Genetic Disorders of Bone Growth and Formation

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Questions and Answers

What is the most common cause of isolated elevated alkaline phosphatase in patients over 40 years old?

Osteoporosis

Paget disease of bone (correct)

Osteomyelitis

Avascular necrosis

Which treatment is contraindicated for patients with osteoporosis?

Estrogen replacement therapy

Vitamin D supplementation

Bisphosphonates

Glucocorticoids (correct)

Which of the following features is associated with Paget disease of bone?

Mosaic pattern of lamellar bone on biopsy (correct)

Decreased alkaline phosphatase levels

Fragile bones that do not fracture easily

Systemic signs of infection like fever

What is a common complication associated with Paget disease of bone?

High-output cardiac failure Signup and view all the answers

Which pathogen is the most common cause of osteomyelitis in children?

Staphylococcus aureus Signup and view all the answers

Which of the following treatments can inhibit osteoclast function in Paget disease?

Calcitonin Signup and view all the answers

Which of the following is NOT a characteristic of osteomyelitis?

Osteoblast predominance Signup and view all the answers

What is a common cause of ischemic necrosis of bone?

Sickle cell anemia Signup and view all the answers

What is the primary source of vitamin D for most individuals?

Sunlight exposure Signup and view all the answers

Which condition is primarily characterized by low vitamin D levels in children?

Rickets Signup and view all the answers

What laboratory finding is typically elevated in osteomalacia due to vitamin D deficiency?

Parathyroid hormone (PTH) Signup and view all the answers

How does vitamin D primarily influence calcium and phosphate levels in the body?

Increases reabsorption in the kidney Signup and view all the answers

Which of the following factors does NOT contribute to peak bone mass?

Bone resorption rate Signup and view all the answers

What is a common clinical feature associated with osteoporosis in older adults?

Fractures in weight-bearing areas Signup and view all the answers

Which condition is characterized by impaired cartilage proliferation in the growth plate?

Achondroplasia Signup and view all the answers

What percentage of bone mass is typically lost each year after peak bone mass is achieved?

1% Signup and view all the answers

What is the typical presentation of rickets in children under 1 year of age?

Frontal bossing and pigeon-breast deformity Signup and view all the answers

What is the primary cause of osteogenesis imperfecta?

Autosomal dominant defect in collagen type I synthesis Signup and view all the answers

What clinical feature is associated with osteopetrosis?

Vision impairment Signup and view all the answers

Which mechanism is responsible for the formation of long bones in achondroplasia?

Endochondral bone formation Signup and view all the answers

Renal tubular acidosis can occur as a complication of which condition?

Osteopetrosis Signup and view all the answers

Which statement describes the clinical features of osteogenesis imperfecta?

Normal hearing ability and blue sclera Signup and view all the answers

What is the impact of FGFR3 mutation in achondroplasia?

Inhibits growth due to overexpression Signup and view all the answers

Which type of bone formation is unaffected in achondroplasia?

Intramembranous bone formation Signup and view all the answers

Study Notes

ACHONDROPLASIA

Impaired cartilage proliferation in growth plates, leading to dwarfism
Caused by activating mutation in fibroblast growth factor receptor 3 (FGFR3), an autosomal dominant trait
FGFR3 overexpression inhibits growth
Many mutations are sporadic, linked to increased paternal age
Clinical features: short extremities, normal head and chest
Endochondral bone formation (long bones): cartilage matrix formation replaced by bone
Intramembranous bone formation (flat bones): bone develops without cartilage precursor
Mental function, lifespan, and fertility are not affected

OSTEOGENESIS IMPERFECTA

Congenital bone formation defect, resulting in weak bones
Primarily due to an autosomal dominant defect in collagen type I synthesis
Clinical features: multiple bone fractures (can mimic child abuse), blue sclera (thinning of collagen), and hearing loss (middle ear easily fractures)

OSTEOPETROSIS

Inherited bone resorption defect, causing abnormally thick, heavy bones prone to fractures
Due to poor osteoclast function
Multiple genetic variants exist; carbonic anhydrase II mutation linked to loss of acidic microenvironment required for bone resorption
Clinical features: bone fractures, anemia, thrombocytopenia, leukopenia, extramedullary hematopoiesis (marrow replacement), impaired vision and hearing, hydrocephalus, and renal tubular acidosis

RICKETS/OSTEOMALACIA

Defective mineralization of osteoid (unmineralized bone matrix)
Osteoblasts produce osteoid that's mineralized with calcium and phosphate to form bone
Low vitamin D levels cause low serum calcium and phosphate, hindering mineralization
Vitamin D activation requires 25-hydroxylation by the liver and 1-alpha-hydroxylation by the kidney
Vitamin D increases calcium and phosphate absorption in the gut, reabsorption in the kidneys, and release from bone
Vitamin D deficiency is due to decreased sun exposure, poor diet, malabsorption, liver failure, or renal failure
Rickets (children): abnormal bone mineralization, presenting as pigeon-breast deformity, frontal bossing, rachitic rosary, and bowing of legs
Osteomalacia (adults): weak bones, increased fracture risk

OSTEOPOROSIS

Reduction in trabecular bone mass, leading to porous bone and increased fracture risk
Risk factors: low peak bone mass (achieved by 30), genetic predisposition, poor diet, lack of exercise, and reduced estrogen (e.g., menopause)
Bone loss accelerates after peak bone mass

AVASCULAR (ASEPTIC) NECROSIS

Ischemic necrosis of bone and bone marrow
Causes include trauma, fractures, steroid use, sickle cell anemia, and caisson disease
Osteoarthritis and fractures are major complications.

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Description

This quiz covers key genetic disorders related to bone growth and formation, including Achondroplasia, Osteogenesis Imperfecta, and Osteopetrosis. It explores their causes, clinical features, and genetic mechanisms. Test your knowledge on these conditions and their impact on skeletal health.