Karma Patel
Musculoskeletal Pathology Summary Notes
1. Intracellular Stage: from amino acid synthesis to
procollagen
2. Extracellular Stage: from procollagen to mature
collagen
Connective Tissue
Fibroblasts: most versatile of connective tissue cells, being
able to differentiate into other cells of the family
No O2
Bone
Cell
Fibroblast
Fat Cell

O2
Chondrocytes
(Avascular)
Smooth Muscle Cell
All cells in fibroblastic family produce collagen
Fibroblasts:
 Least specialized cell in body
 Mesodermal derivative; classified by morphology,
staining & function
 Secretes extracellular matrix:
o Collagen
o Proteoglycans
o Elastin
o Fibronectin
Collagen:
 25% of all mammalian protein
 Major fibrous element in:
o Bone
o Cartilage
o Skin
o Teeth
o Blood vessels
o Tendon
 Present to some extent in nearly all organs; holds
cells together & gives tissue structural integrity
Collagen Synthesis Disorder:
 Fragility: blood vessels are breaking
o Poor wound healing
o Easily bruised
 Skin is more elastic
 Weak bones
 Joint dysfunction
 Joint laxity  hypermobility
 Systemic: congenital, metabolic
Collagen Synthesis (Type I):
In the Fibroblast:
 mRNA transcription/translation in the rough ER
 amino acids arrange into alpha-chains
 sequence of amino acids is genetically predetermined
& critical in determining the collagen end product
Amino Acid Chains:
 1000 amino acid residues with terminal extensions
 AA composition & repeating Gly-X-Y triplets
 X & Y position can be any other amino acid
Chain Composition:
 1/3 of residues are Glycine (333)
 Proline most commonly found in X-position on the
chain (100 residues)
 Hydroxyproline most commonly found in Y-position
on the chain (100 residues)
 Hydroxylysine another common occupier of the Yposition
 Proline & hydroxylproline are Imino Acids; rigid cyclic
structure that limits rotation of the chain
 Glycine: smallest amino acid
 Chain is helical in nature, needs glycine to have
helical structure
Hydroxyproline & Hydroxylysine:
 Occupy Y-position, but can be found in X-position
 Are not added to the chain ‘as is’
 Proline & lysine are hydroxylated after they are
incorporated into the chain
 Hydroxylation requires enzymes
Hydroxylating Enzymes:
 Lysyl hydroxylase acts on lysine in X or Y position
 Prolyl-4-hydroxylase acts on proline in Y-position
 Prolyl-3-hydroxylase acts on proline in X-position
Intracellular Stage:
 For hydroxylation to occur you MUST have:
o A ferrous ion on the enzyme
o Molecular oxygen
o Ascorbic acid
o Alpha-ketoglutarate
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Carboxylation occurs: Glucose & Galactose
3 α-chains twist together to form super-helix &
connect via hydrogen bonds = procollagen
Procollagen molecules leave fibroblast & enters the
extracellular space
Extracellular Stage:
 Cleave off terminal extension from procollagen
molecule
 Requires procollagen peptidase
 With terminal extensions gone  tropocollagen
 Tropocollagen: immature collagen & does not have
necessary tensile strength
 Further cross-linking via inter- & intra-chain hydrogen
bonds is necessary to form a mature collagen fibre
Collagen Synthesis Pathology:
 Scurvy:
o Hydroxylation step interrupted
 Ehlers-Danlos (humans) & Dermatospiraxis (cattle):
o Problem with procollagen peptidase
o Have all S/S listed before
 Marfan’s Syndrome & Osteogenesis Imperfecta:
hereditary problems affecting intracellular evetns in
collagen synthesis
o Vessel fragility
o Hypermobility
Bone
Bone Function:
 Protection
 Support
 Mechanical basis of Movement
 HEMATOPOIESIS
 Mineral Storage
Bone Matrix Consists of:
 Type I Collagen: provides tensile strength; resists
pulling forces
 Solid particles: provides compressive strength;
calcium, phosphate & other crystalline structures
Bone Composition:
 Organic or inorganic ratios:
o Children
1:1
Pliable
o Adults
1:4
o Elderly
1:7
Brittle
Characteristics:
 Bone is a rigid tissue, yet adapts to mechanical
stresses (Wolff’s Law)
 Continuous deposition & removal of bone throughout
life
 7 years to completely turn over skeletal bone in the
