Osteoporosis Prevention _ Treatment - Advanced Clinical Practice

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					       Advanced Clinical Practice Seminar

                    Stand Tall
     Osteoporosis Prevention and Treatment
When: May 12, 2009 2:30 – 3:30 pm
Where: Duke North Lecture Hall 2003
Who: Mary Miller-Bell, PharmD
Did you know:
   • 98% of calcium in the body is present in bones?
   • vitamin C can help prevent fractures?
   • canned salmon is a good source of calcium?
 Risk Factors
 Prevention recommendations
 Pharmacologic Treatment
Definition of Osteoporosis
 A skeletal disorder characterized by
 compromised bone strength predisposing
 to an increased risk of bone fracture

 Note: bone strength = bone density + bone

                   NIH Consensus Conference 2000
Osteoporotic Bone
Female with Osteoporosis
Bone Loss Following Menopause

 Women can lose up to 20% of their bone
 mass during the first 5-7 yrs following
Bone Facts …
 98% of calcium in the body is present in bone
 Bone undergoes continuous remodeling:
   Osteoclasts resorb old bone and osteoblasts lay
   down new bone
 Calcium levels in the body are regulated by
 parathyroid hormone, vitamin D and calcitonin
Prevalence and Epidemiology
 In the US, 8 million women and 2 million men
 have osteoporosis
 An additional 34 million Americans currently
 have low bone mass
 In the US, approximately ½ of women and
 ¼ of men aged 50 yrs or older will suffer an
 osteoporosis-related fracture within their lifetime

                  National Osteoporosis Foundation 2002
Incidence of Osteoporosis
Osteoporotic Fracture Incidence
 Osteoporosis causes over 2 million fractures
 each year in men and women over age 50
 ~ 300,000 hip fractures
 ~ 550,000 vertebral fractures
 ~ 400,000 wrist fractures
 ~ 810,000 fractures at other sites

                     Burge, et. al. JBMR. 2007. 465-75.
Risk Factors for Osteoporotic Fracture
 Race: Caucasian or Asian postmenopausal
 Personal history of osteoporosis or fracture as
 an adult
 History of low trauma fracture in first-degree
 Small, thin frame
   Low body weight ( < 127 lb)
 Current smoking
 Advancing age
Risk Factors for Osteoporotic Fracture
Impaired vision despite correction
Poor health
Estrogen deficiency at an early age (< 45 yrs)
Frequent falls
Lifelong low calcium intake
Low physical activity
Excessive alcohol consumption (> 3 drinks/day)
Medical Conditions that Increase
Osteoporotic Fracture Risk
 Rheumatoid arthritis and other autoimmune
 connective tissue disorders
 Endocrine disorders (hyperparathyroidism, hypogonadism,
 hypoprolactinemia, hypercorticolism, hyperthryroidism)
 Gastrointestinal diseases (inflammatory bowel disease,
 celiac disease, malabsorption syndromes, bariatric surgery)
 Liver diseases (biliary sclerosis, sclerosing cholangitis,
 autoimmune hepatitis, alcoholic cirrhosis
Medical Conditions that Increase
Osteoporotic Fracture Risk continued
 Dietary disorders (anorexia nervosa/bulemia, inadequate
 diet, weight loss, calcium deficiency, excessive alcohol, excessive
 vitamin A, total parenteral nutrition)
 Neurologic disorders (stroke, MS, Parkinson’s disease,
 spinal cord injury, long-term immobilization)
 Renal disease
 Insulin-dependent diabetes mellitus
 Organ transplantation
Medications Associated with
Reduced Bone Mass in Adults
 Prolonged use of corticosteroids (oral,
 high-dose inhaled, suppressive doses)
 Anticonvulsants (phenytoin, phenobarbital)
 Excessive use of aluminum-containing
 Cytotoxic drugs
 Excessive use of thyroid hormone
Medications Associated with
Reduced Bone Mass in Adults
 Aromatase inhibitors - (exemestane
 [Aromastin], anastrozole [Arimidex]
 Long-term heparin use
 Total parenteral nutrition (TPN)
Glucocorticoid-Induced Osteoporosis

 Most common form of secondary osteoporosis
 Long-term use of oral glucocorticoids
 High-dose inhaled glucocorticoids

 Evaluate bone mineral density at the hip and
 Consider prescribing an FDA-approved
 medication to treat osteoporosis
Mechanism of Glucocorticoids on Bone

