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Pharmacologic agents to prevent and treat osteoporosis

Pharmacologic agents to prevent and treat osteoporosis. How do I choose?. Clinical Scenario. 87 yo WF on the orthopedic service after a L intertrochanteric femur fx. PMH – osteoporosis w/ symptomatic vertebral fx, OA, borderline HTN

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Pharmacologic agents to prevent and treat osteoporosis

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  1. Pharmacologic agents to prevent and treat osteoporosis How do I choose?

  2. Clinical Scenario • 87 yo WF on the orthopedic service after a L intertrochanteric femur fx. • PMH – osteoporosis w/ symptomatic vertebral fx, OA, borderline HTN • Meds- ASA,Glucosmine,Miacalcin (pt tried on Fosamax but she did not tolerate) • SH- lives alone, nonsmoker, no ETOH

  3. What is the most efficacious osteoporosis agent for this patient? • Does the data support retrying a bisphosphonate?

  4. Low bone mass and microarchitectural deterioration of bone that leads to increased bone fragility and fracture risk

  5. Personal history of fracture History of fracture in first degree relative Smoking Weight less than 127 lbs Female White or Asian Chronic steroid use Estrogen deficiency Advanced age Low calcium intake Alcoholism Inadequate physical activity Recurrent falls Dementia Impaired eyesight Risk Factors

  6. WHO Classification - DEXA scan • Normal T score ≥ -1 • Osteopenia T score -1 to -2.5 • Osteoporosis T score < -2.5 • Severe osteoporosis T score <- 2.5 and the presence or history of fracture

  7. Alendronate (Fosamax) Risedronate (Actonel) Raloxifene (Evista) Calcitonin (Miacalcin) Calcium/Vitamin D HRT/ERT Treatments

  8. Bisphosphonates • MOA: Bind to hydroxyapatite and inhibit bone resorption by decreasing the number and activity of osteoclast. • Considerations: Renally excreted, not recommended if CrCl < 30, otherwise no dose adjustment. UGI disorders such as dysphagia, esophagitis, esophageal/gastric ulcers. Contraindicated if pt hypocalcemic or unable to be upright for 30 minutes after taking.

  9. SERMS • MOA: estrogen receptor agonist in bone and on lipids, antagonist in breast and uterus. Inhibits osteoclast recruitment and activity. • Considerations: increases thromboembolic disease and lowers breast cancer risk with unknown effect on CAD. Contraindicated in prior DVT, PE.

  10. Calcitonin • MOA: inhibits osteoclast-mediated bone resorption. • Considerations: Nasal spray. May cause nasal irritation or epistaxis.

  11. Difficulties with comparison • Relatively few RCTs with fracture (vertebral or hip) as an endpoint. • Many trials measure BMD or bone turnover; however, the etiology of fracture is multifactorial. • Vertebral fracture is the earliest and most common fragility related fracture in postmenopausal women • Prior vertebral fracture is a risk for future fractures (including hip fx)

  12. RCTs with vertebral fracture as endpoint

  13. RCTs with vertebral fracture as endpoint

  14. But what about hip fracture? There is only one large RCT with hip fracture as the primary endpoint.

  15. HIPS • Risedronate vs Placebo, all on Calcium/Vit D. • n=9331, 3 year study • Women aged 70-79 with Tscore -4 or -3 with one risk factor: RR= 0.6 (0.4-0.9) NNT=99 • Women aged >80 with mostly unknown Tscore and clinical risk factors: RR= 0.8 (0.6-1.2) • Risk factors included everything from smoking to previous fracture.

  16. Show me the money Alendronate (Fosamax) 10mg/d= $85/mo 70mg/w= $84/mo Risedronate (Actonel) 5mg/d= $77/mo 30mg/w= $64/mo Raloxifene (Evista) 60mg/d= $93/mo Calcitonin (Miacalcin) 200IU=$84/mo

  17. Clinical Scenario • 87 yo WF on orthopedic service after L intertrochanteric femur fx • PMH – osteoporosis w/ symptomatic vertebral fx, OA, borderline HTN • Meds- ASA,Glucosmine,Miacalcin (pt tried on Fosamax but did not tolerate) • SH- lives alone, nonsmoker, no ETOH

  18. A more typical case • A 54 y/o WF presents for a routine visit. Her menses stopped 18 mo ago. She is in good health, nonsmoker and social drinker and is concerned about osteoporosis. Has no menopausal sxs. Takes Ca/Vit D daily. Rides bike intermittently. Mom with recent hip fracture requiring nursing home placement. Her Tscore is -1.4 at the spine, and-1.2 at the hip. What do you tell her?

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