WEEK 4 - MINI LECTURES - OSTEOPOROSIS Flashcards Preview

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Flashcards in WEEK 4 - MINI LECTURES - OSTEOPOROSIS Deck (58)
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1
Q

What are the short terms of decrease calcium in extracellular fluid

A
  • increase Na+ permeability of cells

- leads to partial depolarisation which in turn leads to muscle spasm tetany and pins and needles and seizures

2
Q

What are the short term effects of increase calcium concentration in ECF

A
  • decrease Na+ permeability of cells
  • hyperpolariation -> neurolgical dysfunciton, cardiac arrythmias, constipation, anorexia, nausea -> dehydration
  • long term effects induce diuresis -> Dehydration
3
Q

Normal range of serum inorganic phosphate

A

0.8-1.4 mmol/L

4
Q

High PO4 in the long term

A

Soft tiussue mineral deposition

5
Q

Low PO4 in the long term

A

Inadequate bone mineralisation

6
Q

Three systems involved in calcium homeostasis

A
  • gut
  • kidney
  • bone
7
Q

Role of bone in caclium homeostasis (2)

A
  • structural requirement for hydroxyapaetite laying -> gives comrpessive strength
  • alternative store: release in blood to make up for daily losses
8
Q

Parathyroid hormone

A
  • Peptide
  • released from parathyroid glands
    Can be synthesized by Vit D precursor
9
Q

What triggers the release of PTH

A
  • low Ca2+ via calcium sensing receptor
10
Q

What inhibits the release of PTH

A
  • calcitriol

- high Ca2+

11
Q

Sources of Vit D

A
  • sun exposure is the main source
  • Diet as a minor source: fatty fish, meat, liver, eggs, fortified food
  • supplements: 1000 daily
12
Q

Vitamin D metabolism

A

7 dehydrocholesterol -> Vit D -> 25(OH) vit D -> 1.25(OH)2D (= calcitriol)

  • the last conversion is promoted by PTH, low Ca 2+, low PO43-, growth and pregnancy mainly by kidney and other tissues
13
Q

Groups at high risk of Vit D deficiency

A
  • old people in hospital or care
  • dark skinned people
  • infants of motherswith low vit D are at risk of rickets
  • ## chronically ill individuals
14
Q

FGF 23

A
  • produced predominantly in bone by osteocytes
  • also produced by rare tumours
  • acts predominantly in kidneys: increase phosphate wasting, decrease calcitriol production and increase calcitriol degradation
15
Q

FGF23 production is stimulated by

A
  • calcitriol
  • PTH
  • high phosphate
16
Q

Calcitonin

A
  • inhibits bone resorption
  • peptide
  • produced by parafollicular cells
17
Q

What promotes the release of calcitonin

A
  • gastric hormones
  • pentagastrin
  • increase Ca2+
18
Q

Gut: role in mineral homeostasis

A
  • ingestes calcium and phosphate
  • absorb Ca2+ passively or actively ( when stimulated by calcitriol)
  • main function of calcitriol is to acquire Ca 2+ and PO4 from food for bone mineral
  • Vit D role: acquire calcium and phosphate from food
19
Q

Bone: role in mineral homeostasois

A
  • calcium and phosphate required for bone mineral and compressive strength
  • acts as a store of cacium and phosphate in bone turnover
20
Q

Short term release of calcium from bone

A
  • increased by PTH and calcitriol

- inhibition of release by calcitonin

21
Q

Kidney: role in mineral homeostasis

A
  • modulate Ca 2+ and PO4 losses
  • calcium filtration and reabsorption by PTH
  • filter PO4 and reabsorb
  • PTH: reduces PO4 reapsorption and causes dumping of PO4 in urine
  • PTH also increases calcitriol production
22
Q

Summary: 2 role of gut

A
  • increase Ca 2+ abosrption
  • increase PO4 absorption
  • both of these effects are induced by calcitriol
23
Q

SUMMARY: kidney role

A
  • low blood calcium -> increase PTH
  • PTH Acts on kidney
  • increase calcitriol
  • conserve Ca 2+
  • dump PO4 in urine
24
Q

Bone SUMMARY

A
  • PTH increases resorption
  • stimulates release of Ca2+
  • stimulates release of PO4
25
Q

Low blood phosphate mechanism

A
  • sensed directly by kidney -> increase calcitriol production
  • calcitriol acts on gut to increase PO4 absorption and on bone to increase resorption
  • calcitriol also modulates PO4 losses in kidney
26
Q

Affect of changes in hormones

  • high PTH
  • Low PTH
  • High FGF23
  • mild- mod low vitD
  • severe low Vit D
A
  • hypercalcemia
  • hypocalcemia
  • hypophosphatemia (RARE)
  • increase in PTH which maintains blood ca for some time at the expense of bone resorption
  • cant resorb bone anymore -> osteomalacia and rickets
27
Q

Bone mass determinants

A
  • genetics
  • age
  • mechanical loading
  • mineral balance: vit D, PTH, Sex steroids
  • balance between rate of bone resorption and rate of bone formation
28
Q

Contributors to fracture risk

A
  • bone mass (density)
  • measured usually with DEXA
  • T-score: bone mineral density less than 2.5SF below young normal mean - osteoporosis
  • bone quality
    Bone gometry
  • propensity to fall
  • loss of horizontal struts
29
Q

Minimum requirements for bone health

A
  • adequate exercise
  • adequate calcium intake
  • adequate vit D
  • normal sex steroids
  • avoid smoking, excess alcohol, glucocoricoids
30
Q

