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Case 14 > Normal Bone Health and Bone disease > Flashcards

Normal Bone Health and Bone disease Flashcards

1
Q

Two main parts of a long bone

A

Diaphysis and Epiphysis (wider section at each end of the bone- filled with spongy bone)

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2
Q

Two main types of bone

A
  • Cortical - higher density

- Trabecular- spongy bone- more metabolically active

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3
Q

Which type of bone (cortical or trabecular) are long bones?

A

Cortical

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4
Q

Which type of bone (cortical or trabecular) are smaller bones in the wrist and foot

A

Trabecular bone

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5
Q

Cellular composition of bone

A

Inorganic- hyproxyapatite
Water
Organic- collagen, non-collagenous proteins, extracellular, cellular proteins

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6
Q

Properties of articular cartilage- HYALINE

A

Water, collagen, proteoglycans
Sparse distribution of highly specialised cells called chondrocytes
Mainly type 2 collagen

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7
Q

Function of bone

A
  • Structural support
  • Protection
  • Locomotion
  • Metabolic
  • Haematopoeisis
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8
Q

Normal plasma calcium level?

A

2.2-2.6mmol/L in the extracellular fluid

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9
Q

Hypocalcaemia cause and effect

A

When calcium is <2.2mmol/L
Voltage gates ion channels open spontaneously; nerve and muscle cells become hyperactive
- Leads to TETANY- muscle spasms

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10
Q

Hypercalcaemia cause and effect

A

When calcium >2.6mmol/L
- Voltage gated ion channels don’t open as easily
Depressed nervous system function
Deposition of excess calcium and phosphate- KIDNEY STONES

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11
Q

Where is calcium stored?

A

99% in bone

  1. 5% is bound to albumin
  2. 5% is free
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12
Q

Intestine, Kidney roles of calcium regulation

A

Intestine: Dietary calcium reaches intestine; majority is excreted but 200mg enters ECF- ABSORPTION

  • Kidney - excretes calcium in urine; some is reabsorbed but overall net loss Filtering )
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13
Q

Which Two substances control calcium balance?

A

Parathyroid hormone and Vitamin D

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14
Q

Flow chart of how Calcifediol is converted to calcitriol

A
  • Diet- VIT D3
  • VIT D3 Cholecalciferol in liver
  • Converted to 25-OH cholecalciferol by liver and transported to kidney
  • Kidney converts it to 1,25 (OH)2D3- calcitriol
  • Calcitriol released in blood
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15
Q

Active form of vitamin D

A

1, 25 (OH) 2 D3

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16
Q

Main action of calcitriol

A

Stimulation of absorption of Ca2+ and phosphate in the intestine and MOBILISATION of ca2+ from bone

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17
Q

Which hormone is secreted when Ca2+ is low?

A

PTH

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18
Q

PTH effect on Kidney and Bone

A

Kidney-
Stimulates hydroxylation of D3 in kidney
Increases resorption of Ca2+ in kidney
Promotes urinary excretion of Po4-

(Overall, increases Ca2+, decreases PO4-)

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19
Q

Which hormone is secreted when Ca2+ is high

A

Calcitonin

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20
Q

Calcitonin overall effect

A

Osteoclast inhibition - decrease Ca2+

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21
Q

Main action of calcitriol

A

Stimulation of absorption of Ca2+ and phosphate in the intestine and mobilisation of Ca2+ from bone

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22
Q

Primary hyperparathyroidism features

A

Enlargement of one or more of the parathyroid glands
PTH hypersecretion
Adenoma- benign

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23
Q

Hypoparathyroidism causes and features

A

Injury to parathyroid glands- complication of surgery
Results in reduced level of calcium and associated problems- muscle spasms and tetany
Parasthesia around mouth/feet

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24
Q

One factor and one pathway which controls bone remodeling

A

Transcription factors

Cell signaling

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25
Q

How does the remodeling process occur?

A

Osteoclasts form a hollow, called Howship’s lacuma

Osteoblasts lay down new mineral and essential bury themselves in bone

26
Q

Three stages of bone healing after a fracture

A

1) Inflammation- haematoma forms
2) Repair- soft callus to hard callus
3) Remodeling - bone continues to form and returns to its original shap

27
Q

Factors which inhibit bone healing

A 
Poor blood supply
No stability
Malnutrition- reduced callus formation, reduced proliferation of osteochondral cells
Smoking 
Diabetes 
Infection
28
Q

What is osteoporosis?

