© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 155 (1): ITC1-1. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View.

© Copyright Annals of Internal Medicine, 2011Ann Int Med. 155 (1): ITC1-1.

* For Best Viewing:

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in the clinic

Osteoporosis


Who should be screened for osteoporosis?

Advanced age; female sex

Estrogen deficiency

Hx fracture as adult

Hx fragility fracture in 1° relative

Current cigarette smoking

Alcoholism

Low body weight (<127 lbs)

White race or Asian race

Low calcium intake

Low physical activity

Poor health/frailty; falls

Poor eyesight (despite correction)

Dementia; cognitive impairment

Impaired neuromuscular fxn

Residence in nursing home

Hx glucocorticoids >3 mos

Long-term heparin therapy

Anticonvulsant therapy

Aromatase-inhibitor therapy

Androgen-deprivation therapy

Those with clinical risk factors for osteoporosis or fracture


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


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


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


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


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


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


How should osteoporosis be diagnosed?

Also: diagnose if fragility (low-trauma) fracture occurs

Regardless BMD

• 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

Postmenopausal women & men ≥50—WHO diagnostic criteria

Premenopausal women & men <50—don’t use WHO criteria

• Use Z-scores, not T-scores

• Z-score ≤–2.0: below expected range for age


What should the initial evaluation of a patient with osteoporosis include?

History

Diet

Lifestyle

Medications

Family history

Falls, fractures

Focused review of systems


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

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

Physical: Potentially helpful findings for osteoporosis


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


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)


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


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


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


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


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


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


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


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


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


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


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


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)


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. * For Best Viewing: Open in Slide Show Mode Click on icon or From the View.

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