Osteoporosis Flashcards
Define a fragility fracture. (DFCM)
- Fracture occurring spontaneously or following minor injury such as a fall from standing height or less or at walking speed or less
- Excluding craniofacial, hand, foot and ankle fractures
- Fragility fractures of the spine can occur due to bending, coughing, sneezing, reaching or other minor events
What % of fractures in menopausal women over age 50 are fragility fractures? (CMAJ)
- 80%
What proportion of white women and white men will have an osteoporosis-related fracture in their lifetime? (AFP)
- 1 in 2 white women
- 1 in 5 white men
Are postfracture mortality and institutionalization rates higher for men or women? (CMAJ)
- Men
Name 9 risk factors for osteoporotic fractures. (TOP)
- Fragility fracture after age 40 and at risk for future fractures
- Vertebral compression fracture or osteopenia identified on radiography
- Parental hip fracture
- Prolonged use of glucocorticoids (At least 3 months cumulative therapy in the previous year at a prednisone-equivalent dose >7.5 mg daily)
- Use of other high risk medications (e.g. aromatase inhibitors or ADT)
- Rheumatoid arthritis, malabsorption syndrome, other disorders strongly associated with osteoporosis (e.g. primary hyperparathyroidism, hypogonadism)
- Current smoker
- High alcohol intake (>3 units/day)
- Major weight loss (10% below their body weight at age 25)
At what age should men and women be assessed for osteoporosis and fracture risk? (CMAJ)
- 50 years old
What should clinicians do to assess for osteoporosis and fracture risk in the office prior to specific osteoporosis screening? (CMAJ)
- Measure height annually
- Assess history of falls – if there has been a fall, multifactorial assessment should be conducted including the ability to get out of a chair without using arms
What is the definition of osteopenia and osteoporosis according to WHO? (CMAJ/AFP)
- Osteopenia: BMD of 1.0 and 2.5 standard deviations below the peak bone mass for young adults (healthy 30-year olds) (-2.5 < T-score ≤ -1.0)
- Osteoporosis: BMD of 2.5 or more standard deviations below the peak bone mass for young adults (healthy 30-year olds) (T-score ≤ -2.5)
What is the difference between a T-score and a Z-score for osteoporosis?
- T-score – BMD SD compared to healthy 30-year olds
- Z-score – BMD SD compared to same age and body size
What tool is suggested for clinicians to use in the context of case finding individuals 50-64 years of age with no known risk factors who may be at risk of fracture? (TOP/TFP)
- Osteoporosis Self-Assessment Tool (OST)
What is the OST and what are indications for BMD testing? (TOP/TFP)
- OST = Weight (kg) – Age (years)
- <10 à Order BMD (Moderate-High Risk)
- ≥10 à Reassess OST in 5 years
What is the sensitivity and specificity of the OST in identifying femoral neck osteoporosis? (TOP)
- Sensitivity 92%
- Specificity 39%
What differentiates the OST from other tools to assess the risk of osteoporosis? (TOP/TFP)
- OST validated in both sexes and a variety of ages
According to the 2010 Canadian Osteoporosis guidelines, what are indications for measuring BMD in adults <50 years of age? (CMAJ)
- Fragility fracture
- Prolonged use of glucocorticoids
- Use of other high-risk medications (e.g. aromatase inhibitors, ADT)
- Hypogonadism or premature menopause (age <45 yr)
- Malabsorption syndrome
- Primary hyperparathyroidism
- Other disorders strongly associated with rapid bone loss and/or fracture
According to the 2010 Canadian Osteoporosis guidelines, what are indications for measuring BMD in adults ≥50 years of age? (CMAJ)
- Age ≥65 years (both women and men)
- Clinical risk factors for fracture (menopausal women, men age 50-64 yr)
- Fragility fracture after age 40 yr
- Prolonged use of glucocorticoids
- Use of other high-risk medications (e.g. aromatase inhibitors, ADT)
- Parental hip fracture
- Vertebral fracture or osteopenia identified on radiography
- Current smoking
- High alcohol intake
- Low body weight (< 60 kg) or major weight loss (> 10% of body weight at age 25 yr)
- Rheumatoid arthritis
- Other disorders strongly associated with osteoporosis
According to the 2010 Canadian Osteoporosis guidelines, what biochemical tests are recommended for patients being assessed for osteoporosis? (CMAJ)
- Calcium, corrected for albumin
- Complete blood count
- Creatinine
- Alkaline phosphatase
- Thyroid-stimulating hormone
- Serum protein electrophoresis (for patients with vertebral fractures)
- 25-Hydroxyvitamin D
- Should be measured after 3-4 months of adequate supplementation and should not be repeated if an optimal level (at least 75 nmol/L) is achieved
According to Choosing Wisely Canada, who should receive DEXA screening for osteoporosis? (CWC)
- All patients aged 50 years and older should be evaluated for risk factors using tools such as the OST
- DEXA not warranted on women under 65 or men under 70 at low risk
According to Choosing Wisely Canada, what is the minimum amount of time that should pass before repeating a DEXA scan? (CWC)
- Minimum of every 2 years
What is recommended for all women, and men with one or more risk factors, 65 years and older? (TOP)
- An absolute fracture risk assessment (includes BMD)
What is the TOP guideline for screening and treatment for osteoporosis and fracture risk?
