.2020.04.00012

Received October 20, 2019. Accepted March 10, 2020.

DISCLOSURES:
The authors report no relevant financial relationships.

CORRESPONDENCE:
Drishti Tolani, MD, Children’s Hospital of Michigan, 3901 Beaubien St, Detroit, MI 48201 (tolanidrishti@gmail.com)

Nutritional rickets has been commonly reported as a public health problem in Africa and several parts of the Asian subcontinent. However, there has been a recent reemergence of vitamin D deficiency noted in developed countries of North America and Europe.^1,2 The American Academy of Pediatrics (AAP) recommends that all exclusively breast-fed infants, as well as mixed fed (which is both formula and breast milk-fed) or formula-fed infants who consume less than 1 L a day of formula, should receive 400 IU of vitamin D daily to be started within the first few days of life. We present the case of a 4-year-old girl who had been mixed fed with breast milk and formula and who was diagnosed with nutritional rickets by way of incidental findings on physical examination.

CASE REPORT

A 4-year-old African American girl was seen at a general pediatric clinic for her well child visits. She had been born full-term and had been small for gestational age (third percentile for age). She was initially mixed-fed with breast milk and formula until 6 months of age and then transitioned to pureed food. The exact proportion of breast and formula feeds per day could not be provided by the mother; however, as per the history provided by the mother, the girl had been primarily formula-fed and hence no vitamin D supplementation was initiated in the first 6 months of the patient’s life. Her mother continued to breast-feed the girl after transitioning to solid foods.

At her 9-month well-child checkup, the girl was noted to have inadequate weight gain, weighing 6.9 kg (seventh percentile for age) (Figure 1).

Figure 1. Growth chart of the patient showing dropping of growth percentiles and a plateau in the weight gain of the child.

The mother did not follow-up in clinic until the girl was 16 months of age. At this visit, the patient was reported to be a “picky eater,” and her diet primarily consisted of breast milk. She had no history of feeding intolerance, vomiting, or diarrhea. Developmentally, she was appropriate for her age. Her weight was at the second percentile for age, with a growth curve consistent with failure to thrive. She was also found to be stunted, with length for age at the fifth percentile and weight for length at the third percentile for age. Physical examination findings were significant for frontal bossing, an open anterior fontanelle, and widening of the wrists bilaterally. Palpation of chest revealed prominent bony knobs at the costochondral joints bilaterally—the “rachitic rosary.” Additionally, the medial malleolus bore indentation bilaterally consistent with the double malleoli sign, and the patient had findings consistent with genu varum.

Laboratory test findings were significant for an elevated alkaline phosphatase (ALP) level of 1608 U/L (reference range, 50-249 U/L), a low 25-hydroxyvitamin D level of less than 5 ng/mL (reference range, 30-100 ng/mL), a low serum calcium level of 8.4 mg/dL (reference range, 8.8-10.1 mg/dL), and a low serum phosphorus level of 1.5 mg/dL (reference range, 3.8-6.5 mg/dL). The parathyroid hormone (PTH) level was elevated at 636 pg/mL (reference range, 15-69 pg/mL). Screening test results for celiac disease were negative.

Radiographs of the wrist (Figure 2) revealed cupping and fraying of the distal ulnar radial metaphysis and diffuse osseous demineralization, findings that were consistent with rickets.

Figure 2. Wrist radiograph demonstrating cupping and fraying of the distal ulnar radial metaphysis and diffuse osseous demineralization (arrow).

Additionally, the results of a basic metabolic panel (BMP) were significant for non–anion-gap metabolic acidosis with concerns for renal tubular acidosis (RTA) secondary to vitamin D-dependent rickets—a sodium level of 141 mEq/L, a potassium level of 4.2 mEq/L, a chloride level of 111 mEq/L, a bicarbonate level of 18 mEq/L (reference range, 21-32 mEq/L), an anion gap of 12 mEq/L (reference range, 5-15 mEq/L), a serum urea nitrogen level of 12 mg/dL, and a creatinine level of 0.14 mg/dL.

Dietary counseling for consumption of calcium-rich and vitamin D-rich food was provided to the mother. The patient was started on oral vitamin D₃ supplementation, 2000 IU daily, and oral calcium acetate supplementation, 1000 mg daily.

Initially, there was delayed improvement in her laboratory test findings as a result of nonadherence to the supplements; however, the test results eventually improved. Repeated BMP results revealed resolution of the non–anion-gap metabolic acidosis, which was thought to be secondary to malnutrition. Urinalysis with urine electrolytes including creatinine and calcium was done, the results of which were all within normal limits and not concerning for RTA.

Results of repeated imaging of wrist 6 months later, at 2.5 years of age (Figure 3), were significant for development of sclerosis at the zones of provisional calcification consistent with healing rickets.

Figure 3. Interval development of sclerosis at the zones of provisional calcification consistent with healing rickets (arrow). The cupping of the distal radial and ulnar metaphysis is less pronounced than on earlier radiographs.

