Bone 1 Flashcards
Stages of Callus formation
Hematoma Stage- hours to days Inflammatory Stage-within 48hrs Granulation Tissue-2-12 days Soft Callus- one week-several months Hard callus-one week-several months Remodeling-several months
What are common osteoporotic fracture sites?
proximal humerus
spinal compression fractures
hip fractures
distal radius
reduction in trabecular bone mass despite normal bone mineralization
Primary osteoporosis type 1 vs 2
Primary osteoporosis
Type 1
-postmenopausal, increase of bone resorption due to estrogen decrease
Type 2
-senile osteoporosis: affects men and women 70 y/o (age related calcium deficiency)
How does menopause lead to osteoporosis?
- decreased serum estrogen
- increased IL1,IL6, and TNF levels
- Increased expression of RANK, RANKL
- Increased osteoclast activity
How does aging lead to osteoporosis?
- decreased replicative activity of osteoprogenitor cells
- decreased synthetic activity of osteoblasts
- decreased biologic activity of matrix-bound growth factors
- Reduced physical activity
Secondary Osteoporosis Causes
1. Endocrine Hyperthyroidism -accelerated turnover of bone and increased osteoclastic activity Hypogonadism -woman-estrogen men-anabolic androgens Hyperparathyroidism -osteoclast recruitment and increased osteoclastic activity
- Drugs
Corticosteroids
-Inhibit osteoblastic activity (suppression expression)
Alcohol
-direct inhibitor of osteoblast, may inhibit calcium absorption - Gastrointestinal
Malnutrition
Malabsorption
-impaired absorption of calcium, phosphate and vitamin D - Neoplasia
Multiple Myeloma
-Secretion of osteoclast activating factor
What are the symptoms of osteoporosis? What does it look like on xray/labs?
Fractures
Vertebral Fractures
Pain
Additional complication: pulmonary embolism, pneumonia
NOT detectable on x ray until 30-40% bone mass lost
Blood Calcium, Phosphorous, alkaline phosphatase levels NOT diagnostic
Bone densitometry-dual energy xray absorptiometry (DEXA) scans measure what
bone thickness/density at different parts of the body
-two x ray beans of different energy levels
WHat is the bone mineral content of of a normal, osteopenia, osteoporosis patient?
Normal: Bone mineral content not more than 1 SD below the young adult mean (T score above -1)
Osteopenia: Bone mineral content between 1SD and 2.5SD below the young adult mean (T score between-1 to-2.5)
Osteoporosis: Bone mineral density 2.5 or more below the young adult mean (T-score at or below -2.5)
What are the indications for bone density test?
- woman 65 regardless additional risk factors
- Estrogen deficient women at risk for low bone density
- Patient treated with glucocorticoids
- patients with asymptomatic primary or secondary hyperparathyroidism
What are treatments/prevention for osteoporosis?
- exercise
- calcium and vitamin D
- bisphosphonates
- estrogen replacing agents
- recombinant PTH
- RANK ligand inhibitor (denosumab)
Rickets/Osteomalacia
Etiology=vitamin D deficiency
Bone mineralization defect
Accumulation of osteoid (unmineralized bone, soft bone)
Osteomalacia-Adults
Loss of skeletal muscle mass(density)-osteopenia Fractures and microfractures -vertebral bodies and femoral neck Bone pain lots of osteoid
Rickets-children
Pathology
Symptoms
Treatment
Excess unmineralized bone-growing bones
- growth plate not adequately mineralized
- osteoclasts do not resorb growth plate cartilage
- growth plate irregular, thickened, lobulated
- loss of structural rigidity of bones
Symptoms :
- Bowing of legs
- Rachitic Rosary-osteoid deposition at the costochondral junction
- Pigeon Breast Deformity-inward bending of ribs with anterior protrusion of the sternum
- Occipital bones flattened
- Parietal bones buckled
- Frontal bossing (enlarged forehead)/squared appearance of head
How common:
very common!
Treatment:
vitamin D
Hyperparathyroidism are causes of primary and secondary hyperparathyroidism?
Increased parathyroid hormone level
Primary: Adenoma, Hyperplasia, Carcinoma
Secondary: Prolonged hypocalcemia stimulates PTH hypersecretion
Hyperparathyroidism results in increased PTH what does this do?
