Osteomalacia and rickets

Osteomalacia is a disorder of impaired mineralization of the osteoid; rickets is a disorder of impaired mineralization of cartilaginous growth plates. Adults have fused growth plates so they are only affected by osteomalacia. In children, whose growth plates are open, the disorders can occur simultaneously. The most common cause of both osteomalacia and rickets is vitamin D deficiency resulting from inadequate intake, malabsorption, or lack of exposure to sunlight. Patients with osteomalacia usually present with bone pain and tenderness, while patients with rickets exhibit bone deformities and impaired growth. Over time, both conditions may lead to bending of the long bones or even pathologic fractures. Treatment consists of administering vitamin D and ensuring sufficient calcium intake.

Vitamin D‑dependent forms (most common)

Vitamin D deficiency ^[1][2][3][4]

• UV radiation
  • Reduced exposure
  • Dark skin
• Oral intake
  • Low dietary intake
  • Infants younger than 1 year: breast milk has low amounts of vitamin D
• Intestinal absorption can be reduced due to a number of factors, including:
  • Cystic fibrosis, chronic pancreatitis
  • Premature birth
  • Celiac disease
  • Gastrectomy

Defective vitamin D metabolism

• Impaired organ function
  • Liver cirrhosis
  • Renal disease (e.g., chronic renal failure) → ↓ production of vitamin D and metabolic acidosis → impaired calcification
• Drugs: cytochrome P450 inducers increase the metabolism of vitamin D ; ^[5][6]
  • Anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital)
  • Antimicrobial agents (e.g., rifampin, hydroxychloroquine)
• Rare vitamin D-dependent hereditary forms
  • Vitamin D-dependent rickets type 1 ^[7]
    • Mutation in the 25-hydroxyvitamin-D-1α-hydroxylase gene
    • Leads to impaired conversion of inactive vitamin D to the active form, 1,25‑dihydroxyvitamin D3 (calcitriol).
    • Characterized by early onset of rickets, muscle weakness, failure to thrive, hypotonia, and pathological fractures
  • Vitamin D-dependent rickets type 2 ^[8]
    • Mutation in the vitamin D receptor gene causes end-organ resistance to vitamin D.
    • Characterized by early onset of rickets, failure to thrive, and alopecia

Vitamin D‑independent forms (rare)

• Renal tubular defects
  • Renal tubular acidosis
  • Fanconi syndrome
• Phosphate deficiency
• Drugs
  • Bisphosphonates
  • Aluminium
  • Fluoride

Vitamin D deficiency and defective vitamin D metabolism ^[9]

• Hypocalcemia → defective bone matrix mineralization (osteomalacia) or cartilaginous growth plate mineralization (rickets).
• Hypocalcemia → ↑ PTH levels → ↓ phosphate levels → impaired mineralization.
• See “Calcium homeostasis.”

Vitamin D-independent forms

• Phosphate deficiency → ↓ phosphate blood levels → defective bone matrix mineralization (osteomalacia) or growth plate mineralization (rickets).

Osteomalacia

• Occurs in adults and children
• Bone pain and tenderness
• Pathologic fractures
• Waddling gait and difficulty walking
• Myopathy
  • Muscle weakness
  • Spasms
  • Cramps
• Bone deformity only in very severe cases of osteomalacia
• Symptoms of hypocalcemia (see “Clinical features of hypocalcemia.”)

Rickets

• Only occurs in children (growth plates have not fused)
• Bone deformities
  • Bending of primarily the long bones
  • Distention of the bone-cartilage junctions
    • Rachitic rosary: bead-like distention of the bone-cartilage junctions in the ribs
    • Marfan sign: distention of the epiphyseal plate of the distal tibia with widening and cupping of the metaphysis gives the impression of a double medial malleolus on inspection and palpation of the ankle
  • Craniotabes: softening of the skull
  • Deformities of the knee, especially genu varum
• Increased risk of fracture ^{[10] [11]}
• Harrison groove: depression of the thoracic outlet due to muscle pulling along the costal insertion of the diaphragm
• Late closing of fontanelles
• Impaired growth
• Symptoms of hypocalcemia (see “Clinical features of hypocalcemia.”)

Laboratory tests

• ↓ Calcium and ↓ phosphate
• ↑ Alkaline phosphatase and ↑ PTH
• Vitamin D-dependent rickets type 1: ↓ calcitriol concentration
• Vitamin D-dependent rickets type 2: ↑ calcitriol concentration
• See “Laboratory evaluation of bone disease.”

Imaging

Bone biopsy

• Can be useful to establish diagnosis, identify the underlying pathomechanism, and study bone metabolism
• Iliac bone is used for biopsy

Osteomalacia

• Malignancy
• Osteoporosis
• Paget disease of the bone

Rickets ^[12]

• Tumor-induced osteomalacia
• Osteoglophonic dysplasia with dwarfism
• Osteogenesis imperfecta
• Neurofibromatosis
• McCune-Albright syndrome
• Child abuse/neglect

Congenital pseudarthrosis of the tibia

• Definition: unilateral anterolateral bowing of the lower third of the tibia and possibly fibula associated with neurofibromatosis type I
• Clinical features
  • Pseudoarthrosis of the lower leg (false joint formation of the tibia and possibly fibula) may be present at birth or develop over time.
  • Fractures of the tibia and fibula are possible.
• Treatment
  • Removal of pseudoarthrosis tissue
  • Implantation of bone graft
  • Internal or external fixation

The differential diagnoses listed here are not exhaustive.

• Vitamin D deficiency: administration of vitamin D
  • Also indicated in infants who are exclusively breastfed
  • The healing of both osteomalacia and rickets requires adequate daily intake of calcium.
• Defective vitamin D metabolism or vitamin D‑independent forms: treatment of underlying disease