Bikman - Musculoskeletal Pathology Flashcards
What are the functions of osteoblasts, osteocytes, and osteoclasts?
Osteoblasts: Produce osteoid (unmineralized bone)
Osteocytes: Osteoblasts within bone in a lacuna
Osteoclasts (macrophage): Multinucleated, resorbs bone
What regulates RANK-RANKL?
Osteoprotegerin (OPG)
OPG-RANKL then decreases osteoclast formation and bone-resorption
Congenital bone disorders
Osteogenesis imperfecta
Achondroplasia
Osteopetrosis
Fibrous dysplasia
Acquired bone disorders
Osteoporosis Paget disease Rickets-Osteomalacia Hyperparathyroidism Scurvy
Osteogenesis imperfecta
Congenital "Brittle bone disease" Mutations of collagen type I (alpha1 and 2) Autosomal dominant Multiple fractures *Blue sclera* Hearing loss *Dentinogenesis imperfecta - dysplasia, lack of healthy dentin*
Achondroplasia
Congenital Most common form of dwarfism *FGFR3 mutation* - Inhibited chondrocyte proliferation - Repressed growth of normal epiphyseal plates - Autosomal dominant - 80% are new mutations
Avg life span
Affects all bonds that develop via endochondral ossification
Thanatophoric dwarfism (lethal)
Osteopetrosis
Congenital
“Albers-Schonberg disease”; like stone
Reduced osteoclast-mediated bone resorption
- Defective bone remodeling
- Abnormally dense, yet unsound/brittle
Autosomal recessive and dominant
Can cause anemia and infections (due to decreased bone marrow); blindness, deafness, face paralysis (due to narrowing of cranial nerve foramina); delayed eruption of teeth
Fibrous Dysplasia
Congential
Replacement of bone with fibrous CT
Not a malignancy; reduction in healthy bone function
3 types:
(1) Monostotic - affects one bone (most common)
(2) Polyostotic - “Jaffe-Lichtenstein syndrome”; affects more than one bone, cafe au lait pigmentation on trunk and thighs
(3) McCune-Albright Syndrome - Polyostotic and precocious puberty
Osteoporosis
Acquired
An acquired condition characterized by reduced bone mass, not reduced quality.
- Loss of bone: increased fragility, increased fracture risk
- Existing bone has normal mineral content (just less of it)
Primary: You don’t know what’s causing it.
Secondary: You know what’s causing it.
Factors contributing to osteoporosis
Menopause - Decreased estrogen, increased osteoclast activity Aging (senile osteoporosis) - Decreased replicative activity of osteoprogenitor cells - Decreased osteoblast activity -Reduced physical activity Nutrition - Reduced Ca2+ and reduced vitamin D Decreased physical activity Endocrine - Hyperparathyroidism - Addison disease
Paget Disease
Acquired
“Osteitis deformans”
Random excess bone formation; net effect is bone mass gain; frenzied bone growth
(1) Repetitive episodes of frenzied, regional osteoclast activity, and resorption - Osteolytic stage
(2) Exuberant bone formation - Mixed osteoclastic-osteoblastic stage
(3) Exhaustion of cellular activity - Osteosclerotic stage
Can cause
- Osteosarcoma
- Heart disease
- Deafness or blindness
Rickets-Osteomalacia
Acquired
“Soft bones”
Primary cause is vitamin D deficiency Inadequate mineralization of bone Rickets: Children - epiphyseal plates open Osteomalacia: Adults - plates closed Weak tooth enamel, increased caries
What is the role of parathyroid hormone?
Net effect: Increase in plasma Ca2+ concentration
- Increase active transport of Ca2+ out of the proximal and distal tubule of kidney
- Increase Ca2+ release from bone into the plasma (Ca2+ mobilization)
- Stimulates the kidney to activate vitamin D, bringing in more Ca2+
- Lowers plasma phosphate concentration by increasing renal excretion of phosphate (prevents precipitation of calcium phosphate from the blood into bone)
What inhibits PTH secretion?
Plasma Ca2+ concentration
Active vitamin D
Hyperparathyrodism
Acquired.
Too much PTH
Primary: Almost always growth/tumor related
- Excess secretion of PTH from one or more parathyroid glands
Secondary: Some other problem causing too much PTH
- Increase in PTH from a chronic disease that causes hypocalcemia (i.e. renal failure)
What effect might hyperparathyroidism have on teeth?
