Pathoma - MSK - Bones Flashcards
What is the basic premise of achondroplasia
Impaired cartilage proliferation in the growth plate –> failure of longitudinal growth –> common cause of dwarfism
What is the mutation in achondroplasia
Activating mutation in fibroblast growth factor receptor 3 (FGFR3)
Overexpression of FGFR3 inhibits growth
What is a risk factor for mutation of FGFR3 (achondroplasia)
Paternal age
What is endochondral ossification?
Bones of axial skeletal, appendicular skeleton, and base of skull
Chondrocytes lay down a cartilagenous model of bone which is then replaced by osteoclasts and osteoblasts into first woven bone and then lamellar bone
What is membranous ossification?
Bones of skull, face, and chest
Woven bone is formed directly without cartilage and then later remodelled to lamellar bone
What type of bone formation is abnormal in achondroplasia? Endochondral or membranous ossification?
Poor endochondrol bone formation (long bones) - which is why patients have short limb
Normal membranous bone formation (skull and chest) - so patients have normal sized head and chest
What is the defect in osteogenesis imperfecta
Defect in collagen type I synthesis
What is the triad of clinical features of osteogenesis imperfecta?
Multiple bone fractures, blue sclera, hearing loss
Why is there blue sclera in osteogenesis imperfecta?
Thinning of scleral collagen reveals underlying choroidal veins
Why is there hearing loss in osteogenesis imperfecta?
Bones of the middle ear are easily fractured
What is the basic premise behind osteopetrosis?
Inherited defect of bone resorption (defective osteoclasts) resulting in abnormally thick, heavy bone that fractures easily
What is a common mutation leading to osteopetrosis?
Carbonic anhydrase II mutation
Leads to loss of acidic environment required for bone resorption
Why do you get pancytopenia in osteopetrosis?
Bone fills the marrow space leading to myelophthisic process (marrow can no longer carry out hematopoiesis - extramedullary hematopoiesis)
What are common complications of osteopetrosis?
Cranial nerve impingements due to narrowing of foramina
Hydrocephalus due to narrowing of foramen magnum
What is the metabolic/respiratory acidosis/alkalosis commonly found in osteopetrosis?
Metabolic acidosis
Carbonic anhydrase deficiency leads to lack of HCO3- reabsorption
What is the treatment for osteopetrosis?
Bone marrow transplant (osteoclasts are derived from monocytes)
What is the defective process in osteomalacia/rickets?
Defective mineralization of osteoid (osteid is still produced by osteoblasts, but is unable to be mineralized with calcium and phosphate to form bone)
Due to low levels of Vitamin D, leading to low serum calcium and phosphate
Describe the activation of Vitamin D
25-hydroxylation via liver
1-alpha-hydroxylation via kidney
Common clinical findings of rickets
Pigeon-breast deformity
Frontal bossing (enlarged forehead) - due to osteoid deposition on the skull
Rachitic rosary - osteoid deposition at the costochondral junction
Bowing of the legs
Is alkaline phosphatase increased or decreased in osteomalacia and why
Increased - in order to try to create an alkaline environment, wich is necessary to lay down calcium into osteoid
What is the basic premise behind osteoporosis
Loss of mass of trabelular (spongy) and cortical bone
What is the most common cause of osteoporosis?
Increased bone resorption due to decreased estrogen (post-menopausal) or old age
Describe lab values in osteoporosis (calcium, phosphate, PTH, alkaline phosphatase)
Normal lab values
Can be used to help exclude osteomalacia (which will have low calcium, high PTH, low phosphate, and high alkaline phosphatase)
Treatment options for osteoporosis
Weight-bearing exercise, vitamin D, calcuium
Bisphosphonates, SERMs
