Rickets: Symptoms, Types, Causes and Treatment

Rickets is a bone disorder that primarily affects children, resulting in weakened and deformed bones. Despite being largely preventable and treatable, rickets remains a global health issue, affecting children from diverse backgrounds and environments. Understanding its symptoms, different forms, underlying causes, and available treatments is essential for parents, caregivers, and healthcare professionals to ensure healthy growth and development in children.

Symptoms of Rickets

Recognizing the symptoms of rickets early is crucial for timely treatment and prevention of long-term complications. The disease manifests in a range of skeletal and non-skeletal signs, often varying by age and severity. Some symptoms are subtle and may be mistaken for other conditions, while others can significantly impact a child's quality of life.

Symptom	Description	Prevalence/Context	Sources
Bone pain	Discomfort in limbs, spine, pelvis, or back	Common in affected children	2 7 8
Bowed legs	Outward curve of legs (genu varum)	Especially in toddlers	2 4 7
Swollen joints	Thickening of wrists/ankles	Early and visible sign	2 7 8
Muscle weakness	Reduced strength and motor delays	Can lead to delayed walking	2 7
Growth failure	Short stature, delayed milestones	Chronic, untreated cases	2 7 13
Carpopedal spasms	Muscle cramps/spasms in hands/feet	Seen in hypocalcemic states	1
Seizures	Due to hypocalcemia	Severe, especially infants	10 7
Dental issues	Delayed eruption, enamel defects	Sometimes present	15 7

Table 1: Key Symptoms

Skeletal Symptoms

Bone Pain and Deformities:
Bone pain is one of the earliest symptoms and may affect the arms, legs, spine, or pelvis. Children often complain of diffuse limb pain and discomfort during walking or standing. As the disease progresses, bowing of the legs (either bow-legs or knock-knees) becomes evident, especially as children begin to walk. Swelling of wrists and ankles is common due to the widening of metaphyses—areas of bone growth near the joints. In infants, delayed closure of the fontanelles (soft spots on the skull), frontal bossing (prominent forehead), and craniotabes (soft skull bones) may be observed 2 7 8.

Growth Failure:
Chronic or severe rickets can impair overall growth, leading to short stature and delayed developmental milestones 2 7 13. If left untreated, skeletal deformities may become permanent.

Extraskeletal Symptoms

Muscle Weakness and Delayed Motor Skills:
Children may have trouble standing, delayed walking, or display a waddling gait due to muscle weakness. In severe cases, hypocalcemia (low calcium) can trigger carpopedal spasms (painful cramps in the hands and feet) and even seizures 1 10.

Dental Problems:
Rickets may also affect dental health, causing delayed tooth eruption, enamel hypoplasia, dental caries, and, in some forms, spontaneous dental abscesses 15 7.

Age-Dependent Presentation

• Infants: More likely to have delayed fontanelle closure, craniotabes, and poor feeding.
• Toddlers/Children: Bowed legs, swollen joints, and failure to thrive are typical.
• Adolescents: Present more often with limb pain, muscle weakness, and sometimes subtle deformities; overt bone changes may be less pronounced 1.

Types of Rickets

Rickets is not a single disease but a spectrum of disorders that disrupt the normal mineralization of growing bones. Understanding the specific type is critical for choosing the right treatment strategy.

Type	Main Feature/Defect	Common Causes	Sources
Nutritional	Deficient mineralization	Low vitamin D and/or calcium	2 7 11 12
Calcipenic	Low calcium availability	Vitamin D deficiency, malabsorption	7 14 8
Phosphopenic (Hypophosphatemic)	Low phosphate	Renal phosphate wasting, FGF23 excess	7 8 13 15
Vitamin D–dependent	Genetic defects in vitamin D metabolism/action	VDDR type 1A, 1B, 2A, 2B	5 7 8
Renal	Chronic kidney disease	Impaired vitamin D activation, acidosis	7 14

Table 2: Types of Rickets

Nutritional Rickets

Overview:
The most common and preventable form, nutritional rickets is primarily due to inadequate intake of vitamin D and/or calcium. It remains highly prevalent in developing regions and among populations with limited sun exposure 2 7 11 12.

Calcipenic Rickets

Definition:
Calcipenic rickets arises mainly from disorders that lead to low calcium availability in the body. This is most often due to severe vitamin D deficiency, but may also be seen in malabsorption syndromes or chronic liver disease 7 14 8.

• Vitamin D Deficiency: Impairs intestinal absorption of calcium, leading to secondary hyperparathyroidism and bone demineralization.
• Calcium Deficiency: Increasingly recognized, especially in some African and Asian populations, as an independent cause or in combination with low vitamin D 11 12.

