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Flashcards in Bone Deck (37):
1

how are bones formed

appositional bone from mesenchyme, intramembranous or endochodnral ossification

2

differences between intramembranous and endochondral ossification

IO replaces embryonic mesenchyme, endochondral replaces cartilage
IO is mainly intrauterine, endochondral continues up to adulthood

3

Achondroplasia

autosomal dominant and homozygotes tend to die at birth
80% of cases from FGF-3 spontaneous mutations
Normal trunk length, shortened proximal extremities due to premature fusion of growth plate

4

Osteogenesis imperfecta

Defects in type I collagen synth, mutation in alpha-1 and alpha-2 chains
Autosomal dominant as recessive ones are lethal
Too little bone made, blue sclera, lots of fractures, hearing defects, small misshapen teeth
Type I is symptomatic but normal life, type II is fatal with uterine contractions crushing baby

5

Cretinism

Due to maternal iodine deficiency
Large head due to open fontanelles, mental impairment, disproportionally short limbs

6

Seckel Syndrome

Bird-headed dwarfism, mental deficiency
Autosomal recessive mutation in ATR protein, rare condition

7

Acromegaly

Usually GH producing adenoma of pituitary after epiphyseal fusion
Enlarged hands and feet, brow and forehead protrusion, visceral enlargement

8

Gigantism

GH producing adenoma before epiphyseal fusion
Treated with surgery/GH inhibitors

9

Bone composition

Type I collagen, mineral component (hydroxyapatite) and mix of proteins produced by osteoblasts
Very well vascularised so perfused and innervated

10

Osteoblasts function

Produce osteoid (unmineralised bone matrix) with collagen which is then mineralised by hydroxyapatite

11

Osteocytes function

Regulate mineralisation in mature bone, differentiated from osteoblasts
Thins bone in astronauts as mechanical forces are less in space

12

Osteoclasts function

Multinucleate bone resorbing cells from promonocyte precursors
Have ruffled border for large SA for bone resorption
Resorption much faster than formation, activated in low pH conditions e.g. marrow, fractures, tumours
Used in growth as bone tissue added to outside, inside hollowed out

13

Bone resorption process

OC attach to bone, forms carbonic acid which dissociates H+
Ruffled border pumps out acid and proteolytic enzymes to degrade collagen matrix, protons combine with Cl- to form HCl to remove hydroxyapatite

14

Two types of bone architecture (macroscopic)

Cortical - compact, dense e.g. in long bone shafts, less remodelling (approx. 15 years in adult, called tunnelling)
Trabecular (cancellous, spongy) - e.g. in vertebral bodies and ends of long bones, 10x turnover of cortical so remodelled a lot due to larger SA

15

Types of bone (microscopic)

Woven - weaker and more flexible, used in rapid growth where lots of osteoid produced quickly so usually in foetus
Lamellar - stronger and organised, stress orientated collagen, created by remodelling woven bone

16

Osteoblast regulation

Activators - oestrogen, PTH, BMP, LRP/Wnt (blocked by sclerostin)
Inhibition - cortisol

17

Osteoclast regulation

Activators - PTH, vit D, M-CSF, RANK-L
Inhibitors - oestrogen, calcitonin

18

PTH effect on bone regulation

Increases Ca++ which increases OC formation and OB activity

19

Calcitriol effect on bone regulation

Increases gut Ca2+ uptake, high Ca++ so more OC formation and OB proliferation, OB differentiation increases and needed for mineralisation

20

Calcitonin effect on bone regulation

Decreases plasma Ca++ so decreases OC formation, not really seen in healthy adults as is an emergency hormone

21

Sex steroids effect on bone regulation

Decrease OC and increase OB activity

22

Prostaglandin/hypoxia effect on bone regulation

increase OC recruitment

23

CGRP effect on bone regulation

decreases OC formation

24

Phosphate/Ca effect on bone regulation

Both decrease OC recruitment, phosphate more so

25

Fluoride effect on bone regulation

Increases bone formation but with worse mineralisation

26

What is osteoporosis

Trabecular bone plates eroded by OC, cortical bone (occurs slowly) endosteal resorption faster than periosteal formation so thinner bone shaft with increased diameter

27

Osteoporosis definition

bone mass <2.5 SDs below average peak, osteopenia is just <1 SD below so less severe

28

Osteoporosis treatment

HRT with low level oestrogens in post-menopausal women
Intermittent PTH injections (expensive)
Blocking OC action with bisphosphonates/monoclonal RANKL ab

29

Osteomalacia (rickets in kids)

Result of vit D deficiency so impaired mineralisation, no loss of bone mass (rickets affects cartilage growth plate as well)

30

Paget's disease

Overactive OCs with many nuclei, much greater bone resorption at certain sites, caused by paromyxovirus

31

Osteosarcoma vs osteoclastoma

osteosarcoma aggressive, osteoclastoma not metastatic but can result in rapid local bone loss

32

Osteoarthritis

Imbalance of chondrocyte regulation of anabolism/catabolism leads to erosion of matrix so bone to bone articulation occurs
Nociceptors/stretch receptors stimulated and causes inhibition and wastage

33

Types of osteoarthritis

1˚ - unexplained wear becomes common with age e.g. starts in MTP
2˚ - chondrocyte ischaemia may initiate it, erosion occurs after abnormal mechanical loads
Generalised - cartilage wear occurs progressively in a range of joints but often spares hip

34

Pathogenesis of osteoarthritis

Low level of persistent inflammation (not systemic like rheumatoid) with IL-1beta and TNF-alpha, degrades cartilage and then more produced by degradation - vicious cycle

35

Symptoms of osteoarthritis

Reactive sclerosis
Lax ligaments
Hyperhydration as collagen fibrillation occurs and swelling pressure from proteoglycans overtake

36

Treatment of osteoarthritis

Aim to manage pain and mobility as OA is non-reversible after collagen fibrillation
IL-1 neutralisation
Autologous chondrocyte implants
Stem cells into cartilage lesion from bone marrow/adipose

37

Hip replacement

Cemented or non-cemented where connection made between bone and implant or left to grow (hydroxyapatitie collar)
Physiological load distribution needs to be maintained as bone formed in high stress regions and resorbed in low
Particles released from wear which can cause inflammatory reactions (resorption, pseudotumours, necrosis)