body
Bone Formation:
 Mesenchymal condensation gives rise to bone in 2
ways:
o Direct translation of mesenchyme to bone =
Membranous bone
o Majority of bones form in cartilages first, then
undergo ossificiation = Endochondral Bone
 Cartilage swells up & dies  fibroblasts
enter
 Bone cells
 In carpal & tarsal bones, cartilage is replaced at
primary site of ossification
 Vertebra & long bones have multiple sites of
ossification – 1o, 2o, 3o
 Towards the end of puberty, rate of ossification
exceeds growth of epiphyseal cartilage proliferation
& growth plate closes
o Cessation of growth occurs 3 years earlier in
females
 Increased osteoblastic activity increases production
of the enzyme ALKALINE PHOSPHATASE, this can be
measured in blood
Conditions showing presence of Alkaline Phosphatase:
 Osteosarcoma
 Fracture repair
 Children
Disruption of Growth Plate due to:
 Hereditary
 Metabolic: malnutrition
 Endocrine
 Stress
 Trauma: infection (polio), fracture
Pathology of Growth Plates:
 Poliomyelitis: frequent cause of improper growth of a
limb
o Mechanism of disease is unknown
 2 methods of preventing limb length discrepancies:
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Remove growth plate
Put pressure on growth plate by stapling the
epiphysis to metaphysic
Membranous Bone:
 Grows by process of accretion; adding bone to
surface & edges of the bone
 Ex: closure of fontanelles
Formation & Removal of Bone:
 Bone matrix is secreted by osteoblasts that lie at the
surface of existing matrix & deposit fresh layers of
bone onto it
 Appositional Bone Growth:
o Osteocyte
o Osteoid (unmineralized bone tissue
o Ossification
Bone Formation:
 Bone has a remarkable ability to adapt to mechanical
stresses or loads by remodelling its structure (Wolff`s
Law) by:
o Depositing bone matrix
o Eroding bone matrix
Wolff’s Law governs Bone Remodelling:
 Compression leads to bone deposition
 Lack of compression leads to bone erosion
Requirements of Healthy Bone:
 Maintain an equilibrium of calcium & other
metabolites in blood & bone
 Stress, pressure, or load on bone
 Viable blood supply to oxygenate bone cells
Rodahl’s Study of Bone:
 Prolonged bed rest  ↑ urinary calcium levels
 Urinary calcium increase due to lack of longitudinal
pressure on bones NOT inactivity
 Urinary calcium levels unaffected by heavy bicycle
ergometer work performed 1-4h/day in supine
position or 8h/day in wheelchair
 3h/day standing returned urinary calcium levels to
normal
Whedon Study:
 If urinary calcium levels indicate bone mineralization,
then
o
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Gravitational stress essential for bone
Skylab flights:
 ↑ urinary calcium levels for 3 weeks & then
elevated for remaining duration
Fracture: Definition
 To break
 A discontinuity of bone
 A break in cortex
Fracture:
 Most common lesion in bone
 Fracture is a pathology
Bone Failure:
 Force exceeds bone’s compressive or tensile strength
 Factors:
o Metabolic
o Infection
o Trauma
o Neoplasia
Pathologic Fracture:
 Fracture through diseased bone
 Pre-existing conditions affect bone locally or
systemically that compromise bone structure such
that it becomes more susceptible to structural failure
Fracture Repair:
 Factors:
o Metabolic (nutrition)
o Age
o Ability to re-establish blood supply
o Location
o Overall general health
o Need to immobilize
o Infection
Phases of Fracture Repair:
 Phase I: Inflammatory Phase
o Onset approximately 10 days
 Phase II: Reparative Phase
o Approximately 1 week to few weeks
 Phase III: Remodelling Phase
o Several weeks on
Inflammatory Phase:
 1-2days post fracture
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1. Rupture of blood vessels (hemorrhage)
a. In both soft tissue & bone
2. Hematoma – fills ‘gaps’, surrounds injury & seals
off fracture
3. Tearing of periosteum (highly innervated)
4. Necrosis of bone & soft tissue
 2-5 days post fracture
1. Fibrin mesh develops
a. Produced by blood proteins
2. Fibroblasts migrate into area
