Osteoporosis Flashcards
Function of osteoprogenitor cells
Stem cell population, gives rise to osteoblasts
Function of osteoblasts
Responsible for bone formation, cover the surface of bone
What are osteocytes ?
Mature bone cells - embedded in lacunae and are relatively inactive.
Function of osteocytes
Maintain bone matrix through cell-cell communication and influence bone remodelling.
Mechanosensing
What are osteoclasts ?
Multi-nucleated, derived from haematopoetic cells.
Function of osteoclasts
In response to mechanical stresses and physiological demands, they resorb bone matrix by demineralisation.
Age 0-25
Bone gain
Resorption < Formation
Age 25-35
Bone Mass Stable
Resorption = Formation
Age >35
Bone Loss
Resorption > Formation
What is bone mass related to ?
Age
Biological Sex
(female - bone loss due to menopause)
Describe bone loss due to menopause
Hormonal changes associated with menopause.
Increased activity of osteoclasts
Who does osteoporosis affect ?
~ 3 million people in the UK
1 in 3 women
(predominantly due to menopausal shift & regulation of osteoblasts activity)
1 in 12 men
(due to progressive decline in function)
Causes of osteoporosis
Decreased size of osteons
Thinning of trabeculae
Enlargement of Haversian and marrow spaces
State the classifications of osteoporosis
Type 1 - post menopausal
Type 2 - age related in those over 75
Disuse osteoporosis
Describe Type 1- Post menopausal osteoporosis
Affects mainly cancellous (trabecular) bone
Vertebral and distal radius fracture is common
Related to loss of oestrogen
F:M= 6:1
What is Type 1 - post menopausal osteoporosis related to ?
Loss of oestrogen
What does Type 1 - post menopausal osteoporosis affect ?
Affects mainly cancellous (trabecular) bone
Describe Type 2- Age related in those over 75
Affects cancellous and cortical bone
Is related to poor calcium absorption
Hip and Pelvic fractures common
F:M= 2:1
What is Type 2 - age related osteoporosis in those over 75 related to ?
Poor calcium absorption
What does Type 2 - age related osteoporosis in those over 75 affect ?
Affects cancellous and cortical bone
Describe disuse osteoporosis
Conditions resulting in prolonged immobilisation, typically in neurological or muscle disease.
‘Don’t use it, you lose it’
- e.g. living outside the effects of gravity
Clinical consequences of osteoporosis
Increase in bone fragility
Susceptibility to fracture: micro- or fragility fracture
Fragility fracture
“Low energy” trauma
Mechanical forces that would not ordinarily cause fracture
WHO: fall from a standing height or less, that results in a fracture
Number of fragility fractures per year
Est. 500,000 present at hospital with FF
Cost of fragility fractures to the NHS
> £4.4 billion
Hip Fracture (due to fragility) statistics
Fatal in 20-30% of cases
Only 30% fully recover
Permanently disables 50%
Who is at risk of fragility fractures ?
Increased risk from > 45 years old
Women more likely than men
Common sites for osteoporotic fractures
Proximal humerus
Distal radius
Spine
Femoral neck
Vertebral body
Non-modifiable risk factors for osteoporosis
Biological sex
Age
Previous fracture
Family history
Race
Early menopause (<45 year old)
Modifiable risk factors for osteoporosis
Smoking
Alcohol
Inactivity
Low calcium
Low BMI
Oestrogen deficiency
Vitamin D deficiency
State some factors contributing to osteoporotic fracture risk
Bone strength (Material properties)
Postural reflexes
Soft padding tissue
Falls
What is bone remodelling affected by ?
Exercise and Lifestyle
Nutrition
Hormones
Race and Ethnicity - osteoporosis
Prevalence ~50% lower in black Americans than white
Rates of fragility fractures in the UK 4.7x greater in white compared to black women
Chinese women and BMD
Chinese women have lower BMD, but lower rates of hip and spine fractures.
GAHT
Gender-Affirming Hormone Replacement Therapy
BMD
Bone Mineral Density
Transgender patients and Osteoporosis
Adherence to GAHT may protect BMD of both trans women and trans men.
Trans women and BMD
Trans women tend to have lower BMD prior to initiation of GAHT.
- Lower BMD as they are not likely to have been drinking, involved in high impact sports etc.
Impact of puberty blockers on BMD
Currently unclear what impact puberty blockers have on bone mass and fracture risk.
