T3 - L4 Diseases of the bone and new markers Flashcards

1
Q

What is the purpose of bone?

A
  • structural support for the body
  • protection of vital organs
  • blood cell production (bone marrow)
  • storage bank for minerals (especially calcium)
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2
Q

What is cortical bone and trabecular bone?

A

Cortical bone = hard, outer layer

Trabecular bone = spongy, inner layer

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3
Q

What 2 types of cells are associated with bone?

A

Bone forming cells (osteoblasts)

bone reabsorbing cells (osteoclasts)

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4
Q

What is the extracellular component of bone composed of?

A
  • organic matrix = mainly type 1 collagen

- inorganic components; hydroxyapatite and minerals

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5
Q

What is the name for bone before it has mineralised?

A

Osteoid

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6
Q

Bone matrix is mineralised by what? (to form mature bone tissue)

A

Hydroxyapatite (calcium-phosphate-hydroxide salt)

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7
Q

what do osteoblasts do?

A
  • make osteoid
  • communicate with other bone cells
  • make hormones (e.g. osteocalcin), matrix proteins and alkaline phosphatase
  • Prerequisite for mineralisation
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8
Q

what are features of osteoclasts?

A
  • large surface area
  • multi nucleated
  • ruffled-resorption border
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9
Q

Describe some features of bone as a dynamic tissue

A
  • extracellular matrix
  • protein and mineral
  • mainly collagen
  • constant remodelling
  • highly vascular tissue
  • metabolically active
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10
Q

What does collagen do?

A

Provides tensile strength

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11
Q

What are osteoblasts?

A

Terminally differentiated products of mesenchymal stem cells that make osteoid

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12
Q

What is osteoid?

A

Non-mineralised organic matrix, consists of mainly type 1 collagen
- prerequisite for mineralisation

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13
Q

What is the name for osteoblasts that are buried/trapped within the matrix?

A

Osteocytes

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14
Q

Where are osteoclasts found?

A

In bone pits (resorption bays)

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15
Q

What do osteoclasts do?

A
  • break down bone
  • produce enzymes that are secreted to break down extracellular matrix
  • help enhance blood calcium levels
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16
Q

Which enzymes do osteoclasts produce? (secreted to break down extracellular matrix)

A

Tartrate resistant acid phosphatase (TRAP)

Cathepsin K

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17
Q

Which hormones are osteoclasts regulated by?

A

PTH
calcitonin
IL-6

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18
Q

RANK ligand and osteoprotegrin do what?

A

Help with osteoclastic maturation and activity

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19
Q

What are osteocytes?

A

Trapped/buried osteoblasts

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20
Q

Describe the appearance of osteocytes

A

Star-shaped

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21
Q

How do osteocytes communicate with each other?

A

Via cytoplasmic extensions

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22
Q

What are the functions of osteocytes?

A
  • mechanosensory properties (know which bone is being used)

- involved with regulating bone matrix turnover

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23
Q

Describe bone remodelling

A

Normal bone is in a constant state of turnover caused by resorption by osteoclasts and formation by osteoblasts

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24
Q

How often is the adult skeleton completely replaced?

A

Every 10 years

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25
Q

Simply, what is osteoporosis?

A

When there is more bone destruction than there is formation

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26
Q

What are the 4 main stages in the bone cycle?

A
  • resting - lining cells of inactive osteoblasts
  • resorption - osteoclasts are signalled to reabsorb areas
  • osteoid formation - osteoblasts are signalled to form osteoids (non-mineralised type 1 collagen)
  • mineralisation - osteoid becomes mineralised to hard bone.
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27
Q

How is bone mass measured?

A

Total mass of skeletal calcium in grams

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28
Q

How does bone mass change with age?

A

Increases from birth until a peak at around 30-40 where it then starts declining

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29
Q

Where is there is an accelerated bone loss in women around 50 years of age?

A

Due to menopause/oestrogen levels decline

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30
Q

what happens with bone mass as an individual ages?

A
  • under 25’s still acquire their peak bone mass

- From 50’s onwards men and women are gradually losing bone mass year upon year

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31
Q

What 4 things about bone might you want to investigate?

A
  • gross structure
  • bone mass (calcium)
  • cellular function/turnover
  • microstructure/cellular function
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32
Q

How is bone gross structure investigated?

A

X-ray

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33
Q

How is bone mass (calcium) investigated?

