Rakitis/ Rickets

01Pathophysiology

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.

02Classification 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.

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).

03Diagnostic Workup

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.

04Management and Treatment

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.

05Differential Diagnosis and Distractors

06Traps 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.