Basic Science

Bone Biology
Neuromuscular & Connective
Tissue
AAOS Review Course 2007
A. Bobby Chhabra , MD
Assistant Professor
Division Head, Hand & Upper Extremity Surgery
University of Virginia
Department of Orthopaedic Surgery
University of Virginia Hand Center
 Overview

• Bone
– Bone Histology
– Bone Injury & Repair
– Calcium & Phosphate Metabolism
– Disorders of Bone Mineralization
– Disorders of Bone Mineral Density
– Osteoporosis
– Questions
Histology
of Bone
 Types of Bone

• Lamellar
– Cortical
– Cancellous
• Woven
– Immature
– Pathologic
 Types of Bone
Woven vs. Lamellar
 Lamellar Bone

• Organized
• Less Cellularity
• Stress-Oriented (Wolff’s Law)
 Cortical Bone (Compact Bone)

• 80% of skeleton
• Slow turnover rate
• Composed of Osteons
• High Young’s
modulus (E)
• High resistance to
torsion and bending
 Osteons or Haversian System

• Functional Unit of
Bone
– Volkmann’s
canals (vessels)
 Cancellous (Trabecular) Bone

• Less dense than

cortical bone
• High turnover rate
• More elastic than
cortical bone
• Smaller Young’s
modulus (E)
 Woven Bone

• Immature - fracture callus or pathologic

(infection, malignancy, stress reaction)
• Weak
• Random Organization
• Increased turnover
• Not stress oriented
• More cellularity
 Cellular Biology of Bone

• Osteoblasts
• Osteocytes
• Osteoclasts
• Osteoprogenitor Cells
 Osteoblasts

• Bone forming cells

• Derived from undifferentiated
mesenchymal cells
• Synthesize Type I Collagen
• High Alkaline Phosphatase Activity
 Osteoblast Receptors
• Parathyroid Hormone (PTH)
– Releases secondary messenger to stimulate
osteoclastic activity
• 1,25 dihydroxyvitamin D
– Stimulates matrix, Alk Phos Synthesis, and
production of bone specific proteins
(osteocalcin)
Osteoblasts
 Osteocytes

• 90% of cells in mature skeleton

• Former osteoblasts trapped in new matrix
• Maintain bone
• Control extracellular concentration of
calcium and phosphorus
• Directly stimulated by calcitonin and
inhibited by PTH
• Communicate through canaliculi
Osteocytes
 Osteoclasts

• Resorb bone
• Multinucleated irregularly shaped giant
cells originate from monocytes
• “Ruffled” border – increases surface area
for resorption
• Bone resorption at Howship’s lacunae
 Osteoclasts

• Bone formation and resorption coupled

• Osteoclasts synthesize tartrate -resistant
acid phosphatase
• Bind to bone surface via bone anchoring
proteins (integrins)
• Possess specific receptors for calcitonin
which inhibit bone resorption
 Osteoclasts

• Responsible for bone resorption in multiple

myeloma and metastatic bone disease

• IL-1 – potent stimulator for osteoclastic

bone resorption and has been found in
membranes surrounding loose total joint
arthroplasties
• IL-1 – possible role in osteoarthritis
 Question
• A fully differentiated osteoclast has receptors for
which of the following proteins?

1- Parathyroid hormone (PTH)

2- Calcitonin
3- Cholecalciferol
4- Bone morphogenetic protein (BMP)
5- Interleukin-2 (IL-2)
 Answer
• PREFERRED RESPONSE: 2

• DISCUSSION: Osteoclasts resorb bone in response to specific systemic and

intracellular signals. Regulation of osteoclastic bone resorption depends on
the way its physiologic function is regulated through receptor mediated
pathways. Calcitonin is a peptide hormone that directly binds to a cell surface
receptor on osteoclasts to inhibit osteoclast function. Although PTH is
frequently regarded as an agent that stimulates bone resorption, osteoclasts do
not possess receptors for this hormone; instead, they are signaled to resorb
bone by osteoblasts, the cells that possess receptors to PTH. IL-2 is an
immunomodulatory cytokine that does not directly influence osteoclast
function. BMP is the name for a family of osteoinductive proteins, many of
which have receptors in osteoblast progenitor cells, but not in fully
differentiated osteoclasts. Although osteoclast precursors do directly respond
to 1,25 dihydroxycholecalciferol, they do not have a receptor for
cholecalciferol itself (vitamin D).
Osteoclasts
 Osteoprogenitor Cells

• Precursors of osteoblasts
• Mesenchymal cells lining Haversian canals,
endosteum
• Differentiate after receiving appropriate
stimulus
 Bone Matrix

• Organic components (40%)

• Inorganic components (60%)

 Organic Components

• Collagen
• Proteoglycans
• Noncollagenous matrix proteins
– Glycoproteins
– Phospholipids
– Phosphoproteins
• Growth factors
• Cytokines
 Collagen

• Tensile strength of bone

• Type I collagen (Bone)
• Type I collagen (90% of organic matrix)
• Triple helix (2 1 and 1 2 chains) = Fibril
• Cross linking decreases solubility and
increases tensile strength
EM of Bone Collagen
 Proteoglycans

• Compressive strength of bone

• Composed of GAG-protein complexes

 Matrix Proteins

• Promote mineralization and bone formation

– Osteocalcin (bone GLA protein)
– Osteonectin
– Osteopontin
 Matrix Proteins

• Osteocalcin – produced by osteoblasts

– Most abundant noncollagenous matrix
protein
– Attracts osteoclasts
– Regulates bone density
– Inhibited by PTH and stimulated by 1,25
dihydrovitamin D
– Can be measured in serum or urine as a marker
of bone turnover (Paget’s,hyperparathyroidism)
 Matrix Proteins

• Osteonectin
– Secreted by platelets,osteoblasts
– Matrix mineralization

• Osteopontin – cell binding protein

 Cytokines and Growth Factors

• Present in small amounts

• Involved in cell differentiation, activation,
growth,and turnover
• TGF-ß, IGF, IL-1, IL-6, BMP
 Inorganic (Mineral) Components

• 60 % of dry weight of bone

• 1) Calcium Hydroxyapatite
– compressive strength of bone
 Bone Remodeling

• Modulated by systemic hormones and local

hormones
• Affected by stress = Wolff’s law
• Hueter-Volkmann Law – mechanical factors
influence longitudinal growth, bone remodeling
– compression inhibits growth
– tension stimulates growth
– Scoliosis and Blount’s disease
 Bone Remodeling

• Cortical Bone
– Osteoclastic
tunneling (cutting
cones)
– Capillaries
– Osteoblasts
 Tissue Surrounding Bone

• Periosteum –
– Tough connective tissue membrane
surrounding bone
– Highly developed in children
– Inner (Cambium) layer
• Contain osteoblastic progenitor cells
• Responsible for bone diameter and periosteal
callus in fracture healing
 Types of Bone Formation

