There are two main types of vitamin D: D2 (ergocalciferol, derived from ergosterol in plants) and D₃ (cholecalciferol, derived from 7-dehydrocholesterol in animals). D₃ can also be synthesized in human skin under ultraviolet sunlight exposure and is the primary source of vitamin D for the body. Whether obtained from food (exogenous) or synthesized by the body (endogenous), vitamin D is biologically inactive and must undergo hydroxylation in the liver to form 25-(OH)D, followed by hydroxylation in the kidneys to produce 1,25-(OH)₂D, which is the active form. 1,25-(OH)₂D₃ (normally accounting for 84% of 1,25-(OH)₂D) is the primary active form of vitamin D₃, with an activity 2–5 times that of 25-(OH)D₃. The main functions of 1,25-(OH)₂D₃ include promoting intestinal absorption of calcium and phosphorus, mobilizing calcium and phosphorus into the blood by dissolving bone salts, facilitating new bone calcification, and enhancing renal tubular reabsorption of calcium and phosphorus. 1,25-(OH)₂D₃, along with parathyroid hormone and calcitonin, regulates the balance of calcium and phosphorus in tissues and body fluids. When vitamin D is deficient, the production of 1,25-(OH)₂D₃ decreases, leading to disrupted calcium and phosphorus metabolism and insufficient mineralization of growing bones or osteoid tissue, resulting in rickets characterized by skeletal changes or deformities. In China, the incidence of rickets in children under 3 years old is approximately 20–30%, and in some regions, it can be as high as 80% or more, making it one of the common nutritional deficiencies in infants and young children.

bubble_chart Diagnosis

(1) History of vitamin D deficiency, such as insufficient sunlight exposure; history of inadequate dietary vitamin D intake, such as infants whose main diet consists of milk with low vitamin D content; history of relative vitamin D deficiency due to increased demand, such as rapidly growing infants or premature labor infants; history of malabsorption of vitamin D, such as pancreatic or intestinal diseases, biliary tract or lymphatic obstruction, etc.

1. Nonspecific symptoms: Mostly occur in infants under one year old, with onset possible as early as one month after birth. Main symptoms include dysphoria, restlessness, night terrors, night crying, and profuse sweating with a peculiar odor, often soaking pillows and bedding, and occipital alopecia areata (pillow baldness). As the condition progresses, muscle and tendon laxity, hypotonia, abdominal distension (frog belly), joint hyperextension, delayed or regressed motor development may be observed. Hepatosplenomegaly, anemia, and susceptibility to respiratory infections may also occur.
2. Skeletal changes: Early signs may include cranial softening. <3個月的嬰兒可為生理性)，囪門大，顱縫增寬，邊緣發軟。7～8個月以上小兒可見出牙遲、方顱、鞍形顱或十字形顱;肋骨骺部膨大(串珠)，肋骨受膈肌牽引形成肋軟骨溝(郝氏溝)，并可有肋骨下緣外翻;腕、踩部長骨骺端膨大(手鐲徵、腳鐲徵)。一歲以上小兒可出現囪門晚閉、雞胸、漏斗胸,0型腿、X形腿、脊柱後突或側突等。

(3) Laboratory findings: - Blood phosphorus levels decrease in the initial stage [first stage], drop significantly during the active stage, and recover earliest during the stage of convalescence. - Blood calcium levels may remain normal in the initial stage [first stage], decrease during the active stage, and recover later than blood phosphorus during the stage of convalescence. - Alkaline phosphatase levels rise in the initial stage [first stage], increase significantly during the active stage, and decline during the stage of convalescence. Additional tests when available: - 25-(OH)D levels drop significantly in the initial stage [first stage]. - 1,25-(OH)₂D levels may fall below detectable limits. - PTH levels may subsequently rise. Normal ranges: - 25-(OH)D: 25–40 ng/ml (62.4–99.8 nmol/L); - 1,25-(OH)₂D: 2.1–4.5 ng/dl (50.4–108 pmol/L); - PTH: 537.1–909.1 pg/ml (63.2–106.9 pmol/L).

(4) X-ray findings: - In the initial stage [first stage], the provisional calcification zone at the metaphysis of long bones may appear blurred, thinned, with small lateral spurs, thinning of the bone cortex, and slight trabecular rarefaction. - During the active stage, the metaphysis widens and becomes concave, forming a cup-shaped appearance, the provisional calcification zone appears fuzzy, the bone cortex becomes indistinct, bone density significantly decreases, and the distance between the epiphysis and metaphysis (nuclear distance) may widen to 3–8 mm (normal <3mm)，嚴重者幹骺端消失，可見骨折或假性骨折。恢復期時臨時鈣化帶重新出現，骨小梁增多且緻密，骨幹周圍骨膜增生，核距逐漸縮短。重者可遺留骨畸形，如長骨骨幹彎曲，脛骨前突呈弓形，肱骨外翻及髖內翻等。

(5) Staging and grading of rickets

1. Staging of rickets (Table 2-3). Table 2-3: Staging of rickets

   	Clinical manifestations	Blood biochemical changes	X-ray changes	Other reference conditions Active stage
   Initial stage [first stage]	Prominent neuropsychiatric symptoms, minimal or mild skeletal symptoms, no motor impairment	Normal or decreased blood calcium, decreased blood phosphorus, grade I increase in AKP	Normal or initial stage [first stage] changes	Mostly occurs after 3 months of age, often in winter
   Excitement	Neuropsychiatric symptoms are obvious, skeletal symptoms are obvious, and motor dysfunction is obvious	Blood calcium decreases, blood phosphorus decreases significantly, and AKP rises significantly	Changes in the active stage	Age is mostly between 7 months and 2 years, and the season is mostly in winter and spring
   Stage of convalescence	Neuropsychiatric symptoms disappear, skeletal symptoms and motor dysfunction improve	Blood phosphorus recovers earlier than blood calcium, and AKP decreases	Changes in the stage of convalescence	Age is the same as above, and the season is mostly in late spring, summer, and early autumn
   Stage of sequelae	Only skeletal deformities remain, and motor dysfunction gradually returns to normal	Normal	Returns to normal	Age is mostly after 2 to 3 years

