Osteomalacia and Rickets

Overview

Definition

Rickets and osteomalacia are disorders of decreased bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones mineralization. Rickets affects the cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage of the epiphyseal growth plates in children, while osteomalacia affects the sites of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones turnover in children and adults.

Epidemiology

Rickets:

• In the United States, rickets mostly affects infants who have:
  • Chronic malabsorption Malabsorption Malabsorption involves many disorders in which there is an inability of the gut to absorb nutrients from dietary intake, potentially including water and/or electrolytes. A closely related term, maldigestion is the inability to break down large molecules of food into their smaller constituents. Malabsorption and maldigestion can affect macronutrients (fats, proteins, and carbohydrates), micronutrients (vitamins and minerals), or both. Malabsorption and Maldigestion syndromes
  • Renal disease
  • Been exclusively breast-fed
    • Vitamin D deficiency
    • Affecting dark-skinned infants
• Worldwide prevalence depends on:
  • Nutritional deprivation
  • Lack of sun exposure

Osteomalacia:

• Mostly attributed to vitamin D deficiency
• Prevalence is growing worldwide.
• Commonly affects homebound elderly adults
• Can co-exist with rickets in children

Etiology

Rickets and osteomalacia can be caused by vitamin D, calcium, or phosphorus deficiencies. These conditions can cause be caused by abnormalities of the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones matrix deposition.

Vitamin D-related (most common):

• Vitamin D deficiency: 
  • Dietary deprivation 
  • Lack of sunlight
• Vitamin D malabsorption Malabsorption Malabsorption involves many disorders in which there is an inability of the gut to absorb nutrients from dietary intake, potentially including water and/or electrolytes. A closely related term, maldigestion is the inability to break down large molecules of food into their smaller constituents. Malabsorption and maldigestion can affect macronutrients (fats, proteins, and carbohydrates), micronutrients (vitamins and minerals), or both. Malabsorption and Maldigestion: 
  • Postgastrectomy
  • Gastric bypass
  • Celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease
  • Pancreatic insufficiency
  • Cholestyramine treatment
  • Laxative abuse
• Impaired 1-hydroxylation of 25-hydroxyvitamin D:
  • Vitamin D-dependent rickets type 1
  • X-linked hypophosphatemia 
  • Oncogenic osteomalacia
• Impaired target organ response to D3: vitamin D-dependent rickets type II

Hypophosphatemia related:

• X-linked hypophosphatemia 
• Fibrous dysplasia
• Antacid-induced osteomalacia
• Chronic metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis
• Tenofovir
• Cadmium
• Paraproteinemia

Inhibitors of mineralization:

• Etidronate
• Fluoride
• Aluminum 
• Iron

Miscellaneous:

• Hypophosphatasia
• Axial osteomalacia
• Fibrogenesis imperfecta ossium

Pathophysiology

Rickets

• Growth plate thickness is determined by:
  • Chondrocyte proliferation and hypertrophy
  • Vascular invasion of the growth plate
• Vascular invasion requires mineralization of the growth plate cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage.
• In the absence of mineralization, the growth plate cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage accumulates and becomes disorganized, and the growth plate thickens.
• Accumulation of unmineralized osteoid in the metaphysis (right below the growth plate) eventually leads to bowing and deformation of bones.

Osteomalacia

• At any one time, 7% of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones surface is being actively remodeled.
• Osteoclasts resorb the old bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones while osteoblasts lay down new osteoid (organic matrix).
• Osteomalacia can occur if:
  • New osteoid is qualitatively or quantitatively abnormal
  • Insufficient calcium and phosphate are in the extracellular fluid
  • Acidosis is at the calcification site (renal disease)
  • Inadequate activity of alkaline phosphatase is present
  • Calcification is influenced by drugs (e.g., aluminum, fluoride)

Clinical Presentation

Rickets

• Delay in the time of closure of fontanelles and soft skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull bones (craniotabes)
• Parietal and frontal bossing
• Genu varum Genu varum Genu varum is a deformation of the knee joint(s) that creates angulation of the lower limb(s) away from the midline in the coronal plane. Children ages 1-5 years are commonly affected. Genu Varum (toddlers) and Genu valgum Genu valgum Genu valgum is a deformation of the knee joint(s) that creates angulation of the lower limb(s) toward the midline in the coronal plane. Children ages 1-5 years are commonly affected. Genu Valgum (older children)
• Deformity of the spine (kyphoscoliosis) 
• Sulcus at the lower margin of the chest known as Harrison sulcus
• Bending primarily at the long bones and widening of the wrist
• Enlargement of costochondral junctions with “rib beading” (rachitic rosary)
• Problems with the dental architecture
• Greenstick fractures (linear fractures with intact periosteum)
• Short stature

