2c:I[856015,["/_next/static/immutable/chunks/1xzisbplk9czp.js","/_next/static/immutable/chunks/3j2i1faptc_-9.js","/_next/static/immutable/chunks/1bqb83_yclja0.js","/_next/static/immutable/chunks/1on664om2hmh1.js","/_next/static/immutable/chunks/30t4sjq-27eg7.js","/_next/static/immutable/chunks/08tq8rmv423j5.js","/_next/static/immutable/chunks/32zk736rs0hqw.js","/_next/static/immutable/chunks/0lbgs964whs_0.js","/_next/static/immutable/chunks/1a_hqhrsle_n_.js","/_next/static/immutable/chunks/0hcnvyarhzl7i.js"],"default"] 2d:T5f54,

CATEGORY	DETAILS
Risk Factors	Exclusively breastfed infants without vitamin D supplementation, dark skin pigmentation, limited sun exposure, maternal vitamin D deficiency, prematurity, malabsorption (celiac disease, cystic fibrosis), chronic kidney disease, use of anticonvulsants (phenytoin, phenobarbital)
Etiology	Defective mineralization of the growth plate and osteoid due to insufficient calcium, phosphate, or vitamin D activity in growing bone
Patient Presentation	Delayed motor milestones, failure to thrive, bone pain, progressive limb deformity (bowed legs), irritability, and in severe cases hypocalcemic seizures
Classic Physical Exam	Craniotabes (softened skull bones on palpation), frontal bossing, rachitic rosary (palpable enlargement at costochondral junctions), widened wrists and ankles, Harrison groove (subcostal indentation along the diaphragm insertion), genu varum (bowlegs), delayed anterior fontanelle closure
Key Diagnostic Results	Low serum 25-hydroxyvitamin D, low calcium, low phosphate, elevated alkaline phosphatase (ALP), elevated parathyroid hormone (PTH); X-ray shows cupping, fraying, and widening of the metaphyses with generalized osteopenia
Management	Vitamin D repletion (cholecalciferol or ergocalciferol) plus calcium supplementation for nutritional rickets; calcitriol for hereditary forms with enzyme defects; phosphate replacement plus calcitriol or burosumab for phosphate-wasting forms
Keywords	"Rachitic rosary," "craniotabes," "cupping and fraying of metaphyses," "widened wrists," "bowlegs in a breastfed infant," "elevated ALP with low calcium," "Harrison groove"

1. Pathophysiology

Rickets is fundamentally a disease of growing bone. It occurs when the growth plate (physis) and newly formed osteoid fail to mineralize properly. This can only happen while the growth plates are still open, which is why rickets is exclusively a pediatric condition. The adult equivalent, occurring after growth plate closure, is called osteomalacia.

The most common form is nutritional rickets, driven by vitamin D deficiency. Vitamin D is a fat-soluble prohormone that undergoes two hydroxylation steps before becoming active. The first hydroxylation occurs in the liver, producing 25-hydroxyvitamin D (calcidiol), which is the major circulating storage form. The second occurs in the kidney, catalyzed by 1-alpha hydroxylase, producing 1,25-dihydroxyvitamin D (calcitriol), the biologically active hormone. Calcitriol acts on the intestinal epithelium to upregulate calcium and phosphate absorption. Without it, the gut absorbs only about 10 to 15 percent of dietary calcium, far below what growing bones require.

When serum calcium falls, the parathyroid glands respond by secreting PTH (secondary hyperparathyroidism). PTH attempts to restore calcium by three mechanisms: increasing renal tubular calcium reabsorption, stimulating osteoclastic bone resorption, and promoting renal phosphate excretion. This PTH-driven phosphaturia is the critical link to the clinical picture. Even if calcium is partially rescued, phosphate is actively wasted, and the resulting low calcium-phosphate product prevents hydroxyapatite crystal deposition in bone matrix. The growth plate cartilage continues to proliferate but never mineralizes, leading to the characteristic widened, irregular metaphyses seen on X-ray. The unmineralized osteoid accumulates, producing soft, deformable bones that bow under weight-bearing stress.

This pathophysiology explains every clinical sign: craniotabes results from softened, unmineralized skull bones; rachitic rosary is the palpable buildup of unmineralized osteoid at costochondral junctions; widened wrists reflect the expanded, unmineralized distal radial and ulnar growth plates; and genu varum develops because softened long bones deform under the mechanical load of walking.

2. Classification and Clinical Manifestation

Rickets is classified by which mineral substrate is deficient. This distinction is critical because the laboratory profile and treatment differ between categories.

