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Pharmacologic agents to prevent and treat osteoporosis

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Pharmacologic agents to prevent and treat osteoporosis Powered By Docstoc
					   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
   Meds- ASA,Glucosmine,Miacalcin (pt tried
    on Fosamax but she did not tolerate)
   SH- lives alone, nonsmoker, no ETOH
   What is the most efficacious osteoporosis
    agent for this patient?
   Does the data support retrying a
    bisphosphonate?
   Low bone mass and
    microarchitectural
    deterioration of bone
    that leads to
    increased bone
    fragility and fracture
    risk
                      Risk Factors
   Personal history of               Estrogen deficiency
    fracture                          Advanced age
   History of fracture in first      Low calcium intake
    degree relative                   Alcoholism
   Smoking                           Inadequate physical
   Weight less than 127 lbs           activity
   Female                            Recurrent falls
   White or Asian                    Dementia
   Chronic steroid use               Impaired eyesight
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
                  Treatments
   Alendronate                 Calcium/Vitamin D
    (Fosamax)                   HRT/ERT
   Risedronate (Actonel)
   Raloxifene (Evista)
   Calcitonin (Miacalcin)
             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.
                   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.
                 Calcitonin

   MOA: inhibits osteoclast-mediated bone
    resorption.
   Considerations: Nasal spray. May cause
    nasal irritation or epistaxis.
     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)
 RCTs with vertebral fracture as endpoint
Alendronate   n= 2027, 3 year study NNT= 14
              prior vert fx= 100 % RR= 0.53 (0.41-0.68)
FIT-1
Alendronate   n= 4432, 4 year study NNT= 60
              prior vert fx= 0 %    RR= 0.56 (0.39-0.8)
FIT-2
Risedronate   n= 2458, 3 year study NNT= 20
              prior vert fx = 80%   RR= 0.59 (0.43-0.82)
VERT-NA
Raloxifene    n= 2304, 3 year study NNT= 46
              prior vert fx = 11%   RR= 0.5 (0.4-0.8)
MORE
Raloxifene    n= 4524, 3 year study NNT= 16
              prior vert fx = 89%   RR= 0.7 (0.6-0.9)
MORE
Calcitonin    n= 1255, 3 year study NNT= 11
              prior vert fx = 79%   RR= 0.67 (0.47-0.97)
PROOF
 RCTs with vertebral fracture as endpoint
Alendronate   n= 2027, 3 year study NNT= 14
              prior vert fx= 100 % RR= 0.53 (0.41-0.68)
FIT-1
Alendronate   n= 4432, 4 year study NNT= 60
              prior vert fx= 0 %    RR= 0.56 (0.39-0.8)
FIT-2
Risedronate   n= 2458, 3 year study NNT= 20
              prior vert fx = 80%   RR= 0.59 (0.43-0.82)
VERT-NA
Raloxifene    n= 2304, 3 year study NNT= 46
              prior vert fx = 11%   RR= 0.5 (0.4-0.8)
MORE
Raloxifene    n= 4524, 3 year study NNT= 16
              prior vert fx = 89%   RR= 0.7 (0.6-0.9)
MORE
Calcitonin    n= 1255, 3 year study NNT= 11
              prior vert fx = 79%   RR= 0.67 (0.47-0.97)
PROOF
But what about hip fracture?

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