a. But no O2  become cartilage
cells/chondrocytes
3. Beginning to form & lay down cartilage between
bone ends
a. Endochondral ossification
4. Necrosis & macrophage activity continues
 5-10 days post fracture
1. Soft tissue callus (procallus) is beginning to form
2. Macrophage activity is ongoing
Radiographic findings of Inflammatory Stage:
 Discontinuity in bone
 Wider bone
Reparative Phase:
 1 week to few weeks post fracture
1. Early part of this phase occurs with latter part of
inflammatory phase
2. Osteoclasts & mononuclear cells clean up debris
3. Extensive neovascularisation
4. Fracture may appear wider on X-ray
5. Callus formation begins
6. Significant osteoblastic activity occurring
Radiographic findings of Reparative Stage:
 Hazy cloud around fracture
Remodelling Phase:
 1 month post fracture
1. After callus has stabilized bone
2. Bone adjusts its strength & shape
a. Wolff’s Law
Radiographic findings of Remodelling Stage:
 Hazy, cloudy
 Cells: osteoblasts, osteoclasts
 Callus
Clinical Union:
 Point when they take cast off
 Implies fracture is stable
Malunion:
 Heals with residual deformity
Delayed Union:
 Fails to heal up to 6 months post fracture
 Many pieces, elderly, infection
Non-union:
 Fails to heal after 6 months
 Was not immobilized  blood supply not restored
Pseudoarthrosis “False Joint”:
 Non-union fracture heals with pseudojoint
Transverse Fractures:
 Uncommon
 High velocity injury
 Often pathologic
 Paget’s “banana” fracture
Oblique Fractures:
 Shaft of tubular bone
 45o to long axis
 Very common
Spiral Fractures:
 Torsion
 Axial compression
 Angulation
 Pointed ends
Bone Bruise:
 Hemorrhage, edema, trabecular microfracture
 Not seen on radiographs
 MRI: fluid shoes up white & then dark
 Cortex is still intact
Closed Fracture
 Does not break skin
Open Fracture:
 Breaks skin
Incomplete vs. Complete:
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Discontinuous in cortex of bone
In skeletally immature individuals, you see
incomplete fractures (GREENSTICK or TOURS) where
buckling or bending is indicative of fracture
Avulsion Fracture:
 Forcible ripping or tearing of tissue
o Tearing away from bone fragment
o Pull from ligament, tendon or muscle
 Ex. clay shovellers or coal miner’s fracture
o Avulsion of a lower cervical segment spinous
process
o Usually SP of C7
Occult Fracture:
 Radiographically invisible fracture
o Re-radiograph in 7-10 days
 To see widening of bone
o Re-radiograph 2 weeks later
 See callus formation
o Scaphoid (most common)
o Ribs: non-union or pseudoarthrosis
Comminuted:
 2+ fragments that have separated from the bone
o Crushed or pulverized bone
o “Butterfly fragment”
Non-comminuted Fracture:
 One break
 Two fragments
Compression vs. Impaction:
 Frequently due to axial compression
 Compression: used to describe vertebral fractures of
this type
 Impaction: bones in the extremities
Fatigue or Stress Fracture:
 Abnormal stress on normal bone
o Repetitive stress causing gradual formation of
microfracture
o March Fracture of 2nd or 3rd metatarsal
 Stress fracture through diseased bone
o Form of pathological fracture
Chiropractors do sometimes induce fractures as they try
to please their patients:
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MC: rib fractures
Alkaline Phosphatase:
 Secreted by osteoblasts when depositing bone
 ↑ in alkaline phosphatise:
o Fracture: later stages
o Children
o Osteopetrosis
o Osteosarcoma
Erythrocyte Sedimentation Rate:
 Aka ESR or Sed Rate
 Indicates inflammatory process
o ↓ in sed time as inflammatory proteins attach to
RBC & settle faster
Radionuclide Imaging:
 Bone Scans:
o Specific for areas of increased metabolic activity
o Body is scanned with a gamma-camera
o Very sensitive, not specific
Calcium Functions:
 Enzymatic reactions
 Hormone secretion; mediates hormone events
 Neurotransmission: neuromuscular junction; release
of ACh
 Muscle contraction
 Blood clotting
 Major cation in bone & teeth
Calcium:
 Keep Ca+2 within normal physiological limits
 Normal range: 8.6-10.6mg/dl; no more than 10%