TYPE	MECHANISM	INHERITANCE	CLINICAL CLUES
Nutritional (Calcipenic)	Dietary vitamin D deficiency or inadequate sun exposure	None (acquired)	Breastfed infant with dark skin and no supplementation; skeletal deformities appearing at 6 to 18 months
Vitamin D-Dependent Rickets Type I	Deficiency of 1-alpha hydroxylase; cannot convert 25(OH)D to 1,25(OH)2D	Autosomal recessive	Presents in early infancy with severe hypocalcemia; normal 25(OH)D but low 1,25(OH)2D
Vitamin D-Dependent Rickets Type II	End-organ resistance to calcitriol due to defective vitamin D receptor	Autosomal recessive	Severe rickets plus alopecia (hallmark finding that distinguishes it from Type I); elevated 1,25(OH)2D levels
X-Linked Hypophosphatemic Rickets (Phosphopenic)	Loss-of-function mutation in PHEX gene, leading to excess FGF23 and renal phosphate wasting	X-linked dominant	Short stature, lower extremity bowing, dental abscesses; normal calcium, normal PTH, isolated low phosphate
Tumor-Induced Osteomalacia	FGF23-secreting mesenchymal tumor causing phosphate wasting	None (acquired)	Adult or older child with progressive weakness and bone pain; resolves completely with tumor resection
Renal Osteodystrophy	Chronic kidney disease with impaired 1-alpha hydroxylase activity and phosphate retention	None (secondary)	Concurrent renal failure findings; hyperphosphatemia (unlike other forms which show low phosphate)

The key distinction on exams is between calcipenic and phosphopenic forms. In calcipenic rickets, calcium is low and PTH is elevated. In phosphopenic rickets (such as X-linked hypophosphatemic rickets), calcium and PTH are typically normal, and the isolated finding is low serum phosphate with inappropriately normal or low 1,25(OH)2D levels despite hypophosphatemia (FGF23 suppresses 1-alpha hydroxylase).

3. Diagnostic Workup

TEST	ROLE	EXPECTED FINDINGS
Serum 25-hydroxyvitamin D	Best initial test for nutritional rickets	Low (< 20 ng/mL deficient; < 12 ng/mL severe deficiency)
Serum calcium	Screening	Low in calcipenic forms; normal in phosphopenic forms
Serum phosphate	Screening	Low in both calcipenic (from PTH-driven wasting) and phosphopenic (from intrinsic renal wasting) forms
Alkaline phosphatase (ALP)	Marker of osteoblastic activity and defective mineralization	Elevated in all forms of rickets (high yield)
Intact PTH	Assess parathyroid response	Elevated in calcipenic forms (secondary hyperparathyroidism); normal in phosphopenic forms
1,25-dihydroxyvitamin D	Differentiate hereditary subtypes	Low in Type I; elevated in Type II; inappropriately normal or low in X-linked hypophosphatemic rickets
X-ray of wrists and knees	Most accurate test to confirm rachitic changes	Cupping, fraying, and widening of metaphyses; irregular and widened growth plate; generalized osteopenia; possible greenstick fractures
Urine calcium-to-creatinine ratio	Monitor therapy and assess renal handling	Low in vitamin D deficiency (the kidneys are conserving calcium); guides dose adjustments during treatment
FGF23 level	Confirm phosphopenic rickets etiology	Elevated in X-linked hypophosphatemic rickets and tumor-induced osteomalacia

The diagnostic approach begins with serum 25-hydroxyvitamin D, which is the best initial test whenever nutritional rickets is suspected. This reflects total body vitamin D stores and directly confirms deficiency. Simultaneously, a basic metabolic panel will reveal the classic triad of low calcium, low phosphate, and elevated alkaline phosphatase. Elevated ALP is one of the earliest biochemical markers and reflects the futile osteoblastic attempt to mineralize bone that lacks adequate mineral substrate. PTH should be checked next; an elevated PTH in the setting of low calcium confirms secondary hyperparathyroidism, which is the expected compensatory response in calcipenic rickets.

Plain radiographs of the wrists and knees serve as the most accurate (confirmatory) test for rickets. The hallmark findings are metaphyseal cupping, fraying, and widening. "Cupping" refers to the concave, irregular shape of the distal metaphysis. "Fraying" describes the brush-like irregularity of the normally smooth metaphyseal border. These findings result from the disorganized, unmineralized cartilage accumulating at the growth plate. A widened, radiolucent growth plate is also characteristic. In severe or prolonged cases, you may also see generalized osteopenia, cortical thinning, and pathologic fractures.

