Osteoporosis Flashcards
What is the main theme in regards to osteoporosis care?
Prevention!
Define osteoporosis
- Loss of bone mass
- Loss of bone architecture
- Susceptibility to fracture
What is the most common bone disease in humans?
Osteoporosis
Where are the most common osteoporotic fractures?
Hip, vertebrae, and wrist
What is a common reason for loss of height, pain, and kyphosis?
Vertebral fracture
What are some of the effects of vertebral fractures?
- Can impact function (bending/reaching)
- Can impact lung/digestive function
What are some psychological sequelae of osteoporosis?
- Anxiety
- Depression
- Body image
- Self-esteem impacts
What are some quality of life sequelae of osteoporosis?
- Chronic pain management
- Disability
What percentage of adult bone mass is acquired in childhood and adolescence?
90%
At what age does bone mass peak?
- Age 19 in women
- Age 20.5 in men
At what age does bone mass begin to decline?
- Age 40 in women
- Age 50 in men
When does the most rapid bone loss occur in women?
Perimenopause
What causes such a rapid bone loss in women in perimenopause?
Drop in estrogen levels
What are some uncontrollable risk factors for osteoporosis?
- Age >50
- Female
- Menopause (especially early, before age 45)
- FH
- Low body weight/small & thin
- Caucasian/Asian
What are some controllable risk factors for osteoporosis?
- Lifelong inadequate intake of calcium & vitamin D
- Not eating enough fruits and veggies
- Excessive ETOH
- Smoking
- Too much protein, Na, and caffeine
- Lifelong inactive lifestyle
Describe the cortical portion of bones
- Dense, outer covering
- Mechanical strength & protection
Describe the trabecular portion of bones
- “Spongy” bone/mesh-like
- Inside of long bones (especially at ends), vertebrae, pelvis
- Offers mechanical support
- More metabolically active
What are the two continuous processes in bone remodeling?
Resorption and formation
How often does the human skeleton regenerate itself?
Every 10 years
What is the purpose of bone remodeling?
- Replace worn out or damaged bone
- Ensure oxygen & nutrient supply
What are the 4 phases of bone remodeling and what is involved in each?
- Resorption (osteoclasts - cells that break down old bone)
- Reversal (prepping for deposition of bone - formation of “cement line”)
- Formation (osteoblasts - cells that synthesize bone matrix formation)
- Mineralization
What is bone reabsorption?
- Resorption of bone tissue by osetoclasts & release of minerals
- Results in transfer of calcium from bone tissue to the blood
What are osteoclasts?
Multi-nucleated cells that contain numerous mitochondria and lysosomes
What are the 3 major players in regulation of bone remodeling?
- PTH
- Calcitrol (vitamin D)
- Estrogen
How does PTH maintain serum calcium?
- Stimulating bone resorption
- Increasing calcium reabsorption in kidneys
- Increasing calcitrol production in kidneys
How does calcitrol (vitamin D) maintain serum calcium?
- Increases intestinal calcium and phosphorus absorption to provide minerals needed for bones
- In cases of Ca & Phos deficiency, will stimualte bone resorption to maintain serum levels
How does estrogen maintain serum calcium?
- Inhibits bone resorption
- Increase in bone resorbing cytokines
- Can reduce bone formation directly through estrogen receptors on osteoblasts
How does calcitonin play a role in bone remodeling?
- Produced by thyroid gland
- Inhibits osteoclasts/opposes PTH
How does thyroid hormone play a role in bone remodeling?
Stimulates both resorption and formation, causing increased turn-over
How do glucocorticoids play a role in bone remodeling?
Inhibit bone formation
What is the primary treatment goal of osteoporosis?
Prevention of fractures
What does the clinical evaluation for osteoporosis look like?
- PMH: risk factor assessment
- PE: Height assessment
- Lab tests as appropriate to look for secondary causes
- BMD testing with DXA
Who should we screen for osteoporosis, according to USPTF?
- Women 65+
- Women <65 with fracture risk =/> 65+ yo white woman w/o additional risk factors (>9.3%)
- No recommendation for men w/o previous known fx or secondary causes for osteoporosis
Who should we screen for osteoporosis, according to National Osteoporosis Foundation?