change
Calcium in Blood:
 Ionized Ca+2 is biologically active
 Ca+2 bound to albumin is unavailable to body
 Ca+2 complexed in non-ionic filterable form such as
Ca+2 bicarbonate
Important organs: gut, kidney, bone
Gut & Ca+2 Balance:
 GI System: % of dietary intake absorbed is inversely
related to intake
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Maintaining normal Ca+2 levels can be
accomplished by preventing overload with
dietary surplus
With dietary deprivation, adaptive increase in
Ca+2 absorption
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Control of Ca+2 Balance:
 3 hormones regulate Ca+2 movement between bone,
gut & kidney:
o Parathyroid hormone
o Calcitriol
o Calcitonin
Parathyroid Glands:
 Aka PTH
 Major regulator of plasma Ca+2
 Secretion of PTH (dependent) is inversely related to
plasma Ca+2 (independent) levels
 Release of PTH is monitored by Ca+2 sensing receptor
on cell membrane
 PTH & Ca+2 form a negative feedback pair; as Ca+2
levels increase PTH secretion decreases
Parathyroid Hormone:
 Ionized Ca+2 regulates PTH secretion within minutes;
PTH half life less than 20 min
 If sustained over time:
o Elevated Ca+2 levels shut down PTH synthesis &
degrades stores
o Low Ca+2 levels cause gland hypertrophy
PTH stimulates Ca+2 pumps on the ECF side of cells
allowing Ca+2 to diffuse into the cell from bone & be
pumped out into the ECF
Via paracrines stimulate production of osteoclasts &
activates resorption of bone; takes 1-2 hours
All constituents of bone are liberated
PTH Action on Kidney:
 ↑ Ca+2 resorption from distal tubule
 Most dramatic effect: inhibit resorption of phosphate
 Stimulates synthesis of vit. D metabolite
PTH Action on Gut:
 Indirect; via calcitriol & calbindin production &
release (kidney), calbindin facilitates active transport
of Ca+2 across gut wall
 No PTH receptors in gut
PTH Function:
 Cause prompt increase of Ca+2 & decrease of
phosphate in plasma
 Kidney dumps phosphate & conserves Ca+2 initially
 As plasma Ca+2 levels rise, PTH levels accommodate,
kidney filters more Ca+2 & urinary Ca+2 levels will rise
to maintain homeostasis
 Actions on all 3 organs  Ca+2 influx into blood
 Plasma phosphate levels also rise but efflux of
phosphate in urine
Phosphate Important in:
 All glycolytic compounds
 ATP, ADP, AMP, creatine phosphate
 Cofactors – NAD, NADPH
 Lipids like phosphotidyl choline
 Covalent modifier of enzymes
 Major anion in bone
Phosphate:
 Normal range: 2.5-4.5mg/dl
 Amount absorbed from diet is constant; adaptive
regulation at gut level is minimal
 Urinary excretion is major mechanism in phosphate
balance
PTH Action on Bone:
 Stimulates osteolysis by osteocytes in bone &
osteoblasts on bone surface to remove calcium
phosphate salts from bone lying near these cells
PRH & Phosphate:
 Role of phosphate on PTH is indirect through
physiological mechanisms that lower Ca+2 levels
 Inject phosphate, Ca+2 drops & PTH increases
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PTH moderates hyperphosphatemia by increasing
renal excretion of phosphate
Vitamin D:
 Has potent effect on increasing Ca+2 absorption from
gut
 Important effect on bone deposition & resorption
 Vitamin D must be converted, through series of
reactions in liver & kidney to final active metabolites
 2 sources:
o D3 – produced in skin via UV radiation
o D2 – plant steroid ingested in diet
 D2 has 2 more double bonds than D3 but biological
action in body is identical
Vitamin D & Plasma Ca+2:
 Vit D is converted to more metabolically active
metabolites in:
o Liver: 25(OH)D3 which can be stored
o Kidney: Calcitriol made under PTH influence or
24-25 (OH2) D3 when PTH is diminished
Action of 1-25 Metabolite:
 In kidney, metabolite binds with cytosolic receptor &
enters nucleus
o Stimulates protein synthesis of calbindin
o Calbindin facilitates Ca+2 absorption from gut
 Phosphate absorption across gut stimulated
by vitamin D
 In bone: stimulates bone resorption working
synergistically with PTH
o Cytosolic receptor for 1-25(OH2)D3 found in