A

DEXA Dual-Energy X-ray absorptiometry

[Shine two x-ray beams through bones to give a densitometry result of the bone]

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34
Q

How is bone cellular function/turnover investigated?

A

Biochemistry

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35
Q

How is bone microstructure/cellular function investigated?

A

Biopsy (rare)

Quantitative computed tomography (QCT)

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36
Q

What are the biochemical markers of bone formation?

A

Products of active Osteoblasts:

  • alkaline phosphatase (TAP, BAP)
  • osteocalcin (OC)
  • procollagen type 1 prepeptides (P1NP)
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37
Q

What are the biochemical markers of bone resorption?

A

Degradation products of bone collagen:

  • hydroxyproline
  • pyridinium crosslinks
  • crosslinked telopeptides of type I collagen (NTX, CTX)

+ osteoclast enzymes:

  • Tartrate-resistant acid phosphatase (TRACP 5b)
  • Cathepsin K
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38
Q

What are the osteoclast enzymes?

A
  • tartrate-resistant acid phosphatase (TRACP 5b)

- cathepsin K

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39
Q

When is alkaline phosphatase measured?

A

Measured by the lab in LFTs and bone profiles

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40
Q

In health, what are the alkaline phosphatase levels?

A

50% liver

50% bone

NB: elevated alkaline phosphatase can be due to the liver

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41
Q

What is bone alkaline phosphatase involved in?

A

phosphatase involved in Mineralisation

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42
Q

What is bone alkaline phosphatase released by?

A

Osteoblasts

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43
Q

what is release of bone alkaline phosphatase stimulated by?

A

stimulated by increased bone remodelling e.g.:

  • growth spurt
  • fractures
  • hyperparathyroidism (primary/secondary)
  • pagets disease
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44
Q

What is P1NP?

A

Procollagen type 1N propeptide

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45
Q

What is P1NP synthesised by?

A

Osteoblasts

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46
Q

P1NP is the precursor molecule of what?

A

Type 1 collagen

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47
Q

P1NP levels are affected by what?

A
  • increased with increased osteoblast activity
  • decreased by reduced osteoblast activity
  • serum concentrations not affected by food intake
  • has low diurnal and intraindividual variation
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48
Q

What are collagen cross-links (NTX, CTX)?

A

Cross-linking molecules which are released with bone resorption

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49
Q

What do collagen cross-links levels correlate with?

A

Correlate highly with bone resorption

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50
Q

When do levels of collagen cross-links change?

A
  • increased in periods of high bone turnover (hyperthyroidism, adolescents, menopause)
  • decrease with anti-resorptive therapy
  • have diurnal variation (change according to the time of day)
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51
Q

what is a disadvantage of using collagen cross-links as a bone resorption marker?

A

Do not predict bone mineral density

Decrease with anti-resorptive therapy

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52
Q

Collagen cross-links (NTX, CTX) are increased in periods of high bone turnover. Give 3 examples of when the body will experience high bone turnover.

A
  • hyperthyroidism
  • adolescents
  • menopause
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53
Q

Collagen-related bone markers are based primarily on what?

A

type 1 collagen

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54
Q

Are changes in bone markers disease-specific?

A

no

reflect alterations in skeletal metabolism

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55
Q

What are the uses of new bone markers?

A
  • evaluation of bone turnover and bone loss
  • evaluation of treatment effect
  • evaluation of compliance with medication
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56
Q

what is the bone marker CTX used for?

A

CTX used to monitor compliance/response to anti-resorptive therapy

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57
Q

which bone marker us used to measure compliance with teriparatide?

A

P1NP

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58
Q

What is teriparatide?

A

A form of parathyroid hormone - an effective anabolic (bone growing) agent used in the treatment of some forms of osteoporosis

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59
Q

T scores are given when doing a DEXA scan. What do T scores indicate

A

The T score indicates how many standard deviations the person is
away from the mean compared to someone who’s young, healthy and of the same sex

  • 1 and above = normal born density
  • 1 to -2.5 = low bone mass (osteopenia)
  • 2.5 and below = osteoporosis
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60
Q

What is osteopenia?

A

When the protein and mineral content of bone tissue is reduced, but less severely than in osteoporosis

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61
Q

Which scan gives you T scores?

A

DEXA

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62
Q

What is osteomalacia?

A

Softening of the bones, typically through a deficiency of vitamin D or calcium

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63
Q

Why is hyperparathyroidism?

A

An abnormally high concentration of parathyroid hormone in the blood, resulting in weakening of the bones through loss of calcium.

