Osteoporosis Flashcards
What happens if there are imbalances in the collagen and mineral components of bone?
These can impair bone quality leading to reduced bone strength
What is bone made up of?
Collagen and mineral complements
Is bone mass more genetic or modifiable?
Mainly genetic (60-80%)
What are examples of modifiable factors regarding bone mass?
Nutritional intake e.g. Calcium, vitamin D, protein
Exercise
Lifestyle (smoking, hormonal status and certain diseases and medications)
What is the role of bone?
Support and function
Blood cell formation
Site of muscle attachment
Main store of calcium, phosphorous and carbonate (role in maintaining metabolic homeostasis)
What is the bone remodelling process?
Begins with bone resorption by the conversion of quiescent bone surface into a bone resorptive surface.
This conversion transmits signals to osteoclasts and osteoblasts on the bones surface.
What is the role of osteoclasts?
Resorb bone matrix by creating a resorption pit.
They end their function with apoptosis followed by coupling signals sent to osteoblasts
What is the role of osteoblasts?
Synthesise bone matrix which undergoes mineralisation.
Mature osteoblasts produce oestroprotegerin which binds to RANK to stop bone resorption
What regulates bone remodelling ?
Various cytokines such as IL-1, IL-6, IL-11
Calcitrophic hormones like 1,25-dihydroxy vitamin D, calcitonin and oestrogen
What is RANK ligand?
This is expressed by osteoBlasts which interact with the RANK receptors on osteoClasts
What is the role of osteoprotegerin?
Secreted by osteoblasts
Naturally inhibits RANK ligand induced activation of RANK.
In post menopausal women with an oestrogen activity there is an overexpression of RANKL activity which overrides the natural inhibitory activity of osteoprotegerin.
What is osteoporosis?
A complex disorder characterised by imbalance of bone remodelling process governed by the intricate interactions between various hormonal factors, cytokines and novel regulatory system (RANK/RANKL/OPG)
Bone loss occurs where bone resorption exceeds bone formation resulting in a disequilibrium in bone remodelling resulting in lower bone mineral density and bone quality which culminates in bone fracture.
What is the epidemiology of osteoporosis?
Prevalence increases with age (4% in women 50-59 years, 44% in women of 80 years and older)
Predominantly affects white postmenopausal women, (but men, premenopausal and children can develop this condition too)
Most women are hospitalised with a fracture due to osteoporosis than through breast cancer
What are the primary causes of osteoporosis?
These are age related and although they can occur in both sexes, women are at a greater risk especially after menopause
These factors are Idiopathic - arising spontaneously with an unknown cause
What are the different categories of osteoporosis?
Postmenopausal osteoporosis
Male osteoporosis
Age related osteoporosis
What is post menopausal osteoporosis?
Mainly due to loss in ovarian hormone production, especially oestrogen
Oestrogen deficiency increases the proliferation, differentiation and activation of new osteoclasts and prolongs survival of mature osteoclasts. The number of remodelling sites increases and resorption pits are deeper.
Significant bone density is lost and bone architecture is compromised
Trabecular bone is most susceptible, leading to vertebral and wrist fractures
What is male osteoporosis?
Men are generally lower risk for developing osteoporosis me osteoporotic fractures due to larger bone size, greater peak bone mass and fewer falls.
Ageing appears to be the common factor in osteoporosis development in men
What is a age related osteoporosis?
Occurs mainly as a result of our mom lens, calcium and vitamin d deficiencies leading to celebrated bone turnover rate in combination with reduced osteoblast bone formation
What are the secondary causes of osteoporosis?
These can arise at any age and affect men and women equally
They arise from chronic predisposing medical problems or disease
Or prolonged medication use such as glucocorticoids
What are the main medical problems that can cause osteoporosis?
Hyperthyroidism Diabetes mellitus Hyperparathyroidism Hypogonadism Malabsorption syndromes
What are the common medications that can cause osteoporosis?
Glucocorticoids Phenytoin Carbamazepine Levothyroxine Heparin Lithium Tamoxifem PPIs Furosemide SSRIs
Why does glucocorticoid therapy cause osteoporosis?
Glucocorticoid therapy causes decreased proliferation and differentiation as well as enhanced apoptosis of osteoblasts
It also increases resorption by increasing RANKL and decreasing OPG
It can reduce oestrogen and testosterone concentration by decreasing Ca absorption and increasing urinary Ca output
Patients starting glucocorticoid therapy should receive at least 1500mg of Ca and 800-1200mg of vitamin D daily
What are the two main classifications of risk factors of osteoporosis?
Non modifiable
Modifiable
What are non modifiable risk factors?