What two tools are recommended for an absolute fracture risk assessment? (TOP)
- CAROC (Canadian Association of Radiologists and Osteoporosis Canada)
- FRAX (WHO – specific for Canada)
How does the CAROC stratify fracture risk? (TOP)
- Women and men over age 50 stratified into 3 zones of risk for MAJOR osteoporotic fracture within 10 years:
- Low (<10%)
- Moderate (10-20%)
- High (>20%)
What is required to use CAROC? (TOP)
- Age
- Sex
- T-score for the femoral neck CPG (BMD test)
How was the reference range determined for the CAROC? (CMAJ)
- Reference range for white women of the NHANES III
What is an advantage of using FRAX over CAROC and why? (TOP)
- FRAX provides ABSOLUTE (not major) fracture risk over 10 years
- When absolute fracture risk provided, patients have been shown to make better-informed decisions regarding treatment options
- FRAX can be used with or without a BMD T-score
What are 2 clinical factors that increase the risk of fracture REGARDLESS of BMD? How does the presence of these affect a patient’s overall risk? (CMAJ/TOP)
- Presence of a prior fragility fracture after age 40
- Recent prolonged systemic glucocorticoid use (i.e. at least 3 months cumulative use during the preceding year at a prednisone-equivalent dose ≥ 7.5 mg daily)
- Either of these risk factors raises an individual’s risk to the next risk level (i.e. from low to moderate or from moderate to high)
- When BOTH factors are present, the patient is considered at HIGH RISK of fracture, REGARDLESS of BMD
What does the WHO Fracture Risk Assessment (FRAX) tool use to estimate fracture risk? (TOP)
- Age
- Sex
- Body mass index (BMI)
- Prior fracture
- Parental hip fracture
- Prolonged glucocorticoid use
- Rheumatoid arthritis (or secondary causes of osteoporosis)
- Current smoking
- Alcohol intake (three or more units daily)
- BMD of the femoral neck
*** Can be used without BMD – substitutes BMI
In what circumstance would the fracture risk calculated by FRAX underestimate the true risk? (CMAJ)
- Lumbar spine T-score much lower than hip T-score
- Only uses femoral neck in calculation
What tests can be ordered to diagnose a vertebral fracture if suspected by clinical evidence? (CMAJ)
- Lateral thoracic and lumbar spine radiography OR
- Dual-energy x-ray absorptiometry (DEXA)
When should lateral thoracic and lumbar spine radiography be performed to rule out a vertebral fracture? (TOP)
- ONLY if clinical evidence
What are 4 findings on clinical exam that can suggest a vertebral fracture? (CMAJ/DFCM)
- ≥2 cm prospective height loss
- ≥6 cm historic height loss
- Reduced rib to pelvis distance ≤2 fingers’ breadth
- Occiput-to-wall distance >5 cm (kyphosis)
How are vertebral fractures defined on radiography? (CMAJ)
- Vertebral height loss of 25% or more with disruption of the end plate
What biochemical tests should be considered if there is clinical suspicion of secondary causes of osteoporosis? (TOP)
- Calcium, corrected for albumin
- CBC
- Creatinine
- Alkaline phosphatase
- Thyroid-stimulating hormone
- Serum protein electrophoresis (for patients with vertebral fractures)
Do osteoporotic fractures occur more in moderate risk group than high risk group patients? (TOP)
- Moderate risk
Which patients should always be offered pharmacologist therapy for osteoporosis? (TOP)
- High risk group
- Moderate risk group à Discuss risk and benefits/harms of treatment
For patients at low risk of fracture, what should be offered? (TOP)
- Lifestyle measures
- Exercise
- Fall prevention
- Calcium and Vitamin D
- Smoking Cessation (if relevant)
- Alcohol reduction (if relevant)
- Pharmacologic therapy NOT required
What is a dietary modification that may reduce the risk of fracture in osteoporosis? (AFP)
- Caffeine – Limit to ≤2.5 cups of coffee or ≤5 cups of tea per day
What are 4 recommendations for exercise for fracture prevention? (CMAJ/TOP)