- All post-menopausal women 50+ should be evaluated for osteoporotic risk to determine need for BMD testing
- BMD testing via DXA for women 65+ and men 70+
- Postmenopausal women & men 50+ who have had an adult age fx to dx & determine degree of osteoporosis
- Low-trauma fx during adulthood
& Historical ht loss (current ht is 1.5in+ shorter than peak ht age 20)
& Prospective ht loss (current ht 0.8in+ shorter previously documented ht) - Recent or ongoing long-term glucocorticoid tx - if bone density testing not available, vertebral imaging may be considered based on age alone
- Check for secondary cause of osteoporosis
What are some reasons to screen for bone density before age 65?
- PMH fragility fx
- Body weight <127lb
- Medical causes of bone loss, i.e. long-term glucocorticoid use
- 1st degree relative w/ hx hip fx
- Current smoker
- ETOH abuse
- Rheumatoid arthritis
How long does it take for glucocorticoid-induced osteoporosis to cause significant bone loss?
3 months
How many patients taking >7.5mg/dL of prednisone will fx?
50%, regardless of age or gender
What is DXA?
- Dual-energy x-ray absorptiometry (DXA)
- Imaging usually done of lumbar spine and hip
To what does the T score on a DXA refer?
Findings compared to standards for healthy, younger adults of same sex and race
To what does the Z score on a DXA refer?
of standard deviations from the mean for people of the same sex, age, and race
What is the WHO DXA definition of osteoporosis?
- Normal = T score >/= -1
- Low bone mass = -2.5 to -1
- Osteoporosis = = -2.5
What is FRAX?
- Screening tool developed by WHO
- Calculates 10-yr probability of hip fx & 10-yr probability of major osteoporotic fx
- Specific to region & ethnicity
What are some uses of FRAX?
- Helpful in decision to tx for those with low bone density but not osteoporosis
- Helpful in deciding on DXA screen (YES if 10-yr risk >9.3%)
When is consideration of Z score helpful?
Younger people or when considering secondary osteoporosis
In what cohort would you be suspicious of secondary cause?
Osteoporotic fx or low Z score in younger post-menopausal women
What diagnostic tests would you consider if you are suspicious for secondary cause?
- CBC
- CMP (including LFTs)
- 24hr urinary calcium level
- 25-hydroxyvitamin D level
- TSH
Consider: PTH, celiac panel, serum protein electrophoresis, total testosterone/gonadatropin in younger men
Who do we treat pharmacologically?
Post-menopausal women/men age 50+ with
- Hip/vertebral fx (clinically or on imaging)
- T score = -2.5 at femoral neck,hip, or lumbar spine
- Low bone mass (-1.0 > T > -2.5) and 10-yr probability of hip fx 3% or greater or major osteoporosis-related fx 20% or greater based on US FRAX algorithm
How often should we rescreen with DXA?
q2yr after intiiation of tx and then not after if stable/improved
For women 65+ who are not tx:
- 10yr interval if T-score >-1.5
- 5yr interval if T-score -1.5 to -1.99
- 1-2yr interval if T-score -2.0 to -2.49
Diagnostic classification based on T-score
- Normal: >-1.0
- Osteopenia (low bone mass): -1.0 to -2.5
- Osteoporosis:
Indications for tx
- Personal hx of hip or vertebral fx
- T-score 3%)
- Risk of any major fx of 20% (FRAX)
Non-pharmacological interventions for low bone density/osteoporosis
- Adequate calcium & vitamin D
- Tx vitamin D deficiency
- Regualr weight-bearing/muscle-strengthening exercise
- Fall prevention
- Tobacco cessation
- Tx ETOH abuse
Calcium requirements for women and men
- Women <50: 1,000mg/day
- Men <70: 50-70mg/day
- Women 51+/Men 71+: 1,200mg/day
Vitamin D requirements
800-1,000 IU/day
Foods high in dairy
- Calcium
- Dark, leafy greens
- Canned sardines and salmon
- Fortified foods
Foods high in vitamin D
- Dairy (if fortified)
- Salt-water fish: salmon, mackerel, tuna, sardines
- Liver
- Fortified foods
What is diagnosable vitamin D deficiency & what is the vitamin D goal?
- Deficiency: <20ng/mL
- Goal: >30ng/mL
Treatment for vitamin D deficiency
- 50,000 IU D2 or D3 PO weekly (or 6,000 IU daily) for 8-12 weeks
- 1,500-2,000 IU/day maintenance
How do you address fall risk in patients at risk for osteoporotic fx?
- Correct vision, home eval for environmental risks
- Referral for PT/OT for assistive devices (walkers/canes) and balance training/muscle strengthening
What are the goals of osteoporosis tx?