Female Increased age (50years or older) Caucasian or Asian Early menopause or ovaries removed Lactose intolerance Low BMI Family history
What are the modifiable risk factors of OP?
Smoker (>20 a day)
Excess alcohol (no more than 4 standard drinks a day)
Less than 30 mins of physical activity/day
Less than 30 mins of outdoors in sunlight/day
High caffeine intake
Low Ca diet
Long term use of certain medications including steroids and anticonvulsants
What are the clinical presentations of OP?
Common fractures: vertebrae, proximal femur and distal radius
2/3 of the back fractures are asymptomatic
The remainder present with mod to severe back pain that radiates down a leg
Kyphosis
What is kyphosis?
The curving of the spine leading to hunchback or slouching with posture.
Can experience respiratory problems due to the compression of the thoracic region
How is OP diagnosed?
OP is usually asymptomatic until fractures appear.
Fractures can result in pain, deformity and disability
Diagnose with measurement of BMD by dual energy X-ray absorptiometey (DEXA scan)
A T score is obtained which compares the patients measured BMD to the BMD of. Health young, sex matched white reference population
The T score is the number of SDs roar mom the mean of the reference population so
If Tscore > -1 = normal bone mass
- 1 to -2.4 = osteopenia
- 2.5 = osteoporosis
What are the desired outcome so f osteoporosis?
Prevention is the primary goal
Optimising skeletal development and peak bone mass in childhood, adolescence and early adulthood will reduce future incidence of osteoporosis
Once osteopenia or osteoporosis develops objective is to stabilise or improve bone mass and strength and prevent fractures.
Go as in a patients who have already suffered osteoporotic fractures include reducing future falls and fractures, improving functional capacity, reducing pain and deformity, improving quality of life.
What are the pharmacological treatment options?
Calcium and vitamin D supplementation Calcitriol BisphosphonTes Raloxifen or Demosumab Calcitonin Teriparatide HRT Strontium ranelate
Thiazide diuretics
Fluroide
Statins
Vitamin K
Why are calcium and vitamin D supplementation used?
Intended to prevent OP and reduce incidence of fracture
Should be advised with every line of treatment
How much calcium should be supplemented?
1-1.5g/day orally
Treat constipation with water intake
What does cholecalciferol do?
This is vitamin d and regulates levels of Ca and P in the body and in the mineralisation of bone
I.e. It facilitates intestinal absorption of calcium
How is vitamin d produced?
In the skin by exposure to the sun.
This is then metabolised to the active form by the liver of the kidney
What is the effect of renal/liver disease on vitamin D?
It can decrease vitamin D levels
How much vitamin d is given?
Usually 300,000 IU to start with, then 50,000IU once a month
Note that 1IU= 0.025μg
What is Calcitriol?
The biologically active form of vitamin D3
For people with renal or liver impairment
What is the role of Calcitriol?
Increases Ca absorption in gut
Regulates bone mineralisation by stimulating osteoblast activity
Indicated for post menopausal OP and prevention of CS induced OP
How much Calcitriol is given?
0.25μg bd concomitant with Ca supplementation
What are bisphosphonates?
Pyrophosphate mimics. They bind to hydroxyapatite in the bone and decrease resorption by inhibiting osteoclast adherence to bone surfaces.
Bisphosphonates become incorporated into the bone
What is pyrophosphate ?
An endogenous bone resorption inhibitor
What is the half life of bisphosphonates?
Up to 10 years
Why must bisphosphonates be taken in a specific way?
They are poorly absorbed. (<1%)
They should be taken while fasting with a glass of water.
Patient must remain upright and fasting for 30 minutes or may experience GI side effects or inadequate absorption
What are the adverse effects of bisphosphonates?
Oesophageal reactions
Abdominal pain and distension
Dyspepsia
Regurgitation
How is bisphosphonates excreted?
By kidneys.
Hence they are contraindicated in renal impairment with CrCl <30mL/min
What are different bisphosphonates used in OP?
Alendronat Etidronate Palmier onto Zolendronate Risedronate
What is etidronate?
Non N containing bisphosphonate
Inhibits energy production of osteoclasts
Not specific for osteoclasts vs. Osteoblasts
Should be given in cycles (not continuously) e.g. Every 2 weeks every 3 months
How much etidronate should be given?
400mg daily for 14 days followed by Ca supplementation for 76 days
Take on an empty stomach and sit upright for at least 30 mins after
What is alendronate?
N containing bisphosphonate
Binds and blocks farnesyl disphosphate synthetase which would normally cease the inhibition of orotein pentobarbitone which affects many proteins found in osteoclasts.
Alendronate prevents osteoclasts from adhering to the bone surface leading to reduced bone resorption
How much alendronate is given?
Now give 70mg orally once a week.