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64
Q

What is osteoporosis?

A

The bones become brittle and fragile from loss of tissue, typically as a result of hormonal changes, or deficiency of calcium or vitamin D

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65
Q

what are risk factors of osteoporosis?

A

[Risk factors of osteoporosis: steroids, early menopause (earlier then 45), age, female,
smoker, alcohol and inflammatory conditions e.g. ulcerative colitis]

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66
Q

What abnormalities are seen in routine biochemical tests in osteoporosis?

A

None - perhaps because they are too insensitive

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67
Q

Diagnosis of osteoporosis relies on what?

A

DEXA/X-ray

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68
Q

What is the actual definition of osteoporosis?

A
  • LOW BONE MASS
  • MICROARCHITECTURAL DETERIORATION of bone tissue,
  • consequent increase in bone fragility and susceptibility to fracture
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69
Q

Where are the common sites of fracture in osteoporosis?

A
  • spine
  • neck of femur
  • wrist
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70
Q

What is the definition of a fragility fracture?

A

A fracture caused by injury that would be insufficient to fracture a normal bone/ occurs as a result of minimal trauma

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71
Q

What should be suspected in any person with history of fragility fracture?

A

Low bone mass

72
Q

What signs should prompt investigation for vertebral fractures?

A
  • unexplained loss of height
  • kyphosis
  • severe back pain
73
Q

What is the FRAX calculation tool?

A

[Helps calculate the risk of fracture in the next 10 years]

74
Q

What are some endocrine secondary causes of osteoporosis?

A
  • early menopause
  • amennorrhoea
  • hypogonadism
  • Cushings
  • diabetes
  • hyperparathyroidism
  • hyperthyroidism
75
Q

What are some GI secondary causes of osteoporosis?

A
  • coeliac disease
  • IBD
  • chronic liver disease
  • malabsorption
76
Q

What are some rheumatological secondary causes of osteoporosis?

A
  • rheumatoid arthritis

- other inflammatory arthropathies

77
Q

What are some haematological secondary causes of osteoporosis?

A
  • myeloma
  • haemaglobinopathies
  • systemic mastocytosis
78
Q

What are some respiratory secondary causes of osteoporosis?

A
  • COPD

- cystic fibrosis

79
Q

What are some drugs that can cause secondary osteoporosis?

A
  • steroids
  • heparin
  • ciclosporin
  • anti-convulsants
  • aromatase inhibitors
  • androgen deprivation therapy
80
Q

What are some anabolic treatment options for the prevention of osteoporosis?

A

Parathyroid hormone analogue – teriparatide]

81
Q

What is denosumab?

A

Used in preventing fractures and other cancer related bone problems in adults with cancer that has spread to the bone
- monoclonal antibody to RANK ligand

82
Q

What is raloxifene?

A

An oral selective estrogen receptor modulator (SERM) that has oestrogenic actions on bone

83
Q

Which mineral is also used in bone treatment?

A

Strontium

84
Q

Describe the mechanism of action of bisphosphonates

A
  • mimic pyrophosphate structure
  • ingested by osteoclasts
  • Causing the osteoclasts to be destroyed, stopping
    the signalling of osteoclasts and osteoblasts
85
Q

Describe some problems with the use of bisphosphonates?

A
  • poor absorption
  • difficult to take
  • can cause oesophageal/upper GI problems
  • flu-like side effects
  • osteonecrosis of the jaw
  • atypical femur fractures
86
Q

Describe 2 types of bone metastases

A
  • lytic

- sclerotic/osteoblastic

87
Q

What are lytic bone metastases?

A

Destruction of normal bone (osteoclasts)

88
Q

What are sclerotic/osteoblastic bone metastases?

A

Deposition of new bone

89
Q

Which cancers causes lytic bone metastases?

A
  • breast/lung

- kidney/thyroid

90
Q

Which cancers cause sclerotic bone metastases?

A
  • prostate
  • lymphoma
  • breast/lung (15-25%)
91
Q

Where are the usual sites of bone metastases?

A
  • spine
  • pelvis
  • femur
  • humerus
  • skull
92
Q

Describe 5 groups of presenting symptoms of bone mets

A
  • pain
  • broken bones
  • numbness, paralysis, trouble urinating
  • loss of appetite, nausea, thirst, confusion, fatigue
  • anaemia
93
Q

Describe the pain that occurs in born mets

A
  • often worse at night
  • gets better with movement initially
  • usually becomes constant
94
Q

Which bones get commonly broken in bone mets

A
  • femur
  • humerus
  • vertebral column

Pathological fractures

95
Q

Why do you get numbness, paralysis and trouble urinating in bone mets?

