Vitamin D–Deficient Rickets

Rickets, a preventable disease, in infants, children, and adolescents is the softening and weaking of the bones due to poor mineralization at the growth plate from an imbalance in calcium and phosphorous homeostasis. The primary cause of rickets is nutritional, specifically vitamin D deficiency because vitamin D is an essential hormone in calcium and phosphorous equilibria. The clinical presentation of rickets may include short stature; bone pain, fractures, and deformities; delayed closure of the fontanelles; frontal bossing; craniotabes; enlargement of the costochondral junction known as rachitic rosary; widening of the elbow, wrist, knee, and ankle joints; and bowlegs. Other manifestations include delayed dentition, enamel hypoplasia, and hypocalcemia-related signs and symptoms. In 2016, experts from 11 international, mostly pediatric, scientific organizations published global consensus recommendations on the prevention and management of nutritional rickets. They defined vitamin D deficiency as serum 25-hydroxyvitamin D (25(OH)D) levels less than 30 nmol/L, insufficiency as levels 30 to 50 nmol/L, and sufficiency as levels greater than 50 nmol/L. Nonetheless, in 2024, the Endocrine Society, an international medical association, published a clinical practice guideline for the evaluation, treatment, and prevention of vitamin D deficiency in patients of all ages that no longer endorsed specific levels of 25(OH)D to define deficiency, insufficiency, and sufficiency because they “did not find clinical trial evidence that would support establishing distinct 25(OH)D thresholds tied to outcome-specific benefits.” The human body can generate vitamin D, technically making it a hormone, not a vitamin. Exposure of skin to sunlight in the UVB range spectrum (290–315 nm) results in isomerization of 7-dehydrocholesterol from the epidermis into vitamin D3. In the liver, vitamin D3 is hydroxylated to 25(OH)D, also known as calcidiol. Calcidiol is the most abundant circulating form of vitamin D and is therefore measured to assess vitamin D status. In the kidney, calcidiol is converted to 1,25-dihydroxyvitamin D3 (1,25(OH)D), also known as calcitriol, the active form of vitamin D. Given that this physiological process is initiated by UV irradiation, living in higher latitudes and inadequate sun exposure increase a child’s risk for vitamin D deficiency rickets. Sun exposure for 10 to 15 minutes per day may be sufficient in some latitudes to prevent vitamin D deficiency. However, due to the daytime variability in UVB light by geography, time of day, season, and weather, as well as concerns for skin cancer, the recommendation is for children to avoid direct sun exposure and not rely on sun exposure to meet their vitamin D needs. As a result, children require exogenous sources of vitamin D including from foods, such as fatty fish, fish oil, egg yolks, and fortified milk and formula, as well as dietary supplements. Risk factors for vitamin D deficiency rickets include prolonged exclusive breastfeeding without vitamin D supplementation among infants and excessive unfortified beverage consumption and inadequate intake of vitamin D–fortified foods among children. Other risk factors include malabsorption (associated, for example, with celiac disease, inflammatory bowel disease, and cystic fibrosis); chronic use of certain medications (eg, antiseizure medications or steroids); darker skin, which has more melanin, lowering the skin’s ability to produce vitamin D from sunlight; and liver and kidney disease. If rickets is suspected based on risk factors and clinical manifestation(s), the evaluation includes a detailed history and physical examination, as well as biochemical and radiologic workup. In assessing medical history, clinicians should determine a child’s sun exposure, dietary and supplementation intake, and family history of skeletal abnormalities, stunted growth, alopecia, or parental consanguinity, which may suggest a genetic cause for rickets. The physical examination should encompass a thorough assessment of both the skeletal and dental systems. Skeletal abnormalities may present as craniotabes, a ricket rosary (characterized by the widening of the costochondral junction), genu varum, genu valgum, and swelling of the joints, particularly in the knees and ankles, or wrist for a crawling infant. Dental anomalies may manifest as delayed dentition and enamel hypoplasia. The most important laboratory markers to diagnose rickets are a low serum 25(OH)D level and a high serum alkaline phosphatase (ALP) level, the latter due to increased osteoblastic activity. Other