Transcript Clinical Slide Set. Osteoporosis

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© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
in the clinic
Osteoporosis
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
Who should be screened for osteoporosis?
Those with clinical risk factors for osteoporosis or fracture
 Advanced age; female sex
 Poor health/frailty; falls
 Estrogen deficiency
 Poor eyesight (despite correction)
 Hx fracture as adult
 Dementia; cognitive impairment
 Hx fragility fracture in 1°
relative
 Impaired neuromuscular fxn
 Current cigarette smoking
 Alcoholism
 Low body weight (<127 lbs)
 White race or Asian race
 Low calcium intake
 Residence in nursing home
 Hx glucocorticoids >3 mos
 Long-term heparin therapy
 Anticonvulsant therapy
 Aromatase-inhibitor therapy
 Androgen-deprivation therapy
 Low physical activity
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
Indications for Bone Mineral Density Testing
 All women ≥65 and men ≥70
 Postmenopausal women & men aged 50-69 based on
clinical risk profile
 Women in menopausal transition w/ increased fracture risk
 Adults ≥50 who have a fracture
 Adults with a condition or taking a medication associated
with low bone mass or bone loss
 If pharmacologic Rx for osteoporosis considered
 To monitor effect of pharmacologic Rx for osteoporosis
 Postmenopausal women discontinuing estrogen
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
How should screening be done, and
how are the results interpreted?
 Measure BMD with DXA
 To screen for and diagnose osteoporosis
 To assess fracture risk
 To monitor changes in BMD over time
 Use fracture risk assessment tool (FRAX)
 Estimates 10-yr probability of hip fracture & major
osteoporotic fracture in untreated men & women aged 40-90
 Greater clinical utility than relative risk
 Uses limited number easily obtainable clinical risk factors
 Can be used with or without BMD
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
What lifestyle measures are recommended
for prevention?
 Regular moderate physical activity (especially resistance)
 Good nutrition, adequate calcium, vitamin D
 Smoking cessation
 Reduced alcohol consumption
 Avoid or minimize medications with harmful skeletal effects
 Prevent falls in frail, elderly
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
What is the role of calcium and vitamin
D in the prevention of osteoporosis?
 Essential for maintenance of bone mass in adulthood
 Calcium
 RDI: ≥1200mg with diet + supplements if ≥50 yrs
 Tolerable upper limit intake 2500mg/d
 Calcium carbonate: take with meals to optimize absorption
 Calcium citrate: Take with or without food
 Monitor with 24-hr urinary calcium measurement
 Vitamin D
 RDI for vitamin D3: 800-1000 IU/d if ≥50yrs
 Minimum blood level serum 25-hydroxyvitamin D:
≈75 nmol/L (30 ng/mL)
 Suggest fortified food products plus modest sun exposure
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
When should pharmacologic treatment
be considered for prevention?
 If bone loss is rapid or if risk for osteoporosis is high
 Such as during early postmenopausal years
 May prevent or reverse bone loss
 May maintain trabecular microarchitecture
 May reduce fracture risk
 Base decision on expected benefit, potential risks
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
CLINICAL BOTTOM LINE: Screening
and prevention…
 Fundamental components of prevention
 Healthy lifestyle and good nutrition
 Avoidance of medications known to be harmful to bone
 Pharmacologic Rx to reduce fracture risk is indicated when:
 Patients with osteopenia are at high fracture risk
 Patients are anticipated to have rapid bone loss that could
soon result in osteoporosis and high fracture risk
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
How should osteoporosis be diagnosed?
 Postmenopausal women & men ≥50—WHO diagnostic criteria
• Low bone mass (osteopenia): T-score ≤–1.0 and ≥–2.5
• Osteoporosis: T-score ≤–2.5
• Severe osteoporosis: T-score ≤–2.5 + Hx fragility fracture
 Premenopausal women & men <50—don’t use WHO criteria
• Use Z-scores, not T-scores
• Z-score ≤–2.0: below expected range for age
 Also: diagnose if fragility (low-trauma) fracture occurs
 Regardless BMD
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
What should the initial evaluation of a
patient with osteoporosis include?
 History
 Diet
 Lifestyle
 Medications
 Family history
 Falls, fractures
 Focused review of systems
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
 Physical: Potentially helpful findings for osteoporosis
 Loss of height  ? vertebral fracture
 Low body weight  risk for fracture
 Weight loss ? hyperthyroidism or malnutrition
 Fast heart rate ? hyperthyroidism or anemia
 Fast respiratory rate  ? asthma
 Poor gait  ? muscle strength, balance
 Paralysis or immobility  bone loss, increased fall risk
 Joint laxity ? osteogenesis imperfecta, Ehlers-Danlos, Marfan
 Inflammatory arthritis  glucocorticoid use
 OA or lower limb injury  reduced load-bearing, bone loss
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
 Physical: Potentially helpful findings for osteoporosis
 Blue sclera, poor tooth development, hearing loss, fracture
deformities  ? osteogenesis imperfecta
 Poor dental hygiene  ? jaw osteonecrosis w/ bisphosphonates
 Thyromegaly, thyroid nodules, proptosis  ? hyperthyroidism
 Urticaria pigmentosa  ? sytemic mastocytosis
 Kyphosis, short distance ribs to iliac crest  ? vertebral fractures
 Abdominal tenderness  ? inflammatory bowel disease
 Stretch marks, buffalo hump, bruising  ? glucocorticoid excess
 Venous thrombosis  ? may contraindicate estrogen or raloxifene
 Small testicles  ? hypogonadism
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
 Lab studies