 Decreased osteoblast activity
 Increased osteoclast activity
 Increased calcium excretion
 Decreased calcium absorption
 Decreased sex steroid production
Risk Factors for Men
 Low testosterone
 Use of glucocorticoid therapy ≥ 7.5 mg of
 prednisone for more than 3 months
 Heavy alcohol consumption
Increase in Fracture Risk with
Vertebral Fracture
 Prior vertebral fracture:
 Increases vertebral fracture risk 5-fold
 Increases hip fracture risk 2-fold
Vertebral Fracture
 Silent fractures may be more common than non-
 Often hard to quantify because only 25-30%
 come to clinical attention
 Up to ½ of patients with prior vertebral fracture
 experience additional fractures within 3 yrs,
 many within 1 yr
 Up to 20% excess mortality following vertebral
Hip Fracture
 Estimated 10-25% excess death rate in yr
 following fracture
 Up to 30% of hip fracture pts require nursing
 home care
 Six months after hip fracture, only 15% of pts
 can walk unaided
 Fewer than 20% of hospitalized hip fracture pts
 recover their prefracture competence in activities
Diagnosis of Osteoporosis
 The WHO defines osteoporosis in relation to
 expected distribution of bone mineral density
 (BMD) for ‘young, normal’ adults of same sex
 T-score is expressed as standard deviations
 (SD) above (+) or below (-) the young reference
 mean value. Usually one SD equals 10-15% of
 the bone density value
 WHO criteria apply for BMD measured at the
 hip, spine, or wrist
Peak Bone Mass
WHO T-Score Definitions of Bone
Mineral Density (BMD)
 Normal BMD                         T-score b/t -1 & +1 SD
 Low BMD                            T-score b/t -1 & -2.5 SD
                                    T-score of -2.5 SD or
 Osteoporosis                       lower
 Severe osteoporosis                T-score of -2.5 SD or
                                    lower and fracture(s)

          Measured at the hip, spine or wrist
Bone Mineral Density:
BMD Technology
 Central machines (DXA) measure BMD at the
 hip, spine, or total body
   Physicians can diagnose osteoporosis using DXA
   BMD and can predict risk of fractures throughout the
   body using DXA BMD
   Need serial BMD to monitor response to treatment
   BMD every 1-2 yrs
   Can also be used for vertebral fracture assessment
BMD Technology continued
 Peripheral machines measure BMD at the wrist,
 heel or finger using x-ray or ultasound
   Physicians use peripheral technology to identify
   individuals at risk for osteoporosis
   Physicians use peripheral technology to predict risk
   for future fractures
   Central BMD tests are not comparable to results from
   peripheral machines
 Hip BMD single best predictor of fracture risk
Who should have a BMD test?
 All women aged 65 or older regardless of
 risk factors
 Younger postmenopausal women with one
 or more risk factors
 Postmenopausal women who present with
Who should have a BMD test?
 Medicare covers BMD testing every 2 yrs for the
 following individuals:
   Estrogen deficient women at risk for osteoporosis
   Individuals with vertebral abnormalities
   Individuals receiving or planning to receive long-term
   glucocorticoid therapy
   Individuals with primary hyperparathyroidism
   Individuals being monitored to assess their response
   to approved osteoporosis drug therapy
Therapy for Osteoporosis
Nonpharmacologic Treatment
 Adequate calcium, vitamin D, vitamin K
    Vitamin K intake helps protect against hip fractures
         Dose: women 90 mcg/day, men 120 mcg/day
 Supplemental vitamin C may reduce the risk of hip fractures by half
    Dietary vitamin C alone intake does not seem to reduce risk of fracture
    Pts should be counseled to eat more fruit and vegetables as well as take a vitamin C
         Presented September 14, 2008 at the American Society for Bone and Mineral Research 30th annual
         meeting: Abstract 1186.
 Weight-bearing exercise
 No bending or twisting of the spine
 No lifting objects > 15-20 lbs
 Calcium rich foods
Calcium Rich Foods
 Milk (skim, 1%, 2%, whole)
 Fortified orange juice
 Broccoli, collard or turnip greens
 Ice cream
 Cottage cheese
 Swiss cheese, cheddar cheese
 Canned salmon with bones
Summary of Non-pharmacologic
Options for Osteoporosis
National Osteoporosis Foundation (NOF)
Recommendations for Initiation of
Pharmacologic Therapy
 Initiate therapy to reduce fracture risk in
 women with:
 BMD T-scores below -2 by central DXA with no
 risk factors
 BMD T-scores below -1.5 by central DXA with
 one or more risk factors
 History of a prior vertebral or hip fracture
US FDA-Approved Pharmacologic
 Antiresorptive agents (bone-retaining)
   Bisphosphanates (Alendronate [Fosamax], Risedronate
   [Actonel], Ibandronate [Boniva], Zoledronic acid [Reclast] { – 15
   minute infusion})
   Estrogen/Hormone Therapy
   Raloxifene [Evista]
 Anabolics (bone-forming)
   Parathyroid Hormone Therapy (PTH 1-34, Teriparatide [Forteo]
Osteoporosis Pharmacotherapy:
Potency of the Bisphosphonates
    Zoledronic Acid > Risedronate,
     Ibandronate > Alendronate

