Osteomalacia Introduction Etiology Clinical features diagnostics and Treatment

Osteomalacia preeminent and foremost characteristics Introduction Etiology Clinical features diagnostics and Treatment

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Brief Introduction:

  • Osteomalacia and rickets involve bone mineralization disorders.
  • Osteomalacia results from defective remodeling of existing bone, while rickets are due to a deficiency in new bone formation.
  • Osteomalacia can affect individuals of any age, while rickets is limited to children with open growth plates.
  • Both conditions are linked to insufficient calcium, phosphate depletion, and direct inhibition of bone mineralization.
  • Vitamin D deficiency is the primary cause of osteomalacia and rickets.
  • Osteomalacia patients typically experience bone pain and tenderness.
  • Rickets patients often exhibit bone deformities and impaired growth.
  • Over time, both conditions can lead to long bone curvature and pathological fractures.
  • Diagnosis relies on clinical history, and abnormal lab results, and often includes imaging.
  • Treatment aims to address the underlying cause, usually focusing on treating vitamin D deficiency and ensuring sufficient calcium intake.

Etiology

  1. Insufficient Calcium (Calcipenic Rickets)
  1. Phosphate deficiency (phosphopenic rickets) 
    • Renal phosphate wasting due to renal tubular defects (e.g., distal renal tubular acidosis, Fanconi syndrome)
    • Chronic use of phosphate binders
    • Other causes of hypophosphatemia, e.g.:
      • Hereditary hypophosphatemic rickets
      • Tumor-induced osteomalacia
  1. Direct inhibition of bone mineralization
    • Medications, e.g., bisphosphonates, aluminum, fluoride
    • Hereditary hypophosphatasia

Most Common Cause of Osteomalacia and Rickets:

  • Vitamin D Deficiency is the primary and most prevalent cause for both conditions.

Less Common Causes:

  • Vitamin D-independent causes, including hypophosphatemia, hypocalcemia, and medication-induced factors, are less frequently observed.
  • Hereditary factors also contribute to a smaller proportion of cases.

Pathophysiology

Mechanisms of Osteomalacia and Rickets:

  • Calcipenic Rickets:
    • Decreased Calcium Levels → Elevated PTH (Parathyroid Hormone) Levels → Reduced Phosphate → Impaired Bone Mineralization
    • For further details, refer to “Calcium Homeostasis.”
  • Phosphopenic Rickets:
    • Decreased Phosphate Levels → Impaired Bone Mineralization
  • Direct Inhibition of Mineralization: Results in Impaired Bone Mineralization

Effects of Impaired Bone Mineralization:

  • Impaired bone mineralization can impact both the existing bone matrix (osteomalacia) and, if the growth plates are still open, the formation of new bone (rickets).
  • Low phosphate levels are a common factor in both calcipenic and phosphopenic forms of osteomalacia and rickets.

Clinical Features:

Osteomalacia:

  • Occurs in both adults and children.
  • Symptoms:
    • Bone pain and tenderness.
    • Pathologic fractures.
    • Myopathy, predominantly proximal.
      • Muscle weakness leading to a waddling gait and difficulty walking.
      • Spasms and cramps.
    • Symptoms of hypocalcemia.
    • Severe osteomalacia can lead to bone deformities, such as bowing of the lower limbs.
  • Note: Osteomalacia and rickets may sometimes be asymptomatic.

Rickets:

  • Occurs exclusively in children, as their growth plates have not fused.
  • Clinical signs include:
    • Bone deformities, primarily bowing of 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, giving the appearance of a double medial malleolus on inspection and palpation of the ankle.
      • Widened wrists.
    • Craniotabes: softening of the skull.
    • Deformities of the knee, especially genu varum.
    • Increased risk of fracture.
    • Harrison groove: A depression of the thoracic outlet caused by muscles pulling along the costal insertion of the diaphragm.
    • Impaired growth.
    • Symptoms of hypocalcemia, including seizures in infants.
    • Late closing of fontanelles.
    • Delayed walking (beyond 18 months).
    • Cardiomyopathy.

Important Note:

  • Osteomalacia is characterized by defective mineralization of existing bone and can occur in individuals with open or closed growth plates.
  • Rickets involves defective mineralization of new bone formation and, therefore, only occurs in children with open growth plates, typically before the end of puberty.

Subtypes and Variants

Vitamin D-dependent rickets type 1:

  • Pathophysiology:
    • Autosomal recessive mutation in the 25-hydroxyvitamin-D-1α-hydroxylase gene.
    • Results in impaired conversion of inactive vitamin D to the active form, 1,25‑dihydroxyvitamin D3 (calcitriol).
  • Clinical features:
    • Early onset of rickets (in infancy).
    • Muscle weakness.
    • Growth faltering.
    • Hypotonia.
    • Pathological fractures.
  • Diagnostics:
    • Normal or elevated plasma 25-OH.
    • Low or undetectable 1,25(OH)2D.
    • Hypocalcemia, hypophosphatemia, and elevated ALP (alkaline phosphatase).
    • Elevated parathyroid hormones.
  • Treatment:
    • Calcitriol supplementation.

