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Orthopaedics > Bone Metabolism > Flashcards

Bone Metabolism Flashcards

1
Q

Which type of bone is affected worse by diseases with increased bone turnover.

A

Trabecular bone

  • because it has a greater surface area than cortical bone
  • remodelled more rapidly
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2
Q

How much of the skeleton is cortical and how much is trabecular?

A

Cortical - 80%

Trabecular - 20%

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3
Q

What is the function of non-collagenous bone proteins?

A

Involved in the attachment of bone cells to bone matrix

Regulates bone cell activity during the process of bone remodelling

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4
Q

Name and describe the function of the cells involved in the process of bone remodelling.

A

1) Osteoblasts
- bone forming cells
- line the bone surface and synthesise osteoid
- becomes an osteocyte when is has synthesised the bone
2) Osteocytes
- embedded in the bone matrix, each with their own lacuna
- act as sensors of mechanical strain on the skeleton and release signalling molecules such as prostaglandins which modulate the activity of adjacent cells
3) Osteoclasts
- involved in bone resorption and bone remodelling

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5
Q

Describe the bone remodelling cycle.

A

Quiescence
- 90% of bone surfaces in the adult skeleton
Resorption
- 10-14 days
- osteoclast recruitment, differentiation and activation
Reversal
- osteoclasts apoptose and are removed
- osteoclast recruitment, differentiation and activation
Formation
- matrix synthesis and mineralisation
- 150 days

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6
Q

Which systemic hormones stimulate bone remodelling?

A 
PTH
1,25 DHHC
PTH-related protein
Growth hormone
Thyroid hormone
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7
Q

Which locally acting factors stimulate bone remodelling?

A 
IL-1
TNF
Insulin-like growth factor
IL-6
Prostaglandins 
Macrophages-colony stimulating factors
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8
Q

Which systemic hormones inhibit bone remodelling?

A

Oestrogens
Androgens
Progesterone
Calcitonin

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9
Q

Which locally acting factors inhibit bone remodelling?

A

Osteoprotegerin
IF-gamma
IL-4, 10, 13 and 18
Transforming growth factor beta

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10
Q

How does oestrogen deficiency affect postmenopausal bone loss?

A

Causes high bone resorption (bone loss)

  • increases extracellular calcium
  • consequently suppresses renal calcium reabsorption and gut calcium absorption by decreasing PTH and calcitrol
  • this again increases bone resorption and causes osteoporosis
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11
Q

What is the definition of osteoporosis?

A

Skeletal disorder characterised by compromised bone strength predisposing a person to increased risk of a fracture
Bone strength reflects the integrity of the bone density and bone quality

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12
Q

Describe the structure of trabeculae in osteoporosis.

A

Trabecular continuity is disrupted by trabecular perforation
Thin rods replace the normal plate-like trabeculae

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13
Q

Describe the structure of the cortical bone in osteoporosis.

A

Becomes thinner and more porous

Patchy differences in mineralisation

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14
Q

Describe the role of RANK ligand in osteoclast formation, function and survival.

A

Active in the absence of macrophage colony-stimulating factor
RANKL is released from osteoblast lineage cells.
This them binds to its receptor (RANK), found on immature and mature osteoclasts
- leads to maturation of prefusion osteoclasts to multinucleated osteoclasts and finally to activated osteoclasts
So basically RANKL allows osteoclast activation

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15
Q

How are osteoblasts stimulated to produce RANK ligands?

A

PTH
TNF
IL-1
Vitamin D

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16
Q

How is osteoclast activation inhibited?

A

The body produces a protein called OPG to defend against bone loss
- a member of the TNF receptor family
This binds to RANKL, so they cant bind to RANK on the immature osteoclasts

17
Q

How does increased bone loss occur in post-menopausal women?

A

Decreased oestrogen stimulates the osteoblasts to increase RANKL production
This increases the number of activated osteoclasts, and bone resorption increases

18
Q

What are the most common fractures seen in people with osteoporosis?

A 
Colles' fracture
Femoral neck fracture 
Compression fracture of vertebrae
Subcapital fracture of the hip
Fracture of proximal humerus (may be displaced)
19
Q

Why do hip fracture increase with age, while wrist fractures level out?