     Zoledronic Acid (Reclast) - injection
     Alendronate (Fosamax) - tablet
     Risedronate (Actonel) - tablet
     Ibandronate (Boniva) – tablet, injection
Mechanism of Action
 Classified as antiresorptive medications
 Bind to hydroxyapatite cyrstals in bone
 and osteoclast-bone interface, inhibiting
 osteoclast activity
 Inhibit resorption of bone and lead to
 increases in bone density and reduced
 fracture risk
Bisphosphonate Administration
 Bisphosphonates must be taken carefully
 to avoid side effects and to ensure
Adminstration Guidelines
 Alendronate [Fosamax], Risedronate [Actonel], and
 Ibandronate [Boniva] tablet should be taken when the pt
 arises in the morning before eating or drinking with 8
 ounces of tap water (not mineral water or seltzer water)
 Take nothing by mouth (food, drink, other medications)
 for at least 30 minutes
 Ibandronate must be taken 60 minutes before eating or
 Patients must remain upright, walking, standing or sitting
 for at least ½ hour

 **Remind pts this includes not lying down or going back to bed**
Bisphosphonate Adverse Events

 Uncommon, but may include:
 Abdominal or musculoskeletal pain
 Irritation or burning of the esophagus
 Rare: osteonecrosis of the jaw
Osteonecrosis of the Jaw
Alendronate (Fosamax)
 In controlled clinical trials, use of
 alendronate increased or maintained bone
 density and reduced the incidence of
 fractures at the hip, spine, and wrist.
Alendronate (Fosamax):
 Prevention of Osteoporosis (5 mg daily tablet
 and 35 mg weekly tablet)
 Postmenopausal women

 Treatment of Osteoporosis (10 mg daily tablet
 and 70 mg weekly tablet)
 Postmenopausal women
 Glucocorticoid-induced osteoporosis in women and men
Risedronate (Actonel)
 In controlled clinical trials, use of
 risedronate increased or maintained bone
 density and reduced the risk of spine and
 non-spine fractures.
Ibandronate (Boniva)
 In controlled clinical trials, use of
 ibandronate increased or maintained bone
 density and reduced the risk of spine and
 non-spine fractures.
Ibandronate (Boniva)
Available as tablets and injection:

   Prevention and Treatment of Osteoporosis (2.5 mg daily tablet and 150 mg
   monthly tablet and 3 mg injection every 3 months)
   Postmenopausal women

   INJECTION Treatment of Osteoporosis
       Postmenopausal women
           Injection: 3 mg IV every 3 months
       Glucocorticoid-induced osteoporosis in women and men
           Injection: 2 mg IV every 3 months

   Prevention of postmenopausal osteoporosis: 0.5 mg, 1 mg, 2 mg injection
   every 3 months
Risedronate (Actonel):
  Prevention of osteoporosis in postmenopausal
  Treatment of osteoporosis in postmenopausal
  Treatment of osteoporosis in men
  Prevention and treatment of glucocorticoid-
  induced osteoporosis in men and women
Risedronate (Actonel):
Prescribing Information
  Risedronate is available in the following
  5 mg daily for prevention and/or
  35 mg weekly dose for prevention and/or
  75 mg qd x 2 days once per month
                        FDA April 2007
Zoledronic Acid (Reclast):
 Treatment of osteoporosis in
 postmenopausal women
 Treatment of osteoporosis in men
 Prevention and treatment of
 glucocorticoid-induced osteoporosis in
 men and women
Zoledronic Acid (Reclast):
Prescribing Information
 Zoledronic Acid is available in the
 following dose:

 5 mg IV/100 ml of normal saline
 Administer over 15 mins yearly
Calcitonin: Miacalcin – inj, nasal
spray or Fortical –nasal spray
 Classified as an antiresorptive medication
 In controlled clinical trails, calcitonin reduced the
 risk of vertebral fractures
 Calcitonin is prescribed for women who are at
 least 5 years postmenopausal and are unstable
 to tolerate other osteoporosis medications
 Calcitonin has been shown to decrease the risk
 of vertebral fracture but efficacy has not been
 demonstrated for nonvertebral fractures
 Administration is as a nasal spray or injectable
Calcitonin (Miacalcin or Fortical):
Adverse Effects
Nasal Calcitonin:    Injected Calcitonin:
 Nasal irritation       Allergic response
 Runny nose             Backache
 Bloody nose            Headaches
 Backache               Nausea/Vomiting
Raloxifene (Evista)
 Raloxifene is a selective estrogen receptor
 modulator (SERM) that acts as an
 estrogen agonist on bone but acts as an
 estrogen antagonist on both the breast
 and uterus.
Parathyroid Hormone (PTH):
Teriparatide (Forteo)
 PTH is classified as an anabolic agent that
 builds new bones
 PTH decreases the risk of vertebral
 fractures and nonvertebral fragility
 fractures after an average of 19 months
Teriparatide (Forteo): Indications
 Postmenopausal women with osteoporosis at
 high risk of fracture
 Men with primary or hypogonadal osteoporosis
 at high risk of fracture
 High-risk includes:
   Men and women with previous osteoporotic fractures,
   with multiple risk factors for fracture, with extremely
   low BMD (-3 and below)
   Those who are unresponsive or intolerant to other
   osteoporosis therapies
Teriparatide (Forteo):
  Teriparatide is available as a daily
  subcutaneous injection