If the 25(OH)D level returns normal yet the child has clinical and radiographic rickets, you must consider hereditary forms. At this point, measuring 1,25-dihydroxyvitamin D and FGF23 becomes necessary. In Type I vitamin D-dependent rickets, 1,25(OH)2D will be low (enzyme defect). In Type II, 1,25(OH)2D will be paradoxically elevated (receptor resistance). In X-linked hypophosphatemic rickets, FGF23 will be elevated while calcium and PTH remain normal.

4. Management and Treatment

RICKETS TYPE	FIRST-LINE TREATMENT	DOSE AND DURATION	MONITORING
Nutritional Vitamin D Deficiency	Cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2) + oral calcium	Infants < 12 months: 2,000 IU/day for 6 to 12 weeks; Children 1 to 12 years: 3,000 to 6,000 IU/day for 6 to 12 weeks; then maintenance of 400 to 600 IU/day. Oral calcium 30 to 75 mg/kg/day of elemental calcium during the healing phase	Serum 25(OH)D, calcium, phosphate, ALP, and PTH at 1 month, then every 3 months until normalized; repeat wrist X-ray at 3 months to confirm healing
Vitamin D-Dependent Type I	Calcitriol (active 1,25(OH)2D)	0.5 to 2 mcg/day; lifelong therapy required	Serum calcium, urine calcium-to-creatinine ratio (target < 0.2) to prevent hypercalciuria and nephrocalcinosis
Vitamin D-Dependent Type II	High-dose oral calcium (bypass the receptor defect by flooding the gut with calcium)	Elemental calcium up to 1,000 to 3,000 mg/day orally; if oral therapy fails, IV calcium infusions may be required	Radiographic healing, serum calcium levels
X-Linked Hypophosphatemic Rickets	Conventional: oral phosphate + calcitriol; Newer: burosumab (anti-FGF23 monoclonal antibody)	Phosphate: 20 to 40 mg/kg/day in 4 to 5 divided doses; Calcitriol: 20 to 30 ng/kg/day in 2 divided doses; Burosumab: 0.8 mg/kg SC every 2 weeks (pediatric dosing)	Serum phosphate, ALP, urine calcium, renal ultrasound for nephrocalcinosis
Tumor-Induced Osteomalacia	Surgical resection of the FGF23-secreting tumor (curative)	Complete resection; if unresectable, treat as X-linked hypophosphatemic rickets	FGF23 levels normalize post-resection; radiographic healing

Acute stabilization is relevant in the setting of symptomatic hypocalcemia (tetany, seizures, laryngospasm, or prolonged QT interval). These patients require IV calcium gluconate 10% at a dose of 1 to 2 mL/kg given slowly over 10 to 20 minutes with continuous cardiac monitoring. Rapid infusion risks bradycardia. Once the acute crisis is managed, transition to oral calcium and vitamin D repletion.

For standard nutritional rickets, the treatment backbone is oral vitamin D repletion. The Endocrine Society recommends a loading course of vitamin D3 (cholecalciferol) for 6 to 12 weeks, followed by a maintenance dose of 400 IU/day for infants up to 12 months, or 600 IU/day for older children. Co-administration of oral calcium during the repletion phase is essential because the healing bone will rapidly take up calcium ("hungry bone syndrome"), and without supplemental calcium, the initial weeks of vitamin D therapy can actually worsen hypocalcemia. This is a commonly tested concept.

For Type I vitamin D-dependent rickets, the defect is in the 1-alpha hydroxylase enzyme, so giving regular vitamin D (which still requires that enzyme) will not work. The treatment is calcitriol (the already-active form), which bypasses the enzymatic block entirely. This is lifelong therapy.

For Type II vitamin D-dependent rickets, the vitamin D receptor itself is defective. Giving calcitriol in standard doses is ineffective. The strategy is to bypass the receptor altogether by providing very high doses of oral or IV calcium to drive passive, non-vitamin D-dependent calcium absorption across the gut. Some patients require chronic IV calcium infusions.

For X-linked hypophosphatemic rickets, the problem is FGF23-mediated phosphate wasting. Conventional treatment involves frequent-dose oral phosphate supplementation (given 4 to 5 times daily due to its short half-life) combined with calcitriol. The calcitriol is added because phosphate supplementation alone can lower ionized calcium, triggering secondary hyperparathyroidism and worsening the disease. A newer and increasingly preferred option is burosumab, a monoclonal antibody against FGF23, which normalizes phosphate reabsorption at the kidney and reduces the treatment burden to a subcutaneous injection every two weeks.