Adequate exercise

A
  • mechanical loading -> resistance to deformity
  • large changes at low activity levels
  • gravity, weight bearing exercises
31
Q

Regulation of bone mass by osteocytes and sclerostin

A
  • osteocytes is 90% of bone cells
  • secrete sclerostin - negative regulator of bone mass
  • with deformity of bone - sclerostin secretion decreases
32
Q

Wnt pathway in bone

A
  • Wnt 3b secreted by bone cells
  • when binds to receptor, inhibits GSK3b -> b catenin is freed from complex APC -> goes to nucleus -> acts on TF to stimulate bone cell and proliferation
  • Wnt Signalling inhibited by Sclerostin -> b catenin is targetted for defradation
33
Q

Adequate Vit D

A
  • needed to absorb clacium from diet, to mineralize bone and for normal muscle function
  • D3: cholecalciferol - animal sources
  • D2: ergocaciferol: plant sources
34
Q

Mild-moderate deficiency in Vit D

A
  • increased. PTH
  • increased bone resorption, decreae bone density
  • impaired muscle function and increased risk of falls and fracture
35
Q

Severe deficiency in but D

A
  • gut calcium absorption impaired
  • a lot of increase in PTH
  • bone resorption impaired, no capacity to increase gut calcium or phosphate absorption
  • phosphate loss in urine
  • insufficient calcium and phosphare -> impaired bone mineralisation -> rickets and osteomalacia, impaired muscle function
36
Q

Intermittent PTH stimulates bone formation

A
  • main effect is on osteoblasts
  • anabolic effect on bone
  • unclear why, but suppresses sclerostin and stimulation of Wnt pathway
37
Q

Sex steroids: estrogens, androgens

A
  • help to maintain normal balance between bone formation and resorption
  • help to keep bone cells alive
  • estrogen are probably important in men as well
  • androgens give men bigger, more mechanically strong bones
38
Q

Actions of estrogens in bone

A
  • reduce osteoclast generation and lifespan
  • reduces rates of bone turnover
  • promote coupling
  • some evidence of increase formation
  • keep osteoblasts and osteocytes alive longer
39
Q

Glucocorticoids effects

A
  • decrease calcium absorption in gut
  • increase calcium loss in kidney
  • decrease osteoblast and osteocyte viability in bone
40
Q

Non modifiable risk factor for fracture

A
  • advanced age
  • female gender
  • prevalent fractrures
  • bad genes
  • early menopause
  • past comorbidity
  • disability
41
Q

Most important risk factor for fracture

A
  • previous fractures
42
Q

Modifiable risk factors for fracture

A
  • life style and nutrition
  • low bone mass
  • high bone turnover
  • high fall propensity
  • treatable comorbidities
  • bone adverse medicatin
43
Q

T score

A
  • comapred to mean peak bone mass

- used to assess fracture risk

44
Q

Z score

A
  • compared to age and gender matched congtrols

- used to assess what is expected

45
Q

When is a bone density scan recomeded?

A
  • in any person with a minimal trauma fracture

- in any person with significant risk factors for bone loss without a fracrture

46
Q

Clinical examination of osteoporosis:

A
  • early stages are asymptomatic
  • late stages: complication and fracture
  • severe acute or chronic back pain
  • loss of height, stooped posture
  • cardiovascular and respiratory complications
47
Q

Thoracolumbar spine examination

A
  • change in posture, height loss
  • thoracic kyphosis
  • abdominal distension
  • lower ribs to pelvis distance
  • para-spinal skin folds
  • localised tenderness
  • spinal mobility
48
Q

Balance and risk of falling

A
  • neuro-muscular examination
  • sarcopenia, proprioception
  • time-up-and-go
  • gait and tandem speed
  • visual acuity
  • mini mental state
49
Q

Laboratory investigations to exclude secondary causes

A
  • ESR: exclude muyeloma
  • C,P, M: look for problems with homeostasis metabolism
  • Creatinine for renal function
  • 25OH Vit D
  • TFT
  • urine: calcium, phosphate, creatinine
50
Q

Management strategy

A
  • analgesia -> physiotherapy -> life style changes -> Fall prevention -> calcium balance -> Vit D sufficiency -> pharmacotherapy
51
Q

Non pharmaological management

A
  • weight bearing exercise programs improve muscle strength, mobility, balance, bone density, future fracture risk
52
Q

Calcium supplement effect

A
  • decrease PTH secretion

- decrease bone resorption

53
Q

Calcium and Vit D supplement and fracture risk

A
  • each individually has no effect on fracture risk

- in combination can decrease fracture risk by 12%

54
Q

Pharmacotherapy: Inhibitors of bone resorption

A
  • SERM
  • Biphosphonates
  • Strontium Ranelate
  • RANKL inhibitors
55
Q

Specific pharmacotherapy: Stimulators of bone formation

A
  • PTH
56
Q

Effect of oral biphosphonates on incidence of vertebral fracture risk

A
  • risk reduction of 50-60% for vertebral fractures

- 20-40% for non vertebral fractures

57
Q

Persistence with oral anti-osteoporosis treatment is generally poor

A
  • 50% after 1 year
  • 40% after 2 years
  • 20-35% after 5 years
  • if miss half of the dose, its the same thing as not taking it
  • solution is a non oral treatment
58
Q

The true problem: we dont treat patients with osteoporosis

A
  • 70% of patients who have suffered an osteoporotic fracture go untreated
  • 30-50% of these patients fracture again, usually within 3-5 years: domino effect
  • all osteoporotic fractures are associated with increased morbidity and excess mortality