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Medicine Year 1 - Semester 2 - Part 2 > Osteoporosis > Flashcards

Osteoporosis Flashcards

1
Q

Function of osteoprogenitor cells

A

Stem cell population, gives rise to osteoblasts

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2
Q

Function of osteoblasts

A

Responsible for bone formation, cover the surface of bone

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3
Q

What are osteocytes ?

A

Mature bone cells - embedded in lacunae and are relatively inactive.

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4
Q

Function of osteocytes

A

Maintain bone matrix through cell-cell communication and influence bone remodelling.

Mechanosensing

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5
Q

What are osteoclasts ?

A

Multi-nucleated, derived from haematopoetic cells.

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6
Q

Function of osteoclasts

A

In response to mechanical stresses and physiological demands, they resorb bone matrix by demineralisation.

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7
Q

Age 0-25

A

Bone gain

Resorption < Formation

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8
Q

Age 25-35

A

Bone Mass Stable

Resorption = Formation

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9
Q

Age >35

A

Bone Loss

Resorption > Formation

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10
Q

What is bone mass related to ?

A

Age

Biological Sex
(female - bone loss due to menopause)

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11
Q

Describe bone loss due to menopause

A

Hormonal changes associated with menopause.

Increased activity of osteoclasts

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12
Q

Who does osteoporosis affect ?

A

~ 3 million people in the UK

1 in 3 women
(predominantly due to menopausal shift & regulation of osteoblasts activity)

1 in 12 men
(due to progressive decline in function)

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13
Q

Causes of osteoporosis

A

Decreased size of osteons

Thinning of trabeculae

Enlargement of Haversian and marrow spaces

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14
Q

State the classifications of osteoporosis

A

Type 1 - post menopausal
Type 2 - age related in those over 75

Disuse osteoporosis

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15
Q

Describe Type 1- Post menopausal osteoporosis

A

Affects mainly cancellous (trabecular) bone

Vertebral and distal radius fracture is common

Related to loss of oestrogen

F:M= 6:1

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16
Q

What is Type 1 - post menopausal osteoporosis related to ?

A

Loss of oestrogen

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17
Q

What does Type 1 - post menopausal osteoporosis affect ?

A

Affects mainly cancellous (trabecular) bone

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18
Q

Describe Type 2- Age related in those over 75

A

Affects cancellous and cortical bone

Is related to poor calcium absorption

Hip and Pelvic fractures common

F:M= 2:1

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19
Q

What is Type 2 - age related osteoporosis in those over 75 related to ?

A

Poor calcium absorption

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20
Q

What does Type 2 - age related osteoporosis in those over 75 affect ?

A

Affects cancellous and cortical bone

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21
Q

Describe disuse osteoporosis

A

Conditions resulting in prolonged immobilisation, typically in neurological or muscle disease.

‘Don’t use it, you lose it’

  • e.g. living outside the effects of gravity
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22
Q