• Enchondral

• Intramembranous

• Appositional
 Enchondral Bone Formation

• Bone replaces a cartilage model

– cartilage is not converted to bone
• Examples
– embryonic long bone formation
– longitudinal growth (physis)
– fracture callus
– DMB matrix enhanced bone formation
 Physis

• Horizontal Growth Plate (physis)

• Spherical Growth Plate (epiphysis)
• Both have same arrangement , but spherical
less organized
• Divided into zones
 Physis Zones

• Reserve
• Proliferative
• Hypertrophic
• Metaphysis
 Reserve Zone

• Reserve Zone – Matrix Production

– cells store lipids, glycogen, proteoglycan for
later growth
– Low O2 tension
 Proliferative Zone

• Proliferative Zone – Longitudinal growth

– Chondrocytes arranged in columns
– Top cell is dividing cell
– Increased oxygen tension inhibits calcification
– Cellular proliferation and matrix production
 Hypertrophic Zone

• Divided in three zones

– Maturation
– Degeneration
– Provisional calcification
• Cells increase in size, accumulate calcium and
then die
• Osteoblasts migrate from vessels located in
metaphysis and use cartilage as a scaffold
 Metaphysis

• Adjacent to physis
• Osteoblasts use cartilage scaffold
• Primary spongiosa (calcified cartilage bars)
is mineralized to form woven bone and
remodeled to form secondary spongiosa
• Cortical bone remodels in response to stress
 Physeal Abnormalities
• Reserve Zone
– Gaucher’s, Diastrophic dwarfism, Kneist syndrome,
Pseudoachondroplasia
• Proliferative Zone
– Achondroplasia, gigantism
• Hypertrophic Zone
– Rickets, osteomalacia
– Enchondromas
– Mucopolysaccharidoses (Morquio’s, Hurler’s)
– SCFE
– Physeal fractures (Zone of Provisional Calcification)
 Intramembranous Ossification

• Occurs without a cartilage model

• Undifferentiated mesenchymal cells
aggregate into layers and differentiate into
osteoblasts which deposit organic matrix
that mineralizes to bone
– 1) embryonic flat bone formation (pelvis,
clavicle, skull)
– 2) distraction osteogenesis
 Appositional Ossification

• Osteoblasts align on existing bone surfaces

and lay down new bone
– 1) Periosteal bone enlargement (width)
– 2) Bone formation phase of bone remodeling
 Bone Injury and Repair

• Fracture Repair – continuum of events

– Inflammation
– Soft Callus Formation
– Hard Callus Formation
– Remodeling
 Inflammation

• Bleeding at fracture site creates a fibrin clot

(hematoma) which is a source of
hematopoietic cells and growth factors
• Fibroblasts, mesenchymal cells, and
osteoprogenitor cells migrate to site
forming granulation tissue
 Repair

• Primary callus repair occurs within 2 weeks

• Bridging soft callus forms between bone
ends and is converted to hard callus by
enchondral ossification
• Medullary callus supplements bridging
callus at a slower rate
 Repair

• Amount of callus formation is indirectly

proportional to the amount of
immobilization of the fracture
• Primary cortical healing occurs with rigid
immobilization (plate fixation) and
resembles normal remodeling – No visible
callus
 Blood Flow in Fracture Healing

• Blood flow delivers nutrients to site of

fracture
• Initial response – Decreased flow
• Blood flow increases within hours and
peaks at two weeks
• Flow returns to normal 3 – 5 months
• Major determinant of fracture healing
 Type of Fracture Healing Based on
Stabilization
• Cast – periosteal bridging callus – enchondral
ossification
• Compression plate – Primary bone healing –
Cutting cone remodeling
• IM nail – early – periosteal callus, late –
medullary callus – enchondral ossification
• Ex-fix – less rigid – periosteal callus , more rigid
– primary bone healing
• Inadequate – Hypertrophic nonunion – Failed
endochondral ossification – type II collagen
 Remodeling

• Starts at 2 weeks and continues well after

the fracture has healed (7 years)
• Bone assumes normal shape based on stress
it experiences (Wolff’s Law)
• Woven bone replaced with lamellar bone
• Fracture healing complete with
repopulation of the marrow space
 Biochemistry of Fracture Healing

• Mesenchymal --- Collagen I, II, (III, V)

• Chondroid ---- Collagen II, IX
• Chondroid  Osteoid ---- I, II, X
• Osteogenic ---- Collagen I
 Growth Factors and Fracture Healing

• BMP
• TGF-ß
• IGF
• PDGF
Growth Factors Involved in Fracture
Healing
• BMP (Bone Morphogenetic Protein) –
osteoinductive --- causes mesenchymal cell
differentiation to osteoblasts
• Target cell for BMP – Undifferentiated
Perivascular Mesenchymal Cells
 Growth Factors Involved in Fracture
Healing
• Transforming Growth Factor- Beta
– Induces mesenchymal cells to produce type II
collagen and proteoglycans
– Present in fracture callus
– Regulates cartilage and bone formation in
fracture callus
 Growth Factors Involved in Fracture
Healing
• Insulin – Like Growth Factor II
– Stimulates type I collagen, cellular
proliferation, cartilage matrix synthesis
 Growth Factors Involved in Fracture
Healing
• Platelet –Derived Growth Factor
– Released from platelets
– Chemotactic --- attracts inflammatory cells to
fracture site
 Biology of Bone Grafting

• Graft Properties
– Osteoconductive matrix (scaffold or framework
into which bone growth occurs)
– Osteoinductive factors – growth factors such as
BMP, TGF-ß– promote bone formation
– Osteogenic cells – mesenchymal cells,
osteoblasts, and osteocytes
– Structural integrity
 Definitions

• Autografts
• Allografts
– Fresh (increased antigenicity)
– Fresh-Frozen (less immunogenic, BMP preserved)
– Freeze Dried (loses structural integrity and depletes
BMP) – Least immunogenic, purely osteoconductive
– Demineralized Bone Matrix (Grafton) –
osteoconductive and osteoinductive
 Bone Marrow Cells

• Bone Marrow Cells of Bone Allograft

– Incite greatest immunogenic response
compared to other constituents
 Bone Grafting

• Cortical Bone
• Cancellous Bone
• Osteochondral Grafts
• Vascularized Bone Grafts
 Cortical Bone Grafts

• Slow incorporation
• Structural support
• Remodeling of existing haversian systems
via resorption followed by deposition of
new bone
• Weak during resorption phase (fatigue
fracture)
 Cancellous Bone Graft

• Revascularized quickly
• Osteoblasts lay down new bone on old trabeculae
(CREEPING SUBSTITUTION)
 Synthetic Bone Grafts

