Bones and Joints Flashcards
How many bones are there in the adult body?
206
What is the body weight of all the bones in the body?
12%
What are the functions of bones?
Mechanical support Transmission of forces Protection of viscera Mineral Homeostasis Production of blood cells
What are the constituents of bones?
1) ECM
2) Cellsq
What is the ECM of bones made up of?
Osteoids = 35% and Mineral = 65%
What are the cells of bones?
1) Osteoblasts/Osteocytes
2) Osteoclasts
What is osteoid?
Made up of Type 1 collagen and osteopontin
What is osteopontin?
Protein produced by osteoblasts that plays a role in calcium homeostasis
Measures osteoblastic activity
What is the mineral found in bone?
Hydroxyapatite
What is hydroxyapitite?
Stored Calcium and phosphorous
What are osteoblasts?
Bone forming cells
What are osteocytes?
Bone forming cells that have dendrites and perform mechanotransduction
What is mechanotransduction?
Translation of mechanical energy to biological activity
Bones bear body weight or they become weak
Osteocytes feel the pressure and turn this into biological function of building bone
What are osteoclasts?
Bone removing cells
Where is 99% of calcium stored in body?
In bones
What else plays a role in bone growth?
Growth, thyroid, and parathyroid hormones
Want-beta catenin
SOX9
FGF
BMP
What is the percentage of bone that we lose every year?
0.5% - 0.7%
What is the diaphysis?
Elongated hollow central portion of the bone located between the metaphyses
Made of compact tissue and encloses the medullary cavity
What is the epiphysis?
Enlarged terminal part of the bone
Made of spongy tissue and articulating with neighboring bones
Covered with articular cartilage that reduces friction and absorbs shock
What is the metaphysis?
Part of the bone between the epiphysis and the diaphysis
Contains the connecting cartilage enabling the bone to grow and disappears at adulthood
Contains growth plate
What is the Periosteum?
A dense layer of vascular connective tissue enveloping the bones except at the surfaces of the joints
What is compact bone?
Cortical bone
Dense bone in which the bony matrix is solidly filled with organic ground substance and inorganic salts
What is the endosteum?
Covers the inside of bones and surrounds the medullary cavity
What is the medullary cavity?
Central cavity of bones shafts where red bone marrow and/or yellow bone marrow is stored
What is the process of remodeling?
The adult skeleton is constantly turning itself over in this tightly regulated process
This process repairs microdamage or changes the shape of bones in response to structural and mechanical demands
What regulates events at the bone multicellular unit?
Cell-cell interactions and cytokines
What is the pathway in which osteoclasts are made which allows for remodeling to occur?
NF-kapa B pathway
How does the NF-kappa B pathway become activated?
1) RANK ligand on stromal/osteoblast cells binds to RANK receptors on osteoclast precursors cells
2) This binding also causes the binding of MAcrophage colony-stimulating factor (M-CSF) which causes the precursor cell to produce a functional osteoclast
How is the NF-kappa B pathway inactivated?
Stromal/osteoblast cells will produce a decoy receptor, osteoprotegerin (OPG), which prevents RANKL from binding to the RANK receptor on osteoclast precursor cells
What is the function of osteoprotegerin?
Prevents bone resorption by inhibiting osteoclast formation
What percentage of the skeleton is replaced annually?
10%
What are the most common developmental disorders?
Aplasia
Supernumerary digits
Syndactyly
Craniosynostosis
What is aplasia?
Complete absence of a bone or entire digit
What is achondroplasia?
most common form of dwarfism
Autosomal dominant
Retarded growth of cartilage
What are the clinical features of Achondroplasia?
Shortened Proximal extremities
Trunk of relatively normal length
Enlarged head with bulging forehead
Conspicuous depression of the root of the nose
What is achrondroplasia caused by?
A mutation in FGF3 gene which remains always active and causes excessive suppression of bone growth
What is osteogenesis imperfecta?
Deficiency in synthesis of type 1 collagen
Brittle bone disease
Most common inherited disorder of connective tissue
Principally affects bone, but also joints, eyes, skin, ears, and teeth
Autosomal dominant
Helical structure of collagen isn’t formed correctly
What is the fundamental abnormality in Osteogenesis Imperfecta?
Too little bone, resulting in extreme skeletal fragility
What is type 1 osteogenesis imperfecta?
Normal life span but experience childhood fractures
What is type 2 osteogenesis imperfecta?
Fatal in utero
What is osteopenia?
Decreased bone mass < 1-2.5 SD
Reversible
What is Osteoporosis?
Severe osteopenia; bone mass < 2.5 SD
Not reversible
Normal mineral content isn’t effected
Can be generalized or local
What are the types of primary generalized osteoporosis?
Idiopathic
Postmenopausal
Senile
What are the types of secondary generalized osteoporosis?
Endocrine disorders - Diabetes Type 1, Hyperparathyroidism, Hyper/hypothyroidism
Neoplasia
Drugs
Who is most common types of osteoporosis?