Clinical consequences of osteoporosis

A

Increase in bone fragility

Susceptibility to fracture: micro- or fragility fracture

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23
Q

Fragility fracture

A

“Low energy” trauma

Mechanical forces that would not ordinarily cause fracture

WHO: fall from a standing height or less, that results in a fracture

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24
Q

Number of fragility fractures per year

A

Est. 500,000 present at hospital with FF

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25
Cost of fragility fractures to the NHS
> £4.4 billion
26
Hip Fracture (due to fragility) statistics
Fatal in 20-30% of cases Only 30% fully recover Permanently disables 50%
27
Who is at risk of fragility fractures ?
Increased risk from > 45 years old Women more likely than men
28
Common sites for osteoporotic fractures
Proximal humerus Distal radius Spine Femoral neck Vertebral body
29
Non-modifiable risk factors for osteoporosis
Biological sex Age Previous fracture Family history Race Early menopause (<45 year old)
30
Modifiable risk factors for osteoporosis
Smoking Alcohol Inactivity Low calcium Low BMI Oestrogen deficiency Vitamin D deficiency
31
State some factors contributing to osteoporotic fracture risk
Bone strength (Material properties) Postural reflexes Soft padding tissue Falls
32
What is bone remodelling affected by ?
Exercise and Lifestyle Nutrition Hormones
33
Race and Ethnicity - osteoporosis
Prevalence ~50% lower in black Americans than white Rates of fragility fractures in the UK 4.7x greater in white compared to black women
34
Chinese women and BMD
Chinese women have lower BMD, but lower rates of hip and spine fractures.
35
GAHT
Gender-Affirming Hormone Replacement Therapy
36
BMD
Bone Mineral Density
37
Transgender patients and Osteoporosis
Adherence to GAHT may protect BMD of both trans women and trans men.
38
Trans women and BMD
Trans women tend to have lower BMD prior to initiation of GAHT. - Lower BMD as they are not likely to have been drinking, involved in high impact sports etc.
39
Impact of puberty blockers on BMD
Currently unclear what impact puberty blockers have on bone mass and fracture risk.
40
Lifestyle and Nutritional factors affecting osteoporosis
Smoking Excess Alcohol Sedentary - inactive lifestyle Prolonged Immobilisation
41
State some conditions / diseases that influence osteoporosis
Diabetes Inflammatory bowel disease Inflammatory Rheumatic diseases Chronic liver disease HIV Asthma Endocrine diseases
42
State the common factor of coexisting conditions to osteoporosis
Inflammatory link - formation of osteoclasts come from haematopoetic cells Hormonal link Absorption and Ability to process and utilise things from the diet Neurological links
43
State some drugs that increase the chances of osteoporosis
Long term antidepressants Antiepileptics Aromatase inhibitors Oral glucocorticoids
44
Aromatase inhibtors use
Breast cancer
45
Oral glucocorticoids use
Inflammatory/Immune conditions
46
Proton pump inhibitors use
Decrease stomach acid
47
Gonadotrophin releasing hormone agonists use
Prostate cancer
48
Long-term medroxyprogesterone acetate (DMPA)
Injectable contraceptive
49
Thiazolidinediones
Diabetes
50
Risk of another fracture after a previous fragility fracture
A previous wrist fracture: - doubles risk of future hip fracture - triples risk of future vertebral fracture
51
Assessing patients risk of osteoporosis
FRAX WHO- fracture risk assessment test
52
DEXA
Dual-energy x-ray absorptiometry scan
53
Describe DEXA
Low dose x-rays with 2 distinct energy peaks (one absorbed by soft tissue, and the other by bone) Subtracting one from the other gives a patients bone mineral density.
54
How to calculate BMD ?
DEXA scan
55
T score
Comparison with a young adult of the same sex with peak bone mass
56
Normal T score
T score: >-1
57
Osteopenia
Bone thinning T score: -1 to -2.5
58
Osteoporosis
T score < -2.5
59
Z score
Comparison of the patient's BMD with data from same age/sex/size.
60
Investigations for osteoporosis
DEXA score Bone turnover markers Ruling out other things: - thyroid function tests - testosterone and gonadotropin leves in men
61
Bone turnover markers
Urine and/or blood tests, infrequently used but may provide some useful information on treatment success.
62
Bone turnover markers for: - Formation - Resorption
Formation - bone alkaline phosphatase - increased levels, increased formation Resorption - cross linked C-telopeptide of type 1 collagen (CTX) - increased levels, increased resorption
63
CTX
Fragments of collagen caused by osteoclasts dissolving the bone matrix Increased abundance indicates increased osteoclast activity
64
Main agents in the pharmacological treatment of osteoporosis
Bisphosphonates Denosumab Romosozumab Teriparatide
65
Bisphosphonates
Alendronate Risedronate Zolendronic acid
66
Denosumab
Monoclonal antibody against RANKL
67
Romosozumab
Monoclonal Antibody against SOT
68
Teriparatide
Peptide fragment of parathyroid hormone (PTH)
69
Function of bisphosphonates
Anti-resorptive: disrupts the activity of osteoclasts
70
Function of denosumab
Anti-resorptive: disrupts the formation and lifespan of osteoclasts
71
Function of romosozumab
Anti-resorptive and anabolic : disrupts osteoclasts, promotes osteoblasts
72
Function of teriparatide
Anabolic: promotes osteoblasts
73
Side effects of bisphosphonates
GI upset, oesophagitis, mandibular necrosis, uveitis, atypical femur fractures
74
Side effects of denosumab
Hypocalcaemia, Mandibular necrosis and Rebound resorption
75
Side effects of romosozumab
Hypocalcaemia, Mandibular necrosis and Rebound resorption
76
Side effects of teriparatide
Nausea, Headache, Dizziness, Leg Cramps, Hypercalcaemia
77
Describe the mechanism of action of bisphosphonates
Bisphosphonates - inhibit the function of osteoclasts BY: - promoting cell death in osteoclasts - inhibit the pathways that allow survival of osteoclasts - prevent resorption that is mediated by osteoclasts , disrupting their function even before they die - inhibit the formation of osteoclast precursors
78
Function of PTH
PTH (parathyroid hormone) which is naturally found in the body and regulates normal bone function
79
Describe the mechanism of action of teriparatide
Teriparatide is a fragment of PTH. If given infrequently, it promotes osteoblasts activity. It binds to receptors on precursors for osteoblasts, and promotes them to mature into osteoblasts and put down more bone.
80
How should teriparatide be given ?
Infrequently To increases osteoblast activity.
81
What happens if you give teriparatide to a patient constantly what happens ?
High levels of PTH for a long period of time inhibits osteoblasts function and increases osteoclasts function.
82
Describe the mechanism of action of denosumab
Denosumab is a RANK ligand inhibitor - inhibits osteoclasts formation and activity - doesn't affect osteoblasts, maintains osteoblast function
83
SOST
Released from osteocytes and is a mediator of communication between osteocytes.
84
Function of SOST
SOST is released from osteocytes to the surface of bone and it: - negatively regulates osteoblasts, prevents bone formation. - positively regulates osteoclasts, accelerates resorption
85
Describe the mechanism of action of romosozumab
Increases osteoblast activity Decreases osteoclast activity Interacts with SOST - blocks SOST
86
State some other pharmacological options in the treatment of osteoporosis
Strontium ranelate Selective estrogen receptor modulators (SERMS - raloxifene) Ca2+ supplements Hormone replacement therapy - reduced risk of osteoporosis - increased risk of breast cancer
87
Non-pharmacological interventions for osteoporosis
Exercise Nutrition Vitamin D and calcium intake Reduced alcohol / cigarettes
88
Exercise
Weight bearing exercise with 'impact' - jumping - skipping Muscle strengthening exercise
89
Nutrition
Not just calcium and vitamin D, needs a balanced and healthy diet
90
Vitamin D and calcium intake
Sunlight, food, supplements (esp. during pandemic)

Medicine Year 1 - Semester 2 - Part 2 (53 decks)

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