Loss of lamina dura, ground glass appearance, and mandibular cortical width reduction
Scurvy
Acquired
Too little vitamin C
Leads to impaired osteoid matrix formation
Manifestations:
- Bleeding gums
- Subperiosteal hemorrhage
- Osteoporosis
Langerhans’ cell histiocytosis
Acquired
“Histiocytosis X”; “Langerhans’ cell granuloma”
A group of disorders that exhibit histiocyte-like Langerhans cells that cause bone lesions (and others)
Langerhans cells contain Birbeck granules and eosinophils
3 types:
(1) Letterer-Siwe disease: Acute, disseminated, fatal in infants
(2) Hand-Schuller-Christian disease: Chronic (because you can live longer with it)
- Bone lesions - skull, mandible, vertebrae, ribs
- Exophthalmos (bulging eyes)
- Diabetes insipidus (polyuria with no particular taste)
(3) Eosinophilic Granuloma of bone: Localized, least severe; May overcome without tx; more common in young adults
Fractures
Repair process:
(1) Fracture ruptures BVs
(2) WBC activated
- Clot formation
- Bone progenitor cells recruited
- New matrix synthesis
(3) New matrix synthesis
Osteonecrosis
Bone death.
Ischemia causes loss of bone - no infection
May be result of:
- Trauma
- Bone infarction (emboli)
- Corticosteroids
Bisphosphate-associated osteonecrosis (BON)
Occurs in patients with history of bisphosphonate use.
- Drugs aimed at neutralizing osteoclasts - Actonel, Boniva, Fosamax
- Effects are highest among bones with active remodeling (jaw)
Develops after manipulation of bone, extraction, implant, perio or endo surgery
Caution and informed consent for patients >3yr on drug
Phossy jaw
Osteomyelitis
Inflammation of bone and bone marrow.
Can be secondary to systemic infection but more frequently occurs as a primary isolated focus
2 types:
Pyogenic
Tuberculous
Pyogenic Osteomyelitis
Most causes of acute osteomyelitis are caused by bacteria.
Bacteria reaches bone:
(1) Hematogenous (blood borne) dissemination
(2) Contiguous (touching/spreading) infection spread
(3) Traumatic implantation (via fracture or procedure)
Most common causative organism is Staph. aureus
Tuberculous Osteomyelitis
Mycobacterial infection of the bone - gets there via hematogenous dissemination
Bone infections accompany 1-3% of pulmonary TB
Long bones and vertebrae are favored sites.
Pott Disease: Vertebral deformity, collapse, posterior displacement
How do bone tumors typically arise?
Primary bone tumors are uncommon.
Usually the tumor has metastasized to the bone.
- Bone forming
- Cartilage forming
- Misc.
Benign bone-forming bone tumors
Osteoma
- Face, skull
- 40-50yrs
- Similar to normal bone
Osteoid osteoma
- Metaphysis femur, tibia
- 10-20yrs
- Woven bone
Osteoblastoma
- Vertebral column
- 10-20yrs
- Similar to osteoid ostoma
Malignant bone-forming bone tumors
Primary Osteosarcoma
- Metaphysis of distal femur
- 10-20yrs
- Sun burst pattern on rads
Secondary Osteosarcoma
- Femur, humerus, pelvis
Jaw osteosarcoma occurs about a decade after long bones are affected.
Typically includes elevated plasma alkaline phosphatase.
Codman Triangle is a feature.
Benign cartilage-forming bone tumors
Osteochondroma
- Metaphysis of long bones
- 10-30yrs
Enchondroma
- Small bones of hands and feet
- 30-50yrs
- Medullary cavity
Malignant cartilage-forming bone tumors
Chondrosarcoma
- Femur, humerus, pelvis
- 40-60yrs
- Within medullary cavity; malignant cells form cartilage (abnormal)
Miscellaneous bone tumors
Giant Cell Tumor of Bone
- Epiphysis of long bones
- 20-40yrs
- Cortical lesions
Ewing Sarcoma
- Small, undifferentiated round cells
- 10-15yrs
- Genetic component (whites more affected)
- Diaphysis of long bones
How do most bone cancers arise?
Most bone cancers arise from metastatic tumors.
75% arise from prostate, breast, kidney, lung
Osteoarthritis
Degenerative joint disease
Most common joint disorders
Common in 65+ yrs
Fundamental feature: degeneration of the articular cartilage
Primary:
- Appears insidiously with age
- No apparent cause
Secondary:
- Common form in youth
- Caused by trauma, deformity, diseases, etc