  Patients are taught to self-administer the
  medication that comes in a pre-filled
  metered 28-day syringe
Teriparatide BMD Results
 Compared to placebo, 20 mcg of
 teriparatide increased lumbar spine BMD
 by 9 more percentage points
 Compared to placebo, the 20 mcg dose
 increased BMD in the femoral neck by 3
 more percentage points
 BMD effects were similar regardless of
 patient age or baseline BMD
Teriparatide Warnings
 Paget’s disease of bone
 Growing children and young adults
 Pregnant or nursing women
 History of bone cancer
 History of cancer that has metastasized to the
 Radiation to the skeleton from any condition
Teriparatide Adverse Effects
 Leg cramps
 Use is limited to 2 years
 PTH trials were stopped early due to the finding
 of osteosarcomas in animal studies
 No excess osteosarcomas reported in humans
 FDA assigned a BLACK BOX WARNING due to
 osteosarcoma findings in animal studies
Raloxifene (Evista):
 Raloxifene is approved for the prevention
 and treatment of postmenopausal
 In controlled clinical trials, raloxifene
 prevented bone loss in the spine and
 reduced risk of spine fractures
Raloxifene (Evista):
Adverse Effects
 Hot flashes
 Deep vein thrombosis (DVT)
 Leg cramps
 Small increase risk of fatal stroke
Women’s Health Initiative (WHI):
Findings on ET/HT
 In the WHI Study, ET used was Premarin®
 and HT was Prempro®
 While other doses and combinations of
 estrogens and progestins were not
 studied, the FDA believes the risks
 attributed to the combination in the WHI
 Study are applicable to all ET/HT products
Women’s Health Initiative (WHI):
Overall Conclusions
 Over one yr, 10,000 women taking estrogen plus
 progestin compared with placebo experienced:
 7 more CHD events
 8 more strokes
 18 more thromboembolic events
 8 more invasive breast cancers
 6 fewer colorectal cancers
 5 fewer hip fractures
Women’s Health Initiative (WHI):
Key Points
 HT/ET reduces risk of hip, spine, and all
 HT increases risk of CVD, venous thrombosis,
 stroke, cognitive decline, and breast cancer
 HT reduces risk of colon cancer
 ET increases risk of VT, stroke, and cognitive
 decline, but not CVD or breast cancer, and does
 not reduce the risk of colon cancer
 Risk of CVD appears to be lower in younger
 postmenopausal women
Women’s Health Initiative (WHI):
 DO NOT prescribe 0.625 mg/day CEE
 plus 2.5 mg/day MPA
 (medroxyprogesterone acetate) for the
 primary prevention of CHD
 Weigh risk for VTE, cardiovascular
 disease, dementia, and breast cancer
 against fracture benefits
Women’s Health Initiative (WHI):
 Did not look at lower doses of HT/ET drugs
 Did not look at other formulations of oral
 estrogens and progestin
 Did not look at estrogen and progestin
 administered transdermally
 Did not distinguish between the effects of
 estrogen and those of progestin
Estrogen/Hormone Therapy
 Prevent osteoporosis
 Treat moderate to severe vasomotor symptoms
 associated with menopause
 Treat moderate to severe sympyoms of vulvar
 and vaginal atropy associated with menopause
 Consider topical preparations to treat vulvar or
 vaginal symptoms rather than oral ET/HT
FDA Recommendations (ET/HT)

The FDA recommends the following:
  Physicians should consider all non-estrogen
  preparations first
  Prescribe the smallest dose for the shortest time
  to achieve treatment goals
  Prescribe ET/HT products only when benefits
  are believed to outweigh risks for a specific
Investigational Antiresportive
Myths About Osteoporosis
 Is an inevitable part of aging
 Cannot be prevented
 Older white women get osteoporosis
 Is not very common
 Is not serious or deadly condition
 Has no physical or emotional consequences
 The medical costs of osteoporosis are not high
 If you had it, you would know it
 Once you have it, nothing can be done about it
 Bone fractures from falling have nothing to do with
Go Canes!!!

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