• Calcium, Silicone, or Aluminum

– Calcium Phosphate Grafts – Osteoconductive,
degrade at slow rate , are incorporated
– Calcium Sulfate – Osteoconductive (Osteoset)
– Calcium Carbonate – Osteoconductive
– Corraline Hydroxyapatite – Osteoconductive
(Interpore)
 Bone Grafts

Graft Osteoconduction Osteoinduction

Autograft
Cancellous Excellent Good
Cortical Fair Fair
Allograft Fair Fair
Ceramics Fair None
DBM Fair Good
Bone Marrow Poor Poor
 Conditions of Bone
Mineralization, and Bone
Mineral Density
 Normal Bone Metabolism
• 1) Calcium
• 2) Phosphate
• 3) PTH (Parathyroid Hormone)
• 4) Vitamin D
• 5) Calcitonin
• 6) Estrogen
• 7) Corticosteroids
• 8) Thyroid Hormone
• 9) Growth Hormone
• 10) Growth Factors
 Calcium

• Bone is a reserve for 99% of body’s calcium

• Important in muscle & nerve function, clotting
mechanism
• Plasma Calcium (1%) – 50% free, 50% bound to
albumin
• Calcium absorbed in duodenum by active
transport (regulated by 1,25 (OH)2 Vit D) and by
passive transport (jejumun)
• Resorbed in proximal tubules of kidney
 Calcium – Dietary Requirements

• 600 mg/day – children

• 1300 mg/day – adolescents
• 750 mg/day – adult men / women
• 1500 mg/day – pregnant women
• 2000 mg/day – lactating women
• 1500 mg/day – postmenopausal women,
fracture healing
 Primary Regulators of Calcium
• PTH
– Increases calcium, decreases phosphate
• 1,25 (OH)2 Vit D
– Increases calcium and phosphate
 Phosphate

• 85 % of body’s stores in bone

• Plasma phosphate unbound and reabsorbed
in proximal tubules of kidneys
• Dietary Requirement – 1000-1500 mg/day
Calcium and Phosphate
Metabolism
 Parathyroid Hormone
• Synthesized and secreted from chief cells of the 4
parathyroid glands
• Regulates plasma calcium
• Directly activates osteoblasts which stimulate
osteoclasts through 2° messenger
• Modulates renal phosphate filtration
• Decreased calcium levels stimulate PTH release
which acts at intestines, kidneys, and bone
• PTH-related protein and its receptors implicated in
metaphyseal dysplasia
 Vitamin D

• Naturally occurring steroid activated by UV

irradiation from sunlight or from dietary
intake
• Hydroxylated in liver
– 25-(OH)2 vitamin D3
• Hydroxylated again in kidney
– 1,25-(OH)2 (active form)
– 24,25-(OH)2 (inactive form)
Vitamin D Metabolism
 Vitamin D

• Active form (1,25) works at intestines,

kidneys, and bone
• Increases serum Calcium
• Increases serum Phosphate

• Dilantin impairs metabolism of vitamin D

Vitamin D Metabolism
 Calcitonin

• Made by clear cells in the parafollicles of

the thyroid gland
• Main effect is the inhibition of osteoclastic
bone resorption --- decreases serum
calcium levels
• Calctonin release stimulated by increased
serum calcium levels
• Target for osteoporosis treatment
 Estrogen

• Estrogen – Prevents bone loss by inhibiting bone

resorption
• BUT since bone formation and resorption are
coupled , estrogen decreases bone formation
• Supplementation helpful in postmenopausal
women but only if started within first 5 –10
years
• Combine with progesterone therapy to prevent
increased risks of breast and uterine cancer
 Conditions of Bone Mineralization

• Hypercalcemic disorders
• Hypocalcemic disorders
• Hypophosphatasia
 Hypercalcemia

• Presenting signs / symptoms Polyuria

– Kidney stones
– Osteitis fibrosa cystica
– CNS effects (confusion, stupor)
– GI effects (constipation)

“bones, stones, abdominal groans, and

psychiatric overtones”
 Hypercalcemia

• Differential Diagnosis
– Hyperparathyroidism
– Familial Syndromes (MEN syndrome)
– Malignancy
– Vitamin D intoxication
– Prolonged immobilization
– Addison’s disease
– Kidney disease
– PUD (milk alkali syndrome)
– Sarcoidosis
– Hypophosphatasia
 Primary Hyperparathyroidism

• Overproduction of PTH (parathyroid

adenoma)
• Net increase in plasma calcium
• Decrease in plasma phosphate (enhanced
urinary excretion)
• Increased osteoclastic resorption
 Primary Hyperparathyroidism

• Diagnosis
– Signs / Symptoms of Hypercalcemia
– Increased serum calcium, PTH, urinary
phosphate
– Decreased serum phosphate
– Bony changes (Osteitis fibrosa cystica, Brown
Tumors, chondrocalcinosis)
 Primary Hyperparathyroidism
Labs
• Increased
– Serum calcium • Decreased
– PTH – Serum Phos
– 1,25 Vit D *
– Urinary calcium
– Alk Phos (normal)
• Normal
– 25 Vit D
* PTH stimulates Vit D
conversion to (1,25)
 Primary Hyperparathyroidism

• Histologic Changes – osteoblasts and

osteoclasts active on both sides of the
trabeculae, wide osteoid seams

• Treatment – surgical parathyroidectomy

 Hypocalcemia

• Low PTH or Vitamin D

• Results in:
– neuromuscular irritability (tetany, seizures,
Chvostek’s sign)
– Cataracts
– Fungal infections of nails
– EKG changes (prolonged QT interval)
 Hypocalcemia

• Differential Diagnosis
– Hypoparathyroidism
– Pseudohypoparathyroidism (PHP)
– Renal Osteodystrophy
– Rickets
 Hypoparathyroidism
• Decreased PTH
– Diminished plasma calcium
– Increased plasma phosphate
• Common PE findings
– Fungal infections
– Hair loss
– Vitiligo
• Iatrogenic hypoparathyroidism results from
thyroidectomy
 Hypoparathyroidism
Labs
• Decreased • Increased
– Serum Calcium – Serum Phos
– PTH
– 1,25 Vit D • Normal
– Urinary Calcium – Alk Phos
 Pseudohypoparathyroidism

• PHP – rare genetic disorder caused by lack

of PTH effect on target cells (Resistance to
PTH)
• Albright Hereditary Osteodystrophy
– Short 1st, 4th, 5th metacarpals and metatarsals,
obesity, diminished intelligence
 Pseudohypoparathyroidism
Labs
• Decreased • Normal
– Serum calcium – PTH (or
– 1,25 Vit D increased)
– Urinary Calcium – Alk Phos
– 25 Vit D

• Increased
– Serum Phos
 Renal Osteodystrophy

• Spectrum of disorders in bone metabolism

in patients with chronic renal disease
• Impaired renal function compromises
mineral homeostasis
Renal Osteodystrophy
 Rickets