Osteomalacia

• Fatigue
• Diffuse bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
• Muscle weakness
• Pathological fractures
• Difficulty walking/waddling gait
• Can also present with signs of hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia if associated with calcium deficiency

Diagnosis and Management

Diagnosis

History:

• Fractures
• Bone pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
• Family history
• Poor nutrition
• Homebound lifestyle
• Lack of sun exposure

Physical exam: skeletal deformities typical of rickets

Laboratory tests:

• Laboratory values vary depending on the underlying deficiencies.
• Calcipenic rickets:
  • ↑ Parathyroid hormone (PTH) 
  • ↓ Calcium
  • ↓ Phosphate
• Phosphopenic rickets:
  • PTH normal or mildly elevated
  • ↓ Phosphate
• ↓ Vitamin D (in vitamin D deficiency)
• ↑ Alkaline phosphatase levels (except in hypophosphatasia)

X-ray imaging:

• Rickets:
  • Epiphyseal widening
  • Metaphyseal cupping/fraying
  • Genu varum Genu varum Genu varum is a deformation of the knee joint(s) that creates angulation of the lower limb(s) away from the midline in the coronal plane. Children ages 1-5 years are commonly affected. Genu Varum or valgum (bowing of long bones)
  • Rachitic rosary 
  • Craniotabes
• Osteomalacia: 
  • Osteopenia
  • Pseudofractures or “Looser zones,” a band of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones material of decreased density

Management

• Vitamin D supplementation
• Calcium-rich diet; calcium and phosphate supplementation 
• Adequate exposure to sunlight 
• Most deformities of rickets will correct with treatment.
• If severe deformities have occurred, orthopedic correction is sometimes necessary.

Differential Diagnosis

• Hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism: pathologically elevated PTH levels are summarized under the term hyperparathyroidism. Depending on the pathogenesis, distinctions can be made between 3 forms: primary, secondary, and tertiary hyperparathyroidism. Long-standing hyperparathyroidism can result in osteopenia and pathologic bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones fractures. Treatment approach depends on the underlying cause and involves parathyroidectomy for primary hyperparathyroidism.
• Chronic renal failure: defined as an irreversible decrease of not only glomerular and tubular function, but also endocrine renal function. This condition presents as pathologically disturbed excretory and incretionary renal function. Chronic renal failure can cause hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia through decreased formation of active vitamin D, which in turn results in secondary hyperparathyroidism and leaking of calcium from the bones. Treatment is mostly supportive. 
• Blount’s disease: a pediatric orthopedic problem in which the leg Leg The lower leg, or just "leg" in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg is bowed outward or in a varus position. This disease is due to a dysfunctional growth of the posterior medial aspect of proximal physis of the tibia resulting in a lower limb deformity. Diagnosis is established based on clinical picture and imaging, and treatment involves bracing and sometimes surgical correction.
• Achondroplasia: a genetic disorder that results in dwarfism. In those with the condition, the arms and legs are short, while the torso is typically of normal length. Those affected have an average adult height of 131 cm (4 ft 4 in) for males and 123 cm (4 ft) for females. Diagnosis is established clinically and confirmed by genetic testing. Treatment is largely supportive.
• Osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis: a loss of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones mass usually associated with aging and hormonal deficits. Most common in post-menopausal women. Presents with fragility fractures. Diagnosis is based on clinical presentation and measurements of bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones mineral density. Treatment involves vitamin D and calcium supplementation and bisphosphonates Bisphosphonates Bisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix "-dronate" or "-dronic acid" (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption. Bisphosphonates.
• Osteogenesis imperfecta Osteogenesis imperfecta Osteogenesis imperfecta (OI), or "brittle bone disease," is a rare genetic connective tissue disorder characterized by severe bone fragility. Although OI is considered a single disease, OI includes over 16 genotypes and clinical phenotypes with differing symptom severity. Osteogenesis Imperfecta: a genetic disorder associated with extreme bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones fragility. The disease varies in severity, but usually presents in early childhood with multiple fractures and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones deformities.  Osteogenesis imperfecta Osteogenesis imperfecta Osteogenesis imperfecta (OI), or "brittle bone disease," is a rare genetic connective tissue disorder characterized by severe bone fragility. Although OI is considered a single disease, OI includes over 16 genotypes and clinical phenotypes with differing symptom severity. Osteogenesis Imperfecta is diagnosed clinically and with genetic testing. Management includes bisphosphonates Bisphosphonates Bisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix "-dronate" or "-dronic acid" (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption. Bisphosphonates and is mostly focused on fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures prevention.