Congenital and metabolic bone disorders Flashcards
Inheritance of achondroplasia
Autosomal dominant
Mutation in achondroplasia
FGFR3 on chromosome 4, inhibits endochondral growth
Narrow and disorganizes zones of proliferation and hypertrophy of bone
Achondroplasia
Laron dwarfism
Pituitary dysfunction or secondary to a mutation in growth hormone receptor
Inheritance of osteogenesis imperfecta
Autosomal dominant
Deficiencies in type I collagen synthesis related to defects in EC structural proteins
Osteogenesis imperfecta
Mutation in osteogenesis imperfecta
COL1A1 and COL1A2 genes encoding alpha-1 and -2 chains of type 1 collagen due to replacement of glycine
Group of rare genetic disorders characterized by reduced bone resorption due to deficient osteoclast development or function
Osteopetrosis
Mutations and inheritance associated with osteopetrosis
TCIRG1 –> AR
CLCN7 –> AD
CA-II –> AR
Normal function of TCIRG1
Makes an osteoclast proton pump
Normal function of CLCN7
Osteoclast chloride channel
Albers-Schonberg disease
Osteopetrosis caused by CLCN7 mutation
Normal function of CA-II
Generates protons and facilitates the resorption pit acidification by osteoclasts
Deposited bone tends to woven instead of lamellar
Osteopetrosis
Inheritance of infantile osteopetrosis
Autosomal recessive
Inheritance of adult osteopetrosis
Autosomal dominant
Treatment for osteopetrosis
Hematopoietic stem cell transplantation –> osteoclasts are derived from
Radiologic features of osteopetrosis
Lack of medullary canal with misshapen ends of long bones
Histologically normal bone that is decreased in quantity
Osteoporosis
Three phases of Paget disease
Initial osteolytic stage
Mixed osteoclastic-osteoblastic stage
Burned-out quiescent osteosclerotic stage
Marked by increased, but disordered and structurally unsound bone mass
Paget disease or osteitis deformans
Haphazardly oriented lamellae are joined by a prominent cement line
Paget disease
Mutation in Paget disease
SQSTM1 resulting in increased NFkB activity
Platybasia
Flattening of base of skull causing impingement in Paget disease
Increased alkaline phosphatase and urinary excretion of hydroxyproline with normal Ca, phosphorous, and PTH
Paget disease
Complications of Paget disease
Osteosarcoma or fibrosarcoma
High output heart failure
3 skeletal abnormalities associated with hyperparathyroidism
Osteoporosis
Brown tumors
Osteitis fibrosa cystica
Secondary hemorrhage, macrophage recruitment, and ingrowth of reparative fibrous tissue that creates a mass lesion
Brown tumor
Combination of increased bone cell activity, peritrabecular fibrosis, and cystic brown tumors
Generalized osteitis fibrosa cystic or von Recklinghausen disease of bone
Clinical features of hyperparathyroidism
Stones - kidney stones
Bones - skeletal changes
Moans - depression
Groans - GI irregularities
Manifestations of renal osteodystorphy
Osteopenia/porosis
Osteomalacia
Secondary hyperparathyroidism
Growth retardation
3 mechanisms through which kidney disease causes skeletal abnormalities
Tubular dysfunction
Secondary hyperparathyroidism
Decreased biosynthetic function (vit D)
Normal Ca, phosphate, alkaline phosphatase and PTH
Osteoporosis
Normal or decreased CA, normal PTH and phosphate, increased alkaline phosphatase
Paget disease
Decreased Ca and phosphate, increased alkaline phosphatase and PTH
Osteomalacia or Rickets
Increased Ca, alkaline phosphatase, and PTH. Decreased phosphate
Osteitis fibrosa cystica in primary hyperparathyroidism
Decreased Ca. Increased phosphate, alkaline phosphatase, and PTH.
Secondary hyperparathyroidism in CKD