osteocytes & osteoclasts
Action of Vitamin D:
 Normal mineralization of bone dependent on vitamin
D (not the 1-25 metabolite)
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Major storage site for vitamin D is muscle
o Profound muscle weakness seen in vitamin D
deficiency
o 25-OH-D3 may play role in muscle metabolism &
function
Calcitonin:
 Hormone produced by parafollicular cells of thyroid
gland
 PTH raises plasma Ca+2 levels & calcitonin acts to
lower plasma Ca+2
Actions of Calcitonin:
 Binds to membrane receptors & cAMP levels increase
 cAMP as 2nd messenger initiates calcitonin action
 sequesteration of Ca+2 into mitochondria acts to
lower cystolic Ca+2  lowering plasma concentrations
by allowing more Ca+2 into cell
Effects of Calcitonin:
 Rapid fall in plasma Ca+2
o Magnitude of fall is proportional to baseline rate
of bone turnover
o Some Ca+2 lost in urine
 Inhibition of osteolysis & bone resorption by bone
cells
 Physiological antagonist to PTH with respect to Ca+2
 Same results as PTH on Phosphate
o Mechanism is different
o Calcitonin enhances Ca+2 & phosphate uptake
into bone
Hyperparathyroidism:
 Most common cause: single parathyroid adenoma (1
of 4)
 Stimulates production of osteoclasts & activates
resorption of bone
 PTH down-regulates osteoblasts & inhibits collagen
synthesis (vitamin D)
Clinical Presentation of Hyperparathyroidism:
 Signs & symptoms of hypercalcemia:
o Dulled mentation: slowed down mental
processes
o Lethargy: tired
o Muscle weakness
o Hyporeflexia: calcium channels down-regulate
o Anorexia: weight-loss
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o Constipation
o Excessive urinary Ca+2 filtration = renal stones
Present hypercalcemia = reduced renal function &
irreversible renal failure
Peptic ulcers are sequela
Hyperparathyroidism:
 Long-term effects of PTH secretion on bone:
o Massive irregular resorption
o Weakening of bone
o Pain
o Fracture (pathological)
Radiological Features:
 Decreased bone density & accentuated trabecular
patterns
 Loss of cortical definition:
o Frayed; irregular; “lace-like”
 Subperiosteal resorption
 Osteolysis
 Brown tumour:
o Not a neoplasia but enlarging radiolucency
 Soft tissue calcification
 In the spine, generalized deossification & trabecular
accentuation with condensation in end plates called
“rugger-jersey” spine
Hyperparathyroidism:
 Distinguished from other causes of hypercalcemia:
o ↑PTH levels
o ↑ plasma Ca+2 levels
o ↓ plasma PO4- levels at kidney
 Treatment: surgical removal of tissue
Primary Hyperparathyroidism:
 Common endocrine disorder where gland does not
respond to rising Ca+2 levels
o 80-85% due to single parathyroid adenoma
 Patients found through blood analysis; symptoms are
mild if any
Secondary Hyperparathyroidism:
 PTH released but Ca+2 levels not rising  gland
becomes hyperplastic
 Blood profile:
o Ca+2 levels: low (≤8.6)
o Phosphate levels low if kidney intact
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Most frequent cause: chronic renal failure or
malabsorption of Ca+2
Hypoparathyroidism:
 Most common cause: autoimmune idiopathic atrophy
(unknown)
 Rarely end organ resistance to PTH
 Ca+2 absorbed from gut is diminished
 Little Vit D metabolite around
 ↓ bone resorption
Clinical Presentation of Hypoparathyroidism:
 Hypocalcemia:
o Hyperactive reflexes: upregulate Ca+2channels , ↑
sensitivity
o Spontaneous muscle contractions
o Convulsions
o Laryngeal spasm with airway obstruction
Hypoparathyroidism:
 Low plasma Ca+2 & elevated plasma phosphate levels
o Plasma PTH levels low in gland destruction
o Plasma PTH levels elevated when target tissue
unresponsive
 Treatment:
o Supplement with 1-25(OH)2-D3
o Supplement with calcium
Vitamin D Toxicity:
 Due to excessive administration or abnormal
sensitivity to ordinary amounts of vit D
 Absorption of Ca+2 from gut & resorption from bone
enhanced
 ↑ plasma & urinary levels of Ca+2
Clinical Presentation of Vitamin D Toxicity:
 Signs & symptoms similar to Hypercalcemia:
o Dulled mentation
