Osteoporosis

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2. Osteoporosis

3. Who should be screened for osteoporosis? Those with clinical risk factors for osteoporosis or fracture • 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 • Hxglucocorticoids >3 mos • Long-term heparin therapy • Anticonvulsant therapy • Aromatase-inhibitor therapy • Androgen-deprivation therapy

4. 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

5. 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

6. 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

7. 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: takewith 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

8. 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 trabecularmicroarchitecture • May reduce fracture risk • Base decision on expected benefit, potential risks

9. 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

10. How should osteoporosis be diagnosed? • Postmenopausal women & men ≥50—WHO diagnostic criteria • Premenopausal women & men <50—don’t use WHO criteria • Also: diagnose if fragility (low-trauma) fracture occurs • Regardless BMD

11. What should the initial evaluation of a patient with osteoporosis include? • History • Diet • Lifestyle • Medications • Family history • Falls, fractures • Focused review of systems

12. 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 ? osteogenesisimperfecta, Ehlers-Danlos, Marfan • Inflammatory arthritis glucocorticoid use • OA or lower limb injury reduced load-bearing, bone loss

13. Physical: Potentially helpful findings for osteoporosis • Blue sclera, poor tooth development, hearing loss, fracture deformities  ? osteogenesisimperfecta • Poor dental hygiene  ? jaw osteonecrosisw/ bisphosphonates • Thyromegaly, thyroid nodules, proptosis? hyperthyroidism • Urticariapigmentosa? sytemicmastocytosis • 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

14. 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 • Lab studies

15. 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)

16. 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

17. CLINICAL BOTTOM LINE: Diagnosis… • History and physical • Lab tests • CBC + serum calcium, phosphorus, creatinine, aspartate & alaninetransaminase, 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

18. 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

19. 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

20. 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

21. Teriparatide • Increases BMD; decreases fractures • SEs: Dizziness, nausea • Contraindicated with osteosarcoma, Paget disease, unexplained AlkPhos elevation, open epiphyses, Hx skeletal radiation • 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 • 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

22. How should they be chosen? • Injectabledenosumab, ibandronate, zoledronate • If oral bisphosphonatesineffective or contraindicated • Oral bisphosphonatesalendronate, risedronate, ibandronate • 1st-line therapy • Raloxifene • Early postmenopausal women with high breast cancer risk + no thromboembolic disease + low risk stroke, hip fracture • Nasal salmon calcitonin • Forwomen ≥5y postmenopausalunable to take other agents • Teriparatide • If multiple risk factors for osteoporotic fracture + failure/ intolerance other therapy

23. 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

24. 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

25. 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

26. 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

27. 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)

28. 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