Osteoporosis Flashcards
What are osteoprogenitor cells
precursors for othe bone cells
undifferentiated cells
can divide to replace themselves
found in inner layer or periosteum and endosteum
What are osteoblasts
builder cells
secrete collagen and other matrix components
from mesenchymal stem cells
secrete mand mineralise osteoid
some control over osteoclasts–> building and reabsorbing needs to be balanced
What do mesenchymal cells differentiate into
osteoblasts, chondrocytes, myocytes, adipocytes
What are osteocytes
mature bone cells located in lacunae (area surrounding an osteoblast bacomes calcified and results in osteoblast becoming encapsulated
Carry out daily maitenance of bone, nutrients and removal of wastes
Maintain mineral concentration of matrix
Direct the timing and location of remodelling
What are osteoclasts
Reabsorb bone and release calcium into blood stream
Work at surfaces such as endosteum
From hematopoietic precursors (stem cells that are precursors for blood cells)
When do you reach PBM/PBD
approx 30yrs
after 30yrs, reabsorption>formation
What role does collagen protein play in bone strength
Collagen proteins provides tensile strength= able to twist and bend without breaking
What role does mineralised osteoid play in bone strength
calcium gives compressive strength
Cells with mesenchymal cells origin
Structural/muscle cells Osteoblasts chondrocytes fibroblasts adipocytes muscle cells due to same origin, they produce the same cytokines and colony stimulating factors as fibroblasts--> hence build bone/muscle
Cells with hematopoietic cells origin
Blood cell line Monocytes macrophages osteoclasts due to same origin, they produce the same cytokines which are destructive--> stimulating osteoclastic activity
What is the time frame within which osteoblasts and osteoclasts work
osteoblasts= take months to produce new bone
osteoclasts=take weeks to reabsorb
What influences the difference in PBM b/w individuals
Activity
nutrition
Sunlight
Hormones
What is osteoporosis
The failure to reach optimal PBM as a result of bone reabsorption > bone formation
Normal mineralisation occurs, but decreases bone mass and decreased bone quality–> predisposing it to #’s
What type of disease is osteporosis
Progressive
common and systemic
What is the epidemiology of OP
Elder white women most common
Majority of cases affect women
Risk increases with age
Asia>white>black
What are the predisposing factors for OP
Genetics–> determines about *0% of PMB
decreased physical activity (sedentary lifestyle)
decreased vitamin D intake and calcium intake
Oestrogen and androgen deficiency (postmenopausal women at higher risk of OP, prevented with oestrogen supplement)
Increased parathyroid hormone level or function
How does parathyroid hormone affect calcium levels in blood
Parathyroid hormone promotes mobilisation of calcium from bone to blood, hence increased parathyroid hormone decreased calcium in bone, which results in softening of bone
What is primary juvenile OP
Occurs b/w 8-14yrs
normal gonadal function
abrupt bone pant and/or # following trauma
Condition usually goes away spontaneously, although early diagnosis is important to protect child’s spine
what is the cause of primary OP
idopathic hence no know cause–> occurs spontaneously
What is postmenopausal primary OP
Primary OP–> type I
Accelerate loss of bone post menopausal
Occurs as a result of oestrogen deficiency
Thin, white, sedentary smoker female at greatest risk
(sedentary affects PMB and wolffs law; smoking has toxins which cause inflammation)
Brest feeding-> lose calcium and hence reduced bone mass
females lose 30-40% cortical and 50% trabecular bone in their lifetime–> hence trabecula will contribute 50% less to weight
generally takes 10yrs post menopause for effects to start showing
What is senile OP
Primary OP–> type II
Age associated bone loss and calcium deficiency
Hence deterioration of bone structure
Decreased activity–> therefore decreased stress on bones (Wolffs law)
What is secondary OP
OP as a result of an underlying drug/deficiency or disease
What are genetic underlying causes of secondary OP
cystic fibrosis
Hypogonadal states
what are endocrine causes of OP
Acromegaly--> disorder where pituitary produces too much growth hormone Oestrogen deficiency Diabetes mellitus Hyperparathyroidism Hyperthyroidism
What are chronic inflammatory conditions of secondary OP
AS RA SLE--> systemic lupus erythematosus (autoimmune, affects skin, joints kidneys brain and other organs) Alcoholism Depression Emphysema Kidney disease--> reabsorbs calcium Pregnancy/lactation
What sort of deficiences contribute to OP
Malabsorption Malnutrition Calcium Magnesium Protein Vitamin D
How does celiac disease affect OP
An autoimmune disease immune response to eating gluten creates inflammation damages small intestine lining prevents absorption of some nutrients (e.g. Ca) associated with diabetic pts
How will OP present clinically
Asymptomatic
Usually silent and not clinically apparent till well advanced or spontaneous #
Small stress will cause #
Pain in thoracic and lumbar–> usually as a result of vertebral #’s caused by loss of beams (trabeculae)
Height loss and spine deformity–> kyphosis, lordosis, kyphoscoliosis
What are some common # risk sites
NOF
wrist
vertebrae
WB exercises and diet help in prevention
How can OP be identified from x-rays
not apparent in x-rays till 30% bone mass gone
thin cortices–> loss of cancellous bone
vertebral bodies–> anterior wedging and #
Changes in vertebrae from OP
WB in vertebral body is longitudinal forces
Greater loss of beams therefore less support for compressive forces–> only left with struts which break from longitudinal forces causing them to collapse and hence #
What is the oestrogen independent mechanism of OP
Parathyroid hormones regulates calcium
physical stress on bone
vitamin D intake/synthesis
calcium intake
What are oestrogen dependent mechanisms of OP
Menopause–> decrease in oestrogen
osteoblasts/clasts/cytes–> all have oestrogen receptors
oestrogen moderates osteoclast production, activity and apoptosis (keeps osteoclasts under control)
hence decreasedoestrogen = increased osteoclast production and activity (also prolonged survival of osteoclasts)
oestrogen also affects bones indirectly through cytokines and local growth factors which have a ‘turn-off’ effect on osteoblasts and osteoclasts
Affect of exercise on OP
Works/benefits only when regular exercise
Spinal density is shown to increase by 4% in exercisers
What is the final common pathway of bone reabsorption
RANKL-RANK (OPG System)
What is RANKL
RANKL= recetor activator of nuclear factor-Kappa B Ligand–> a cytokine produced by osteoblasts and activated by T cell lymphocytes
RankL is moderate by estrogen
What is RANK
Receptor Activator of Nuclear factor-kappa B–> on osteoclasts
What is OPG system
Osteoprotegerin system
OPG secreted by stromal cells and osteoblasts a soluble decoy receptor
Receptor inhibits RANK-RANKL by binding and sequestering RANKL
Takes RANKL receptor spot for RANKL binding to RANK therefore blocking or decreasing bone reabsorption cycle, therefore more OPG promotes bone formation
Explain the RANK-RANKL pathway/process
RANKL binds to RANK expressed on osteoclasts and osteoclast precursors to promote osteoclast differentiation
Increased RANKL results in recruitment of higher numbers of preosteoclasts as well as increased activity, vigor and lifespan of mature osteoclasts
osteoporotic menopausal changes= increased bone turnover as a remodelling imbalance with increased bone reabsorbing osteoclast activity with pro-inflammatory cytokines and decrease bone forming osteoclast activity