A

As people get older the are less likely to reach out in front of them when they fall
They are also more likely to fall backwards or sideways and land on their hip
- due to decreasing balance or a neuromuscular condition

20
Q

Name some risk factors for osteoporotic fractures.

A 
Being over the age of 65
Vertebral compression fracture 
Family history
Systemic glucocorticoid therapy 
Malabsorption syndrome
Primary hyperparathyroidism 
RA
Smoker
Alcohol
Caffeine 
Weighing less than 57kg
21
Q

Name some of the complications of an osteoporotic fracture.

A 
Pain
Deformity
Disability 
Physical deconditioning caused by inactivity 
Changes in self image
22
Q

What are the four determinants of fracture risk?

A 
Bone strength
Likelihood of falling
- and fall conditions 
Age
Previous history of fractures
23
Q

What is a T-score?

A

The number of SD above or below the mean for a healthy adult population of the same sex and ethnicity of the patient
- based on bone mineral density

24
Q

What T-scores indicate a metabolic bone direase?

A

Normal is -1 and above
Osteopenia is between -1 and -2.5
Osteoporosis is below -2.5
Established osteoporosis is below -2.5 and with a fracture

25
Q

What is DXA?

A

A estimation of bone strength by finding out the bone mineral density with a dual-energy X-Ray absorptiometry

26
Q

What lifestyle changes could prevent osteoporosis and associated fractures?

A

Dietary calcium and vitamin D supplements
Weight bearing and muscle strengthening exercise
Smoking cessation
Alcohol reducation

27
Q

What lifestyle changes could minimise risk of falling?

A 
Avoid drugs with sedative effects
Treat any sensory deficits 
Treat neurologic and rheumatologic conditions that contribute to falls
Gait and balance training 
Occupational therapy 
- anchor rugs
- non-skid mats
- improved lighting
- handrails
- hip protector
28
Q

Which women should be considered for osteoporotic therapy?

A

Low BMD or presence of osteoporotic fracture
Borderline BMD and additional risk factors
When non-pharmalogical measures haven’t worked

29
Q

What are the pros and cons of oestrogen and progesterone in osteoporosis treatment?

A

Pros
- increases BMD
- reduces fracture risk (predominantly non-osteoporotic)
Cons
- no benefit in women who are high risk of fracture
- breast cancer

30
Q

Describe the mode of action of SERMs

A

Acts like oestrogens
All SERMS bind to an oestrogen receptor
Each SERM binds to the receptor and causes a different conformational change that permits spontaneous dimerisation
- allows it to interact with oestrogen response elements which are located within target genes
This leads to binding of various coregulator proteins

31
Q

Name a SERM.

A

Raloxifene

32
Q

What is the function of bisphosphonates?

A

They have an ability to bind strongly to the surface of bone where there is active remodelling of bone
- nitrogen containing ones decrease osteoclast activity by inhibiting enzymes in the 3-hydroxy-3-methyglutaryl coenzyme A pathway
- non-nitrogen containing ones increase osteoclast death by producing cytotoxic analgoues of ATP
These decrease bone remodelling

33
Q

What are the used treatments for osteoporosis?

A 
SERMS
Bisphosphonates 
Vitamin D and calcium supplements 
Teriparatide 
Denosumab
34
Q

On which part of the skeleton does cyclical etidronate work best to reduce fracture risk?

A

Vertebrae

35
Q

Name some bisphosphonates.

A

Cyclical etidronate
- not effective in non-vertebral fractures
Alendronate
Risedronate
- only effective when related to BMD risk factors
Ibandronate
- doesn’t help non-vertebral fracture risk
Zolecdonic acid

36
Q

What is teriparatide?

A

A recombinant form of PTH

  • intermittent exposure to PTH activates osteoclasts more than osteoblasts
  • doesn’t help hip fractures
37
Q

Describe the mechanism of action of Denosumab.

A

A fully monolconal antibody that specifically targets RANK ligand

  • RANK ligand inhibitor
  • prevents osteoclast formation, function and survival
38
Q

How do you know is treatment is working?

A

Fewer fractures
Bone density (DXA) measurement
Use of bone markers

Orthopaedics (13 decks)

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