Senile and postmeopausal
What is Rickets and Osteomalacia?
Vit. D deficiency causing impairment of mineralization which leads to accumulation of unmineralized matrix
What are the causes of osteoporosis?
Age related changes Reduced Physical activity Genetic factors Calcium nutritional state Hormonal influences
What is senile osteoporosis?
Low turnover and age related
Decreased osteoclasts
What is postmenopausal osteoporosis?
HIgh turnover and hormonally influenced
Increased osteoclasts
What is the clinical course of osteoporosis?
Vertebral fractures = painful
Complications of fractures of femoral neck, pelvis, or spine such as pulmonary embolism and pneumonia
What can prevent and treat osteoporosis?
Exercise
Vitamin D and calcium intake = osteopenia
Pharmalogical agents - bisphosphates for osteoporosis
What is pagets disease (osteitis deformans)?
Disorder of increased, but disordered and structurally unsound bone mass
Usually begins in late adulthood ~ 70
What are the three stages of Pagets?
1) Initial Osteolytic stage = Overfunctioning of osteoclasts
2) Mixed Osteoclastic-osteoblastic stage = both are functioning
3) Final Osteosclerotic stage = Silent stage when bone becomes really dense
What is the cause of pagets?
Uncertain but genetics and environmental factors play a role
Two possible causes are mutations in SQSTM1 gene which increases NF-kappa B pathway or RNA virus infection which makes osteoclasts more sensitive by effecting Vit. D and IL6
What are the symptoms of Pagets?
Usually asymptomatic
Pain localized to effected bone
What bones are mostly effected in Pagets?
Axial skeleton or proximal femur
What are the common clinical features of Pagets?
Enlargement of craniofacial skeleton = leontiasis ossea
Invagination of skull base = platybasia
Compression of posterior fossa
What are the complications of Pagets?
Weight bearing - anterior bowing of femurs and tibiae which distorts the femoral heads causing secondary osteoarthritis
Chalk-stick fractures in long bones of lower limb
Compression fractures of spine causing kyphosis
Osteosarcoma or fibrosarcoma
What is renal osteodystrophy?
Skeletal changes that occur in chronic renal disease
What are the manifestations of Renal osteodystrophy?
Osteopenia/Osteomalacia
Secondary Hyperparathyroidism
Growth Retardation
What are the histological changes seen in renal osteodystrophy?
High-turnover osteodystrophy
Low-turnover or aplastic
Mixed
What is the pathogenesis of renal osteodystrophy?
1) Tubular dysfunction causing renal tubular acidosis which decreased pH and dissolves hydroxyappatite –> Osteomalacia
2) Renal failure causes decreased phosphate excretion which leads to chronic hyperphosphatemia and hypocalcemia –> Secondary hyperparathyroidism
3) Decreased secreted factors like Vitamin D and proteins BMP-7 and Klotho
What is a fracture?
Break in the rigid structure of the bone
most common traumatic musculoskeletal disorders
What are the causes of fractures?
Falls
Motor vehicle accidents
Sports-related injuries
Conditions that weaken the bone like osteoporosis, Pagets and bone cancer
What is a simple fracture?
A single break with bone ends maintaining their alignment and position
What are the types of simple fractures?
Transverse fracture
Oblique fracture
Spiral fracure
What is a transverse fracture?
Break straight across the bone shaft
What is an oblique fracture?
At an angle to the bone shaft
What is a spiral fracture?
Twists around the bone shaft
What is a comminuted fracture?
Multiple fracture lines and bone pieces
What is a greenstick fracture?
An incomplete break in which the bone is bent and only the outer curve of the bend is broken
What is a compression fracture?
Bone is crushed or collapses into small pieces
What is a pathologic fracture?
Involving bone weakened by an underlying disease process such as tumor
What are the steps of healing of a fracture?
1) Hematoma formation
2) Necrosis of the broken bone ends
3) Fibroblasts invade the clot within a few days
4) Fibrblasts secrete collagen fibers which form a mass of cells and fibers called a callus
5) Callus bridges the broken bone ends together inside and outside over 2 - 6 weeks
6) Osteoblasts invade the callus and slowly converts it to bone over 3 weeks to several months
How long does it take for a fracture to completely heal?
12-15 weeks
What is osteomyelitis?
Inflammation of bone and marrow secondary to infection
What is the most common organism that causes pyogenic osteomyelitis?
Staph aureus
How do the organisms reach the bone?
1) Hematogenous spread
2) extension from a contiguous site
3) direct implantation
What are the symptoms of osteomyelitis?
Malaise Fever Chills Leukocytosis Throbbing pain over the affected region
How do you diagnose osteomyelitis?
X-ray lytic focus of bone destruction surrounded by a zone of sclerosis which can only be seen if 60% of bone is lysed
What are the complications of osteomyelitis?