A key contraindication to remember: do not give phosphate without calcitriol in X-linked hypophosphatemic rickets, as unopposed phosphate supplementation can cause hypocalcemia, secondary hyperparathyroidism, and nephrocalcinosis.

5. Differential Diagnosis and Distractors

DIFFERENTIAL	WHY IT IS SIMILAR	KEY DISCRIMINATOR
Physiologic bowing	Bilateral genu varum in a toddler, which is the same chief complaint as rickets	Resolves spontaneously by age 2 to 3 years; normal growth velocity; normal labs and normal X-rays (no metaphyseal changes)
Blount disease (tibia vara)	Progressive unilateral or bilateral bowing of the legs in a child	Focal abnormality of the proximal medial tibial metaphysis and physis (beaking); no systemic metabolic derangement; ALP, calcium, phosphate, and vitamin D all normal
Osteogenesis imperfecta	Multiple fractures and skeletal deformity in a young child	Blue sclerae, wormian bones on skull X-ray, hearing loss, family history of fragile bones; normal calcium-phosphate metabolism
Scurvy (vitamin C deficiency)	Bone pain, irritability, and subperiosteal changes in a young child	Perifollicular hemorrhages, corkscrew hairs, gingival swelling and bleeding; X-ray shows a white line of Frankel (dense zone of provisional calcification) and Pelkan spurs rather than cupping/fraying
Hypophosphatasia	Rachitic-appearing bones, failure to thrive, skeletal deformity	ALP is low (the opposite of rickets, where ALP is always elevated); caused by defective tissue-nonspecific alkaline phosphatase
Non-accidental trauma (child abuse)	Multiple fractures in a young child	Fractures at various stages of healing; metaphyseal corner fractures ("bucket handle"); inconsistent history; no metabolic abnormalities
Celiac disease with secondary rickets	Bowing, short stature, and low vitamin D in a child	Accompanying GI symptoms (chronic diarrhea, abdominal distension, failure to thrive); positive tissue transglutaminase antibodies; the rickets is secondary to malabsorption

6. Traps and High-Yield Pearls

The most common way students get questions about rickets wrong falls into three categories.

First, students confuse rickets with osteomalacia. Both represent defective bone mineralization, but rickets occurs only in children with open growth plates, while osteomalacia occurs in adults after growth plate closure. The question stem will often test this by asking what condition an adult with the same metabolic profile would have.

Second, students fail to distinguish between calcipenic and phosphopenic forms based on the lab profile. When a vignette presents a child with bowing, elevated ALP, but normal calcium and normal PTH with isolated hypophosphatemia, the answer is X-linked hypophosphatemic rickets, not nutritional rickets. The normal calcium and PTH are the giveaway. Many students default to "vitamin D deficiency" for any rickets question without analyzing the labs carefully.

Third, the "hungry bone" trap is commonly tested. After initiating vitamin D repletion in a severely deficient child, the rapidly healing bones pull calcium from the serum. If calcium supplementation is not given concurrently, the child can develop worsening hypocalcemia, seizures, or tetany during the first week of treatment. The tested concept here is that you must always co-administer calcium with vitamin D during the repletion phase.

Additional high-yield points: ALP is elevated in every form of rickets without exception. If the question gives you low ALP with rachitic-looking bones, the answer is hypophosphatasia, not rickets. The presence of alopecia in a child with rickets points to Type II vitamin D-dependent rickets (receptor defect). And finally, remember that the best initial test is serum 25(OH)D, while the most accurate test for confirming the skeletal disease itself is a plain X-ray of the wrists and knees showing cupping, fraying, and widening of the metaphyses.

1d:["$","$L2c",null,{"article":{"id":"76c24e2d-36e7-470f-94c2-1c764ae7ec54","title":"Rakitis/ Rickets","content":"$2d","category":"Muskuloskeletal","created_at":"2026-09-05T16:08:47.418342+00:00","status":"published","subcategory":null},"questionCount":0,"sections":[{"id":"section-pathophysiology","num":"01","title":"Pathophysiology"},{"id":"section-classification-and-clinical-manifestation","num":"02","title":"Classification and Clinical Manifestation"},{"id":"section-diagnostic-workup","num":"03","title":"Diagnostic Workup"},{"id":"section-management-and-treatment","num":"04","title":"Management and Treatment"},{"id":"section-differential-diagnosis-and-distractors","num":"05","title":"Differential Diagnosis and Distractors"},{"id":"section-traps-and-high-yield-pearls","num":"06","title":"Traps and High-Yield Pearls"}],"hasSummaryTable":true}]