Osteomalacia and Rickets

Author: Emma K. Landes, MD and John Hanna, MD

Definition

Rickets is a result of deficient mineralization of the osteoid matrix before closure of the epiphyseal plate causing softening and weakening of bones in infants and children. The mineralization impairment may be secondary to abnormal calcium, phosphorus, or vitamin D metabolism leading to accumulation of osteoid before epiphyseal closure, compromising bone stability at sites of rapid bone growth.¹ When this process occurs in adulthood after epiphyseal closure, it is referred to as osteomalacia. Renal osteodystrophy is a term used to describe a similar condition in patients with chronic kidney disease. Vitamin D-resistant rickets (VDRR) is a certain form of the disorder that only responds to high doses of vitamin D.²

ICD-10CM CODES
E55.0		Rickets, active
E83.30		Disorder of phosphorus metabolism, unspecified
M83.9		Adult osteomalacia, unspecified
N25.0		Renal osteodystrophy

Epidemiology & Demographics

Studies reporting the prevalence of rickets are difficult to generalize to larger populations as they are geographically and resource specific, and they vary in methods of diagnosing rickets. Higher resource countries typically have fewer cases of rickets. One study in the U.S. reported an incidence of 24.1 per 100,000 cases.³ The true incidence of osteomalacia is likely underestimated.

Risk Factors:

•Children ages 6 to 24 mo
•Premature infants
•Residents of northern latitudes with inadequate sunlight exposure
•Solely breastfed infants
•Darker skin pigmentation
•Use of anticonvulsants ⁴

Physical Findings & Clinical Presentation

Table E1 summarizes the clinical features of rickets. The classic clinical presentation of children with rickets includes:

•Apathy, muscle weakness, muscle cramps, delayed growth, and short stature
•Skeletal pain and swollen joints (Figs. E1 and E2)
•Protuberant abdomen due to muscle hypotonia ⁵
•Widened cranial sutures, delayed closure of fontanelles, and frontal bossing of head ¹
•Craniotabes (softening of skull bones)⁵
•Delayed eruption of teeth and poorly mineralized teeth ⁵
•Bowing deformity of lower extremities, specifically femur and tibia (Fig. E3)
•Rachitic rosary (enlargement and prominence of the rib head at the costochondral junctions)¹
•Harrison groove (indentation of the lower ribs)¹
•Breastbone that is pushed forward (pigeon chest)⁶
•Pathologic fractures
•Scoliosis or kyphosis

Figure E1 Rachitic "rosary" in a child with rickets.

(Courtesy Dr. Thomas D. Thacher, Rochester, MN. In Kliegman RM et al: Nelson textbook of pediatrics, ed 22, Philadelphia, 2025, Elsevier.)

Figure E2 Hands and forearms of a young child with rickets.

Prominence above the wrist is shown, resulting from flaring and poor mineralization of the lower end of the radius and ulna.

(From Bullough PG: In Kliegman RM et al: Nelson textbook of pediatrics, ed 22, Philadelphia, 2025, Elsevier.)

Figure E3 A, A Typical Example of Rickets

Note the Bowing of the Femurs and Tibiae, Which May Result from Vitamin D Deficiency, Phosphate Deficiency, or Other Causes. B, A Skeletal Radiograph of a Child with Rickets. Note that the Weight-Bearing Bones of the Lower Extremities are Bowed and that the Epiphyses are Open, Mottled, and Overgrown. C, Looser Zones or Pseudofractures that are Characteristic of Osteomalacia or Rickets. Because the Epiphyses are Closed, the Patient is an Adult. This Radiograph is Diagnostic of Osteomalacia.

(From Stewart A: Metabolic bone diseases. In Andreoli TE et al [eds]: Cecil essentials of medicine, ed 8, Philadelphia, 2010, Saunders.)

TABLE E1 Clinical Features of Rickets

General
•Failure to thrive (malnutrition) •Listlessness •Protruding abdomen •Muscle weakness (especially proximal) •Hypocalcemic dilated cardiomyopathy •Fractures (pathologic, minimal trauma) •Increased intracranial pressure
Head
•Craniotabes •Frontal bossing •Delayed fontanel closure (usually closed by 2 yr) •Delayed dentition •No incisors by age 10 mo •No molars by age 18 mo •Caries •Craniosynostosis
Chest
•Rachitic rosary •Harrison groove •Respiratory infections and atelectasis *
Back
•Scoliosis •Kyphosis •Lordosis
Extremities
•Enlargement of wrists and ankles •Valgus or varus deformities •Windswept deformity (valgus deformity of one leg with varus deformity of other leg) •Anterior bowing of tibia and femur •Coxa vara •Leg pain
Hypocalcemic Symptoms^†
•Tetany •Seizures •Stridor caused by laryngeal spasm

^*These features are associated most frequently with vitamin D deficiency disorders.

