11. Age-related changes in bone health Flashcards
bone is a _________, ___________ tissue made up of (2) explain
- 99% of ___________ is stored in body and teeth. where is remaining 1%?
- what are the 5 key functions of bone?
- Bone is a dynamic, living tissue made up of:
a) collagen: protein that provides a soft framework –> allows bone to deform wherever you put weight on bones
b) hydroxyapatite: mineral form of calcium and phosphate that adds strength and hardens the framework - > 99% of body’s calcium is stored in bones and teeth –> Remaining 1% found in the blood and interstitial fluids (for nervous system function + muscle contraction)
- support structure
- movement
- protection of vital organs (brain, heart)
- calcium reservoir
- blood cell production (bone marrow)
bone anatomy: contains 7 components ish
one of them has 2 types ish explain
- Bone tissue (osseous tissue)
- Fibrous connective tissue
- Cartilage tissue
- Bone marrow –> red marrow for RBC vs yellow marrow for fat storage
- Lymphatic and adipose tissue
- Vascular tissue
- Nervous tissue
what are the 2 types of bones? + explain
- most bones have both types?
CORTICAL BONE:
- dense and compact
- made up of cylindrical units (osteons)
TRABECULAR BONE:
- spongy, honeycomb vertical and horizontal bracing
- structure enhances strength
- Most bones have both cortical bone (compact) on the outside and trabecular (cancellous, spongy) bone on the inside
ie ribs are >75% trabecular, forearm is >95% cortical, hip is 75% cortical, 25% trabecular VS femur is 50-50
what is bone remodeling?
- happens when?
- explain the steps
- how long does it take?
- why is bone resorption important? (3)
- predominant process by which old bone tissue is removed (resorption) and replaced with new bone tissue (formation) via the biologically coupled actions of osteoclasts and osteoblasts
- happens after bones reach peak bone mass
1. osteoclasts to excavation and remove damaged tissue –> release growth factors that signal osteoblasts
*this lasts about 3 weeks
2. osteoblasts lay down new bone
3. cavity is refilled and mineralized into hydroxyapatite using Ca2+ and Phosphorus
*steps 2 and 3 lasts about 3 months
*entire remodeling cycle lasts 4-6months!
- Releases calcium into the bloodstream
- Obtains minerals needed to repair bone damage
- Heals bone injuries (microcracks, fractures)
explain bone turnover across lifespan
*schéma with formation vs resorption, male vs female
- during growth and development, formation > resorption –> high turnover rate, allows to accumulate peak mineral content
- during adulthood, you maintain bone mass: formation = resorption
- by age 40-45 ish resorption is slightly higher than formation –> start to lose bone mass
- for females: big decrease in bone mass at around 50 = menopause - by 60 ish: resorption > formation, but both are A LOT lower than in the 3 previous stages –> overall low turnover, continuous bone loss
how much bone mass can you gain during growth period?
vs how much bone loss happens at menopause?
- after age 50, decrease bone mass __-___% per year
- factors that influence peak bone mass? (4)
- 1300g gain
- 400g loss
- 1-3% per year
- dietary calcium intake
- vit D
- exercise (weight bearing, loading)
- genetics
what is osteoporosis? (national institutes of health definition)
“a skeletal disease characterized by compromised bone strength predisposing a person to an increased risk of fracture.”
- Bone strength reflects the integration of 2 main features: bone density and bone quality.
what is a fragility fracture? WHO def VS clinically
examples
“…a fracture caused by injury that would be insufficient to fracture normal bone: the result of reduced compressive and/or torsional strength of bone.”
- Clinically: a fracture that is a result of minimal trauma or no identifiable trauma
ie: bending forward (and fracturing vertebrae), fall from standing height (and fracturing hip or wrist), hug, cough, turning over in bed, transfer from bed to chair
fractures occur when…..? *schéma!
- what are 3 common fracture sites? + describe/give details
when applied load (falls, spine loads, shock absorption) is much bigger than bone strength (structural and material properties)
WRIST
- most common type of fracture in women <75
- when you have enough reaction time to try to break your fall
- younger old
SPINE
- usually undiagnosed unless pain or height loss (or other injury)
HIP
- increases mortality risk (well established relationship)
- decrease mobility and independence
what are 6 clinical consequences of vertebral fractures?