Take on an empty stomach with water
Avoid milk or Ca for 4 hours
It is 1000x more potent than etidronate with half life of 10 years
What is pamidronate?
N containing bisphosphonate
Suppresses accession of osteoclast precursors onto bone and their subsequent transformation into mature resorting osteoclasts.
How much pamidronate is given?
30mg infusion every 3 months
It is not funded in the community so is mainly adminstered in the hospital
Why is pamidronate not licensed for use in nz?
It is give in as IV due to oesophageal indication
What is zolendronate?
The most potent bisphosphonate and given as an infusion
Give if suspected non compliance.
At low doses it maintains bone mass, reduces bone porosity and increases mechanical bone strength without affecting bone mineralisation
It also inhibits farnesyl pyrophosphate synthetase
How much zolendronate is given?
5mg/100ml IV infusion once per yea reduce dose in impaired renal function. Only use if benefit > risk where CrCl <30ml/min
What is raloxifen or Demosumab?
Demosumab is a human monoclonal antibody that inhibits osteoclast formation function and survival
Raloxifene is a selective estrogen receptor modulator and mimics the beneficial effects of oestrogen on bone and lipids without stimulating estrogen receptors in breast and endometrium
How does raloxifene work?
Inhibits vertebral bone loss by blocking activity of cytokines which stimulate bone resorption
What are the adverse effects of raloxifene ?
May cause hot flushes and increase risk of VTE
However it is associated with a decreased breast cancer risk
How much raloxifene is given?
60mg OD (NS)
How does Demosumab work?
Targets RANKL and inhibits development and activity of osteoclasts
Decreases bone resorption and increases BMD
How is denosumab given?
60mg subcutaneously every 6 months
What are the side effects of denosumab?
Infections of respiratory and urinary tract Constipation Rashes Joint pain Osteo necrosis of the jaw
What is calcitonin?
A hormone produced naturally in the thyroid that is a powerful inhibitor of osteoclasts
It has opiate mediated analgesic properties for bone pain and increases urinary excretion of Ca but also increased BMD significantly
What are the side effects of calcitonin?
GI discomfort
Rhinitis
Congestion
Redness and epistaxis (nasal spray)
How much calcitonin is give?
200units in one nostril OD
Funded
What is calcitonin used for?
Bone pain
Crushed vertebrae?
What is teriparatide?
Synthetic form of human parathyroid hormone
How does teriparatide work?
Increases intestinal absorption of Ca,
Increases tubular resorption of Ca
Increases excretion of P by the kidneys
Stimulates bone formation by direct effects on osteoblasts
Causes greater increase in BMD than antiresorptives
Improves bone micro architecture
What are the side effects of teriparatide?
Hypercalcaemia Raised uric acid levels Leg cramps Nausea Headaches
How much teriparatide is given?
20mg SC OD
What is HRT ?
Hormone replacement therapy
Why is HRT used?
Oestrogen helps maintain and increase bone mass after menopause
HRT should only be used short term in women who need oestrogen therapy for menopausal symptoms such as not flushes
What are the adverse effects of HRT?
Increases risk of pulmonary embolism
Stroke
Breast cancer
Dementia
Hence only reserved for women <60
How does strontium ranelate work?
It has a dual action on the skeleton by stimulating bone formation and decreasing bone resorption
Resulting in marked increase in bone mass, size and strength of bone with decreased risk of vertebral fractures
What is the adverse effects of strontium ranelate?
Nausea Diarrhoea VTE Headache Dermatitis Dress
Also not funded in nz
What is risedronate?
Quite a potent bisphosphonate. (5000x)
Used in fosamax with alendronate
How do thiazide diuretics help with OP?
Increase urinary Ca reabsorption therefore decreasing excretion of Ca
How does fluoride help OP?
Potent osteoblast mitogen which stimulates bone formation and significantly increases BMD.
It has not been shown to reduce fractures
How do status help with OP?
Stimulate bone formation and have a potential to decrease fracture risk, though more trials are required
How does vitamin K help with OP?
Plays a role in bone metabolism
What are the non pharmacological treatments of OP?
Balanced diet rich in Ca energy vitamins
If inadequate dietary intake cannot be achieved, Ca supplements are necessary
Smoking cessation to help optimise peak bone mass, minimise bone loss and ultimately reduce fracture risk
Limit alcohol consumption
Weight bearing aerobic and strengthening exercises can decrease eisk of falls and fractures by improving muscle strength, coordination, balance and mobility
Limit caffeine consumption as it increases Ca excretion
Caffeine intake should ideally be limited to 2 servings per day (2-4 servings a day concerning if adequate Ca is not achieved)
Hip protectors can decrease force of impact form a side ways fall