- Resistance training (as appropriate for age and function capacity) and/or weight-bearing aerobic exercises
- Core stability exercises will improve weak or postural abnormalities especially for individuals who have had vertebral fractures
- Balance type exercises (e.g. tai chi and gait training)
- Hip protector for older adults in LTC at high risk for fracture (poor compliance in those living independently)
What type of exercise should not be recommended in patients with osteoporosis and why? (AFP)
- Aerobic exercise programs that do NOT incorporate strength and balance training
- Increased risk of fracture
What has better evidence to reduce the risk of hip fractures: exercise programs or moderate to vigorous walking? (TOP)
- Moderate to vigorous walking
What is effective for those at high risk for falls and/or visually impaired to reduce the risk of fracture? (TOP)
- Home safety assessment
- Cataract surgery (CMAJ)
What is the maximum total daily intake of elemental calcium (through diet and supplements) for individuals age 50 and older? (CMAJ/TOP)
- 1200 mg
What is the maximum calcium supplement dosage (given usual dietary sources of calcium and normal intestinal absorption)? (TOP)
- 500 mg
What are 2 concerns with calcium supplementation for osteoporosis? (TOP)
- Efficacy for reducing fractures is controversial
- Possible adverse effects resulting from high dose supplements
What are 2 potential risks of high dose calcium supplementation? (TOP)
- Renal calculi
- Cardiovascular events
What is the evidence for calcium supplementation increasing the risk of CVD? (TFP)
- Absolute risk <1%
- NNH for one MI 135 to 211
- MIGHT slightly increase risk, different results based on meta-analyses used
What is an estimate for how much pharmacotherapy can reduce the relative risk of fracture? (TOP)
- 30-40%
Name 5 types of pharmacotherapy for osteoporosis? (TOP)
- Bisphosphonates (antiresorptive agent)
- Denosumab (antiresorptive agent)
- SERM (antiresorptive agent)
- Hormone therapy (antiresorptive agent)
- Teriparatide or Forteo (bone-forming agent)
Which therapies currently available in Canada reduce vertebral fracture risk in menopausal women with osteoporosis (based on RCTs)? (TOP)
- All 5 of them
What are potential adverse effects for bisphosphonates, denosumab, raloxifene (SERM) and hormone therapy, and teriparatide? (TOP)
- Bisphosphonates
- 10% have self-limiting flu-like symptoms (especially after first dose of zoledronate infusion)
- GI intolerance
- Esophagitis
- Denosumab
- Serious infection/Cellulitis
- Raloxifene
- Thromboembolic events (including PE)
- Menopausal hormone therapy (estrogen)
- Breast cancer only after 10 years
- Teriparatide
- Hypercalciuria and Hypercalcemia (usually transient)
How should oral bisphosphonates be taken by patients and why? (AFP)
- Only with water and a wait of at least 30 minutes before reclining or ingesting other medication or food
- Decreases upper GI adverse effects and allows for appropriate absorption
What are 4 serious potential adverse effects (and controversial) of bisphosphonates? (CMAJ/TOP)
- Osteonecrosis of the jaw
- Atypical fractures of the femur
- Esophageal cancer
- Atrial fibrillation
What is the rate of osteonecrosis of the jaw among patients with primary osteoporosis on bisphosphonates? (CMAJ/TOP)
- 1 per 10,000 patient years
Define osteonecrosis of the jaw. (CMAJ/TOP)
- Area of exposed alveolar bone in the mandible or maxilla that does not heal after 8 weeks
What are 6 risk factors for osteonecrosis of the jaw? (CMAJ/TOP)
- Malignancy undergoing radiation and chemotherapy
- Taking high-dose bisphosphonates for bone metastases
- Taking glucocorticoids
- Diabetes
- Poor dental hygiene
- Undergoing invasive dental procedures such as tooth extractions or implants