- Acute and chronic pain
- Breathing difficulties, reflux and other gastrointestinal symptoms (bc your ribs are super close to your hips so your organs are squished)
- Pulmonary volume loss
- Mobility limitations
- Depression, fear of falling
- Increased risk of death
burden of osteoporotic fractures
- stats for men vs women to have an osteoporotic fracture?
- ____% of women and ____% of men with a hip fracture die within 1 year
- osteoporotic fractures cost _____$ annually in Canada
- do osteoporotic hip fractures consume a lot of hospital bed days?
- 1 in 3 women and 1 in 5 men
- 22% women, 33% men
- 4.6 billion $
- osteoporotic hip fractures consume more hospital bed days than diabetes, stroke and heart attack
OSTEOPOROSIS:
- more common in (2) why?
- which racial groups are more likely to experience osteoporosis and related fractures?
- older individuals + women –> women bc after menopause: loss of estrogen
- caucasian and asian
what are risk factors for osteoporotic fractures (13)
- Age ≥65 years
- Fragility fracture after age 40
- Vertebral fracture or low bone mineral density identified on X-ray
- Parental hip fracture (genetic predisposition)
- High-risk medications, such as oral glucocorticoid treatment (i.e.,≥5 mg/d for ≥3 months), aromatase inhibitors, and androgen deprivation therapy
- Malabsorption disease (i.e., Crohn’s disease), rheumatoid arthritis, liver and kidney disease
- Endocrine disorders (i.e., primary hyperparathyroidism, hypogonadism, hyperthyroidism)
- Early menopause (before age 45)
- Higher falls risk (≥2 falls or ≥1 injurious fall in the past year)
- Height loss (≥6 cm or 2 ½ inches since young adult height)
- Low dietary calcium intake and vitamin D intake
- Lifestyle behaviours – smoking, high alcohol intake (≥3 drinks/d)
- Low body weight (i.e., <132 lbs or 60 kg) or weight loss since age 25 >10%
FRACTURE RISK ASSESSMENT:
- guidelines determine 10-year fracture risk based on 2 big + 6 sub
- what are 2 fracture risk assessment tools?
1) Risk factors:
- Prior fragility fracture after age 40
- Parental hip fracture
- Glucocorticoid use (especially for more than 3 months)
- Secondary osteoporosis
- Current smoking
- High alcohol intake
2) Bone density: aBMD g/cm2
(areal = 2D measure)
1) FRAX (WHO fracture risk assessment tool)
2) CAROC (10-year fracture risk assessment tool)
- what is the gold standard for assessment of bone mineral density?
- at which sites?
- suggest BMD testing in postmenopausal females and males who (3)
dual energy x-ray absorptiometry (DXA)
- forearm, lumbar spine, nondominant hip
- are aged 50-64 yo with previous osteoporosis-related fracture or >=2 clinical risk factors
- are aged >=65 yo with 1 clinical risk factor for fracture
- are aged >= 70 yo with no risk factors
how to determine bone health using BMD measurements?
- for which populations?
- 3 options
- how to calculate score?
what is another method?
- for which populations
- 2 options ish
- for Postmenopausal women and men ≥50 years
a) NORMAL: BMD no lower than 1 SD below the mean value; T-score >-1 SD
b) OSTEOPENIA (low bone mass): BMD between 1 and 2.5 SD below mean value; T-score ≤-1 and >-2.5 SD
c) OSTEOPOROSIS: BMD 2.5 SD or more below the mean value; T-score ≤-2.5 SD - T-score = standard deviation from the peak bone mass that a woman or man achieves in young adulthood
OTHER METHOD:
- females prior to menopause and men <50 years
*at risk if 2° condition, or athletes, etc.
- Z-scores should be used – comparison to AGE-MATCHED
a) Within expected range for age: Z-score >-2 SD
b) Below the expected range for age: Z-score <-2 SD
what are 4 methods suggested by osteoporosis canada to prevent fractures?