• Spectrum of disorders
• Failure of mineralization (zone of
provisional calcification) leading to
changes in physis and cortical bone
– Physis – increased width
– Bone – cortical thinning, bowing
 Causes of Rickets

• Nutritional Deficiency
• Gastrointestinal Absorption Defects
• Renal Tubular Defects (Renal Phosphate
leaks)
• Renal Osteodystrophy
• Miscellaneous Causes
 Nutritional Rickets

• Vit D deficiency
• Calcium deficiency
• Phosphate deficiency
 Vitamin D Deficient Rickets

• Vitamin D Deficiency Rickets

– Rare in U.S. after addition of Vit D to milk
– Premature infants
– Malabsorption syndromes
• Treatment
– Vitamin D 5000 IU/day
Rickets
 Vitamin D Deficiency Rickets
Labs
• Decreased • Increased
– Serum Ca (normal) – PTH
– Serum Phos – Alk Phos
– 25 Vit D
– 1,25 Vit D
– Urinary Calcium
 Calcium Deficiency Rickets

• Hypocalcemia leads to increase in PTH

• Increased PTH = 25 Vit D  1,25 Vit D
• Labs
– Decreased: Serum Calcium, Serum Phos,
Urinary Calcium
– Increased: PTH, 1,25 Vit D, Alk Phos
• Causes Osteomalacia (adults)
• Treatment: Oral Calcium (700mg/day)
 Phosphate Deficiency Rickets
• Decreased serum phosphate  increase in 1,25
Vit D
• No secondary hyperparathyroidism or Vit D
deficiency
• Labs
– Normal: serum Ca, PTH, 25 Vit D, Urinary Ca
– Decreased: Serum Phosphate
– Increased 1,25 Vit D
• Treatment: Oral Phosphate
 Hereditary Vitamin D-Dependent
Rickets

• Rare disorder , two types

• Type I and II
• Similar presentation to Vitamin D
deficiency but worse
 Type I
(Pseudovitamin D Deficiency)
• Defect in renal Vit D alpha hydroxylase
– Inhibition of inactive form to active form of
Vitamin D
– Autosomal Recessive (AR)
– Gene on chromosome 12q14
• Treatment: Oral 1,25 Vit D
 Type I
(Pseudovitamin D Deficiency)
Labs
• Decreased • Increased
– Serum Ca – Alk Phos
– Serum Phos – PTH
– 1,25 Vit D – 25 Vit D
– Urinary Ca
 Type II
(Hereditary Resistance to Vit D)
• Defect in intracellular receptor for 1,25
(OH)2 Vit D
• No response to active form of Vitamin D
• Similar presentation to Vit D deficiency but
more severe
• Treatment: High dose Vit D and Calcium
 Type II
Labs
• Decreased • Increased
– Serum Ca – PTH
– Serum Phos – 1,25 Vit D
– Urinary Ca – 25 Vit D
– Alk Phos
 Familial Hypophosphatemic Rickets

• a.k.a. Vit D Resistant Rickets and “Phosphate

Diabetes”
• X-linked dominant disorder that results in
impaired renal tubular resorption of phosphate
• Most common form of rickets
• Treatment : Phosphate and Vitamin D replacement
(Vit D needed to negate hypocalcemic effect of
phosphate supplementation)
 Hypophosphatemic Rickets
Labs
• Decreased • Normal
– Serum Phos – Serum Ca
– PTH
– 25 Vit D
– 1,25 Vit D*
– Urinary Ca

* Low given serum level

of phosphate
 Question
• When counseling a patient with
hypophosphatemic rickets, which of the following
scenarios will always result in a child with the
same disorder?

1- Female patient who has a female child

2- Female patient who has a male child
3- Male patient who has a female child
4- Male patient who has a male child
5- Disorder not inherited
 Answer
• PREFERRED RESPONSE: 3
• DISCUSSION: Hypophosphatemic rickets is an inherited disorder that
is transmitted by a unique sex-linked dominant gene. Therefore, if a
male patient has a female offspring, his affected X chromosome will
be transmitted and all of his female children will have
hypophosphatemic rickets. All male offspring of a male patient will
be unaffected. All offspring of a female patient have a 50% chance of
having the disorder. Understanding the inheritance of
hypophosphatemic rickets facilitates early diagnosis and early
treatment. Medical treatment with phosphorus and some types of
vitamin D (most authors recommend calcitriol) improves, but does not
fully correct, the mineralization defect in hypophosphatemic rickets.
However, if medical treatment is begun before the child begins
walking, the growth plate is then adequately protected and a bowleg
deformity will most likely be prevented.
 Hypophosphatasia

• AR disorder
• Inborn error that leads to low levels of
alkaline phosphatase (required for synthesis
of inorganic phosphate)
• Features similar to rickets, osteomalacia
• Diagnosis: increased urinary
phosphoethanolamine
• Treatment: ????
 Hypophosphatasia

• Decreased • Increased
– Alk Phos – Serum Ca
– Urinary Ca

• Normal
– PTH
– 25 Vit D
– 1,25 Vit D
Conditions of Bone Mineral
Density
Decreased Bone Mineral Density
Increased Bone Mineral Density
Both
 Osteopenia
(Decreased Bone Mineral Density)
• Osteoporosis
• Osteomalacia
• Scurvy
• Marrow Packing Disorders (myeloma,
leukemia)
• Osteogenesis Imperfecta
 Osteoporosis

• Age related decrease in bone mass

– Postmenopausal women
• 1 million fractures / year
• Quantitative not Qualitative defect in bone
• Risk Factors: sedentary lifestyle, thin, Northern
European descent, smokers, drinkers, dilantin
• Cancellous bone most affected
 Bone Loss

• Peak bone mass – 16 – 25 y/o

• Decreases by .3 - .5% / year
• Decreases 2 –3 % / year for untreated
women during 6 – 10 years after menopause
 Bone Loss – Osteoporosis

• Occurs at onset of menopause

• Markers of bone resorption
– Urinary hydroxyproline
– Pyridoline cross-links
• Markers of bone formation
– Serum alkaline phosphatase
 Osteoporosis

• Two determinants in development of

osteoporosis
– Peak Bone Mass
– Rate of Bone Loss Thereafter
• Rate of Bone Loss
– Normal Aging Process
– Accelerated Bone Loss with Menopause
– Genetic, environmental influences
 Osteoporosis

• Type I (Postmenopausal)
– Affects trabecular bone
– Vertebral and distal radius fractures are
common
• Type II (Age-Related)
– Patients older than 75 y/o
– Affects both trabecular and cortical bone
– Poor calcium absorption
– Hip and pelvis fractures are common
 Osteoporosis

• Clinical Features
– Kyphosis
– Vertebral fractures
– Hip fractures
– Distal radius fractures
 Osteoporosis