^†These symptoms develop only in children with disorders that produce hypocalcemia.

The less pronounced clinical presentation of adults with osteomalacia includes ⁵:

•Skeletal pain and bone tenderness
•Muscle hypotonia and proximal muscle weakness
•Pathologic fractures and decreased bone density
•Gait disturbances

Etiology

The most common cause of rickets and osteomalacia is vitamin D deficiency. Insufficient calcium and phosphorus intake can also lead to rickets. Vitamin D and parathyroid hormone (PTH) play an important role in calcium homeostasis. Vitamin D is required for adequate calcium absorption in the gastrointestinal tract. Low vitamin D leads to reduced intestinal absorption of calcium, causing a compensatory increase in PTH and resorption of bone, leading to increased alkaline phosphatase levels.⁴ Vitamin D deficiency may arise from various conditions including inadequate dietary intake, malabsorption, chronic parenteral nutrition, and the additional risk factors listed previously. Malabsorption that causes inefficient mineralization is observed in diseases such as cystic fibrosis, intestinal disorders such as celiac disease, and in many chronic illnesses, including severe liver disease.⁴

Chronic renal failure can produce bone mineralization deficiency due to electrolyte abnormalities causing hypocalcemia and renal osteodystrophy (renal rickets). This results in decreased excretion of phosphate, therefore elevating serum phosphorus, along with elevated PTH and low levels of 1,25-OH vitamin D.¹

Other causes specifically include vitamin D-dependent rickets (VDDR type I and II) and VDRR, also known as hereditary hypophosphatemic rickets ⁵ (Table E2).

•VDDR type I (VDDR-1) results from mutations in the vitamin D 1-alpha hydroxylase enzyme that converts inactive vitamin D to the active metabolite of 1,25(OH)₂D.
•VDDR type II (VDDR-II), also known as hereditary vitamin-D resistant rickets (HVDRR), results from defective vitamin D receptors due to a mutation in the vitamin D receptor gene (Table E3).

TABLE E3 Causes of Hypophosphatemic Rickets or Osteomalacia, or Both

Genetic
•Autosomal dominant rickets •Autosomal recessive rickets •X-linked dominant rickets (X-linked hypophosphatemia) •X-linked recessive •Hypophosphatemic hypercalciuric hereditary rickets (or Dent disease) •Neurofibromatosis •Fibrous dysplasia •Genetic Fanconi syndrome (may have renal failure)
Acquired
•Tumor-induced osteomalacia (most common acquired cause) •Renal tubular damage or nonfamilial Fanconi syndrome •Paraproteinemia •Wilson disease •Galactosemia •Tyrosinemia •Glycogenosis •Drug induced •Tenofovir and adefovir (second most common acquired cause) •Phosphate-binding antacids •Cadmium poisoning •Use of outdated tetracycline •Amphotericin

From Melmed S et al: Williams textbook of endocrinology, ed 15, Philadelphia, 2025, Elsevier.

TABLE E2 Causes of Vitamin D-Deficiency Rickets or Osteomalacia, or Both

Extrinsic
•Inadequate dietary intake of vitamin D •Decreased exposure or avoidance of sunlight •Use of sunscreens (especially a solar protective factor >8) •Excess clothing (veil/hijab) •Increased dark skin pigmentation
Intrinsic
•Advancing age with decreased cutaneous production of vitamin D •Malabsorption due to various gastrointestinal disorders •Gastrectomy (partial, total, or bypass procedure) •Small intestinal disease, resection, or bypass •Gluten enteropathy (celiac sprue) •Biliary cirrhosis (uncommon) •Pancreatic insufficiency including cystic fibrosis (uncommon) •Impaired or genetically defective vitamin D 25-hydroxylase enzyme •Immaturity •Neonatal hepatitis •Cirrhosis of the liver •Genetic defect (vitamin D-dependent rickets type 1B) •Impaired or genetically defective 25-hydroxyvitamin D 1α-hydroxylase enzyme •Genetic defect (vitamin D-dependent rickets type 1A) •Chronic renal failure •"Acquired" vitamin D deficiency •Increased catabolism due to microsomal enzyme induction •Anticonvulsants •Calcium deficiency with secondary hyperparathyroidism

From Melmed S et al: Williams textbook of endocrinology, ed 15, Philadelphia, 2025, Elsevier.

