2.02

Question 1

Define Osteoporosis

Risk factors

Answer 1

Imbalance of bone remodelling causing a decrease in bone mass and bone density, and a deterioration of bone microarchitecture. Affects areas of high trabecular bone the most, (spine, wrist, head of femur).
Risk factors - Age, female, menopause, genetics, low physical activity, smoking, alcohol, low Vit. D levels, low dietary Ca, drugs (e.g. corticosteroids), diseases (e.g. hyperthyroidism)

Question 2

Describe the concept and mechanism of osteoporosis

Answer 2

Osteoporosis occurs when the coupling of bone resorption and bone formation is disrupted.

Question 3

Role of hormones in the development and maintenance of bone mass

Answer 3

Vitamin D
• Ensures that enough blood Ca and PO4 is available
• Low Vit. D leads to increased PTH > low blood phosphate and calcium > impaired bone mineralization (rickets)
PTH
• Increases bone resorption
• Reduces bone density
• Increased by both low Vit. D or low Calcium
Sex Hormones:
• Maintains coupling between osteoblasts and osteoclasts, keeps bone cells alive, reduce bone turnover, mechanically strengthen bone

Question 4

Interaction between mechanical loading, calcium-regulating hormones and sex steroid hormones
in maintenance of bone mass

Answer 4

Mechanical Loading is needed to promote formation of bone. Causes bone to remodel in areas that experience stresses
Sex hormones maintain bone - test - causes remodelling, strengthening. Estrogen - balances bone turnover
Calcium-reg hormones - PTH, Vit D

Question 5

Bone loss due to glucocorticoid excess or sex steroid deficiency, smoking and alcohol

Answer 5

High concentration of GC (glutocorticoids) are CATABOLIC and associated with reduced bone mass/increased fracture risk. Via decreasing Ca absorption in gut, Ca loss in kidney, loss of osteoblasts.
Smoking can decrease blood supply to bone. Alcohol increases PTH

Question 6

Mechanisms of drugs treating osteoporosis

Answer 6

Bone resorption inhibitors
o Bisphosphonates → Kill osteoclasts on bone surface; inhibit bone remodelling (e.g. Risedronate, Alendronate, and Zoledronic Acid)
o RANKL-inhibitor
• Bone formation stimulators
o Calcium
o Vitamin D

Question 7

Anatomical organization of the vertebral column

Answer 7

Primary curvature in fetus and new born. Reflect in-utero shape of vertebral column, remain in thoracic and sacral regions
Secondary curvature develops in cervical and lumbar spines to bring trunk above lower limbs for efficient bipedal locomotion

Question 8

Issues with curvature

Answer 8

Kyphosis = Excess primary curvature 
Lordosis = Excess secondary curvature 
Scoliosis = Abnormal lateral Curvature of Spine

Question 9

Basic components of a typical vertebrae

Answer 9

Vertebral column protects spinal cord, support for head and neck, movement – multi segmental, articulated, plus attached muscles
Articular process – region of bone. Articular facet – region covered with cartilage
Vertebral foramen – opening in single bone. Vertebral canal – passageway where all articulated together. Intervertebral foramen – foramen between articulated vertebrae

Question 10

Features of C1, C2, C7, thoracic and lumbar vertebrae

Answer 10

C1 Atlas, ring of bone, no vertebral body, no spinous process, large lateral masses
C2 Axis, Dens, large superior articular facets
C7 Vertebra prominins, long spinous process
Thoracic vertebrae, demifacets on lateral sides of body for rib attachments, long downward projecting spinous process
Lumbar vertebrae - large body

Question 11

Function of intervertebral discs

Answer 11

25% of intervertebral column, it is a secondary cartilaginous joint and functions to tie vertebral bodies together, tansfer weight, allow movement, shock absorber

Question 12

Parts of intervertebral disks

Answer 12

Annulus Fibrosus → Fibrous outer ring; comprised of collagen
Vertebral Endplate → Cartilage plates adjacent to vertebral bodies
Nucleus Pulposus → Semifluid shock absorber in center

Question 13

Location and general function of ligaments

Answer 13

Ligamentum flavum → Between lamina, behind vertebral canal - to maintain upright posture Interspinous ligament → Between spinous processes - to limit flexion (bending forwards) through restricting separation of the spinous processes of the vertebral column.
Supraspinous ligament → Between tips of spinous processes - helps maintain the upright position of the head
Posterior longitudinal lig. → Run along posterior sides of vertebral bodies and disks - Limits flexion of the vertebral column and reinforces the intervertebral disc
Anterior longitudinal lig. → Run along anterior sides of vertebral bodies and disks