What can develop in patients on long-term bisphosphonate (especially >5 years) or denosumab therapy and how do they present? (CMAJ/TOP)
- Spontaneous “atypical” subtrochanteric or diaphyseal fractures
- Thigh or groin pain prior to developing a complete fracture à radiography or bone scan (or both) should be considered
- Such fractures tend to appear as clean transverse or oblique “chalk-like” breaks
In postmenopausal women with low bone density, what is first-line therapy for osteoporosis with evidence for all three types of fracture prevention (vertebral, hip, nonvertebral)? (CMAJ/TOP)
- Alendronate 70 mg PO weekly for 3-5 years
- Risedronate 35 mg PO weekly for 3-5 years
- Zoledronate 5 mg IV yearly for 3 years
- Denosumab 60 mg SC every 6 months
In postmenopausal women with low bone density, what is first-line therapy for osteoporosis with evidence for all three types of fracture prevention (vertebral, hip, nonvertebral)? (CMAJ/TOP)
What is first-line therapy for prevention of glucocorticoid induced osteoporosis? (TOP)
- Alendronate 70 mg PO weekly for 3-5 years
- Risedronate 35 mg PO weekly for 3-5 years
- Zoledronate 5 mg IV yearly for 3 years
What is the concern with Raloxifene, another first-line agent, in postmenopausal women with low bone density? (TOP)
- Raloxifene 60 mg PO daily à has NOT been demonstrated to prevent hip or nonvertebral fractures
Who are the best candidates to take raloxifene for osteoporosis? (AFP)
- Postmenopausal women with osteoporosis
- Unable to tolerate bisphosphonates
- No vasomotor symptoms or history of VTE
- High breast cancer risk score
What is first-line therapy for osteoporosis in men? (TOP)
- Alendronate 70 mg PO weekly for 3-5 years
- Risedronate 35 mg PO weekly for 3-5 years
- Zoledronate 5 mg IV yearly for 3 years
- Denosumab 60 mg SC every 6 months
In which case can hormone therapy (estrogen) be used as first line therapy for women? (TOP)
- Postmenopausal women with low bone density and estrogen deficiency symptoms (e.g. vasomotor symptoms)
- Under age 60 OR under 10 years post menopause
According to the 2010 Canadian Osteoporosis guidelines, for menopausal women intolerant of first-line therapies, what can be considered for prevention of vertebral fractures? (CMAJ)
- Calcitonin
- Etidronate
What is teriparatide (Forteo) 20 ug SC daily (2 years lifetime exposure) approved in Canada for? (TOP)
- Severe postmenopausal osteoporosis
- Severe osteoporosis in men
- Glucocorticoid osteoporosis
According to the 2010 Canadian Osteoporosis guidelines, what are 2 osteoporosis medications that may decrease the pain associated with vertebral fractures? (CMAJ)
- Calcitonin
- Teriparatide
Why was synthetic calcitonin (Salmon) nasal spray withdrawn from the Canadian market in October 1, 2013? (TFP)
- Increased risk of overall malignancy with a NNH of 63
- Meta-analysis of 17 RCTs
Is testosterone recommended for the treatment of osteoporosis in men? (CMAJ/TOP)
- No
What are 4 reasons to consider referral to a specialist for osteoporosis? (TOP)
- Multiple fractures despite adherence to therapy
- Secondary cause of osteoporosis/metabolic bone disease outside the expertise of the primary care physician (e.g. glucocorticoid use)
- Extremely low BMD, not explained by the patient’s known risk factors
- Presence of CKD (eGFR >30 mL/min)
According to the 2010 Canadian Osteoporosis guidelines, what should all individuals over age 50 on long-term glucocorticoid therapy have? (CMAJ)
- Bisphosphonate (alendronate, risedronate, zoledronic acid) initiated at the outset and should be continued for at least the duration of the glucocorticoid therapy
Should patients on treatment for osteoporosis get serial testing of BMD? (TOP)
- Probably not necessary – no randomized trials that directly assess the value of repeat BMD testing with ongoing treatment for reduction of fractures
- If follow-up BMD deemed necessary, should initially be performed NO EARLIER than 3 years
