week 6 - ageing and degeneration Flashcards
functions of musculoskeletal system
enables an efficient means of limb movement
acts as an endoskeleton for protection and support
serves as a reserve for organic and inorganic molecules
provides an environment for marrow
impact of ageing on body
affects the balance of mechanisms which ensure homeostasis within organs
alters tissue response to injury
associated with accumulation of genetic damage
elicits antagonistic or compensatory mechanisms - initially beneficial but chronicity leads to further damage resulting in phenotypic alterations
age related changes may overlap significantly with pathological syndromes
generic processes with ageing
decreased amount of tissue
altered molecular disposition of the matrix
accumulation of degraded molecules
reduced efficiency of functional tissue elements
reduced synthetic capacity of differentiated cells
altered levels of trophic hormones, GFs and cytokines, or altered ability of cells to respond
alterations in the loading patterns of tissues or the tissues response to loading
MSK ageing syndromes
osteoporosis - bones
osteoarthritis - joints
sarcopenia - muscle
ageing within articular cartilage
very low rate of replication so vulnerable to ageing
50% of chondrocytes last between 40 and 80 years
ECM contains hydrophilic proteoglycans essential for maintaining internal swelling pressure
composition changes with age leading to reduction of water content with fragmentation of protein components and collagen leading to reduced tensile strength
osteoarthritis pathogenesis
joint damage occurs (repeated loading and stress or injury) which triggers repair processes
these repair processes alter the structure of the joint over time causing features of:
localised loss of cartilage
remodelling of adjacent bone and foundation of osteophytes
mild synovitis
bone ageing
reduction in number of osteoblasts and osteoblast proliferation
diminished ability of osteoblasts to sense and respond to mechanical forces
relative increase in numbers of osteoclasts
increase in bone turnover and a disruption of remodelling activity
gradual decline in secreted growth hormone with fall in levels of IGF-1
hormonal changes in bone ageing
gradual decline in secreted growth hormone with fall in levels of IGF-1 along with decreased sensitivity to its effect (required for differentiation of osteoblasts)
oestrogen has an inhibitory effect on osteoclasts - increased bone resorption following menopause (decreased oestrogen levels after menopause)
increase in inflammatory cytokines from a lifetime exposure to antigens
bone remodelling
activation - preosteoclasts are stimulated and differentiate under the influence of cytokines and GFs into mature active osteoclasts
resorption - osteoclasts digest mineral matrix
reversal - end of resorption
formation - osteoblasts synthesise new bone matrix
quiescence - osteoblasts become resting bone lining cells on the newly formed bone surface
risk factors for osteoporosis
age, female, family, previous fracture, early menopause, long term glucocorticoid therapy, rheumatoid arthritis
alcohol, smoking, low BMI, poor nutrition, vitamin D deficiency, eating disorders, insufficient exercise, low dietary calcium intake
diagnosis of osteoporosis
bone strength strongly related to its density
inverse relationship between BMD and fracture risk
to assess BMD use dual energy x-ray absorpsiometry (DXA) at hip and spine
reported in terms of t scores with t=0 as normal bone mass in young healthy women
t
fragility fractures
from mechanical forces that would not normally result in fracture
force equivalent to a fall from standing height or less
most common in vertebrae, proximal femur and distal radius
prevention of osteoporosis
maximise peak bone mass: regular weight bearing exercise healthy diet sufficient vit D avoid smoking alcohol in moderation
treatment of osteoporosis
antiresorptive - reduces bone turnover by inhibiting osteoclast activity:
bisphosphonates
denosumab
raloxifene
hormone replacement therapy
anabolic - stimulates bone formation:
teriparatide - stimulates osteoblast activity
sarcopenia
progressive and generalised skeletal muscle disorder that is associated with increased likelihood of adverse outcomes including falls, fractures, physical disability and mortality
severe sarcopenia
when all 3 criteria met:
low muscle strength
low muscle quality or quantity
low physical performance