Osteoporosis Flashcards
Which component of bone comprises the majority of skeletal mass? Which component of bone has a higher turnover rate?
- cortical bone (80% of bone mass)
- trabecular bone has a higher turnover rate - markers are matrix proteins
When is peak bone mass achieved?
Describe the decline in bone mass.
- Around 20 in white women, plateaus and then decreases around 40-50
- Femoral neck is 18.5
- Spine is 23
- decreases 0.5-1% from peak, then 1-2% around menopause, then back to 0.5-1%
- men have a more flat and slower rate of change
What are some factors causing bone loss? Medications?
- cigarettes, alcohol, physical inactivity
- prednisone (corticosteroids), glucocorticoids, anticonvulsants, anticoagulants, androgen deprivation (medroxyprogesterone)
What are three ways we assess bone quality?
- High-Res Peripheral Quantitative CT –> distal radius and tibia CT
- Trabecular Bone Scan –> pixels to estimate microarchitecture, images of trabecular bone in spine
- Bone Microindentation Testing –> 1mm probe to anterior tibia measures strength while cycling
What are outcome measurements of TBS?
1.35+ (normal)
1.2-1.35 (partially degraded)
under 1.2 (degraded)
Definition of Osteoporosis
- low bone mass and micro architectural deterioration leading to bone fragility and susceptibility to fracture
- low BMD is a result of low peak bone mass and increased bone loss
How do we assess bone quantity? Outcome scores?
- Normal X-ray
- Dual energy x-ray absorptiometry (DXA) –> special scanners
-1 or above (normal)
-1 to -2.5 (osteopenia)
- 2.5 and lower (osteoporosis)
- 2.5 and lower plus fracture (severe osteoporosis)
When should someone receive treatment for osteoporosis?
- hip or vertebral fracture
- 2+ falls in last year
- T score under -2.5 after excluding secondary causes
- low BMD between -1 to -2.5
- 10 year probability of hip fracture over 3%
- 10 year probability of any fracture over 20%
If someone is low risk –> lifestyle changes
If someone is mod/high risk –> medications
CAROC
- When would you increase someone to the next risk category?
- When would someone be automatically high risk? Moderate risk?
- femoral neck T-score on y axis, age on the x axis (different graph for men vs women)
- calculates 10 year absolute fracture risk (uses lowest T-score)
- Increase to next category if –> prior fragility fracture over 40 or prolonged corticosteroid use
- Med risk if lumbar/hip T score is under -2.5
- High risk if prior hip or vertebral fracture or 1+ non-vertebral fragile fracture
*EASIER FOR RADIOLOGISTS, HOW 10Y FRACTURE RISK IS CURRENTLY REPORTED IN CANADA
low risk –> 10% (year fracture risk)
moderate –> 10-20%
high –> 20%
FRAX
- estimates fracture risk, determine if patient needs treatment
- takes into consideration age, sex, height, weight, previous fracture, family history, smoking, RA, glucocorticoids, alcohol
- does not require a BMD but can include femoral neck T-score
Resporption vs formation time
- resorption is fast (~3 weeks)
- formation is slow (3-4 months) and mineralization can take years in cancellous bone
How do osteoclasts respond to calcitonin? What do clasts dissolve?
- Calcitonin inhibits clasts –> their pseudopodia will retract. They dissolve type I collagen.
- Calcitonin can be given to reduce risk of vertebral fractures in post-menopausal women.
What stimulates/ inhibits osteoblasts?
Stimulates –> testosterone and progesterone
Inhibits –> cortisol
What is periosteal apposition?
- external cortical diameter increases but the cortical thickness decreases due to endosteal resorption
- increases with age and exercise
What are some genetic conditions that can affect bone?
- osteogenesis imperfecta
- hypophosphatasia
What hormones decrease resorption and increase formation? (Overall formation of bone)
- Estrogen in M/F and testosterone in M inhibit resorption
- Progesterone in F and testosterone in M promote formation
What hormones increase resorption and inhibit formation? (Overall loss of bone)
- Excess cortisol (stress), and an acute drop in estrogen and testosterone increases resorption (women on aromatase inhibitors for BC are at risk)
- Excess cortisol (stress) inhibits formation
How does starting OCPs affect peak bone mass?
- OCPs increase ethinyl estradiol, this suppresses modelling leading to a decrease in peak bone mass.
How is bone resorption affected by menstruation?
-Drop in estrogen during mid-cycle peak and rapid increase in progesterone (acute drop of estrogen promotes resorption) –> thus bone resorption is slightly increased and you are more at risk for fracture
- ovulatory disturbances can also cause a drop in progesterone (no formation to counter resorption)
Distribution of serum calcium? What factors can affect serum Ca?