• Lab Studies – Normal

• Radiographs – Helpful if > 30% bone loss
• DEXA (dual-energy x-ray
absorptiometry) is the most accurate
diagnostic tool
• Histology : thinning of trabeculae,
decreased size of osteons, enlargement of
Haversian and marrow spaces
Osteoporosis
 DEXA

• Used for bone mass measurements in the

central skeleton (femur, spine)
• Bone Mineral Content (BMC) – varies with
age, sex, & race
• Normative data base necessary when
reporting BMC
 DEXA Interpretation
• Z-score
– Measure of patient’s results as a deviation from the
mean of age-matched controls divided by the standard
deviation of this mean
• T-score
– Bone density of a patient compared to the peak bone
mass of young normal adults
– Gives patient’s result as a deviation from the mean of
young normal adults divided by the standard deviation
of the mean
 DEXA Interpretation
T- Score
• Normal
– BMC not more that 1 SD below average value of young
adults
• Osteopenia (low bone mass)
– BMC between 1 – 2.5 SD below young adult average
• Osteoporosis
– BMC more than 2.5 SD below young adult average
• Severe Osteoporosis
– BMC > 2.5 SD plus insufficiency fractures

WHO Guidelines
 Osteoporosis
• Treatment
– Physical activity
– Calcium/ Vitamin D supplementation
– Bisphosphonates (Fosamax, Actonel) (inhibit osteoclastic
membrane ruffling without destroying the cells)
– Evista (selective estrogen receptor modulator)
– Recombinant PTH (Forteo – pulsatile release ??)
– Calcitonin
– Combination therapies
– Estrogen-Progesterone Therapy (less common since WHI
study results)
 Osteoporosis

• Prophylaxis
– Diet with adequate Calcium and Vitamin D
– Weight-bearing exercise program
 When to Treat for Osteoporosis??
• Controversial
– T-score greater than - 2.5 SD
– Any osteoporotic fracture
– No indications to treat for osteopenia ( < -2.5)
• What agents?
– Calcium & Vitamin D supplementation
– Bisphosphonates (1st line – if tolerated)
 Osteomalacia

• Defect in mineralization
• Unmineralized osteoid (qualitative defect)
• Vitamin D-deficient diet, GI disorders,
renal osteodystrophy, drugs (antacids,
dilantin)
• Associated with alcoholism
• Looser’s Zone (microscopic stress fxs)
 Osteomalacia

• X-rays: biconcave vertebral bodies, trefoil

pelvis
• Biopsy – required for diagnosis
– Widened osteoid seams
• Treatment – Large doses of Vitamin D
 Osteoporosis vs. Osteomalacia
• Osteoporosis • Osteomalacia
– Bone Mass Decreased – Bone Mass Variable
– Mineralization Normal – Mineralizaion Decreased
– Elderly – Any Age
– Postmenopausal – Labs abnormal
– Labs normal
 Scurvy

• Vitamin C (ascorbic acid) deficiency

– Decrease in chondrotin sulfate
synthesis
– Defective collagen growth and repair
– Impaired intracellular hydroxylation
of collagen peptides
• Clinical features: fatigue, bleeding gums,
joint effusions
 Scurvy

• Labs: normal
• Histology: primary trabeculae replaced with
granulation tissue; widening of the zone of
provisional calcification in physis
• Greatest effect on bone formation in
metaphysis
• Treatment: Vitamin C supplementation
 Question
In children, scurvy has the greatest effect on
bone formation in the
1-physis.
2-diaphysis.
3-epiphysis.
4-metaphysis.
5-articular surface.
 Answer
• PREFERRED RESPONSE: 4

• DISCUSSION: Deficiency of vitamin C produces a decrease in chondroitin

sulfate synthesis, and a deficiency in collagen cross-linking is seen in the
metaphysis. The microscopic appearance of the cartilaginous portion of the
growth plate is normal but the metaphysis is quite abnormal. It appears that
the deficiency in the metaphysis is related to the large amount of type I
collagen normally found in this region. Radiographic findings may include
the accumulation of calcified cartilage at the metaphysis-growth plate junction
that results in a white line on the radiograph (white line of Fraenkel). The
trabeculae are sparse and there is a generalized osteoporosis. The metaphyseal
bone is weakened with microfractures and marginal spurs (Pelkin sign).
Displacement of the growth plate may occur. The epiphyseal nucleus is also
markedly radiolucent, but the calcified cartilage is unaffected, producing an
appearance of ringed epiphyses (Wimberger sign).
 Osteogenesis Imperfecta

• Abnormal collagen synthesis (failure of normal

collagen cross-linking)
• Mutation in gene responsible for production of
Collagen Type I
 Increased Osteodensity

• Osteopetrosis (Marble Bone Disease)

• Paget’s (Both increased and decreased
osteodensity)
 Osteopetrosis

• Increased sclerosis and obliteration of

medullary canal
• Due to decreased osteoclast function
• Histologically – osteoclasts lack normal
ruffled border
• Marrow space filled with necrotic calcified
cartilage
 Osteopetrosis

• AR infantile malignant form – severe

– Hepatosplenomegaly
– Aplastic anemia
– Death
– Treatment : Bone marrow transplant
• AD tarda benign form (Albers-Schonberg Disease)
– Generalized osteosclerosis
– Pathologic fractures (brittle bone)
Osteopetrosis
 Question
In some cases of osteopetrosis, bone resorption and
remodeling are impaired because of a defect in carbonic
anhydrase. The function of this enzyme in bone is to

1. promote maturation of mononuclear phagocytes into

osteoclasts.
2. degrade osteoid..
3. generate hydrogen ions at the ruffled border.
4. promote coupling between osteoblasts and osteoclasts.
5. initiate stress-related remodeling.
 Answer
• PREFERRED RESPONSE: 3

• DISCUSSION: Osteoclasts are attached to underlying

bone via integrin receptors in the clear zone. This
effectively seals the space below the osteoclasts.
Hydrogen ions produced by carbonic anhydrase are
pumped into the space across the ruffled border of the
osteoclasts. In the ruffled border space, the underlying
hydroxyapatite is solubilized in the low pH and calcium
ions are released. Patients who are deficient in carbonic
anhydrase cannot resorb bone by this mechanism.
 Paget’s Disease
• Discussed in Orthopaedic Pathology
• 2 phases – active and inactive phase
• Elevated serum alkaline phosphatase and urinary
hydroxyproline
• Active phase
– Lytic phase – intense osteoclastic bone resorption
– Mixed Phase
– Sclerotic phase – osteoblastic bone formation
predominates
Paget’s Disease
Test Questions

Bone
 At what time after fracture is there a
maximal vascular response (blood flow
rate) at the fracture site maximized?
• Immediately after injury
• 2 weeks
• 4 weeks
• 6 weeks
• 12 weeks
 The common pathologic process that
occurs in patients with rickets, regardless
of the cause, is a failure to:
• Mineralize the matrix in the zone of
provisional calcification
• Adequately synthesize chondroitin sulfate
• Adequately synthesize type II collagen
• Metabolize and degrade glycoproteins
• Resorb the primary spongiosum
 What is the primary effect of vitamin D?