o Muscle weakness
o Hyporeflexia
o Lethargy
o Anorexia
o Constipation
Hyperparathyroidism vs. Vit. D Toxicity:
 Same clinical presentation
Hyperparathyroidism Vit D Toxicity
↑
Calcium
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PTH
Phosphate
↑
Low hypo
↓
Normal-elevated
Treatment for Vitamin D Toxicitiy:
 Block effects of vitamin D by administering calcitonin
or cortisol
 Wait for excess Vit. D to clear
Vit. D Deficiency:
 Due to:
o Inadequate sun: location
o Dietary intake
o Decreased absorption: age
o Or defective hydroxylation in liver or kidney
 Deficiency leads to:
o Decreased GI absorption of Ca+2 & PO4o Plasma Ca+2 levels fall & this is buffered by
increased PTH secretion
o PO4- is lost in urine & Ca+2 is retained
 Resulting strongly negative phosphate balance + ↓ in
Ca+2 levels  decrease in rate of bone mineralization
o Further aggravated by lack of vitamin D needed
for mineralization
o Excessive osteoid accumulates
 Results:
o Rickets or osteomalacia
 Diagnostic Profile:
o Slightly reduced plasma Ca+2
o Greatly reduced plasma phosphate & elevated
levels of PTH
 Treatment: replacement doses of Vitamin D. &
supplemental Ca+2
Osteomalacia:
 ‘soft bone’ that defective mineralization of osteoid in
adults
 Symptoms:
o Bone pain
o Muscle weakness
o Pseudo fracture
 Excessive osteoid accumulates over time
 Generally a reversible condition when there is
minimal deformity
 Radiographically:
o Body attempts fracture repair: reparative stage
o Abnormal density
o Discontinuity at cortex
Rickets:
 Osteomalacia in a person with open growth plates
 More severe consequences in a child with rickets
than a person with osteomalacia
 Lack of control over epiphyseal cartilage
mineralization
 Lack of control over endplate growth
 Radiographically:
o Bilateral LE
o Radiolucency of growth lines
Osteoporosis:
 Not a pathology until a fracture occurs
 Not one specific problem
 Metabolic disorder of bone mass where reabsorption
exceeds deposition
Peak Bone Mass:
 30-35 years of age
 Males are more dense
 Factors:
o Nutrition
o Exercise
o Hormone levels
o Family history
o Gender
o Behaviours
o Ethnicity
Conceptual Graphs of Bone Mass:
 Organic:Inorganic
o Child = 1:1
o Adult = 1:4
o Elder = 1:7
 Peak Bone Mass = 32 y.o.
 Assumed physical activity during childhood  ↑ bone
mass throughout life  FALSE, ↑ bone mass will last
only 7 years
 Prolonged physical activity will maintain bone mass
until you stop
Peak Bone Mass:
 Factors affecting loss of bone:
o Gender
o Frame Size
o Family History
 Contributing Factors to Osteoporosis:
o Inactivity
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Diet
Stress
Soda (too much phosphate)
Drugs:
 Steroids leach minerals out of bone
 PPI for gastric reflux
 Heparin – blood thinner
 Chemotherapy
Osteoporosis:
 Most common cause of pathological fracture
o Radiographically identical to osteomalacia
 Economic impact: large due to costs & down time
 Human impact: maintenance of independence
Clinical Presentation:
 Vertebral body fracture
 Height loss
 Hip fracture
 Colle’s fracture: FOOSH
 Loss of teeth
Osteoporosis: Laboratory Values
 ESR
 Blood Profile: Calcium & Phosphate
o Normal
 Alkaline Phosphatase
Osteoporosis: Treatment
 Exercise
 Diet
 Fall Prevention
 Drugs:
o Calcitonin
o Hormone Replacement
o Fosamax: ↓ osteoclastic activity
Acromegally = distal (hands, feet) enlargement
 Rare condition (3 in 1 million births)
 More common in females (3:2)
 Growth hormone abnormality in skeletally mature
individuals
 1o adenoma of pituitary
 Can be drug induced
Signs & Symptoms of Acromegally:
 Big hands, big feet
 Fat pads
 Hoarsened facial features
 Joint pain
 Enlargement of soft tissues & organs as well
 Excess GH secretion  progression of acromegally
 Facial features:
o Frontal boss: protrusion @ glabella
o Lantern jaw
o Big nose
o Large mandible  gaps between teeth &
underbite
Acromegaly: Treatment
 Removal of pituitary gland
 Radiation therapy
 Somatostain therapy: counteracts GH
Gigantism:
 Excess GH of immature skeleton