What are the symptoms
- sensed by osteoblast receptors
- release mediators of osteoclastogenesis
- increased osteoclast activity
- bone resorption
- decreased bone mass
- pain
- fractures-stress fractures
How does this hyperparathyroidism appear histologically?
dissecting osteitis
railroad tracks
What type of tumor can hyperparathyroidism lead to?
brown tumor
What is osteitis fibrosa cystica?
hyperparathyroidism
-bone replaced with fibrous tissue and cystic change
Paget’s disease
Etiology
Histology
Disease caused by osteoclast dysfunction
- characterized by excessive breakdown of bone tissue followed by abnormal bone formation
- affecting MEN 2:1
- mid adulthood
- axial skeleton, proximal femur involved up to 80% of patients
Etiology:
- slow virus infection
- Paramyxovirus (remains hypothesis)
- Induces IL6 secretion, increased RANK expression
- stimulates osteoclast activity - Genetic
- gene mutation leading RNK mediated osteoclast stimulation
- Mutations in RANKL and RANK/OPG
Histology:
1. mosaic pattern of bone -prominent cement lines
What are the three stages of Paget Disease?
- Osteolytic (osteoclasts)
- Osteolytic-osteoblastic (mixed osteoclasts + osteoblasts)
- osteosclerotic (osteoblasts)
what are the symptoms of paget’s disease? HOw do you diagnosis it?
Symptoms:
- Pain in affected bones
- microfractures
- bone overgrowth compressing nerves, spinal roots - Platybasia-flattening of the skull base impinging on foramen magnum
- Leontiasis ossea
- secondary arthritis
- thickening of skull
- bowing of tibia
What can paget’s disease lead to?
- High output cardiac failure
- hypervascularity of Pagetic bones-polyostotic-increased blood flow
- elevated resting cardiac index beyond normal range 2.5-4 L/min per m2 - Sarcoma
- 5-10%
- osteosarcoma, fibrosarcoma
HOw do you diagnosis it?WHat are the labs in paget’s disease f
Diagnosis:
radiographs-bone scan-increased osteoblast activity
Labs:
elevated serum alkaline phosphatase
-serum calcium , phosphorus unaffected
What is the treatment of paget disease?
Acetaminophen Nsaids
Bisphosphonates- (induce apoptosis of osteoclasts)
Calcitonin-(inhibits osteoclast function)
Osteogenesis Imperfecta
Defect
Symptoms
Goals of treatmetn
brittle bone disease
Defect in extracellular structural protein
-type 1 collagen (mutation for the alpha 1 and alpha 2 chains of the collagen molecule)
Symptoms:
- Too little bone
- Hearing loss
- Dental imperfection (blue yellow-teeth)
- blue sclera
Treatment
- maximize mobility/function
- minimize fracture risk
- pain control
- psychosocial
What are the types of osteogenesis imperfecta?
Type 1-mildest form -autosomal dominant Type 2-lethal, perinatal disease -autosomal recessive Type 3- progressive, most severely deforming type -usually autosomal dominant Type 4-similar to type 1 (normal sclerae) -autosomal dominant
Achondroplasia
- Most common disease of growth plate
- –Dwarfism
- Autosomal dominant
- 80% new mutations
- failure of longitudinal bone growth (endochondral ossification)-short limbs
- membranous ossification not affected-large head
Defect in signal transduction system-Mutation in FGF receptor 3
- Activating mutation of FGFR3
- FGFR3 normally inhibits cartilage proliferation - constant activation
- Inhibits chondrocyte differentiation and proliferation
- Retards growth plate development
Osteonecrosis (avascular necrosis)
bone death (infarction)
-bone and bone marrow
Gross: subchondral wedge shaped pale yellow area
Histology:dead bone-empty lacunae
Pathogenesis: Ischemia-Mechanical, corticosteroids, thrombosis/embolism, vessel injury(vasculitis, radiation), vascular compression
Etiology: trauma, corticosteroids, infection dysbarism, radiation therapy, connective tissue disorders, sickle cell anemia, tumors, pregnancy, gaucher disease, idiopathic
What causes osteonecrosis of the Jaw?
high dose IV disphosphonates
Predisposing factors: dental disease, dental surgery, periodontitis, poor dental hygiene, treatment with chemo or corticosteroids