1) Pharmacotherapy when indicated (when high fracture risk):
- Bisphosphonate therapy (most common, anti-resorptive drug)
- Denosumab therapy (if contraindications to bisphosphonates) (injection, bone forming medication, $$$)
- Menopausal hormone therapy
2) Balance, functional, and resistance training ≥2 times/week
3) Calcium (prioritize diet; supplements if necessary) – 1200 mg/day (females >50 years and males >70 years); 1000 mg/day (males 50-70 years)
4) Vitamin D – minimum of 400 IU supplement daily plus vitamin D rich foods (adults >50 years)
SUMMARY: AGE-RELATED BONE CHANGES:
- Osteoporotic fractures may by caused by WHAT and are associated with (5)
- what are two commonly used fracture risk assessment tools that incorporate WHAT into their calculations
- WHAT is the clinical measure for bone mass because it reflects bone __________ and __________
- Fractures can be prevented through appropriate prevention strategies including (4)
- by mild to moderate trauma
- physical disability
- reduced mobility
- depression
- social isolation
- increased degree of dependence
- FRAX and CAROC –> evidence-based risk factors
- bone mineral density (BMD) –> bone strength and quantity
- phamacotherapy (if necessary)
- exercise
- calcium
- vit D
CASE STUDY:
Charles is an 80-year-old man who has a T-score of -2.2 at the lumbar spine and a T-score of -1.8 at the femoral neck and had a hip fracture after tripping on a curb and falling when he was 72. He also lost a significant amount of weight while he was recovering from his fracture and is now 56 kg. Charles has had 2 injurious falls in the past year and was identified at a high risk of falling based on recent mobility tests he completed with a physical therapist. He also has a diagnosis of rheumatoid arthritis and has taken oral glucocorticoids for prolonged periods over his lifetime.
1) Does Charles have osteoporosis based on his BMD T-scores?
2) Which risk factor(s) is/are Charles presenting with? Does Charles have a high 10-year fracture risk?
1) no! has osteopenia/low BMD bc t-score between -1 and -2.5
2)
- age >=65 yo
- fragility fracture after age 40
- oral glucocorticoid treatment
- rheumatoid arthritis
- higher falls risk (>=2 falls)
- low body weight
*not even osteoporosis but so many risks already!
what are causes of age-related bone loss/osteoporosis? (6)
- Advanced age
- Low peak bone mass
- Hormonal deficiency
- Glucocorticoid therapy
- Calcium or vitamin D deficiency
- Sedentary lifestyle/physical inactivity
what are age-related changes to bone –> MATERIAL properties?
- 2 main + 2 subs in the first main
what is the analogy she gave of young vs old bone?
1) Bone strength is reduced when bone becomes more BRITTLE
a) Decrease in collagen content –> gives soft, deformable bones
- decrease of resistance to fatigue and toughness of bone with age
b) Increase in mineralization
- Amount of deformation that can occur prior to failure decreases with age leading to increase bone fragility
2) Microcracks accumulate at a faster rate in older bone
- young bone like chocolate filled egg –> needs a lot of strain to increase the stress (fracture risk (?))
VS old bone = hollow chicken egg –> much more risk of faillint/more stress
what are age-related changes to bone –> STRUCTURAL properties? (6)
- decrease Total bone volume
- decrease Trabecular thickness
- decrease Trabecular number
- decrease Plate connectivity (less connected to each other)
- Preferential loss of horizontal plates and struts
- Greater cortical porosity
what are age-related changes to bone –> BONE GEOMETRY
- men vs women?
MEN
- increase bone size
- decrease cortical thickness
*but greater protection with age bc distribution of formation (on outer border) vs resorption inside
FEMALE:
- increase/ish bone size
- decrease cortical thickness
*less periosteal bone formation (on outer bone) = weaker
when do females vs males have their peak BMD velocity?
90% of peak bone mass is acquired by age _____ for females and age ____ for males
females: 12-13
males: 14-15
*corresponds to ages where biggest height growth too!
- 18 for females, 20 for males
- menopause = WHAT? (main “symptom ish)
- decrease in which hormone, starts when?
- what happens to rate of bone loss during menopause?
- lose __% of BMD per year after menopause, leading to a potential loss of up to ___% of BMD within first 5 years post-menopause
RESULTS in what?
men?