Diagnosis ⬆ ⬇

Differential Diagnosis

•Osteoporosis (Table E4 contrasts features of four metabolic bone diseases)
•Hyperparathyroidism
•Hyperthyroidism
•Hypophosphatasia
•Skeletal dysplasia
•Blount disease

TABLE E4 Contrasting Features of Four Major Metabolic Bone Diseases

Variable	Rickets and Osteomalacia	Osteoporosis	Osteitis Fibrosa	Osteitis Deformans
Basic abnormality	Defective mineralization of cartilage and bone	Insufficient replacement of normal lamellar bone	Replacement by woven bone and fibrous tissue	Abnormal woven bone
Prevalence	Second most common	Most common	Uncommon	Not uncommon
Serum calcium	Normal/low	Normal	High/very high	Normal
Serum phosphate	Normal/low/very low	Normal	Frequently low	Normal
Alkaline phosphatase	High	Normal/high	High/very high	High
Parathyroid hormone	High	Normal/high	High/very high	Normal
25-Hydroxyvitamin D	Low/normal	Normal/low	Frequently low	Normal/low
Cortical thinning	Yes, except in X-linked hypophosphatemia	Sometimes	Yes	No
Vertebral deformities	Biconcave or cod fishlike	Wedged/compressed	Variable	Enlarged size
Long bone deformities	Bowing and pseudofractures	None, except fragility fractures	Brown tumors	Bowing and stress fractures

Workup

•Rickets is a clinical diagnosis. It is often challenging to determine the exact etiology; however, clinical, biochemical, and radiologic findings can be useful.
•A thorough dietary and medication history for children is important. Bone biopsy is generally not performed; however, it is the diagnostic gold standard.⁷
•Fig. E4 illustrates a clinical algorithm based on biochemical abnormalities in evaluating patients suspected of having rickets or osteomalacia.

Figure E4 Suggested Clinical Algorithm Based on Biochemical Abnormalities in Evaluating Patients Suspected of Having Rickets, Osteomalacia, or Both

1,25-D, 1,25-dihydroxyvitamin D; 25-D, serum 25-hydroxyvitamin D; AA, urine amino acid analysis; Ca, serum calcium; Glu, urine glucose; HCO₃, urine bicarbonate excretion; HHRH, hereditary hypophosphatemic rickets with hypercalciuria; HVO I, hypovitaminosis D osteopathy stage I; P, serum phosphate; PTH, serum parathyroid hormone; TIO, tumor-induced osteomalacia; TmP/GFR, tubular maximum for phosphate reabsorption/glomerular filtration rate; TRP, tubular reabsorption of phosphate; VDD, vitamin D deficiency; VDDR, vitamin D-dependent rickets; XLH, X-linked hypophosphatemic rickets and osteomalacia.

(From Melmed S et al: Williams textbook of endocrinology, ed 15, Philadelphia, 2025, Elsevier.)

Laboratory Tests

Blood testing (Table E5) should include serum calcium, inorganic phosphorus (Pi), alkaline phosphatase, PTH, 25-OH vitamin D, creatinine, and liver enzymes. Tables E6 and E7 summarize laboratory findings in various disorders that cause rickets and osteomalacia. Children may present solely with an elevated alkaline phosphatase level and characteristic physical findings.⁵

TABLE E5 Evaluation of Osteomalacia

In all patients: Calcium, phosphorus, alkaline phosphatase, urinary calcium levels; 25-hydroxyvitamin D and intact parathyroid hormone levels
In selected patients: •1,25-Dihydroxyvitamin D levels (e.g., renal insufficiency and vitamin D-resistant osteomalacia or rickets) •Vitamin D absorption test: Obtain 25-hydroxyvitamin D levels at 0, 4, and 8 h (e.g., some cases of malabsorption) •Tubular reabsorption of phosphate (e.g., vitamin D-resistant osteomalacia or rickets) •Bone biopsy with double tetracycline labels

From Firestein GS et al: Firestein & Kelley’s textbook of rheumatology, ed 12, Philadelphia, 2024, Elsevier.

TABLE E6 Relevant Abnormalities in Various Types of Vitamin D-Related Rickets and Osteomalacia

Variable	Vitamin D Deficiency	Vitamin D Dependency Type 1B	Vitamin D Dependency Type 1A	Vitamin D Dependency Type 2	Hypophosphatemic Vitamin D Resistant ^a
Basic defect	Nutritional/malabsorption	25-Hydroxylase defect	1α-Hydroxylase defect	VDR defect	Excess FGF23
Gene locus	Not applicable	Chromosome 11p15.2	Chromosome 12q13.1	Chromosome 12q12-q14	Xp22.11
Enzyme defect	Not applicable	CYP2R1	CYP27B1	Receptor defect	PHEX gene defect
Serum calcium	Low/normal	Low	Low	Low	Normal/high
Serum phosphate	Normal/low	Normal/low	Normal/low	Normal/low	Very low
Alkaline phosphatase	High	High	High	High	High
Parathyroid hormone	High	High	High	High	Normal/high
25-Hydroxyvitamin D	Low	Low/very low	Normal	Normal	Normal
1,25-Dihydroxyvitamin D	Variable	Low/low normal	Low	High	Low
Urine calcium	Low	Low	Low	Low	Normal/high
Vitamin D dose required to heal/cure rickets ^b	1000-2000 IU daily Few weeks to months	10,000 IU daily Lifelong	10,000 IU daily Lifelong	100,000 units daily Lifelong	100,000 units daily Lifelong
Calcitriol dose required to heal/cure rickets	0.04 μg/kg per day Few weeks to months	0.04 μg/kg per day Lifelong	0.04 μg/kg per day Lifelong	1-2 μg/day Lifelong	1-2 μg/day and oral phosphate Lifelong

CYP, Cytochrome P-450; FGF23, fibroblast growth factor 23; PHEX, phosphate-regulating endopeptidase homolog, X-linked; VDR, vitamin D receptor.