Lifestyle and Nutritional factors affecting osteoporosis
Smoking
Excess Alcohol
Sedentary - inactive lifestyle
Prolonged Immobilisation
State some conditions / diseases that influence osteoporosis
Diabetes
Inflammatory bowel disease
Inflammatory Rheumatic diseases
Chronic liver disease
HIV
Asthma
Endocrine diseases
State the common factor of coexisting conditions to osteoporosis
Inflammatory link
- formation of osteoclasts come from haematopoetic cells
Hormonal link
Absorption and Ability to process and utilise things from the diet
Neurological links
State some drugs that increase the chances of osteoporosis
Long term antidepressants
Antiepileptics
Aromatase inhibitors
Oral glucocorticoids
Aromatase inhibtors use
Breast cancer
Oral glucocorticoids use
Inflammatory/Immune conditions
Proton pump inhibitors use
Decrease stomach acid
Gonadotrophin releasing hormone agonists use
Prostate cancer
Long-term medroxyprogesterone acetate (DMPA)
Injectable contraceptive
Thiazolidinediones
Diabetes
Risk of another fracture after a previous fragility fracture
A previous wrist fracture:
- doubles risk of future hip fracture
- triples risk of future vertebral fracture
Assessing patients risk of osteoporosis
FRAX
WHO- fracture risk assessment test
DEXA
Dual-energy x-ray absorptiometry scan
Describe DEXA
Low dose x-rays with 2 distinct energy peaks (one absorbed by soft tissue, and the other by bone)
Subtracting one from the other gives a patients bone mineral density.
How to calculate BMD ?
DEXA scan
T score
Comparison with a young adult of the same sex with peak bone mass
Normal T score
T score:
> -1
Osteopenia
Bone thinning
T score:
-1 to -2.5
Osteoporosis
T score
< -2.5
Z score
Comparison of the patient’s BMD with data from same age/sex/size.
Investigations for osteoporosis
DEXA score
Bone turnover markers
Ruling out other things:
- thyroid function tests
- testosterone and gonadotropin leves in men
Bone turnover markers
Urine and/or blood tests, infrequently used but may provide some useful information on treatment success.
Bone turnover markers for:
- Formation
- Resorption
Formation
- bone alkaline phosphatase
- increased levels, increased formation
Resorption
- cross linked C-telopeptide of type 1 collagen (CTX)
- increased levels, increased resorption
CTX
Fragments of collagen caused by osteoclasts dissolving the bone matrix
Increased abundance indicates increased osteoclast activity
Main agents in the pharmacological treatment of osteoporosis
Bisphosphonates
Denosumab
Romosozumab
Teriparatide
Bisphosphonates
Alendronate
Risedronate
Zolendronic acid
Denosumab
Monoclonal antibody against RANKL
Romosozumab
Monoclonal Antibody against SOT
Teriparatide
Peptide fragment of parathyroid hormone (PTH)
Function of bisphosphonates
Anti-resorptive: disrupts the activity of osteoclasts
Function of denosumab
Anti-resorptive: disrupts the formation and lifespan of osteoclasts
Function of romosozumab
Anti-resorptive and anabolic : disrupts osteoclasts, promotes osteoblasts
Function of teriparatide
Anabolic: promotes osteoblasts
Side effects of bisphosphonates
GI upset, oesophagitis, mandibular necrosis, uveitis, atypical femur fractures
Side effects of denosumab
Hypocalcaemia, Mandibular necrosis and Rebound resorption
Side effects of romosozumab
Hypocalcaemia, Mandibular necrosis and Rebound resorption
Side effects of teriparatide
Nausea, Headache, Dizziness, Leg Cramps, Hypercalcaemia
Describe the mechanism of action of bisphosphonates
Bisphosphonates - inhibit the function of osteoclasts BY:
- promoting cell death in osteoclasts
- inhibit the pathways that allow survival of osteoclasts
- prevent resorption that is mediated by osteoclasts , disrupting their function even before they die
- inhibit the formation of osteoclast precursors
Function of PTH
PTH (parathyroid hormone) which is naturally found in the body and regulates normal bone function
Describe the mechanism of action of teriparatide
Teriparatide is a fragment of PTH.
If given infrequently, it promotes osteoblasts activity.
It binds to receptors on precursors for osteoblasts, and promotes them to mature into osteoblasts and put down more bone.
How should teriparatide be given ?
Infrequently
To increases osteoblast activity.
What happens if you give teriparatide to a patient constantly what happens ?
High levels of PTH for a long period of time inhibits osteoblasts function and increases osteoclasts function.
Describe the mechanism of action of denosumab
Denosumab is a RANK ligand inhibitor
- inhibits osteoclasts formation and activity
- doesn’t affect osteoblasts, maintains osteoblast function
SOST
Released from osteocytes and is a mediator of communication between osteocytes.
Function of SOST
SOST is released from osteocytes to the surface of bone and it:
- negatively regulates osteoblasts, prevents bone formation.
- positively regulates osteoclasts, accelerates resorption
Describe the mechanism of action of romosozumab
Increases osteoblast activity
Decreases osteoclast activity
Interacts with SOST - blocks SOST
State some other pharmacological options in the treatment of osteoporosis
Strontium ranelate
Selective estrogen receptor modulators (SERMS - raloxifene)
Ca2+ supplements
Hormone replacement therapy
- reduced risk of osteoporosis
- increased risk of breast cancer
Non-pharmacological interventions for osteoporosis
Exercise
Nutrition
Vitamin D and calcium intake
Reduced alcohol / cigarettes
Exercise
Weight bearing exercise with ‘impact’
- jumping
- skipping
Muscle strengthening exercise
Nutrition
Not just calcium and vitamin D, needs a balanced and healthy diet
Vitamin D and calcium intake
Sunlight, food, supplements
(esp. during pandemic)