- 45% bound to albumin
- 40% in free ionized active form
- 15% bound to phosphate/citrate anions
- serum Ca can be altered by hypoalbuminemia and pH
Where is the majority of calcium found in the body? What regulates calcium?
- 99.9% in bone
- regulated by diet, kidney (excretes 100-400mg/day), PTH, and calcitriol
Role of Calcitonin wrt Calcium? Where is it produced?
- Calcitonin is made by the parafollicular cells of the thyroid
- Decreases serum Ca, minor control of calcium
- Protects the skeleton in pregnancy/lactation, helps restrict post-prandial hypercalcemia
Role of calcitriol (1,25-dihydroxy-vitamin D)? Where is it produced?
- Increases absorption of dietary calcium and phosphorus (increases serum calcium)
- Made by the kidney
Role of PTH wrt bone and kidney?
- Kidney –> Calcium resorption, phosphate excretion, renal conversion of 25-OH Vitamin D to calcitriol
- Bone –> increases resorption IF SUSTAINED, increases formation IF NORMAL EPISODIC RELEASE
(increases serum calcium when given exogenously)
Different causes of hypercalcemia? Signs of each?
- Malignancy (decreased or normal PTH)
- higher/more rapid increase in serum Ca, more sx
- Primary hyperparathyroidism (increased PTH)
- longstanding asymptomatic/mild, postmenopausal,
normal physical exam, family history
- longstanding asymptomatic/mild, postmenopausal,
Symptoms of mild/longstanding/ acute hypercalcemia?
Mild –> constipation, fatigue, depression
Longstanding –> renal stones, polyuria/dipsia, osteoporosis, fractures, bone pain, anorexia, GI pain, depression
Acute –> stupor, coma, short QT
Treatment of mild/ moderate/ severe hypercalcemia?
Mild (under 3) –> hydration, avoid lithium/ dietary/ thiazide diuretics
Moderate (3-3.5) –> see below
Severe (3.5+) –> IV saline, calcitonin, bisphosphontaes (Zolendronic Acid)
Different causes of hypocalcemia?
If decreased PTH –> surgical, autoimmune, congenital, destruction or infiltration
If increased PTH –> vitamin D deficiency, sepsis, pancreatitis, CKD, hemorrhage, post-surgery
Symptoms of acute vs chronic hypocalcemia?
Acute –> tetany, seizures, ventricular arrhythmia, long QT
Chronic –> dental, cataracts, Parkinsons
Treatment of mild/chronic vs acute/severe hypocalcemia?
Mild/chronic –> oral calcium and vitamin D, treat cause
Severe/ acute –> rapid IV correction
Why should you always check magnesium when hypocalcemic?
- low Mg levels can decrease PTH
- causes of low MG include malabsorption, diarrhea, alcoholism and malnutrition
Sources of vitamin D? Recommend Vitamin D dose?
- Sunlight
- Cod liver oil, salmon, mushrooms, fortified milk, plant beverages, egg yolk
- Higher incidence of vitamin D deficiency in darker skins
- 600-1000 IUD (over 800 if 50+)
Signs of vitamin D deficiency/ insufficiency? Associated comorbidities? Who is at risk for Vitamin D deficiency?
Deficiency –> rickets, osteomalacia, proximal myopathy
Insufficiency –> bone loss, falls, decreased BMD, fractures
- cancer, RA, MS, T1DM, TB, glu, lung infections
- at risk –> obese, malabsorption, institutionalized
Recommended dietary calcium?
1000mg/day
1200mg/day if 70+ or a 50+ female
*do see increased BMD in female teens who ingested more calcium and milk
*giving too much results in renal stones, NOT linked to CV disease
*calcium or vitamin D are not sufficient treatment for osteoporosis
What is sarcopenia? Myostatin?
- decreased skeletal muscle and quality functioning with age –> decreased bone mass and more fractures
- influenced by exercise, nutrition, immune/endocrine, genes
- Myostatin results in poor muscle development, and thus we have developed an Ab against it
What is a fragility fracture?
- occurs spontaneously or from a minor trauma (fall from standing, sitting, supine, atypical movement, missed 1-3 steps)
- FRAGILITY FRACTURE = OSTEOPOROSIS REGARDLESS OF BMD
Risk factors for fracture?
Comorbidities?
- 65+, fragility fracture, family history, 3+ months on glucocorticoids, malabsorption (Celiac’s, Crohn’s), primary hyperparathyroidism, hypogonadism, early menopause, RA, under 60kg, alcohol, smoking
- COPD, T2DM, IBD, Celiac’s, RA
What tests should you order when looking at osteoporosis?
