Osteoporosis

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

* For Best Viewing:

Open in Slide Show Mode Click on icon or

From the View menu, select the Slide Show option

* To help you as you prepare a talk, we have included the relevant text from ITC in the notes pages of each slide


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

Documents

Osteoporosis