 Symmetric & proportional overgrowth of all tissues
Osteoporosis:
 Juvenile: diagnosed in teens & 20s
o Bones are failing
o FOOSH during ADL
 Disuse: long-term immobilization
o Casting
o Paraplegia; quadriplegia
Paget’s Disease:
 A thickening & disturbance of the architecture of
bone
 Not systemic, not neoplastic, not infection
 Remodelling Problem:
o Excessive resorption of bone
o Excessive remodelling of bone
o Osteoclasts & osteoblasts not working together
 Aka Osteitis Deformans
 Frequency = 5-11% of population; over 60
 More common in males than females
 Rare in some genetic populations
Chances of Osteoporotic fracture:
 50% for females
 25% for males
Paget’s Disease:
 Monostotic (1 bone) or polystotic (2+ bones)
presentation
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Common locations:
o Pelvis: bigger in comparison to other side
o Skull: hats don`t fit; cortical margins are fuzzy &
thicker
o Spine: larger, whiter
o Tibia: “sabre shin” with neovascularisation
o Femur
Paget’s Disease: Stages
 Stage 1: Osteolytic – osteoclastic activity
o Tx: fosamax
 Stage 2: Mixed Lytic & Blastic
 Stage 3: Sclerotic (burnout)
o Slow down of cellular activity
o Makes it BIGGER & WHITER
Clinical Presentation:
 95% asymptomatic
 Enlarged hat size
 Sabre shin: anterior bowing of tibia, not bilateral
 Pathological fracture
 Pagetic Steal: orthostatic HTN as bone keeps blood in
new vascularisation
 Heart Failure: cardiomegaly
Treatment:
 None
 Fosamax @ early stage
 Calcitonin: stabilizes abnormal bone loss
Clinical Complication:
 Malignant degeneration:
o Rare
o 1-2% of polyostotic disease
Hereditary Disease of Bone:
 Achondroplasia
 Marfan’s syndrome
 Osteogenesis imperfect
 Osteopetrosis
Achondroplasia:
 Lack of cartilage growth
 Affects appendicular skeleton
 Most common form of Dwarfism
 1/40,000 births
 Most common disorder of growth plates
Clinical Features:
 Normal torso, short limbs
o Proximal bones affected most
 Normal life expectancy
 Protruding buttocks, hyperlordosis
 Small attachment site on bone  more curvy bone
due to Wolff’s Law & wider
 Obturator pointing down
 Vertebrae have scalloped  cause stenosis of spinal
canal
 Sacrum is almost parallel to floor
Syndrome:set of expected & predictable findings
Marfan’s Syndrome:
 Connective tissue disorder (during cross-linking of
collagen fibres) involving:
o Skeleton
o Lens of eye
o Mitral valve prolapsed
o Vascular system: aneurysm
 1/10,000 births
 Long, slender extremities
 Arachnodactyly: spider digits – skinny fingers & toes;
not much soft tissue
 “Double-Jointed”: hypermobile
o Ligament laxity
 Life expectancy affected by 5-7 years
o 95% of deaths due to cardiovascular issues
Osteogenesis Imperfecta:
 Aka Brittle (Fragile) Bone Disease
 Defect in Type I Collagen synthesis
 4 genetic types of OI (I-IV)
o II – Congenita
o I – Tarda
Type II – O.I. Congenita
 A uniformly fatal condition
o Rare
o Don’t live long
 Extremely brittle bones
o C-section
Type I – OI Tarda
 Characteristics include abnormal skeletal fragility
o Decreased bone density
o (pathological) fractures
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o Bowing deformities
Sclera of eye appears blue (80%)
Hearing loss due to bony deformities
Dental imperfections
Osteopetrosis:
 Aka Marble Bone Disease or Albers Schonberg
Disease
 2 forms:
o Mild: autosomal dominant
o Lethal: autosomal recessive; very rare
 Hypofunctioning of osteoclasts
o ↓ resorption
o Can’t build medullary cavity
 Radiographic appearance:
o Thickened bones
o Absence of medullary cavity
o “PADDLES”
o “SANDWICH” vertebrae
o Distal femur = “E. Flask”
 Too much bone but very brittle
 Shortened life span as absence of medullary cavity
o ↓ hematopoeisis (RBC)  anemia
o ↓immune system
o ↑ PTH levers to maintain Ca+2
Infection:
 Bone: Osteomyelitis = Bone marrow inflammation
 Joint: septic arthritis or fungal arthritis
Osteomyelitis:
 Acute: sudden onset; < 6 months
 Chronic: > 6 months
 Subacute: Brodie’s Abscess
Osteomyelitis:
 Due to infectious agent residing in bone
 Small & clinically insignificant