Phosphopenic (Hypophosphatemic) Rickets

Explanation:
Phosphopenic rickets stems from renal losses of phosphate, usually due to genetic defects affecting phosphate reabsorption or excess fibroblast growth factor 23 (FGF23) activity. This group includes:

• X-linked hypophosphatemic rickets (XLH): The most common hereditary form, caused by mutations leading to FGF23 excess 7 8 15 18.
• Other Renal Causes: Fanconi syndrome, hereditary defects in phosphate transporters 7 8 13.

Vitamin D–Dependent Rickets

Types:
These rare forms are due to genetic mutations affecting vitamin D metabolism or its receptor:

• Type 1A (VDDR1A): Deficiency in 1α-hydroxylase enzyme, leading to low active vitamin D 5 7.
• Type 2A (VDDR2A): Mutations in the vitamin D receptor, causing end-organ resistance 5 7 8.

Renal Rickets

Description:
Seen in chronic kidney disease, where impaired activation of vitamin D and metabolic acidosis disrupt calcium and phosphate homeostasis. Treatment usually requires activated vitamin D analogs and correction of metabolic acidosis 7 14.

Causes of Rickets

Understanding what leads to rickets is critical for both prevention and effective intervention. The disease arises due to a combination of nutritional, genetic, and environmental factors that disrupt calcium and phosphate homeostasis.

Cause	Mechanism/Trigger	At-Risk Groups	Sources
Vitamin D deficiency	Low sunlight, poor dietary intake	Breastfed infants, children indoors, dark-skinned populations	2 4 7 10 12
Calcium deficiency	Inadequate dietary calcium	Children in Africa/Asia, vegan diets	11 12 17
Genetic mutations	Defects in vitamin D metabolism or phosphate handling	Family history, early onset	5 7 8
Renal disease	Impaired vitamin D activation, phosphate loss	Chronic kidney disease	7 14
Malabsorption	Poor absorption of vitamin D/calcium	Celiac, cystic fibrosis	7
Limited sun exposure	Urban living, cultural clothing, pollution	Adolescents, infants	1 4 7 [29]

Table 3: Causes of Rickets

Nutritional Deficiencies

Vitamin D Deficiency:
Vitamin D is synthesized in the skin upon exposure to sunlight (UVB rays) and is also obtained from foods like oily fish, eggs, and fortified products. Inadequate sun exposure—due to indoor lifestyles, high latitudes, pollution, or clothing—leads to deficiency, especially in exclusively breastfed infants and individuals with darker skin 2 4 7 10 12. Maternal vitamin D deficiency during pregnancy can also predispose infants to rickets [31].

Calcium Deficiency:
In some regions, especially Africa and Asia, low dietary calcium is a major factor. Diets lacking dairy or rich in plant-based foods with low bioavailable calcium increase risk, even in the presence of adequate sunlight 11 12 17. Vitamin D supplementation alone may not prevent rickets in these cases 11.

Genetic and Hereditary Factors

Genetic Mutations:
Hereditary rickets can result from:

• Defects in vitamin D metabolism (VDDR1A, VDDR1B)
• Resistance to vitamin D action (VDDR2A, VDDR2B)
• Mutations affecting renal phosphate handling, such as those causing XLH or other forms of hypophosphatemic rickets 5 7 8.

Renal and Metabolic Causes

Chronic Kidney Disease:
The kidneys activate vitamin D into its active form. Impaired kidney function disrupts this process, causing secondary rickets. Kidney diseases may also cause phosphate wasting or metabolic acidosis, further impairing bone mineralization 7 14.

Environmental and Sociocultural Factors

• Limited Sunlight: Urbanization, air pollution, clothing customs (e.g., full-body covering), and living in apartments during lockdowns contribute to lower vitamin D synthesis 1 4 7 [29].
• Dietary Patterns: Vegetarian or vegan diets without adequate supplementation, or reliance on unfortified foods, increase risk.

Other Medical Conditions

• Malabsorption Syndromes: Conditions such as celiac disease or cystic fibrosis interfere with the absorption of fat-soluble vitamins, including vitamin D 7.
• Medication Side Effects: Certain drugs, like anticonvulsants, can impair vitamin D metabolism 7.

Treatment of Rickets

Timely and targeted treatment of rickets can result in full recovery if the underlying cause is addressed early. Approaches vary depending on the type and severity of rickets, but the core principle is restoring normal calcium and phosphate levels to enable healthy bone growth.