• Strongly stimulates intestinal absorption of

calcium and phosphate
• Stimulates parathyroid hormone release
• Stimulates calcium release from bone
• Promotes urinary excretion of phosphate
• Inhibits osteoclastic bone resorption
Which of the following is considered a key
characteristic of osteoblasts?
• Produce acid phosphatases
• Produce osteocalcin when stimulated by 24,
25 - dihydroxy vitamin D
• Responsive to parathyroid hormone
• Completely surrounded by mineralized
bone matrix
• Resorb mineralized bone
 What term describes the extensive processes of
osteons that establish contact and communication
between osteocytes ?
• A. Haversian Canals
• B. Canaliculi
• C. Ruffled Borders
• D. Howship’s Lacunae
• E. Pseudopodia
During the repair process of an unstable fracture,
the expression of major collagen types during
fracture callus formation can best be
characterized by
• Type I collagen only
• Type II collagen only
• Type I collagen early, followed by type II
collagen
• Type II collagen early, followed by type I
collagen
• Type I and type II collagen equally
throughout
 What organ secretes calcitonin?

• Parathyroid
• Thyroid
• Kidney
• Bone
• Skin
 Which of the following groups is most at
risk for osteoporosis?
• Caucasian men
• Caucasian women
• African-American women
• Hispanic men
• Hispanic women
 What is the major source of nutrition of the
growth plate ?

• A. Synovial Blood Vessels

• B. Terminal Branches of the Nutrient Artery
• C. Metaphyseal Artery
• D. Perichondrial Artery
• E. Synovial Fluid
 What is the most abundant noncollagenous
protein in bone?

• A. Osteocalcin
• B. Osteonectin
• C. Osteopontin
• D. Aggrecan
• E. Fibronectin
 What is the primary function of 1,25-
dihydroxyvitamin D ?

• Inhibits osteoclast bone resorption

• Promotes urinary excretion of phosphate
• New osteoblast bone formation
• Increases calcium and phosphate absorption
from the GI tract
• Decreases serum calcium
 During fracture healing, which of the
following cartilage types is expressed by
hypertrophic chondrocytes as the
extracellular matrix undergoes
calcification?
• I
• II
• V
• X
• XI
 Osteoclasts are signaled directly via
receptors to stop resorbing bone by
which of the following substances ?

• Parathyroid hormone
• Calcitonin
• Vitamin D
• Interleukin – 6
• Osteoprotegerin ligand
What metabolic bone disease is associated
with abnormal osteoclastic function?
• X-linked hypophophatemic rickets
• Fanconi’s syndrome
• Osteopetrosis
• Osteomalacia
• Paget’s disease of bone
 What is the chemical structure of
hydroxyapatite?

• 1. Ca10(PO4)6(OH)2
• 2. Ca10(Na4)6(OH)2
• 3. Ca10(Mg4)6(OH)2
• 4. Mg10(Ca4)6(OH)2
• 5. Na10(Ca4)6(OH)2
 What is the mechanism of action of
bisphosphonates ?
• Inhibition of osteoclast-mediated bone
resorption
• Inhibition of leukotriene synthesis
• Blockage of T-cell mediated inflammation
• Irreversible inhibition of prostaglandin
synthesis
• Binding of antithrombin III that causes a
conformational change
 All of the following substances are
osteoconductive except:
• Autogenous bone graft
• Calcium sulphate
• Frozen allograft
• BMP-2
• Beta tricalcium phosphate
A 65 year old man who has had a dull ache in the
tibia for several years now has pain so acute that
he must use crutches. Levels of serum calcium
and phosphorus are normal but the alkaline
phosphatase level is elevated. The diagnosis most
likely is

• Chronic osteomyelitis
• Histiocytic lymphoma
• Hyperparathyroidism
• Paget’s disease
• Fibrous dysplasia
 Which of the following is not a
manifestation of hyperparathyroidism?

• Increased excitability of the central nervous

system
• Muscular weakness
• Anorexia
• Lace-like subperiosteal resorption of the
phalanges
• Metastatic calcification
An 8 year old is dwarfed and has bow legs.
The calcium is low, the BUN, phosphate
and alkaline phosphatase are elevated. The
most likely diagnosis is
• Nutritional rickets
• Vitamin D resistant rickets with
aminoaciduria
• Renal osteodystrophy
• Hypophosphatasia
• None of the above
 Parathyroid hormone exerts an effect on
the intestine by
• Increasing the level of cyclic adenosine
monophosphate
• Increases calcium transport across the intestinal
wall
• Stimulating production of 24
hydroxycholecalciferol
• Stimulating production of 1,25
dihydroxycholecalciferol
• Increasing calcium binding protein
The major physiologic effect of calcitonin is

• Inhibition of bone resorption

• Enhancement of bone deposition
• To increase parathyroid hormone release
• To depress parathyroid hormone release
• To produce osteoclastic cell multiplication
A three year old boy with frequent fractures and
progressive deformity of the long bones with a
normal serum calcium and phosphorous and low
serum alkaline phosphatase most likely has

• Hypophosphatasia
• Rickets
• Renal rickets
• Osteogenesis imperfecta
• Hypophosphatemia
 Vitamin D is converted to 25-
hydroxycholecalciferol in which organ?

• Skin
• Kidney
• Liver
• Intestine
• bone
 25-hydroxycholecalciferol is changed to
1,25-hydroxycholecalciferol in which
organ?

• Skin
• Kidney
• Liver
• Intestine
• Bone
Bisphosphonates are a family of compounds used
in the treatment of a variety of metabolic bone
disorders. Which of the following osteoclastic
functions is most directly affected by these
compounds?
• Intracellular carbonic anhydrase activity
• Pumping of protons into the extracellular
space
• Attachment to the extracellular matrix by
integrin-RGD protein interactions
• Development of a ruffled border
• Phagocytosis of calcium and phosphate
complexes
What component of frozen allograft bone has the
least amount of immunogenicity?
• Bone marrow cells
• Proteoglycans
• Hydroxyapatite
• Cytokines
• Cell surface proteins
 A fully differentiated osteoclast has
receptors for which of the following
proteins?
• Parathyroid hormone
• Calcitonin
• Cholecalciferol
• Bone morphogenetic protein
• Interleukin-2
Which of the following substances has been
implicated in the pathogenesis of
osteoarthritis
• Interleukin – 1
• Tissue inhibitor of matrix metalloproteinase
• Cyclooxygenase-1
• BMP-2
• T-cells
In patients with osteoporosis, the incidence
of fracture is directly related to

• Age at the time of peak bone massage

• Age at the onset of menopause
• Serum calcium levels
• The degree of bone mass loss
• Osteoclast and osteoblast activity
 Acknowledgements and Thanks

• Frank Frassica, M.D.