Routes to Get to Bone:
 Hematogenous Spread: blood/lymph
 Implantation: bone comes out, something goes in
 Direct extension: bore through CT to bone
Acute Pyogenic Osteomyelitis:
 Bacterial in origin: S. aureus 80-90%
 Hematogenous spread
 Metaphysical area of bone:
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o Child: metabolically active
o Adult: where blood supply enters
Common in children: immune system still developing
Can be extremely aggressive depending on virulence
of organism
Difficult to radiographically visualize:
o Virulence of organism
o Film: 40-60% gone
Cellular Events:
 Localized suppurative (swelling) edema creates:
o ↑ intramedullary pressure
o Mechanical compression of capillaries
 Hyperemia accompanied by osteoclastic activity
causing focal osteolysis; regional osteopenia
 Bacteria contact & lyse osteocytes
 Bacteria move through lacunar & Haversion systems
& reach subperiosteal space
 Necrotis debris creates a localized pressure & causing
lifting of periosteum  reactive bone formation to fill
in space  widening of bone
 Periostitis & increased pressure cause loss of blood
supply to cortical bone contributing to necrosis
Osteomyelitis: High Risk Patients
 Children: immature immune system
 Diabetics: Type I – sores they don’t check
 Elderly: tired immune system
 Immunocompromised:
o Chemotherapy
o HIV/AIDS
o Transplant patients
o Autoimmune
 IV drug abuses
 Homeless
 Post-surgical patients (hospitals)
Acute Pyogenic Osteomyelitis:
 Signs & symptoms:
o Rapid, high fever
o Severe throbbing pain that worsens rapidly
o Pathogenic fracture
Acute Pyogenic Spondylodiscitis:
 2 vertebrae & 1 disc affected
Chronic Pyogenic Osteomyelitis:
 10% go on to become chronic
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Pathologic fracture: many holes in bone cause
vertebrae to collapse; periosteal lifting  widening
of bone
Draining sinus or cloaca
Squamous cell carcinoma (rare)
Bone sarcoma (rare)
Brodie’s Abscess: pus-filled area
 Subacute metaphyseal infection of bone that often
begins in children (immature immune system)
 Osteolytic lesion gets walled off  stops bacteria
from spreading
 Sclerotic margin develops
 Spontaneous sterilization
 Found in tibia, femur, fibula, radius
Tuberculosis:
 1-3% of patients with pulmonary TB develop osseous
complications
 Skeletal TB most prevalent <30, rare <1
Tuberculosis in Bone:
 Extremely destructive & difficult to treat
 Likes areas of bone with high O2 content
o Hematopoietic bones: long bones & vertebral
bodies
 Most common site of involvement is spine,
particularly vertebral body
TB of Spine = Pott’s Disease
 Insidious onset of back pain, focal tenderness, &
decreased ROM
 Spinal pain may be with or without neurological
involvement
 Advanced cases have a draining sinus & vertebral
collapse
 Sharply angled kyphosis due to vertebral collapse 
GIBBUS DEFORMITY
Syphilis:
 A chronic bone infection with resurgence seen in US
 2 varieties to consider:
o Congenital: mother to child in utero
o Acquired: STD
Congenital Syphilis:
 Spirochetes lodge in growth plate
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Normal vascularised tissues underneath plate are
replaced by granulation tissue
Bone formation & remodelling is ↓ or absent; appears
to have widened growth plates or broad radiolucent
metaphyseal bands
o ~ Rickets
Osteitis & periostitis can develop in ineffectively or
untreated patients
Sclerosis & cortical overgrowth create an undulating,
thickened cortex to long bones
Frequently creates classic anterior bowing (Sabre
Shin) with osteolytic defects (gumma) scattered in
bone
Acquired Syphilis:
 <10% of patients develop osseous lesions; involves
cortical bone & periosteum
 Layering of bone on anterior tibia (Sabre shin without
bowing), skull & clavicles
 Lysis & collapse of nasal bones & palate
 Osseous symptoms 2-5 years post-infection
Syphilis Features:
 Skull with gumma: areas of coagulative necrosis
 Hutchinson’s teeth
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