2. Grading of rickets (1) Grade I: cranial softening and large fontanel can be seen, Grade I square skull, beading, and Harrison's groove. (2) Grade II: typical beading, bracelets, Harrison's groove, mild or Grade II pigeon breast, funnel chest, O-shaped or X-shaped legs, and delayed fontanel closure or delayed tooth eruption may also be seen. (3) Grade III: obvious Harrison's groove, pigeon breast, funnel chest, spinal deformity, obvious O-shaped or X-shaped legs affecting gait, and possible pathological fractures.

bubble_chart Treatment Measures

(1) General Treatment: Strengthen nursing care, provide proper feeding, maintain outdoor activities, and prevent complications.

(2) Special Treatment

1. Initial stage [first stage]: Oral administration of vitamin D preparations (such as calciferol or concentrated cod liver oil) at 5,000–10,000 IU/day for 1 month, then switch to preventive dosage; or intramuscular injection of vitamin D2 400,000 IU or vitamin D₃ 300,000 IU once or twice, with a 1-month interval between doses.
2. Active stage: Oral administration of vitamin D preparations at 10,000–20,000 IU/day for 1 month, then switch to preventive dosage; or intramuscular injection of vitamin D2 400,000 IU or vitamin D₃ 300,000 IU 2–3 times, with a 1-month interval between doses. Calcium supplements should be taken for 3 days before intramuscular injection to prevent hypocalcemic convulsions. Calcium supplements should also be given concurrently during vitamin D therapy. After vitamin D treatment, serum 25-(OH)D and 1,25-(OH)₂D levels may begin to rise within 1–2 days, serum phosphorus levels rise in about 10 days, followed by an increase in serum calcium. X-ray improvements can be observed after 3 weeks, with complete normalization taking approximately 2–4 months. Alkaline phosphatase levels may take several months to return to normal. Severe skeletal deformities may persist for life.
3. Sequelae stage: Prevent recurrence and correct deformities. For pigeon breast, prone positioning, push-ups, and pull-ups may be recommended; for O-shaped or X-shaped legs, small splints or tuina (Chinese therapeutic massage) during sleep can be used to increase muscle tone, with surgical correction if necessary.

bubble_chart Prevention

Prevention starts from the perinatal period, with infants under 1 year as the focus, continuing until age 3. (1) **Fetal period**: In the last three months of pregnancy, mothers should be supplemented with 400 IU/d of vitamin D, appropriate calcium, and outdoor activities. (2) **Neonatal period**: Begin outdoor activities as early as possible. For premature births, twins, formula-fed infants, winter births, or children unable to maintain outdoor activities, start oral vitamin D supplementation at 500–1000 IU/d or a single intramuscular injection of 100,000–200,000 IU at 1–2 weeks after birth, which can last for 1–2 months. (3) **Infancy**: Maintain outdoor activities or oral vitamin D supplementation at 400–800 IU/d without interruption. (4) **Toddler period**: Increase outdoor activities in summer, and vitamin D supplementation may be unnecessary. In winter (mid-October), children in northern regions should take 200,000–400,000 IU orally (as calciferol sugar pills) or via intramuscular injection, while those in southern regions should take 100,000–200,000 IU. In high-risk areas, repeat the dose in spring (mid-January). Generally, avoid adding calcium or limit it to no more than 0.5 g to prevent affecting appetite. Children with a history of hypocalcemic convulsions or those on a starch-based diet may receive appropriate calcium supplementation.

bubble_chart Differentiation

(1) Vitamin D metabolic disorder rickets shares similarities with rickets in that both involve reduced production of the active form of vitamin D, 1,25-(OH)₂D, and exhibit identical skeletal changes. The difference lies in the fact that this disorder occurs despite sufficient vitamin D intake, as liver or kidney pathologies lead to decreased production of 25-(OH)D and/or 1,25-(OH)₂D, thereby causing the disease. Antiepileptic drugs such as phenytoin and phenobarbital can induce liver enzyme activity, converting 25-(OH)D into inactive metabolites and reducing the production of 1,25-(OH)₂D, thus contributing to the disease. Treatment for this condition requires increasing the vitamin D dose or administering 25-(OH)D₃, 1,25-(OH)₂D₃, or 1,25-(OH)D₃ separately.

(2) Non-1,25-(OH)₂D deficiency rickets In this disorder, the production of 1,25-(OH)₂D is not reduced. Instead, congenital or acquired renal tubule pathologies result in a lack of response to 1,25-(OH)₂D, or the pathologies themselves impair the kidney's ability to regulate calcium-phosphorus balance and acid-base balance, thereby directly or indirectly affecting skeletal calcium-phosphorus metabolism and causing the disease. This is seen in conditions such as Fanconi syndrome and renal tubular acidosis. Treatment involves addressing the primary disease, increasing the vitamin D dose, or using 25-(OH)D₃, 1,25-(OH)₂D₃, or synthetic preparations like dihydrotachysterol.

(3) Others Other conditions such as cretinism, chondrodystrophy, hydrocephalus, osteogenesis imperfecta, and large joint disease should also be differentiated.