• Mark D. Miller, M.D.
• Mark R. Brinker, M.D.
• Robert B. Day, M.D.
• Richard Thomas, M.D
• Brian Leo, M.D.
 References

• AAOS – Orthopaedic Basic Science Text

(editors: Buckwalter, Einhorn, Simon)
• Miller’s Review of Orthopaedics, 4 th edition
• AAOS – OITE 2000, 2001, 2002, 2003,
2004, 2005, 2006; Self Assessment Exam
2000
 Basic Science
Neuromuscular and Connective
Tissue
AAOS Review Course 2007
A. Bobby Chhabra , MD
Assistant Professor
Division Head, Hand & Upper Extremity Surgery
University of Virginia
Department of Orthopaedic Surgery
University of Virginia Hand Center
 Overview

• Skeletal Muscle
• Peripheral Nervous System
• Connective Tissues
• Questions
 Skeletal Muscle

• Noncontractile Elements
• Contractile Elements
• Action
• Types of Muscle Contraction
• Types of Muscle Fibers
• Athletics and Training
 Skeletal Muscle
• Noncontractile Elements
– Muscle Body
• Epimysium = surrounds muscle bundles
• Perimysium = surrounds muscle fascicles
• Endomysium = surrounds individual muscle fibers
– Myotendon Junction
• Weakest link – site of injury with eccentric
contraction
– Sarcoplasmic Reticulum
• Stores calcium necessary for muscle contraction
 Skeletal Muscle
• Contractile Elements
– Derived from myoblasts
– Muscle = fascicles fibersmyofibrils
– Myofibril is a collection of sarcomeres
Skeletal Muscle
 Sarcomere

• Composed of thick and thin filaments in an

intricate arrangement that allows fibers to
slide past each other
• Thick filaments = myosin
• Thin filaments = actin
 Sarcomere

• H Band = myosin (thick) filaments

• I Band = actin (thin) filaments
• Z line = attachment site of thin filaments
• A Band = Contains both actin and myosin
• M line = interconnecting site of thick filaments
Sarcomere = Z line to Z line
 Action
• Stimulus for muscle contraction
– Originates in cell body of a nerve
– Propogated down axon
– Reaches motor end plate and acetylcholine is released
by presynaptic vesicles
– Acetylcholine diffuses across synaptic cleft (50nm) to
bind to a specific receptor on the muscle membrane
– Depolarization of the sarcoplasmic reticulum and
release of calcium
Motor End Plate
 Calcium Regulation of Muscle
Contraction
• Troponin & Tropomyosin = regulatory
proteins
• Tropomyosin = prevents cross bridges
from binding actin
• Troponin
– Calcium sensitive
– Induces change in tropomyosin allowing
cross bridges
Mysoin/Actin Cross Bridges
 Types of Muscle Contraction

• Isotonic
• Isometric
• Isokinetic
 Isotonic
• Muscle Tension constant through range of motion
• Muscle length changes
• Measure of dynamic strength
• Biceps curls
• Phases
– Concentric Contraction (Curl)
– Eccentric Contraction - potential for muscle
injury (Negative)
 Isometric
• Muscle length constant
• Tension changes
• Measure of static strength
• Example: Pushing against immovable
object
 Isokinetic
• Muscle velocity constant
• Tension generated through range of motion
• Measure of dynamic strength
• Best for maximizing strength
• Eccentric isokinetic exercises most
efficiently strengthens skeletal muscle
• Isokinetic exercises require special
equipment (Cybex machine)
 Types of Muscle Fibers
• Slow Twitch (Type I)
• Fast Twitch (Type II A and IIB)
 Slow Twitch
• Type I fibers
• Oxidative (Red)
• Aerobic = More Mitochondria
• Specialize in endurance activities
 Fast Twitch
• Type II (A and B)
• White Fibers
• Glycolytic
• Contract more quickly, motor units stronger and
larger
• Anaerobic (Less efficient)
• Suited for high-intensity short duration activities
(sprinting)
• Fatigue rapidly
 Athletes and Training

• Distribution of Fast Twitch and Slow

Twitch Fibers = genetically determined
• Selective training can improve function and
efficiency of fibers
• Endurance Athletes = Slow Twitch
• Sprinters = Fast Twitch
 Athletes and Training

• Plyometric Exercises
– Muscle Stretching Cycle followed by Rapid
Shortening Cycle
– Stretching leads to storage of elastic energy

• Plyometrics = Power
 Muscle Injury

• Muscle Strains  Myotendinous Junction

• Muscle Soreness  eccentric muscle contraction
and changes in the I band of the sarcomere
• Muscle tears  Myotendinous Junction
– Rapid eccentric contraction
– Heal with dense fibrosis
– Midsubstance Muscle Belly Tears  ½ muscle strength
recovery after healing
Myotendinous Junction
Peripheral Nervous System
 Peripheral Nervous System

• Nerves – Bundle of axons enclosed in

connective tissue sheath
• Nerve Fiber – Axon plus surrounding
Schwann cell sheath
– Myelinated Fibers – Axons 1-2 µm
• Faster conduction velocity
– Unmyelinated Fibers
• Slower conduction velocity
Myelination
 Neuron

• Cell body = metabolic center

• Axon = conduction of action potential
• Dendrites = receives input from
surrounding nerve cells
• Presynaptic Terminal = transmit
information from one neuron to another
Neuron
 Nerve – Glial Cells

• Schwann Cells
– Myelinate peripheral nerve axons
– Loss of myelin sheath disrupts conduction
velocity
– Myelin = 70% lipid , 30% protein
 Signal Transmission

• Stimulus
• Increased cell permeability to Na +
• Depolarization
• Action Potential
• Transmitter released at presynaptic junction
Action Potential
 Peripheral Nerve

• Composed of nerve fibers, blood vessels,

connective tissues
• Nerve fibers surrounded by endoneurium
• Fibers grouped into bundles called fascicles
• Fascicles covered by perineurium
• Peripheral nerves composed of fascicles
which are surrounded by epineurium
Peripheral Nerve Anatomy
Fascicles
 Nerve Fibers

• 3 types
• Type A
– Largest, heavy myelination, fast speed (touch)
• Type B
– Intermediate myelination, medium speed
(Autonomic Nervous System)
• Type C
– No myelination, slow speed (pain)
 Peripheral Nerves

• Conduction facilitated by gaps between

Schwann cells = Nodes of Ranvier
• Blood Supply
– Extrinsic Blood Supply
– Intrinsic Blood Supply vascular plexus in
epineurium, perineurium, endoneurium
 Peripheral Nerve Injury

