Medical brain notes 15

  NORMAL BONE Normal bone  is composed of organic matrix and inorganic matrix. •           The organic matrix includes cells, type I collagen (90% of bone protein), osteo-calcin, glycoproteins, and proteoglycans. •           The inorganic matrix includes calcium hydroxyapatite Ca10(PO4)6(OH)2, mag-nesium, potassium, chloride, sodium, and fluoride. There are 3 cell types. •           Osteoblasts  are responsible for the production of osteoid (unmineralized bone); they contain high amounts of alkaline phosphatase, have receptors for parathyroid hormone (PTH), and modulate osteoclast function. •           Osteocytes  are responsible for bone maintenance; they are osteoblasts that have become incorporated in the matrix. •           Osteoclasts  ...

HEREDITARY BONE DISORDERS Achondroplasia  is the most common form of inherited dwarfism. It is caused by an autosomal dominant mutation in fibroblast growth factor receptor 3 (FGFR3). Activation of FGFR3 inhibits cartilage synthesis at the epiphyseal growth plate, resulting in decreased enchondral bone formation and premature ossification of the growth plates. •           Long bones are short and thick, leading to dwarfism with short extremities. •           Cranial and vertebral bones are spared, leading to relatively large head and trunk. •           Intelligence, life span, and reproductive ability are normal. Osteogenesis imperfecta (OI) (“brittle bone disease”) is a hereditary defect leading to abnormal synthesis of type I collagen. •           Patients have generalized osteopenia (brittle bones), re...

  PAGET DISEASE Paget disease  (osteitis deformans) is a localized disorder of bone remodeling, result-ing in excessive bone resorption followed by disorganized bone replacement, pro-ducing thickened but weak bone that is susceptible to deformity and fracture. There is an association with paramyxovirus and mutations of  SQSTM1 .   •           Seen in those age >40   •           Common in those of European ancestry   •           Common sites of involvement include the skull, pelvis, femur, and vertebrae   •           Majority of cases are polyostotic and mild   Paget disease develops in 3 stages:   •           Osteolytic stage  (osteoclastic activity predominates)   •        ...

  OSTEOPOROSIS   Osteoporosis  is decreased bone mass (osteopenia), resulting in thin, fragile bones   susceptible to fracture. It is the most common bone disorder in the United States. It most commonly occurs in postmenopausal Caucasian women and the elderly. Primary causes of osteoporosis include the following: • Estrogen deficiency (postmenopausal, Turner syndrome) • Genetic factors (low density of original bone) • Lack of exercise • Old age • Nutritional factors   Secondary causes include immobilization, endocrinopathies (e.g., Cushing disease, thyrotoxicosis), malnutrition (e.g., deficiencies of calcium, vitamins C and D, protein), corticosteroids, smoking/alcohol consumption, genetic disease (e.g., Gaucher disease).   • Patients may experience bone pain and fractures; weight-bearing bones are predisposed to fractures. • Common fracture sites include vertebrae (compression fracture); femoral neck (hip fracture); and distal radius (Colles fracture). • K...

OSTEOMALACIA AND RICKETS   Osteomalacia  and  rickets  are both characterized by decreased mineralization of   newly formed bone. They are usually caused by deficiency or abnormal metabolism of vitamin D. Specific causes include dietary deficiency of vitamin D, intestinal malabsorption, lack of sunlight, and renal and liver disease. Treatment is vitamin D and calcium supplementation.   Osteomalacia  (adults) is due to impaired mineralization of the osteoid matrix result-ing in thin, fragile bones susceptible to fracture. The patient may present clinically with bone pain or fractures (vertebrae, hips, and wrist). X-rays show transverse lucencies called Looser zones. Lab studies show low serum calcium, low serum phos-phorus, and high alkaline phosphatase.   Rickets  (children) occurs in children prior to closure of the epiphyses. Both remod-eled bone and bone formed at the epiphyseal growth plate are undermineralized. Enchondral bone formation ...

  OSTEOMYELITIS   Pyogenic osteomyelitis  is bone inflammation due to bacterial infection. The most   common route of infection is  hematogenous spread  (leading to seeding of bone after bacteremia); this type of spread often affects the metaphysis. Other routes of spread include direct inoculation (e.g., trauma) and spread from an adjacent site of infection (e.g., prosthetic joint).   The most common infecting organism is  S. aureus  ; other important pathogens include  E. coli , streptococci, gonococci , H. influenzae ,  Salmonella  (common in sickle cell disease), and  Pseudomonas  (common in IV drug abusers and diabetics).   Clinically, osteomyelitis is characterized by fever and leukocytosis; and localized pain, erythema, and swelling. X-ray studies may be normal for up to 2 weeks, and then initially show periosteal elevation followed by a possible lytic focus with sur-rounding sclerosis. MRI and nuclear med...

  MISCELLANEOUS BONE DISORDERS Avascular necrosis (or aseptic necrosis and osteonecrosis) is the term used for isch-emic necrosis of bone and bone marrow. Causes include trauma and/or fracture (most common); idiopathic; steroid use; sickle cell anemia; Gaucher disease; and cais-son disease. Avascular necrosis can be complicated by osteoarthritis and fractures. Osteitis fibrosa cystica  (or von Recklinghausen disease of bone) is seen when exces-sive parathyroid hormone (hyperparathyroidism) causes osteoclast activation and generalized bone resorption, resulting in possible bone pain, bone deformities, and fractures. •           Seen commonly in primary hyperparathyroidism •           Excess parathyroid hormone may be produced by parathyroid adenoma or parathyroid hyperplasia •           Can be resolved if hyperparathyroidism is treated Microscop...

  BENIGN TUMORS OF BONE   Osteoma  is a benign neoplasm that frequently involves the skull and facial bones.   Osteoma can be associated with Gardner syndrome. Malignant transformation doesn’t occur.   Osteoid osteoma  is a benign, painful growth of the diaphysis of a long bone, often   the tibia or femur. Males are affected more than females, with peak age 5–25. Pain tends to be worse at night and relieved by aspirin. X-rays show central radiolucency surrounded by a sclerotic rim. Microscopically, ostoblasts line randomly connected trabeculae.   Osteoblastoma  is similar to an osteoid osteoma but larger (>2 cm) and often involves   vertebrae.   Osteochondroma  (exostosis) is a benign bony metaphyseal growth capped with car-tilage, which originates from epiphyseal growth plate. It typically presents in ado-lescent males who have firm, solitary growths at the ends of long bones. It may be asymptomatic, cause pain, produce def...

  MALIGNANT TUMORS OF BONE Osteosarcoma   (osteogenic sarcoma) is the most common primary malignant tumor   of bone. It occurs more frequently in males than in females, with most cases in teenage years (ages 10–25). Patients with familial retinoblastoma have a high risk.   Osteosarcoma presents with localized pain and swelling. The classic x-ray findings are Codman triangle (periosteal elevation), “sun burst” pattern, and bone destruc-tion. Treatment is surgery and chemotherapy. The prognosis is poor, but is improved with aggressive management such as resection of single pulmonary metastases (hematogenous metastasis to the lungs is common).  Secondary osteosarcoma  is seen in the elderly; these highly aggressive tumors are associated with Paget disease, irradiation, and chronic osteomyelitis. Grossly, osteosarcoma often involves the metaphyses of long bones, usually around the knee (distal femur and proximal tibia). It produces a large, firm, white-tan mass...