According to the 2010 Canadian Osteoporosis guidelines, should patients on treatment for osteoporosis get serial testing of BMD? (CMAJ)
- Yes – after 1-3 years to monitor for rapid bone loss
What is the evidence against BMD monitoring in patients on bisphosphonate therapy? (TFP)
- In the Fracture Intervention Trial:
- Individuals’ BMD readings were more variable than readings between people
- Alendronate increased BMD 0.013 g/cm2 per year BUT individuals’ reading varied by a similar amount (0.012 g/cm2, standard deviation)
- DEXA BMD measurement precision limited:
- Variability at the hip of 2.4% (trochanter) to 5% (Ward’s triangle) in patients scanned twice over 2-4 weeks
- Average rate of bone loss in postmenopausal women is 0.5-2% per year, while most treatments increased BMD 1-6% over three years
What could be the cause of continued loss of BMD or a new fracture in patients being treated for osteoporosis? (TOP)
- Non-compliance
- Failure to respond
- Secondary cause of osteoporosis not previously identified
What is the evidence for discontinuing bisphosphonate therapy? (TOP/TFP)
- 10-year extension of the original alendronate Fracture Intervention Trial (FLEX)
- 1,099 post-menopausal women with osteoporosis (mean age 73, 60% with previous fracture) previously on alendronate for 4-5 years randomized to alendronate 5 mg, 10 mg, or placebo for 5 additional years
- Subjects continuing on alendronate for a total of 10 years had significantly fewer clinical vertebral fractures compared to those receiving placebo for the last 5 years, although no significant difference in fractures at any other sites
- NNT 36 (2.4% vs 5.3% placebo)
- HORIZON – Pivotal Fracture Trial extension: RCT of 1,233 patients randomized to stopping or continuing zoledronic acid for 3 years (after 3 years of therapy) found no difference in clinical fractures
- Therefore, cessation of alendronate for up to 5 years after 5 years of therapy may be safe for patients NOT at high risk of vertebral fractures
- Consider extending therapy to a maximum 10 years in patients at HIGH fracture risk (e.g. previous fragility fracture or risk >20%)
What is the evidence for anti-fracture efficacy in any patient group beyond 10 years continuous bisphosphonate use? (TOP)
- No evidence
What is the risk of discontinuing risedronate in the first year? (TOP)
- BMD loss
What is the expert opinion for consideration of re-assessment of fracture risk after bisphosphonate discontinuation? (TOP)
- Reassess 3-5 years post discontinuation
What is the recommendation for vitamin D testing in adults, children and pregnant/lactating women who may be at risk for low vitamin D levels as a result of low dietary intake or seasonal (sunlight) exposure? (TOP/CWC)
- Do NOT order testing
- Recommend vitamin D supplementation
- Do NOT monitor vitamin D levels
According to the 2010 Canadian Osteoporosis guidelines, should vitamin D be measured after starting supplements? (CMAJ)
- Yes, measure 3-4 months after starting and do not repeat I an optimal level (≥75 nmol/L) is achieved
Who can order vitamin D testing and what are 9 indications? (TOP)
- Specialists (in Alberta)
- Significant renal or liver disease
- Metabolic bone disorders
- Abnormal blood calcium
- Unexplained bone pain or unusual fractures
- Malabsorption syndromes
- Chronic renal disease
- Chronic liver disease
When clinically indicated, what is the best test for determining vitamin D levels? (TOP)
- Serum 25-hydroxyvitamin D
What are the indications for ordering serum 1,25-dihydroxyvitamin D levels? (TOP)
- Suspicions of 1 α -hydroxylase activity abnormality
- Deficiency in renal tubule disorders
- Excessive (ectopic 1 α-hydroxylase)
- Sarcoidosis
How much does a vitamin D (25-OHD) assay cost? (TFP)
- $61.32
What is the evidence for different levels of serum vitamin D levels? (TFP)