Treatment	Main Approach/Agent	Best For	Sources
Vitamin D	Cholecalciferol or ergocalciferol	Nutritional, calcipenic rickets	7 16 17 [23]
Calcium	Dietary/supplemental calcium	Calcium-deficiency, nutritional	7 17
Active vitamin D analogs	Calcitriol, alfacalcidol	Genetic, renal forms	7 9 15
Phosphate supplements	Oral phosphate salts	Hypophosphatemic rickets	9 15 18
Burosumab	Anti-FGF23 monoclonal antibody	XLH and other FGF23-related forms	7 9 18
Surgical intervention	Orthopedic correction	Severe, unresponsive deformities	7 15

Table 4: Treatment Options

Nutritional and Calcipenic Rickets

Vitamin D Supplementation:
The cornerstone of treatment is vitamin D, given as cholecalciferol (D3) or ergocalciferol (D2). Dosages depend on age and severity. Typical regimens include a high "intensive" phase followed by maintenance dosing 7 [22] [23]. For example:

• Infants: 3,000–6,000 IU/day initially, then 400–600 IU/day maintenance
• Children/Adolescents: Up to 10,000 IU/day for severe cases 7

Calcium Supplementation:
Essential, especially in calcium-deficiency rickets. Recommended daily allowances vary by age, but children with rickets may need ≥1,000 mg/day 7 17. In areas with low dietary calcium, supplementation is as important as vitamin D treatment 11 17. Studies show that combining vitamin D and calcium improves healing more than vitamin D alone 17.

Sunlight Exposure:
Encouraging sensible sun exposure is a natural and effective preventive measure, but may not suffice in high-risk populations or during periods of restricted outdoor activity (e.g., COVID-19 lockdowns) 4 16.

Hypophosphatemic (Phosphopenic) Rickets

Conventional Therapy:
Treatment historically involved frequent oral phosphate supplements coupled with active vitamin D analogs (calcitriol or alfacalcidol) to counteract phosphate wasting and impaired vitamin D activation 9 15. Monitoring for side effects, such as hypercalciuria and nephrocalcinosis, is crucial.

Burosumab:
A major recent advance, burosumab is an anti-FGF23 monoclonal antibody now approved for XLH and tumor-induced osteomalacia. It improves bone mineralization, height, and quality of life, with fewer adverse events than conventional therapy 7 9 18. Regular monitoring of serum phosphate and renal function is required.

Disease-Specific Treatments:
Some forms, such as those due to Fanconi syndrome or Dent disease, require additional therapies targeting the underlying renal disorder 9.

Vitamin D–Dependent and Renal Rickets

Active Vitamin D Analogs:
Because of defects in vitamin D metabolism or action, these forms require treatment with active forms like calcitriol or alfacalcidol, often at higher doses 7 9.

Surgical and Dental Care:
In severe or persistent skeletal deformities, orthopedic surgery may be necessary. Dental care is critical in hypophosphatemic rickets due to a high rate of dental abscesses and enamel defects 15.

Monitoring and Prevention

• Biochemical Monitoring: Regular follow-up of calcium, phosphate, alkaline phosphatase, parathyroid hormone, and vitamin D levels is essential to assess response and prevent side effects 9.
• Growth Assessment: Monitoring height, weight, and skeletal changes helps track treatment success.
• Preventive Strategies: Universal vitamin D supplementation for infants, ensuring adequate maternal vitamin D, and community-based education on nutrition and sunlight exposure are vital for prevention 7 12.

Conclusion

Rickets remains a significant, yet preventable, childhood disease worldwide. Its diverse causes require tailored diagnostic and therapeutic approaches. Early recognition of symptoms and an understanding of its various types and causes enable more effective treatment and prevention.

Key takeaways:

• Rickets presents with bone pain, limb deformities, muscle weakness, and growth failure; early symptoms can be subtle.
• It is classified into nutritional, calcipenic, phosphopenic (hypophosphatemic), vitamin D–dependent, and renal types.
• Causes range from nutritional deficiencies (vitamin D, calcium), genetic mutations, chronic kidney disease, to environmental and cultural factors limiting sun exposure.
• Treatment depends on the type: nutritional rickets responds well to vitamin D and/or calcium supplementation, while genetic forms may require active vitamin D analogs, phosphate supplements, or novel therapies like burosumab.
• Prevention through adequate nutrition, sun exposure, and supplementation is crucial, especially in high-risk populations.

Armed with this comprehensive understanding, caregivers and healthcare providers can work together to ensure every child has the opportunity for healthy skeletal growth and lifelong well-being.