^aPreviously referred to as vitamin D-resistant rickets because of the large doses of vitamin D required to heal rickets; the current name is X-linked hypophosphatemic rickets and osteomalacia.

^bShown only to illustrate comparative effective doses. Both calcitriol and alfacalcidol are now widely available and used to treat all vitamin D-dependent rickets and osteomalacia.

TABLE E7 Key Abnormalities in Various Types of Rickets and Osteomalacia

Variable	Vitamin D Deficiency	Vitamin D-Resistant Hypophosphatemic	Tumor-Induced Osteomalacia	Drug-Induced Osteomalacia
Basic defect	Nutritional/malabsorption	PHEX gene defect Defective catabolism of FGF23	Ectopic production of FGF23	Renal tubular damage Direct effect on bone mineralization
FGF23 levels	Not applicable	Usually high	Almost always high	High/variable
Serum calcium	Low/normal	Normal/high	Normal	Variable
Serum phosphate	Normal/low	Very low	Low/very low	Variable
Alkaline phosphatase	High	High	High	Variable
Parathyroid hormone	High	Normal/high	Normal	Variable
25-Hydroxyvitamin D	Low	Normal	Normal	Low/normal
1,25-Dihydroxyvitamin D	Variable	Low	Low	Low/variable
Bone mineral density	Low	Normal/high	Often low	Often low
Therapeutic strategy	Vitamin D + calcium	Calcitriol and phosphate Burosumab	Resection of the tumor Other therapies (see text)	Discontinuation of offending drug

FGF23, Fibroblast growth factor 23; PHEX, phosphate-regulating endopeptidase homolog, X-linked.

From Melmed S et al: Williams textbook of endocrinology, ed 15, Philadelphia, 2025, Elsevier.

Imaging Studies

•In rickets, characteristic radiologic findings include irregular epiphyseal-metaphyseal junctions with widening and flaring of the epiphyses of long bones, causing bowing.¹^,⁵
•Pseudofractures (Looser zones) and narrow radiolucent lines may be seen as a result of microfractures at high stress points or at the location of entry of blood vessels into the bone. These findings are observed in severe rickets and osteomalacia.⁵

Treatment ⬆ ⬇

•Treatment is dependent on the underlying etiology, but high doses of vitamin D resolve most deficiencies. Nutritional deficiency of vitamin D is rare with the amount of vitamin D currently present in milk and dairy products; however, if a deficiency is detected, initial treatment with 2000 IU vitamin D₂ or D₃ daily is recommended, with periodic monitoring of vitamin D levels and dose adjustment as needed to maintain normal levels.¹
•VDDR type I is treated with both vitamin D and phosphate replacement. After initiation of treatment, the first biochemical change is an increase in the level of phosphorus followed by a rise in calcium level. Serum calcium, phosphorus, alkaline phosphatase, calcidiol levels, and urine calcium and phosphorus levels should be obtained within 2 wk of initiation of therapy and at periodic intervals thereafter.⁵ The treatment of VDDR type II is more complex and requires the expertise of an endocrinologist and/or nephrologist.
•Familial hypophosphatemic rickets is treated with calcitriol or alfacalcidol and oral phosphorus supplements.⁵
•Oral phosphorus alone is the treatment of choice for hereditary hypophosphatemic rickets with hypercalciuria.⁵

Referral

•Because of the complex nature of many of these disorders, a qualified endocrinologist and nephrologist should be consulted for treatment.
•Orthopedic consultation may be required for some cases of bowlegs or spinal deformities, which may require specific bracing for long-term growth of the bones. Corrective surgery may be necessary if the deformity is very severe.
•Surgical care is also indicated for slipped capital femoral epiphysis, which is common in renal rickets.

Prevention

During well-child visits, physicians should consider educating patients on newborn dietary habits (vitamin D and calcium intake) as well as history of sun exposure in early life.

Related Content

Neurofibromatosis (Related Key Topic)
Osteoporosis (Related Key Topic)
Vitamin D Deficiency (Patient Information)
Vitamins and Their Functions (Patient Information)

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Basic Information ⬇

Diagnosis ⬆ ⬇

Treatment ⬆ ⬇

Reference(s) ⬆