serum test findings include normal 1,25(OH)D values, low-to-normal calcium values, low-to-normal phosphorus values, and elevated parathyroid hormone (PTH) values. The radiologic workup includes radiographs of the distal ends of rapidly growing bones, such as the wrist and ankle, due to the high incidence of radiologic changes in these areas. This manifests as an expansion of the cartilaginous growth plate with delayed mineralization, appearing as a lucent gap between the metaphysis and epiphysis. The metaphysis appears indistinctly frayed and irregular on radiography.Vitamin D deficiency rickets can be cured. The 2016 global consensus publication recommends vitamin D 2000 IU/d (50 μg/d) for a minimum of 3 months, followed by 600 IU/d (15 μg/d) of vitamin D daily for maintenance. A one-time intramuscular high dose of vitamin D is an option, but the oral route is more effective in restoring serum vitamin D levels to normal range. It is important to ensure adequate calcium intake of 500 mg/d from food and/or supplementation. In 2008, the American Academy of Pediatrics Section on Breastfeeding and Committee on Nutrition recommended checking serum ALP, calcium, and phosphorus levels 1 month after initiating treatment and serum ALP, calcium, phosphorus, 25(OH)D, and PTH levels 3 months after. Follow-up radiography should be done at 3 months, and spot urine calcium/creatinine ratio can also be considered at that time. The major goals of monitoring are to assess whether serum calcium and phosphorus levels are maintained within normal range, ALP normalizes, and skeletal changes regress. With treatment, any bone pain typically improves by 2 weeks, metaphyseal swelling by 6 months, and bow leggedness by 2 years.There are steps to prevent vitamin D deficiency rickets. The first is education for pregnant and breastfeeding women and parents about empirical supplementation as either fortified foods or vitamin supplements. The summary of the literature included in the 2024 Endocrine Society’s clinical practice guideline found that supplemental vitamin D ranging from 600 IU (15 μg/d) to 5000 IU (125 μg/d), with an average of 2500 IU (62.5 μg/d) in pregnant women, was associated with reduced risk of preeclampsia, fetal demise, preterm or small-for-gestational-birth, and overall neonatal mortality. Infants that are exclusively breastfed or drinking less than 1000 mL of fortified formula per day should take 400 IU/d (10 μg/d) of vitamin D supplements. For children and adolescents aged 1 to 18 years, the Endocrine Society’s review of the literature found that empirical vitamin D supplementation ranging from 300 IU (7.5 μg/d) to 2000 IU (50 μg/d), with an average of approximately 1200 IU (30 μg/d) among children aged 1 year and older, was associated with a lower risk of respiratory tract infections. Untreated nutritional rickets can lead to poor linear growth, pathological fractures, and abnormal dentition, among other complications. As such, it is important that pregnant women and parents are educated on the importance of vitamin D supplementation. Clinicians should have a high index of suspicion and take a good history and do a complete physical examination to determine the need for a rickets workup. Once identified, vitamin D deficiency rickets should be promptly treated with additional vitamin supplementation and appropriate follow-up.Comment: Beyond bone health, the potential health benefits of vitamin D sufficiency is an exciting area of emerging research evidence. That said, the existing clinical trial evidence supporting the use of vitamin D in asymptomatic children beyond infancy could be stronger. The potential benefit of supplementation for preventing rickets among school-aged children relies on assumptions extrapolated from infant studies conducted in the early 1900s. The Endocrine Society’s meta-analysis of vitamin D’s impact on pediatric lower respiratory tract infection found a non–statistically significant effect. Thus, although counseling families of school-aged children about adequate dietary intake of vitamin D–fortified foods as a part of a well-balanced diet remains an important component of pediatric nutritional guidance, it may be premature to commit asymptomatic children with inadequate dietary vitamin D intake to years of supplements. Although vitamin D has low toxicity potential and is relatively inexpensive, it would behoove clinicians to know the reimbursement policies of their most commonly accepted insurance plans so they can advise families if there will be long-term, out-of-pocket costs for supplementation.Linda Y. Fu, MD, MSAssociate Editor, In Brief