- no period for a full year (avg age 52)
- decrease in ovarian hormone production = gradual –> starts several years before last period
- During menopause, women experience a significantly INCREASED rate of bone loss due to declining estrogen and progesterone levels
- around 1% of her BMD per year after menopause –> up to 10% of BMD within the first 5 years post-menopause (much higher than the 1-3%)
RESULT: Women are at higher risk of osteoporosis and fracture - Age-related decrease in testosterone levels in males occurs and is associated with bone loss and an increased risk of osteoporosis (but to a lesser extent than females)
what are the effects of estrogen on bone cells?
OSTEOCLAST
OSTEOCYTE
OSTEOBLAST
OVERALL?
OSTEOCLAST
- decrease osteoclast precursor
- decrease cytokines that stimulate osteoclast differentiation, recruitment and activity
- increase apoptosis
OSTEOCYTE
- decrease apoptosis
OSTEOBLAST
- increase osteoblastogenesis
- decrease apoptosis
OVERALL: protective effect! anti-resorptive!
what are the effects of estrogen deficiency on bone cells?
OSTEOCLAST
OSTEOCYTE
OSTEOBLAST
OVERALL?
- increase bone resorption (bc no more decrease in osteoclasts)
- decrease osteoblast number (bc no more increase in osteoblasts) –> decrease bone formation
- no more decrease in osteocyte apoptosis
- overall: decrease bone quality = fracture
GLUCOCORTICOIDS = class of _______ hormones
- example
- pharmacologic uses (4)
- side effects (7)
- steroid
- Cortisol (or hydrocortisone): produced by adrenal cortex
- suppress allergies
- asthma
- inflammatory disorders (e.g., arthritis)
- autoimmune diseases
SIDE EFFECTS:
- Muscle breakdown and weakness
- decrease intestinal calcium absorption, increase urinary calcium & phosphate loss
- decrease Bone mineral density, altered bone structure
- decrease Gonadal steroid (estrogen, testosterone) production (anovulation, menstrual irregularity)
- Growth failure, pubertal delay
- increase Gluconeogenesis, insulin resistance
- increase Visceral and truncal fat deposition –> weight gain
explain the effect of glucocorticoid-induced bone loss on
OSTEOCLAST
OSTEOCYTE
OSTEOBLAST
OVERALL?
OSTEOCLAST
- increase osteoclast survival
*increase bone resorption
OSTEOCYTE
- increase osteocyte apoptosis
- decrease osteocyte viability
*decrease bone quality
OSTEOBLAST
- decrease proliferation of osteoblast precursors
- increase osteoblast apoptosis
- decrease osteoblast number
*decrease bone formation
OVERALL?
increase bone resorption + decrease bone formation –> decrease bone quality = fracture
GLUCOCORTICOIDS AND FRACTURE RISK
- ___-___% of those on prolonged glucocorticoid therapy (> __ months) will develop osteoporosis
- predictor of WHAT independent of WHAT
- as little as ____ mg/day can cause alterations in bone strength
- 30-50%, >3months
- fractures at higher bone mineral density than women with bone loss after menopause –> PREDICTOR OF FRACTURE INDEPENDENT OF BONE MINERAL DENSITY
*ie might increase risk of fracture even with normal BMD - 2.5mg/d
SUMMARY; CAUSES OF BONE LOSS
- after peak bone is reached, there is subsequent loss of bone where? (4)
- with aging, increase in bone formation/resorption with decrease in bone formation/resorption –> leads to WHAT (2) which leads to WHAT
- estrogen has a __________ effect on bone and increase/decrease sharply when women reach __________ leading to what?
- glucocorticoids cause profound effects on (4) leading to (2)
- lumbar spine, hip, forearm
- increase bone resorption alongside decrease bone formation: decrease in bone mass + deterioration in bone strength and structure –> increase risk of osteoporosis and fractures in older individuals
- PROTECTIVE –> decrease sharply when women reach menopause, leading to rapid and significant bone loss
- Glucocorticoids cause profound effects on
- bone cell proliferation
- differentiation
- function
- increase bone resorption
*leading to bone loss and greater fracture risk
