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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
How does the remodeling process occur?
Osteoclasts form a hollow, called Howship's lacuma | Osteoblasts lay down new mineral and essential bury themselves in bone
26
Three stages of bone healing after a fracture
1) Inflammation- haematoma forms 2) Repair- soft callus to hard callus 3) Remodeling - bone continues to form and returns to its original shap
27
Factors which inhibit bone healing
``` Poor blood supply No stability Malnutrition- reduced callus formation, reduced proliferation of osteochondral cells Smoking Diabetes Infection ```
28
What is osteoporosis?
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
What causes osteoporosis
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
Endocrine/metabolic causes of osteoporosis
``` Hypogonadism Hyperparathyroidism Thyrotoxicosis Cushings Prolactinoma Acromegaly Hypopituitarism IDDM Hypophosphatitis ```
31
Nutritional causes of osteoporosis
``` Calcium deficiency VIT D deficiency Malabsorption Malnutrition Cholestatic Liver disease Gastric operations ```
32
Drugs that cause osteoporosis
``` Glucocorticoids Aromatase inhibitors Androgen deprivation therapy Depoproverva GnRH agonists Heparin Phenytoin Carbamezepine Excess thyroxine ```
33
Disorders of collagen that cause osteoporosis
Osteogenesis impercta Elher Danlos syndrome Marfans syndrome Homocystinuria
34
Other causes of osteoporosis
Rheumatoid arthritis SLE, multiple myeloma CKD, Renal tubular acidosis, Immobilisation, Organ transplantation, Mastocytosis
35
Osteoporosis diagnosis
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
Osteoporosis managements (interventions)
-Exercise - Calcium (+/- VIT D supplements) Dietary calcium Smoking cessation Reduced ETOH Falls prevention Hip protectors
37
First line pharma treatment for osteoporosis
Alendronate, Risedronate, Ibandronate
38
2nd Line therapy pharma for osteoporosis
Reloxifene, Strontium ranelate
39
Specialist treatment for osteoporosis
Denosumab, IV zolendronic acid, IV ibrnadronate, Terpiaratide, PTH (1-84)
40
Bisphosophonates MOA
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
PTH analogues
PTH analogues- teriparatide | MOA- increase formation of new bone and increase osteoblast activity
42
How is osteomalacia related to osteoporosis?
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
What is osteomalacia?
Vitamin D deficiency- leads to insufficient calcium and phosphate and so new osteoid cannot be mineralised. Bones become softer and more pliable
44
Treatment of of Vitamin D deficiency
Vitamin- oral D2/D3 Oral 1- alphacalcidol Oral calcitrool
45
Paget's disease
``` Disordered bone metabolism Osteoclast overactivity Followed by compensatory osteoblast activity MOSAIC BONE Weaker than normal 70-90% asymptomatic ```
46
Direct symptoms of Paget's
Bone pain Deep, constant boring pain Worse on weight-bearing Pathological fracture
47
Indirect symptoms of Paget's
High cardiac output | Compression effects depending on site
48
Paget's Blood tests
``` High ALP (NB liver disease) Normal Calcium, vitamin D, PTH, phosphate ```
49
Paget's disease drugs
Bisphosphonates- stable analogues of pyrophosphate Risedronate- 30mg daily 2 months Zolendronate 5mg x1 infusion
50
Common cancers which may metastasize to bone
Breast, kidney, thyroid, prostate, lung
51
Common sites for bone mets are
Vertebrae, pelvis, proximal femur. humerus/ ribs/skull
52
Bone mets presentation
Pain, pathological fracture, spinal cord compression, Elevated alk phos and calcium
53
Bone mets treatment
Bisphosphonates Radiotherapy Surgicall Chemo
54
Bloods in Osteomalacia
Calcium- Low Phosphate- Low Alk phos- high/normal PTH- High/normal
55
Bloods in osteoporosis
Calcium- normal Phosphate- normal Alk phos- normal PTH- normal
56
Bloods in Paget's
Calcium-normal Phosphate- normal Alk phos- high PTH- normal
57
Primary hyperparathyroidism bloods
Calcium- High/normal Phosphate- Low/normal Alk phos- high/normal PTH- High
58
Renal osteodystrophy bloods
Calcium- normal or low Phosphate- high Alk phos- high PTH- High
59
Bone mets bloods
Calcium- High Phosphate- high Alk phos- high PTH- High
60
Cause of Primary hyperparathyroidism
Excess PTH secretion leading to hypercalcaemia
61
Secondary hyperparathyroidism cause
Chronically low calcium levels due to renal dysfunction

Case 14 (2 decks)

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