Essential tests
 Complete blood count
 Serum calcium
 Serum phosphorus
 Serum creatinine
 Serum TSH
 Serum liver enzymes
 Serum alkaline phosphatase
 Serum total/free testosterone
(men)
 24-hr urinary calcium
Optional tests*
 Serum 25-hydroxyvitamin D
 Serum PTH
 Serum/urine protein
electrophoresis, κ/λ light
chains
 Serum celiac antibodies
 24-hr urinary free cortisol or
overnight dexamethasone
suppression test
 Serum tryptase
*based on clinical circumstance
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
 Imaging studies
 Appropriate for carefully selected patients:
 Spine imaging: height loss or kyphosis (? unrecognized
vertebral fractures)
 Nuclear bone scan or x-ray: unexplained increase in alkaline
phosphatase
 Barium swallow: swallowing difficulties (? stricture)
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
When should consultation be considered?
 Osteoporosis & metabolic bone disease specialist
 Non-traumatic fracture with normal BMD
 Recurrent fracture or bone loss despite therapy
 Unexpectedly severe or unusual features
 Complex management / comorbidites: renal failure,
hyperparathyroidism, malabsorption
 Suspect 2° causes
 Discordant clinical and lab findings
 Gastroenterologist
 Small bowel biopsy if celiac disease suspected
 Oncologist
 Labs suggest multiple myeloma, other forms of cancer
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
CLINICAL BOTTOM LINE: Diagnosis…
 History and physical
 Lab tests
 CBC + serum calcium, phosphorus, creatinine, aspartate &
alanine transaminase, alkaline phosphatase, and TSH and
24h urinary calcium levels (plus testosterone for men)
 Additional lab or imaging tests
 Depending on clinical circumstances
 Refer to osteoporosis specialist
 When complex or unusual diagnostic issues arise
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
What are the goals of treatment?
 Improve bone strength
 With regular physical activity, calcium & vitamin D,
pharmacologic agents
 Surrogate markers of bone strength: BMD / markers of bone
 Measure at baseline and 1 to 2 yrs after starting therapy
 Prevent falls
 With quadriceps strengthening, balance training
 Assess in office (observe; ? can patient walk in straight
line, balance on 1 foot)
 Reevaluate periodically  risk may increase with age
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
What lifestyle measures are recommended?
 Smoking cessation
 Reduced alcohol use
 Weight-bearing and muscle-strengthening exercise
 Adequate calcium and vitamin D intake
 Home safety evaluation (to reduce risk from falls)
 Minimize mind-altering medications
 Sedatives, hypnotics, narcotic analgesics
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
What pharmacologic interventions are
effective for treatment?
 IV bisphosphonates (zoledronate, ibandronate)
 Oral bisphosphonates (alendronate, risedronate, ibandronate)
 Increase bone mass; decrease fractures
 IV SEs: flu-like symptoms after first dose
 Oral SEs: esophageal irritation; discontinue if musculoskeletal
pain occurs; jaw osteonecrosis & atypical femur fractures
 Raloxifene
 Increases BMD; decreases fractures; reduces risk for
invasive breast cancer
 SEs: thromboembolic risk; vasomotor symptoms; fatal stroke
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
 Teriparatide
 Increases BMD; decreases fractures
 SEs: Dizziness, nausea
 Contraindicated with osteosarcoma, Paget disease, unexplained
Alk Phos elevation, open epiphyses, Hx skeletal radiation
 Denosumab
 Increases bone mass; decreases fractures
 SEs: cellulitis, eczema, and flatulence
 Calcitonin
 Slightly increases BMD; decreases vertebral fractures; may
decrease pain from acute or subacute vertebral fractures
 SEs: Rhinitis, irritation of nasal mucosa
 Estrogen (with or without medroxyprogesterone)
 Improves BMD and reduces the risk for fracture
 Not approved for osteoporosis Rx — risks outweigh
benefits, even in women at high risk for fracture
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
How should they be chosen?
 Oral bisphosphonates alendronate, risedronate, ibandronate
 1st-line therapy
 Injectable denosumab, ibandronate, zoledronate
 If oral bisphosphonates ineffective or contraindicated
 Raloxifene
 Early postmenopausal women with high breast cancer risk
+ no thromboembolic disease + low risk stroke, hip fracture
 Nasal salmon calcitonin
 For women ≥5y postmenopausal unable to take other agents
 Teriparatide
 If multiple risk factors for osteoporotic fracture + failure/
intolerance other therapy
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
How should patients be monitored?
 Measure BMD to assess changes
 Measure bone turnover marker to monitor therapy
 Untreated patients
 Significant bone loss may influence decision to start treatment
 Treated patients
 Significant decrease in BMD usually = nonresponse or
suboptimum response to therapy
 Reevaluate treatment + evaluate secondary causes
 Consider contributing factors: ? medication compliance; ?
sufficient calcium and vitamin D intake
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
When should consultation be considered
for management?
 When expertise needed for associated disorders
 Hyperparathyroidism, hyperthyroidism
 Vitamin D deficiency, hypercalciuria, osteomalacia
 Cushing syndrome, glucocorticoid-induced osteoporosis
 Hypopituitarism or hypogonadism (males)
 Elevated alkaline phosphatase levels or bone turnover
 When routine therapy is not possible or effective
 Significant bone loss after ≥1y Rx or combination Rx considered
 Standard therapies not tolerated or patients have fractures
 Vertebroplasty or kyphoplasty needed
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
CLINICAL BOTTOM LINE: Treatment…
 Those at high risk for fracture most likely to benefit from Rx