Chronic osteomyelitis Pathologic fracture Secondary amyloidosis Endocarditis Sepsis Carcinoma
What causes non-pyogenic osteomyelitis?
M. Tuberculosis
What does M. tuberculosis cause?
Pott disease
What is Potts disease?
Destruction of discs and vertebrae which causes scoliosis or kyphosis and neurologic deficits
What is the dead bone called?
sequestrum
What is the newly deposited bone that forms a shell of living tissue around the segment of devitalized infected bone called?
involucrum
What are osteoid osteoma and osteoblastoma?
Benign bone-producing tumors that have identical histologic features but differ in size, sites of origin, and symptoms
Malignant transformation is rare
What is osteoid osteomas?
< 2 cm in diameter
Teens and 20s
Appendicular skeleton
What is osteoblastoma?
> 2 cm in diameter
Involves posterior spine
What is osteosarcoma?
Most common primary malignant tumor of bone
cancerous cells produce osteoid matrix or mineralized bone
Bimodal age distribution
What are the predisposing factors of osteosarcoma?
Paget disease
Bone infarcts
Prior radiation
What are the symptoms of osteosarcoma?
Painful, Progressively enlarging masses
Pathological fracture
What causes osteosarcoma?
Mutations in:
RB
TP53
Inactivated INK4
MDM2 and CDK4
What is the radiological finding for osteosarcoma?
Sun ray appearance
What is the function of joints?
Allow movement while providing mechanical stability
What are solid, non-synovial joints?
Provide structural integrity and allow only minimal movement
They lack a joint space
Ex. cranial sutures
What are synovial joints?
Elbow, knee, shoulder
Have a joint space that allows for a wide range of motion
What is osteoarthritis?
Most common type of joint disease
Degeneration of cartilage causing structural/functional failure of joints
What is most commonly affected area of osteoarthritis in women?
Knees and hands
What is most commonly affected are of osteoarthritis in men?
hip
What is the pathogenesis of osteoarthritis?
Chondrocytes response to biochemical and mechanical stresses resulting in breakdown of matrix
Breakdown occurs because tissue macrophages are activated and they secrete TNF-alpha, IL6, and IL1
These cytokines cause proteases to be secreted and they destroy the bone even more
What are the primary causes of osteoarthritis?
Aging
What are the secondary causes of osteoarthritis?
Obesity
Diabetes
When do symptoms of osteoarthritis start to appear?
age 50
What are the symptoms of osteoarthritis?
Deep, achy pain that worsens with use Morning stiffness Crepitus Limitation of ROM Nerve root compression and radicular pain Muscle spasms Muscle atrophy Neurologic deficits
Where does osteoarthritis typically occur?
Hips Knees Lower lumbar and cervical vertebrae Proximal and distal IP joints of the fingers First CMC joints First TMT joints
What occurs over time with osteoarthritis?
Joint deformity but NOT fusion
What is Rheumatoid arthritis?
Chronic inflammatory disorder of autoimmune origin principally affecting the joints, producing a non-suppurative, proliferative and inflammatory synovitis
What does RA involve?
Extra-articular
Skin (nodules)
Hear (MI)
Blood vessels (atherogenesis)
Lungs
What is caused by RA?
Inflammation Articular cartilage destruction Bone erosion Angiogenesis Ankylosis
What is the pathogenesis of RA?
1) CD4+ T helper cells initiate the autoimmune response by reacting with arthitogenic agent
2) T cells produce cytokines that stimulate other inflammatory cells to effect tissue injury = IFN-gamma, IL-17, TNF, and IL-1
3) These cytokines recruit and activate other immune cells causing cartilage damage
4) RANKL is expressed on activated T cells and this stimulates bone resorption
5) Serum IgM and IgA autoantibodies are formed and bind to Fc portions of the patients own IgG - RA factor
What are the symptoms of RA?
Malaise
Fatigue
Generalized musculoskeletal pain, likely mediated by IL-1 and TNF-alpha
Symmetrical joint involvement - small joints first
Swollen, warm, painful joints that are stiff in morning or not used
Progressive joint enlargement
Decreased ROM
What are the clinical features of RA?
Radial deviation of wrist = Swan-neck deformity
Ulnar deviation of the fingers and flexion hyperextension of the fingers = Boutonniere deformity
How is RA diagnosed?
1) Radiographic findings
2) Sterile, turbid synovial fluid with decreased viscosity, poor mucin clot formation, and inclusion-bearing neutrophils
3) RA factor and anti-CCP antibodies
What is Gout?
Transient attacks of acute arthritis initiated by crystallization of monosodium urate within and around the joint
What is gout caused by?
hyperuricemia = plasma urate > 6.8 mg/dL
What are the risk factors for Gout?
Age Genetic predisposition Heavy alcohol consumption Obesity Drugs Lead toxicity
What are the morphologic changes of gout?
Acute arthritis
Chronic tophaceous arthritis
Tophi in various sites
Gouty nephropathy