DISCUSSION

Nutritional rickets secondary to vitamin D deficiency usually presents within the first 18 months of life.¹ There has been a recent resurgence of nutritional rickets (an increased incidence from 0 in 1970 to 24.1 per 100,000 in 2000 in one study³), and it is associated with breastfeeding, low birth weight, African American ethnicity, and stunted growth.³ The exact reason for this increased incidence is unknown, but it likely stems from poor education and low knowledge among parents about the importance of supplementing breast milk with vitamin D, as well as from vitamin D deficiency in breastfeeding mothers themselves.⁴ Infants with mothers who had a poor vitamin D status during pregnancy and those exclusively breast-fed for a prolonged time with little skin exposure to UV-B radiation are commonly affected.⁵

The etiology of nutritional rickets has a wide spectrum.¹ A 3-stage categorization for sufficiency, insufficiency, and deficiency of vitamin D has been defined by several organizations.⁶ The AAP defines severe vitamin D deficiency as a serum level of 25-hydroxyvitamin D less than 5 ng/mL, vitamin D deficiency as a level of 5 to 15 ng/mL, and insufficiency as a level of 15 to 20 ng/mL; sufficient levels are defined as being above 20 ng/mL.^2,7

Nutritional rickets is an ultimate manifestation of a spectrum of nutritional deficiencies ranging from an isolated calcium deficiency to an isolated vitamin D deficiency, with some overlap between the two. While rickets is multifactorial and continues to evolve, geographic differences between the nutritional causes for rickets have been identified, with calcium deficiency being a significant cause of rickets in Africa and Asia and vitamin D deficiency being a significant cause of rickets in Europe.¹ The 2008 AAP guidelines of vitamin D supplementation amounting to 400 IU/day for breast-fed and mixed-fed infants are inconsistently followed, with only one-tenth of breast-fed infants and one-third of mixed-fed infants actually meeting this daily requirement.⁷ Fewer than 1 in 5 breast-fed infants met the vitamin D recommendations compared with nearly 1 in 3 non–breast-fed infants.⁸

Nutritional rickets can present with a variety of clinical manifestations, including musculoskeletal deformities, tetany, bone fractures, and failure to thrive. Isolated case reports of nutritional rickets with hypocalcemia resulting in dilated cardiomyopathy have also been reported.⁴ The diagnosis of nutritional rickets is most often an incidental finding based on an astute physical examination, as in our patient’s case. The physical findings are delayed closure of the anterior fontanelle, craniotabes, enlargement of wrists, frontal bossing, the rachitic rosary, enamel hypoplasia and delayed teething, the Harrison groove, pectus carinatum, and in extreme cases costal or lower extremity fractures.¹ Genu varum and genu valgum are common lower-extremity deformities seen when children with untreated vitamin D deficiency begin walking.⁹

A thorough physical examination and a detailed dietary history can help direct a clinician to the initial diagnosis of nutritional rickets, which can be confirmed with laboratory biochemical tests; elevated ALP and serum PTH levels are the earliest biochemical signs seen, followed by hypocalcemia and a decrease in 25-hydroxyvitamin D levels.⁶ In fact, there is a significant lag, varying with each patient, between these early biochemical findings and the development of clinical and radiologic signs of rickets.⁹ Radiographic findings consistent with nutritional rickets include osteopenia and fraying and cupping of the distal radius and ulna, as was seen in our patient’s case. Children with radiographically confirmed rickets have an increased risk of fracture.⁶

Global recommendations for the treatment of nutritional rickets are a minimal recommended dose of 2000 IU/day for a minimum of 12 weeks.¹ Response to treatment is monitored with repeated radiography and laboratory testing of levels of serum calcium, phosphorous, ALP, PTH, and 25-hydroxyvitamin D levels after 3 months of treatment. If the response to treatment is inadequate, treatment is continued for a longer period with 3 monthly interval evaluations.¹ Following normalization of laboratory and radiological signs, yearly evaluations are recommended.¹

Both vitamin D₂ and D₃ are equally efficacious for daily dosing, and oral treatment is preferred to intramuscular dosing, given the fact that oral treatment rapidly replenishes the deficient stores of vitamin D.⁶ Higher concentrations of hydroxyvitamin D at 6 weeks have been seen in patients who receive a single high dose of 150,000 IU of vitamin D when compared with daily dosing.¹⁰ When single doses are used, vitamin D₃ is preferred over D₂ given its longer half-life and thus more-sustained action.⁶ Moreover, it has been found that all patients with nutritional rickets should receive calcium supplements of at least 500 mg/day in addition to vitamin D, since this combination therapy has proven to provide a better healing response compared with vitamin D only.¹⁰ Calcium supplementation is essential in conjunction with vitamin D therapy to avoid further hypocalcemia that can occur as a consequence of remineralization of bones, commonly known as hungry bone syndrome.¹¹ Twelve weeks of therapy with a single intramuscular dose of 60,000 IU of vitamin D₃ and daily oral calcium has demonstrated radiological healing and normalization of ALP levels.¹²

Our patient was treated with daily vitamin D supplements in addition to calcium, leading to a healing response seen in follow up radiologic imaging within 6 months of therapy and normalization of her laboratory values.

TAKE-HOME MESSAGE

Clinicians need to recognize that nutritional rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents.⁶ Initiation of vitamin D supplementation in exclusively breast-fed and mixed-fed infants, and appropriate education of all parents regarding the same, is imperative for prevention of this disease. A through physical examination and dietary history are essential in screening for nutritional rickets. The confirmation of the diagnosis can be made easily on biochemical testing and radiologic findings. The treatment is safe and effective with a good response rate if adherence can be achieved.

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