- Prevent fx by maintaining bone strength & reducing falls/trauma to bones
- Stable/increase bone mass
- Promote wellness
- Avoid disability
- Reduce suffering
- Tolerability of tx
What are some FDA-approved pharmacologic options for osteoporosis?
- Bisphosphonates (alendronate, ibandronate, risedronate, and zoledronic acid), which inhibit osteoclast activity & decrease bone resorption
- Calcitonin - decrease bone resorption
- Estrogen agonist/antagonist (raloxifene)
- Estrogens and/or hormone therapy, tissue-selective estrogen complex (conjugated estrogens/bazedoxifene)
- Parathyroid hormone 1-34 (teriparatide) - daily injections used with PM women with prior fractures
- Denosumab - inhibits RANK ligand (modulator of osetoclast activity)
What is the class, MOA, dosing, and side effects of Fosomax (alendronate)?
- Class: bisphosphonate
- MOA: specific inhibitor of osteoclast mediated bone resorption
- Dosing:
Therapeutic=10mg/day or 70mg/wk
Prevention=5mg/day or 35mg/wk - Alendronate + cholecalciferol (vit D3):
70mg + 2,800 or 5,600 IU vit D once/wk - Side effects: esophageal sx, MS aches, HA
What is the class, MOA, dosing, pt instructions and side effects of Actonel, Atlevia (risedronate)?
- Class: bisphosphonate
- MOA: specific inhibitor of osteoclast mediated bone resorption
- Dosing (therapeutic/prevention):
5mg/day or 35mg/wk or 150mg/mo - Actonel + calcium: 35mg (4 tabs) + 500mg calcium carbonate (24 tabs)
- Can be taken after breakfast *
- Side effects: esophageal sx, MS aches, HA
What is the dosing and pt instructions of Boniva (ibandronate)?
- Daily dose: 2.5 mg
- Monthly dose: 150mg
- Wait 60 min before eating, drinking, or lying down *
Instructions and side effects for bisphosphonates
- If PO, must be taken 1st thing in AM w/ 8oz water, wait 30min (alendronate/Fosamax and risendronate/Actonal/Atlevia) to 60 min (ibandronate/Boniva) before eating and be upright 30 min (alend/risend) to 60 min (iband) after taking
- SE: GI & esophageal sx
- Contraindicated w/ GFR <30-35
- Rare reports of osteonecrosis of jaw, femur fx
What is the MOA, dosing, pt instructions and side effects of Miacalcin or Fortical (calcitonin)?
- Regulates plasma calcium
- Decreases bone resorption/helps decrease bone pain
- Dose: 200U/spray once in nostril daily
- Miacalcin: 200U/mL 100 units SC or IM every other day
- Adverse rx: rhinitis, GI upset, flushing, rash (inj)
- Not indicated for prophylactic dosing
What is the class, MOA, dosing, and side effects of Evista (raloxifene)?
- SERM - Selective Estrogen Receptor Modulator
- May reduce risk of breast cancer
- Less likely than tamoxifen to lead to uterine cancer, hysterectomy, or cataracts
- Therapeutic/prophylactic dose: 60mg/day
- Adverse rxn: hot flashes, increased risk blood clots
What is the class, MOA, dosing, pt instructions and side effects of Forteo (teriparatide)?
- Human parathyroid hormone
- Anabolic: increases bone remodeling & increases skeletal mass & bone strength
- Hx osteoporotic fx/multiple risk factors for fx/failed or intolerant to osteoporosis tx
- Dosing: 20mcg SC once daily into thigh/abd wall
- May tx for up to 2 years
- Adverse rxn: dizziness, leg cramps, hypercalcemia, hyperuricemia, inj site rxn
What are other options for bisphosphonates?
Boniva (IV):
- Administered every 3mo
- 15sec injection w/ butterfly needle
- Can be obtained at OBGYN/Rheum & Endocrine
Reclast
- Indicated for elderly
- Reduces risk of second fracture
- Given IV 5mg once a month
What is Prolia and what does it do?
- RANK ligand inhibitor
- Inhibits formation, function, & survival of osteoclasts
What are some less widely used medications?
- Hormone therapy: NOT typically initiated for sole tx of osteoporosis
- If initiated for perimenopausal sx, does have benefits for bone density*
- Raloxifene/tamoxifen
What are some considerations in regards to tx duration?
- Consider benefits
- Consider specific tx
- Evidence of efficacy beyond 5yr limited
- Risk of ONJ & atypical femur fx increases after 5yr w/ bisphosphonates
- If modest, tx 3-5yr
- If still high risk after this duration, consider continuation/change to alternative tx