- Ca, CBC, creatinine, ALP, TSH, Spep (multiple myeloma), 25(OH) Vit D
Which osteoporosis drugs are antiresorptives? How do they work?
- bisphosphonates
- denosumab
- raloxifene
- HRT (estrogen)
- target clasts, decrease remodelling
Which osteoporosis drugs are anabolics? How do they work?
- teriparatide
- romosozumab
- target blasts, increase remodelling
How do bisphosphonates work? Side effects?
- inhibit clasts at the bone surface
- i.e. alen/risen/zole/etidronate
- can be either oral or IV
- GI (need to take on an empty stomach following 2h fast, no food for 30-60m), hypocalcemia (IV), flu-like sx
- Osteonecrosis of the jaw
- Esophageal cancer
- Potentially atypical femoral fracture if prolonged use
How does denosumab work? Side effects?
- binds RANK-L which prevents binding to RANK, thus inhibiting clast formation/function/survival
- more potent than bisphosphonates
- given subcutaneously every 6 months, expensive
- eczema, cellulitis, flatulence, hypocalcemia, ONJ and atypical fractures of femur
- if discontinued, can lead to decreased BMD and increased fractures
How does teriparatide work? Side effects? Main indication? Contraindications?
- PTH analog given INTERMITTENTLY –> increases ca reabsorption, increases blasts (because given intermittently), increases vitamin D
- injection, expensive
- dizziness, orthostatic hypotension, leg cramps, mild hypercalcemia
- mainly indicated for glucocorticoid osteoporosis
- cannot use for hip fractures
- hypercalcemia, major renal impairment, hyperparathyroidism, Paget’s, radiation, malignancies, pregnancy, nursing, youth with open epiphyses
How does romosozumab work? Side effects? Main indication?
- inhibits sclerostin released from osteocytes
- injection, expensive
- MI, stroke, CV death (avoid if any of these in last year)
- main indication is normal osteoporosis
How does raloxifene work?
- selective estrogen receptor modulators
- 1st line for vertebral fractures
- decreases risk of breast cancer in ER+ women
When would you give HRT?
- only give if significant symptoms of menopause and NO history of CHD/ stroke
- increases risk for CHD/ stroke/ VTE/ breast cancer
How do you monitor treatment effectiveness? Should you stop treatment for people at high risk for fracture?
- look at BMD - DXA every 1-3 years for new or moderate risk
- if someone is at high risk do not stop therapy, benefits outweigh any risks
Which drugs (especially in poly pharmacy) increase the risk of falls?
- antihypertensives
- anticholinergics
- pain medications (i.e. morphine)
What is likely cause of fall if:
- preceded by LOC?
- preceded by dizziness?
LOC –> seizure, stokes-dams attack, get an ECG and cardiac workup
Dizziness –> change of posture –> orthostatic
–> spinning –> being positional vertigo
–> unsteady –> dizziness of legs, check gait
–> decreased vision/ hearing/ near –> astronaut
Which order of drugs may be beneficial in severe osteoporosis?
- anabolics followed by antiresorptives
- build up more bone and earlier fracture prevention
Osteoporosis in Men
- same risk factors as women
- higher rates of fracture related mortality
#1 primary, #2 glucocorticoids, #3 hypogonadism, #4 excessive alcohol intake, #5 anticonvulsants
BMD in different ethnicities
- blacks have increased BMD, and Mexicans compared to whites
Effect of androgens on bone? Should we test it often? How?
- helps periosteal bone formation, larger peak bone mass in men
- if deficient –> less bone formation/ vertebral width/ femoral neck width (i.e. could happen with androgen deprivation therapy)
- No data showing replacement leads to less fractures
- 8am bioavailable testosterone
Which is the only drug not recommended for male osteoporosis?
Calcitonin, which is only prescribed for Paget’s
What drug is the only treatment for male and female hormone inhibition?
Denosumab
Glucocorticoid effect on bone
- stimulate clasts by increasing PTH, and inhibit blasts and cytes
- get a FRAX within 6 months if over 40 and on GCs
- Most common secondary cause of OP! See initial rapid loss w early fractures, trabecular bone affected first, fractures occur at higher BMD than normal
What to do following GC discontinuation? Which drugs can you not use for GC osteoporosis?
- can discontinue bisphosphonate/ transition denosumab to BP, etc. as long as fracture risk is low
- Romosozumab and calcitonin
Which drugs should never get a drug holiday?
What to do once stopping a BP?
- HRT, raloxifene, denosumab
- reassess BMD after 1-3 years based on which drug