A

Spinal cord compression from bone metastases

96
Q

Why do you get anaemia in bone mets?

A

Disruption of bone marrow

97
Q

What are the mild symptoms of hypercalcaemia?

A
  • polyuria, polydipsia
  • mood disturbance
  • anorexia
  • nausea
  • fatigue
  • constipation
98
Q

What are the severe symptoms of hypercalcaemia?

A
  • abdominal pain
  • vomiting
  • coma
  • pancreatitis
  • dehydration
  • cardiac arrhythmias
99
Q

What are the non-PTH mediated causes of hypercalcaemia?

A
  • malignancy
  • vitamin D intoxication
  • chronic granulomatous disorders eg. sarcoidosis
  • medications eg. thiazide diuretics, teriparatide
  • immobilisation
  • other endocrine conditions eg. hyperthyroidism, acromegaly
100
Q

What are the PTH-mediated causes of hypercalcaemia?

A
  • sporadic primary hyperparathyroidism

- familial (MEN1 and 2A, familial hypocalciuric hypercalcaemia, familial isolated hyperparathyroidism)

101
Q

Where are the parathyroid glands?

A

2 on each side of the thyroid gland, at the back

102
Q

What is parathyroid hormone (PTH) secreted by?

A

Chief cell of parathyroid gland

103
Q

What type of molecule is PTH?

A

Polypeptide containing 84 amino acids

104
Q

What stimulates the parathyroid gland to release PTH?

A
  • low levels of blood calcium
  • decreased serum magnesium
  • increased vitamin D
105
Q

What 3 main things does PTH do?

A
  • increases decomposition of bone, releasing calcium
  • increases absorption of calcium from food by intestines
  • increases reabsorption of calcium from urine by kidneys

These all increase levels of blood calcium

106
Q

What effect does increasing levels of calcium have on the parathyroid gland?

A

Negative feedback back to the parathyroid gland so less PTH produced

107
Q

What are the 3 different types of hyperparathyroidism (HPT)?

A
  • primary
  • secondary
  • tertiary
108
Q

What are the calcium levels in hyperparathyroidism?

A

primary = high

secondary = normal or low

tertiary = high

109
Q

What are the phosphate levels in HPT?

A

primary = low phosphate and high alkaline phosphate

secondary = high phosphate if due to chronic kidney disease

tertiary = phosphate can be high or low

110
Q

What are the causes of primary HPT?

A

Sporadic or familial

111
Q

What are the causes of secondary hyperthyroidism?

A

Mainly CKD or vitamin D deficiency

112
Q

What are the causes of tertiary HPT?

A

After prolonged secondary HPT, usually in CKD

113
Q

What is tertiary hyperthyroidism?

A

A state of excessive secretion of parathyroid hormone (PTH) after a long period of secondary hyperparathyroidism and resulting in a high blood calcium level

114
Q

What is secondary hyperparathyroidism?

A

Excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia (low blood calcium levels) and associated hyperplasia of the gland

115
Q

How does primary hyperparathyroidism present?

A

Used to present with severe hypercalcaemia and/or symptomatic renal and skeletal disease

Now presentation is much earlier and is usually asymptomatic

116
Q

Majority of cases of PHPT present at what age?

A

Over 45

117
Q

Which gender is more affected by PHPT?

A

Women are 2x as likely to be affected compared to men

118
Q

What blood test results suggest PHTP?

A

Inappropriately elevated PTH in the presence of high calcium

119
Q

what is the most common cause of primary HPT?

A

Benign adenomas

85% = single adenoma
5% = double parathyroid adenomas
120
Q

Describe typical parathyroid adenomas

A

Most adenomas are encapsulated and consist of parathyroid chief cells

121
Q

Describe the features of glandular hyperplasia of the parathyroid gland, causing primary HPT

A
  • all 4 glands enlarged
  • lower glands usually larger than upper ones
  • usually composed of chief cells
122
Q

Glandular hyperplasia of the parathyroid gland, causing primary HPT, can be sporadic or caused by which genetic syndromes?

A

MEN1, MEN2A or familial hyperparathyroidism

123
Q

what is an ectopic adenoma of the thyroid gland?