- >75 nmol/L – “are not consistently associated with increased benefit”
- >50 nmol/L – “practically sufficient for all persons”
- 30-50 nmol/L – “places some, but not all, persons at risk for inadequacy”
- <30 nmol/L – “at risk relative to bone health”
What proportion of Canadians have serum vitamin D levels <75 nmol/L, <50 nmol/L and <40 nmol/L? (TFP)
- <75 nmol/L = 97%
- <50 nmol/L = 61%
- <40 nmol/L = 13%
How much does every 800 IU of vitamin D increase serum 25-OHD levels? (TFP)
- 8 – 16 nmol/L
- Dose-response relationship not directly linear and is affected by many factors such as season, adiposity, and skin pigmentation
What is the coefficient of variation for Vitamin D assays? (TFP)
- 10-20%
- Therefore changes in levels with doses of 800 IU/day may not be discernable due to variability in testing
What is the evidence for vitamin D supplementation improving mood? (TFP)
- Evidence poor
- 10 RCTs – most found no effect, the few that did found small benefits and are at very high risk of bias (only one with statistically significant result studied 44 people for five days)
- Most studies looked at patients with normal mood
What is the evidence for vitamin D treatment on falls, fractures and mortality? (TFP/USPSTF)
- Vitamin D 800 – 1000 IU reduces fractures, fall and overall mortality in older patients (likely 50+ years old)
- Falls improved by RR 28%
- Fractures improved by RR 14% for non-vertebral fractures
- Mortality improved by RR 5% over 2 years (NNT = 223)
What does the USPSTF recommend to prevent falls in community-dwelling adults 65 years or older who are at increased risk of falls? (USPSTF/AFP)
- Exercise or physical therapy
- Vitamin D supplementation
What is the recommended vitamin D supplementation dose for healthy individuals (in Alberta)? (TOP)
- Infants (breast or formula fed) from birth to adults 70 years old and younger à 400 IU/day
- Adults 71 years of age and older à 800 IU/day
What is the recommended vitamin D supplementation dose for individuals at risk of osteoporosis from vitamin D deficiency? (CMAJ/TOP)
- Adults at lower risk of vitamin D deficiency à Minimum of 400 IU up to 1000 IU/day
- Adults over age 50 at moderate risk of vitamin D deficiency à 800 to 1000 IU/day
- Adults over age 50 at moderate risk of vitamin D deficiency and to prevent osteoporosis and reduce risk of fragility fractures à 2000 IU/day
What is the upper limit of intake of vitamin D supplementation suggested for most individuals and what dose is usually required for toxic levels? (TOP)
- 4000 IU/day safe for most
- 10,000 IU/day toxic
What are weekly and monthly dosing regimens for vitamin D supplementation that have been shown to be safe? (TOP)
- 7,000 IU once each week
- 50,000 IU once each month
In which individuals are vitamin D supplements almost always contraindicated and in which individuals should it be used with caution? (TOP)
- Contraindicated à Hypercalcemia
- Caution à Hyperphosphatemia
What is the diagnostic serum level for vitamin D toxicity (or hypervitaminosis D)?(TOP)
- >500 nmol/L (or >200 ng/mL) of serum 25-hydroxyvitamin D
What doses of vitamin D and what conditions are necessary for vitamin D toxicity? (TOP)
- Vitamin D3 in excess of 10,000 IU/day
- Doses up to 10,000 IIU/day for as long as 5 months have been shown to be tolerated by adults
- Normal gut function
- Concurrent ingestion of excessive calcium
Why are patients with granulomatous disease at risk of hypercalcemia? (TOP)
- Increased 1 -hydroxylase activity (converts 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D)
- Toxicity reported during vitamin D treatment of tuberculosis and in patients with active sarcoidosis
What is the recommended test for investigating vitamin D toxicity? (TOP)
- Serum calcium (albumin-corrected)
- ONLY if calcium level is elevated would vitamin D testing be indicated