• Injury leads to death of distal axons and

Wallerian Degeneration of myelin
• Proximal axonal budding occurs (1 month
after injury)
• Nerve Regeneration = 1 mm/day
• Pain is first modality to return
 Peripheral Nerve Injury

Injury Problem Prognosis

Neuropraxia Local Ischemia Good
Selective demyelination

Axonotmesis Axon, Myelin sheath Fair

disrupted, epineurium
intact

Neurotmesis Complete division Poor

 Peripheral Nerve Recovery

• Influenced by:
– Contact guidance (basal lamina Schwann cell)
– Neurotrophism (factors enhancing growth)
– Neurotropism (attraction to nerve tissue)
• EMG/ NCS helpful to determine extent of
injury and monitor recovery
 Peripheral Nerve Repair
• Younger patients better chance of recovery
• Line up fascicles in correct orientation to optimize
results
• Several methods available
– Direct Muscular Neurotization
– Epineural Repair
– Grouped Fascicular Repair
– Conduit Repair
– Nerve Grafting (Cable)
– Vascularized Nerve Repair
Connective Tissues

Tendons
Ligaments
 Tendons

• Dense, regularly arranged tissues that attach

muscle to bone
• Composed of fibroblasts arranged in
parallel
• Fibroblasts produce Type I collagen (85%)
• Composed of fascicles (collagen bundles)
• Fascicles separated by endotenon and
surrounded by epitenon
Tendon Histology
Tendon Fascicles & Epitenon
 Tendon Insertion into Bone

4 transitional tissues (for force dissipation)

– TendonFibrocartilageMineralized
Fibrocartilage (Sharpey’s)  Bone
 Question
• The order of tissue types seen at the site of direct
insertion of a tendon to bone is:

1. tendon, fibrocartilage, mineralized fibrocartilage,

bone.
2. tendon, mineralized fibrocartilage, fibrocartilage,
bone.
3. tendon, cartilage, fibrocartilage, bon.
4. tendon, cartilage, mineralized cartilage, bone.
5. tendon, fibrocartilage, cartilage, bone.
 Answer
• PREFERRED RESPONSE: 1

• DISCUSSION: Soft-tissue insertions to bone provide a

means of attaching a flexible yet strong, tension-bearing
structure into a rigid, noncompliant bone. Tendon and
ligament insertions to bone are adapted to force
dissipation. The composite material of the insertion
sites provides a gradual increase in stiffness from soft
tissue to bone, thus diminishing stress concentrations at
the interface. The progression is from tendon to
fibrocartilage to mineralized fibrocartilage to bone.
 Tendons

• Paratenon-covered Tendons (Achilles)

– Vascular tendons – rich capillary system
• Sheathed Tendons (Hand flexors)
– Mesotenon (vincula) carries a vessel that
supplies one segment of tendon
– Avascular areas receive nutrition via diffusion
from vascularized segments
• Paratenon tendons – better healing
Paratenon Vascularity
Sheathed Tendons
 Tendon Healing

• Healing initiated by fibroblasts and

macrophages
• Tendon Repair = weakest at 7 –10 days
• Maximum strength = 6 months
• Immobilization increases strength of tendon
repair but at expense of motion
 Ligaments

• Type I collagen (70%)

• Stabilize joints
• Similar structure to tendons, but fibers more
variable and higher elastin content
• Ligaments have uniform microvascularity
(from insertion site)
• Mechanoreceptors, nerve endings
 Ligament Insertion

• Ligament Insertion into Bone (2 types)

– Indirect Insertion (common)
• Superficial fibers insert at acute angles into
periosteum
 Ligament Insertion

Direct Insertion
• Superficial and deep fibers
• Deep fibers insert at 90 degree angles to bone
• LigamentFibrocartilageMineralized
Fibrocartilage Bone
 Ligament Healing

• Healing is improved with normal stress and

strain across joint
• Early ligament healing = Type III collagen
• Type III collagen later converted to Type I
• Immobilization decreases elastic modulus
 Ligament Injury

• Most common mechanism of failure is

rupture of sequential series of collagen fiber
bundles
• Midsubstance tears = adults
• Avulsion injuries = children
– Avulsion of ligaments occurs between
unmineralized and mineralized
fibrocartilage layers
 Test Questions

Neuromuscular and Connective

Tissues
 Healing after complete midsubstance
laceration of skeletal muscle in an adult is
characterized by:
• Hypertrophy of the distal muscle
• Dense connective scar tissue
• Complete functional recovery
• Denervation of the proximal muscle portion
• Proximal muscle atrophy
 What muscle action is defined by muscle
activation with simultaneous muscle
lengthening?

• Concentric
• Eccentric
• Isokinetic
• Isotonic
• Isometric
 Type I skeletal muscle fibers are
characterized by

• Fast speed of contraction

• Low strength of contraction
• Low aerobic capacity
• High anaerobic capacity
• Larger motor unit size
 In muscle anatomy, what characteristic is
seen in fast glycolytic (type IIb) fibers?

• Low strength
• High fatigue resistance
• High aerobic capacity
• High anaerobic capacity
• Small motor unit
To maximize the potential for functional recovery
of the cut nerve during surgical repair, it is of
utmost importance to

• Repair the intrinsic blood vessels

• Repair the internal layer of the perineurium
• repair the epineurium
• Properly align the nerve ends during repair
• Restore the blood-nerve barrier
A woman sustains a grade II partial tear of
the hamstring muscle during a sudden
stretch while sprinting. The tear usually
occurs at the
• Insertion of the muscle
• Origin of the muscle
• Myofibril
• Myotendinous junction
• Neuromuscular junction
Which of the following techniques most
efficiently strengthens skeletal muscle ?
• Isotonic
• Isometric
• Plyometric
• Eccentric
• Concentric
Microscopic examination of ligaments with direct
insertion into bone reveals what morphology
adjacent to the bony attachment ??
• A. Ligament
• B. Fibrocartilage
• C. Mineralized Fibrocartilage
• D. Periosteum
• E. Sharpey Fibers
Strength training at a constant velocity using
submaximal and maximal contraction
describes what type of training ?

• Isometric
• Isotonic
• Isokinetic
• Eccentric
• Proprioceptive neuromuscular facilitation
 Acknowledgements and Thanks

• Frank Frassica, M.D.

• Mark D. Miller, M.D.
• Mark R. Brinker, M.D.
• Robert B. Day, M.D.
• Richard Thomas, M.D
• Brian Leo, M.D.
 References

• AAOS – Orthopaedic Basic Science Text

(editors: Buckwalter, Einhorn, Simon)
• Miller’s Review of Orthopaedics, 4 th edition
• AAOS – OITE 2000, 2001, 2002, 2003,
2004, 2005, 2006; Self Assessment Exam
2000
Thank You!!!