A
  • any parathyroid gland that is not next to they thyroid (para) is “ectopic”
  • adenoma of the “ectopic” parathyroid gland.
  • Parathyroid cells which migrated during embryogenesis.
  • rarely in the mediastinum
  • often found around the thymus gland.
124
Q

What are the classical clinical manifestations of PHPT?

A
  • hypercalcaemia
  • renal disease
  • bone disease
  • proximal muscle wasting
125
Q

What drug is used in imaging to identify parathyroid adenomas in primary HPT?

A

Tc 99 sestamibi

  • can also identify ectopic parathyroid tissue in mediastinum for example
126
Q

What are the indications, that a patient with an ectopic parathyroid adenoma, may need surgery?

A
  • symptomatic hypercalcaemia
  • in asymptomatic patients with:
  • calcium over 0.25mmol/L above normal
  • renal stone disease
  • creatinine clearance less than 60ml/min
  • age under 50 yeas
  • osteoporosis at any site or history of fragility fracture
127
Q

Why are calcimimetics (cinacalcet) used in HPT?

A

Activates CaSR (calcium sensing receptor) in the parathyroid gland, therefore leading to reduced PTH secretion

128
Q

When would you use calcimimetics for patients with HPT?

A

Used to normalise calcium in symptomatic patients, or those who are not fit for or unwilling to have surgery

  • does not seem to alter bone disease
  • no data on renal outcomes or QoL
129
Q

What are the limitations of calcimimetics?

A

GI side effects, particularly nausea

130
Q

What happens in Paget’s disease of bone?

A
  • rapid bone turnover and formation
  • leading to abnormal bone remodelling

Can be polyostotic or monostotic

131
Q

What type of people does Paget’s disease of bone often occur in?

A
  • over 50 years old

- higher prevalence in men

132
Q

Does Paget’s disease generally come with family history?

A

FH in 10-15% of cases

Probably genetic and environmental triggers

133
Q

There are elevated levels of what in Paget’s disease of bone?

A

Elevated alkaline phosphatase

  • reflecting increased bone turnover
134
Q

What are the clinical features of Paget’s disease of bone?

A
  • bone pain
  • bone deformity
  • fractures
  • arthritis
  • cranial nerve defects if skull affected (hearing and vision loss)
  • risk of osteosarcoma
135
Q

Which bones does Paget’s disease most commonly affect?

A
  • pelvis
  • femur
  • lower lumbar vertebrae
136
Q

What investigations would you do into Paget’s disease?

A
  • lab assessment
  • plain X-rays
  • nuclear medicine bone scan
137
Q

What is osteomalacia?

A

Lack of mineralisation of bone due to vitamin D deficiency or lack of calcium and/or phosphate

138
Q

What are the differences between the adult and child forms of osteomalacia?

A

adult form = widened osteoid seams with lack of mineralisation

classic childhood rickets = widened epiphyses and poor skeletal growth

139
Q

What is an osteoid seam? (these are widened in osteomalacia)

A

On the surface of a bone, the narrow region of newly formed organic matrix not yet mineralised

140
Q

What are the main causes of osteomalacia?

A
  • insufficient calcium absorption from intestine (due to lack of dietary calcium or vit D deficiency/resistance)
  • excessive renal phosphatase excretion (rare genetic forms eg. hereditary hypophosphataemic rickets)
141
Q

What are the clinical features of osteomalacia?

A
  • diffuse bone pains, usually symmetrical
  • muscle weakness
  • bone weakness
142
Q

What are the levels of alkaline phosphatase, calcium etc that you would find in osteomalacia?

A
  • high alkaline phosphatase
  • low vitamin D
  • possibly low calcium
  • high PTH (secondary hyperparathyroidism)
143
Q

Summarise the biochemistry of primary hyperparathyroidism, in terms of alkaline phosphatase, calcium, phosphate and parathyroid hormone.

A

Alkaline phosphatase = increased

Calcium = increased

Phosphate = decreased

PTH = increased

144
Q

Summarise the biochemistry of osteomalacia, in terms of alkaline phosphatase, calcium, phosphate and parathyroid hormone.

A

Alkaline phosphatase = increased

Calcium = (low)

Phosphate = low

PTH = (high)

145
Q

Summarise the biochemistry of osteoporosis, in terms of alkaline phosphatase, calcium, phosphate and parathyroid hormone.

A

Alkaline phosphatase = nil

Calcium = nil

Phosphate = nil

PTH = nil

146
Q

Summarise the biochemistry of Paget’s, in terms of alkaline phosphatase, calcium, phosphate and parathyroid hormone.

