Pharmacologic agents to prevent and treat osteoporosis

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Pharmacologic agents to prevent and treat
osteoporosis

• How do I choose?

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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
  

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

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

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Risk Factors

• 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

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WHO Classification - DEXA scan

• Normal T score -1
• Osteopenia T score -1 to -2.5
• Osteoporosis T score lt -2.5
• Severe osteoporosis T score lt- 2.5 and the
  presence or history of fracture

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Treatments

• Alendronate (Fosamax)
• Risedronate (Actonel)
• Raloxifene (Evista)
• Calcitonin (Miacalcin)

• Calcium/Vitamin D
• HRT/ERT

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Bisphosphonates

• MOA Bind to hydroxyapatite and inhibit bone
  resorption by decreasing the number and activity
  of osteoclast.
• Considerations
• Renally excreted, not recommended if CrCl lt 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.

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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.

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Calcitonin

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

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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)

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RCTs with vertebral fracture as endpoint
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RCTs with vertebral fracture as endpoint
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But what about hip fracture?

• There is only one large RCT with hip fracture as
  the primary endpoint.

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HIPS

• Risedronate vs Placebo, all on Calcium/Vit D.
• n9331, 3 year study
• Women aged 70-79 with Tscore -4 or -3
• with one risk factor RR 0.6 (0.4-0.9) NNT99
• Women aged gt80 with mostly unknown Tscore and
  clinical risk factors RR 0.8 (0.6-1.2)
• Risk factors included everything from smoking to
  previous fracture.

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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) 200IU84/mo

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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
  

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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?