Question 14

Extrinsic back muscles

Answer 14

Move the upper limbs and ribs, supplied by anterior rami, except trapezius CNXI, lie most superficial on the back

Question 15

Intrinsic back muscles

Answer 15

Located posterior to vertebral column, move the back and head, supplied by posterior rami

Question 16

Intrinsic cont. Splenius, erector spinae, transversospinalis

Answer 16

Splenius group (Superficial) - extension, rotate to same side 
Erector spinae group (Middle) - straighten the back and provide for side-to-side rotation 
Transversospinalis group (Deepest) - rotate vertebral column to opposite side

Question 17

Neural structures and meninges in the vertebral column

Answer 17

• Nerve roots join to form spinal nerve. Posterior roots (sensory fibers) and anterior roots (motor fibers).
  Segments of spinal column - 7 Cervical, 12 Thoracic, 5 Lumbar, 5 pelvic sacral (fused), <5 coccygeal (fused)
• Spinal nerves exit from intervertebral foramen
• Meninges: Pia mater – adherent to spinal cord and nerve roots, Arachnoid mater, Dura mater

Question 18

Define dermatome and myotome

Answer 18

Dermatome – Area of skin innervated by sensory fibers from a single spinal nerve

Myotome – Area of muscle innervated by motor fibers from a single spinal nerve

Question 19

Spinal plexus

Answer 19

Spinal Plexus: 
C1 – C5 = Cervical Plexus 
C5 – T1 = Brachial Plexus 
L1 – L4 = Lumbar Plexus 
L4 – S4 = Sacral plexus

Question 20

Anterior and posterior rami

Answer 20

Posterior rami – supply skin of back, zygaopophyseal joints and intrinsic back muscles
Anterior rami – supply skin, joints and muscles of neck, limbs and trunk, larger than posterior rami, contribute to plexuses or continue as intercostal or subcostal nerves (T12)

Question 21

Impacts of rise and fall of calcium

Answer 21

A drop in calcium – partial depolarization, channels open to sodium, tetanus and even seizures

Too much calcium – partially closes the channels, reduced ability to depolarize, cannot elicit action potentials, neurological dysfunction, cardiac arrythmia, dehydration, long term: kidney calcification and stones

Question 22

Impacts of changes in phosphate levels

Answer 22

High phosphate long term – soft tissue mineral deposition, short term – inadequate bone mineralization – osteoid produced (not fully mineralized – causes Rickets/osteomalacia)

Question 23

PTH - Source, function and regulation

Answer 23

Parathyroid gland has lots of calcium sensing receptors, which detect increases/decreases in body’s calcium levels, increases Ca release from bone
Released by low calcium via calcium sensing receptor (main modulator)
Decreased by calcitriol and by high calcium in circulation

Question 24

Sources and metabolism of vitamin D, its regulation and actions

Answer 24

Main source of vitamin D is UVA radiation. Vitamin D is a fatty hormone, UVA radiation opens carbon rings and helps create vitamin D
Regulated by PTH
Action - facilitate intestinal absorption of calcium as well as helping form hydroxyapatite

Question 25

Calcitonin function

Answer 25

Minor role – Non-essential
Inhibits Osteoclast activity
Released in high Ca and gut hormones
Calcitonin is a hormone that is produced in humans by the parafollicular cells (commonly known as C-cells) of the thyroid gland

Question 26

FGF23

Answer 26

FGF23 produced by osteocytes and rare benign tumors sometimes
Causes dumping of phosphate from kidney, produced when too much phosphate
Reduces enzymes that add hydroxyl groups to vitamin D and increases its breakdown
Calcitriol, PTH and high phosphate stimulate osteocytes to produce FGF23
Excess FGF23 -> low phosphate, low calcitriol, osteomalacia

Question 27

Excess or deficiency of parathyroid hormone, vitamin D and FGF23

Answer 27

PTH excess - high blood calcium, PTH deficiency - low blood calcium
High FGF23 - low blood phosphate
Mild vit D - increase in PTH
Low vit D - cannot resorb bone, not enough Ca and PO to mineralize bones > osteomalacia and rickets