A

A disease characterised by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk

29
Q

What causes osteoporosis

A

Imbalance in remodelling
Osteoclast> osteoblast
Increased breakdown relative to bone formation resulting in low bone mass
Some struts of trabecular bone are lost completely leading to loss of connectivity between adjacent bone plates

30
Q

Endocrine/metabolic causes of osteoporosis

A 
Hypogonadism
Hyperparathyroidism
Thyrotoxicosis
Cushings
Prolactinoma
Acromegaly 
Hypopituitarism
IDDM
Hypophosphatitis
31
Q

Nutritional causes of osteoporosis

A 
Calcium deficiency
VIT D deficiency 
Malabsorption 
Malnutrition
Cholestatic Liver disease
Gastric operations
32
Q

Drugs that cause osteoporosis

A 
Glucocorticoids
Aromatase inhibitors
Androgen deprivation therapy
Depoproverva
GnRH agonists
Heparin 
Phenytoin
Carbamezepine
Excess thyroxine
33
Q

Disorders of collagen that cause osteoporosis

A

Osteogenesis impercta
Elher Danlos syndrome
Marfans syndrome
Homocystinuria

34
Q

Other causes of osteoporosis

A

Rheumatoid arthritis
SLE, multiple myeloma
CKD, Renal tubular acidosis, Immobilisation, Organ transplantation, Mastocytosis

35
Q

Osteoporosis diagnosis

A

BMD in g/cm2 (bone marrow density)
Usually measured using dual energy X-ray DEXA
WHO -Osteoporosis- more than 2.5 T score below the mean
Men diagnosed using z scores

36
Q

Osteoporosis managements (interventions)

A

-Exercise
- Calcium (+/- VIT D supplements)
Dietary calcium
Smoking cessation
Reduced ETOH
Falls prevention
Hip protectors

37
Q

First line pharma treatment for osteoporosis

A

Alendronate, Risedronate, Ibandronate

38
Q

2nd Line therapy pharma for osteoporosis

A

Reloxifene, Strontium ranelate

39
Q

Specialist treatment for osteoporosis

A

Denosumab, IV zolendronic acid, IV ibrnadronate, Terpiaratide, PTH (1-84)

40
Q

Bisphosophonates MOA

A

Orally active, stable analogues of pyrophosphate- incorporated into bone remodeling
Reduce bone resorption- inhibit osteoclast function. Reduce rate of bone turn over

Simple compounds similar to pyrophosphate - etidronate- promotes osteoclast apoptosis

Potent aminobisphosphonates- pamidronate, alendronate- prevent osteoclast attachment to bone

41
Q

PTH analogues

A

PTH analogues- teriparatide

MOA- increase formation of new bone and increase osteoblast activity

42
Q

How is osteomalacia related to osteoporosis?

A

Osteomalacia is a secondary cause of osteoporosis

Osteoporosis = less bone but normal ratio of matrix to mineral
Osteomalacia = normal volume but reduced mineral component
43
Q

What is osteomalacia?

A

Vitamin D deficiency- leads to insufficient calcium and phosphate and so new osteoid cannot be mineralised. Bones become softer and more pliable

44
Q

Treatment of of Vitamin D deficiency

A

Vitamin- oral D2/D3
Oral 1- alphacalcidol
Oral calcitrool

45
Q

Paget’s disease

A 
Disordered bone metabolism
Osteoclast overactivity
Followed by compensatory osteoblast activity
MOSAIC BONE 
Weaker than normal 
70-90% asymptomatic
46
Q

Direct symptoms of Paget’s

A

Bone pain
Deep, constant boring pain
Worse on weight-bearing
Pathological fracture

47
Q

Indirect symptoms of Paget’s

A

High cardiac output

Compression effects depending on site

48
Q

Paget’s Blood tests

A 
High ALP (NB liver disease)
Normal Calcium, vitamin D, PTH, phosphate
49
Q

Paget’s disease drugs

A

Bisphosphonates- stable analogues of pyrophosphate

Risedronate- 30mg daily 2 months
Zolendronate 5mg x1 infusion

50
Q

Common cancers which may metastasize to bone

A

Breast, kidney, thyroid, prostate, lung

51
Q

Common sites for bone mets are

A

Vertebrae, pelvis, proximal femur. humerus/ ribs/skull

52
Q

Bone mets presentation

A

Pain, pathological fracture, spinal cord compression, Elevated alk phos and calcium

53
Q

Bone mets treatment

A

Bisphosphonates
Radiotherapy
Surgicall
Chemo

54
Q

Bloods in Osteomalacia

A

Calcium- Low
Phosphate- Low
Alk phos- high/normal
PTH- High/normal

55
Q

Bloods in osteoporosis

A

Calcium- normal
Phosphate- normal
Alk phos- normal
PTH- normal

56
Q

Bloods in Paget’s

A

Calcium-normal
Phosphate- normal
Alk phos- high
PTH- normal

57
Q

Primary hyperparathyroidism bloods

A

Calcium- High/normal
Phosphate- Low/normal
Alk phos- high/normal
PTH- High

58
Q

Renal osteodystrophy bloods

A

Calcium- normal or low
Phosphate- high
Alk phos- high
PTH- High

59
Q

Bone mets bloods

A

Calcium- High
Phosphate- high
Alk phos- high
PTH- High

60
Q

Cause of Primary hyperparathyroidism

A

Excess PTH secretion leading to hypercalcaemia

61
Q

Secondary hyperparathyroidism cause

A

Chronically low calcium levels due to renal dysfunction

Case 14 (2 decks)

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