Individualize drug selection according to…

Clinical circumstances

Magnitude of fracture risk

Comorbid conditions

Patient preference
 Encourage a healthy lifestyle, adequate calcium & vitamin D
 Monitor Rx effect using BMD testing or bone turnover markers
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
What should patients be taught?

The association between low BMD and fracture risk

Importance of adequate calcium & vitamin D intake

Weight-bearing exercise to maintain bone mass

To avoid: smoking, excess alcohol consumption

Benefits and potential risks of pharmacologic agents
for osteoporosis
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
How can falls and bone fractures be
prevented?
Comprehensive fall-reduction program
 Home safety evaluation
 To identify potential physical or structural problems at home
(slippery floors, impeded pathways)
 Exercises that improve strength and balance
 Reduction in use of drugs that impair cognitive abilities
 Patient education
 One-on-one instruction and community resources
 Consultation with nutritionist, PT, & exercise physiologist
 Regular contact with health care professional improves
therapy adherence (BMD increases > with no monitoring)
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.
CLINICAL BOTTOM LINE: Treatment…
 Keep patient well-informed
 Can lead to improved clinical outcomes
 Equip patient to make appropriate decisions on lifestyle
and nutrition to optimize skeletal health
 Inform patient on benefits and risks of pharmacologic
therapy
 Monitor patient regularly
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 155 (1): ITC1-1.