Vitamin D-dependent rickets type 2:

  • Pathophysiology:
    • An autosomal recessive mutation in the vitamin D receptor gene causes end-organ resistance to vitamin D.
  • Clinical features:
    • Early onset of rickets (in infancy).
    • Growth faltering.
    • Alopecia (hair loss).
  • Diagnostics:
    • Normal or elevated plasma 25-OH.
    • Extremely elevated plasma 1,25(OH)2D.
    • Hypocalcemia, hypophosphatemia, elevated ALP.
    • Elevated parathyroid hormones.
  • Treatment:
    • Very high-dose vitamin D therapy.
    • In cases of refractory disease, elemental calcium may be required.

Diagnostics

General Principles:

  • Diagnosis is primarily based on characteristic laboratory and imaging findings.
  • In cases of diagnostic uncertainty, consider referring patients to endocrinology for advanced studies.

Laboratory Studies:

  • Common laboratory findings in vitamin D deficiency include:
    • Decreased serum calcium (↓ Ca)
    • Decreased phosphorus (↓ phosphorus)
    • Increased parathyroid hormone (↑ PTH)
    • Increased alkaline phosphatase (↑ ALP)
  • If laboratory findings are not consistent with osteomalacia/rickets, refer to “Laboratory evaluation of bone disease.”

Laboratory Findings in Osteomalacia and Rickets by Etiology:

  • Calcipenic Rickets:
    • Serum calcium: Initially normal or decreased (↓)
    • Serum phosphorus: Initially normal or decreased (↓)
    • Urine calcium: Decreased (↓)
    • Urine phosphorus: Variable
    • ALP: Increased (↑)
    • Parathyroid hormone (PTH): Increased (↑)
    • Serum 25-OH (vitamin D levels): Decreased (↓) or normal
  • Phosphopenic Rickets:
    • Serum calcium: Normal or increased (initially)
    • Serum phosphorus: Decreased (↓)
    • Urine calcium: Variable
    • Urine phosphorus: Increased (↑) unless dietary phosphate deficiency
    • ALP: Increased (↑)
    • Parathyroid hormone (PTH): Normal
    • Serum 25-OH (vitamin D levels): Normal

Imaging:

Imaging findings in osteomalacia and/or rickets may include:

  • General:
    • Evidence of bone loss.
      • Decreased bone mineral density, resulting in osteopenia or osteoporosis.
      • Thinning of the cortical bone.
    • Pathological Fractures: Occur due to weakened bone.
    • Looser Zones (Pseudofractures):
  • These are characteristic radiolucent bands representing insufficiency stress fractures seen in osteomalacia and severe rickets.
  • Typical features of Looser zones include:
    • Multiple and symmetrical distribution.
    • Perpendicular orientation to the periosteal surface.
    • Most often located in the ribs, scapulae, pubic rami, and medial cortex of long bones.
  • Additional Findings in Rickets:
    • Epiphyseal Plate Widening: Widening of the growth plate regions.
    • Metaphyseal Changes: Cupping, stippling, and fraying in the metaphysis.
    • Bone Bowing: Seen in conditions like genu varum (bow legs).
    • Chest X-ray: Prominent costochondral junctions of the ribs, known as the rachitic rosary.
    • X-ray of the Skull: Persistently widened suture lines (open fontanelles), occipital flattening, and a more squared appearance.
    • X-ray of the Spine: Spinal curvature can be observed.
  • Additional Findings in Osteomalacia:
    • Increased Uptake on Bone Scintigraphy:
      • Due to increased bone turnover. 
      • This can sometimes mimic metastatic cancer.

Advanced Studies:

  • Indications for advanced studies include diagnostic uncertainty and when rare etiologies are suspected, such as tumor-induced osteomalacia or vitamin D-dependent rickets type I or type II.
  • Potential advanced studies may involve serum 1,25(OH)2D levels, FGF23 levels, and iliac bone biopsy with tetracycline labeling.

Treatment

General Principles:

  • Treat any acute electrolyte abnormalities, such as:
    • Calcium repletion for severe and/or symptomatic hypocalcemia.
    • Phosphate repletion.
  • Review the patient’s diet and medication list to identify reversible causes of osteomalacia and rickets.
  • Determine the underlying etiology, and if necessary, refer the patient to a specialist for further management.
  • For persistent bone deformities that do not respond to medical management, consider referring the patient to orthopedics for potential surgical correction.

Treatment of Vitamin D-Associated Osteomalacia and Rickets:

  • Pharmacological Therapy:
    • Administer treatment doses of vitamin D as appropriate.
    • Ensure adequate daily intake of calcium.
    • In selected cases, calcitriol may be required for specific indications.
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