A

Alkaline phosphatase = high

Calcium = nil

Phosphate = nil

PTH = nil

147
Q

Summarise the biochemistry of bone mets, in terms of alkaline phosphatase, calcium, phosphate and parathyroid hormone.

A

Alkaline phosphatase = high

Calcium = (high)

Phosphate = nil

PTH = (low)

148
Q

what does cortical bone provide?

A

tensile strength

structural support

(80% of the body’s bone mass)

149
Q

what does trabecular bone provide?

A

provides a large surface area for metabolically active reactions to occur

home to the bone marrow (which gives blood cell production)

150
Q

what is an osteocyte?

A

Osteoblasts that are buried/trapped within the matrix [osteoids]

151
Q

individuals with less osteoblasts will result in what?

A

production of less bone

152
Q

what is the bone called before mineralisation?

A

osteoid

153
Q

what mineralises the bone matrix?

A

hydroxyapatite (calcium-phosphate-hydroxide salt)

154
Q

bone is AVASCULAR, true or false?

A

false

generally highly vascular - highly metabolically active due to osteoblasts constantly building and osteoclasts constantly breaking

155
Q

can bone be considered an endocrine organ?

A

yes it produces hormones

156
Q

do women or men have a lower peak bone mass?

A

Women have lower peak bone mass than men

157
Q

what effect does oestrogen have on bone mass?

A

protects bone density

158
Q

what effect does the oral contraceptive pill have on bone density

A
  • exposed to more oestrogen

- higher bone density

159
Q

what effect will a woman who started her menstrual cycle at an early age have on her bone density?

A
  • exposed to more oestrogen

- higher bone density

160
Q

A young woman’s menstrual periods have stopped due to extremely low body weight and excessive exercise, what affect will this have to her bone density?

A
  • decline in oestrogen exposure

- may lose significant amounts of bone density

161
Q

what does Tartrate-resistant acid phosphatase (TRACP 5b) do?

A

TRAP prompts the dephosphorylation of bone matrix.

162
Q

what does Cathepsin K do?

A

responsible for the proteolytic activation of TRAP.

163
Q

what is pagets disease?

A

Paget’s disease/osteitis deformans:

  • excessive bone breakdown and subsequent disorganised new bone formation in one or more bones (but never the whole skeleton)
164
Q

symptoms of pagets disease?

A

Mild or early cases of Pagets are asymptomatic

most common symptom: bone pain.

When symptoms do occur, they may be misdiagnosed with arthritis or other disorders.

Paget’s disease affecting the skull may cause frontal bossing, increased hat size, and headaches. Often patients may develop loss of hearing in one or both ears[5] due to auditory foramen narrowing and resultant compression of the nerves in the inner ear. Rarely, skull involvement may lead to compression of the nerves that supply the eye, leading to vision loss.

165
Q

what are the two main sites where a DEXA scan is performed?

A
  • lumbar spine

- hip

166
Q

what anti-resorptive treatments are available for the prevention of osteoporosis?

A

● Bisphosphonates are the first line or oral therapy

● Denosumab – injections once a year

● Raloxifene

167
Q

what are the 4 types of PHPT adenomas?

A
  • adenoma (benign)
  • glandular hyperplasia
  • ectopic adenomas
  • parathyroid carcinoma (malignant)
168
Q

what is a malignant cancer of the thyroid glands called?

A

parathyroid carcinoma

169
Q

what is a benign cancer of the thyroid glands called?

A

adenoma

170
Q

what test would you use to detect parathyroid adenoma in patients with primary hyperparathyroidism (PHPT)?

A

CT SPECT (Tc-99m MIBI)

171
Q

with reference to Paget’s disease of bone, what does polyostotic mean?

A

many bones

172
Q

with reference to Paget’s disease of bone, what does monostatic mean?

A

one bone

173
Q

what would be the best treatment for paget’s bone disease?

A

Bisphosphonates

reduce osteoclastic and osteoblastic function

174
Q

How could you monitor disease activity?

A

Bone markers: alkaline phosphatase or P1NP

175
Q

how do bisphosphonates

reduce osteoclastic and function?

A
  • attach to hydroxyapatite bony surfaces
  • when osteoclasts resorb bone impregnated with Bisphosphonate - it is released to impair ability of osteoclast
  • osteoclast can not adhere to bony surface or produce protons necessary for continued bone resorption
  • promotes osteoclast apoptosis