Pharmacotherapy of Osteoporosis

Marie Meyer, PharmD Candidate 2007

Epidemiology / Osteoporosis is the most common disease of the bones
Prevalence: ~55% of the US population over age 50 are at risk (~44 million Americans)
~12% of the US population already have osteoporosis (~10 million Americans)
~43% have low bone mass… may develop into osteoporosis in their lifetime (~34 million Americans)
Incidence: ~ 1.5 million fractures per year
Location of fractures: vertebrae ~700,000, hip ~300,000, wrist ~250,000, other sites ~300,000
Distribution: 80% of cases are in females, 20% in males
People of all ethnic backgrounds are at risk
Females: White and Asian > Hispanic > Black
Males: White and Asian > Black and Hispanic
DiseaseState Definition / Osteoporosis = “porous bone”
Characteristics:
low bone mass
structuraldeterioration of bone tissue micro-architecture
decreased bone strength  bone fragility
increased risk of fractures, especially of the hip, spine, or wrist
Clinically defined by low bone mineral density (BMD)
Significant clinical outcome fractures of the vertebrae, hips, wrists, and other bones
Patho-physiology / Bone remodeling: theconstantprocess of bone formation and resorption.
Bone development: in children and adolescents bone formation exceeds bone resorption
Peak bone mass: bone is at maximum density and strength, occurs around age 25-30
Bone loss occurs when bone resorption exceeds bone formation, typically after age 30
Post-menopausal estrogen deficiency accelerates the age-related bone formation/resorption imbalance
Other risk factors (below) also accelerate bone loss or cause a low peak bone mass
Adult bone mass = peak bone mass – subsequent bone loss
Increased bone loss or low peak bone masslow bone density
Low bone density  increased risk of fractures
Clinical Presentation / “silent disease”… often undiagnosed until fragility fracture occurs
fragility fracture = bone fracture occurring in the absence of trauma or from very mild trauma
 disability
pain
deformity
vertebral compression fracturesinternal organ crowding, disability, pain, increased mortality
changes in body appearance… height loss
curved shoulders and back
thickened waistline
Risk Factors / Age
risk increases with age beyond 30
Gender
menopause causes women to lose bone mass faster than men
PMH
history of fracture as an adult (fragility or traumatic fractures)
history of recent falls
early onset estrogen deficit (< 45 years old)
visual impairment
dementia
general poor health
FH
1st degree relative with history of fragility fracture
Race
Caucasian and Asian women are at the greatest risk
Black and Hispanic women also have a significant risk
Bone structure
small body frame increases risk
osteopenia = low bone mass
Body weight
< 127 lbs (57.7 kg) increases risk
Medications
*steroids* (glucocorticoids, andrenocorticotropin)
anticonvulsants (phenobarbital, phenytoin)
aluminum antacids
cholestyramine
cytotoxic drugs (methotrexate)
estrogen antagonist (tamoxifen – before menopause)
gonadotropin releasing hormone (GnRH)
heparin (long-term use)
immunosuppresants (cyclosporine A)
lithium
thyroid hormones (thyroxine in excessive doses)
Lifestyle factors
current smoking
excessive EtOH intake (>2 drinks daily)
lifelong inadequate calcium intake
physical inactivity
Diagnosis
Diagnosis
Continued / Bone mineral density (BMD) measurement
lower BMD correlates with higher fracture risk
Hip BMD = best predictor of hip fractures, also predicts fractures at other sites
Z-score = expected BMD for age and sex of the patient
T-score = expected BMD for young normal adults of the same sex as the patient
Normal = T-score ≥ –1 =BMD within 1 standard deviation (SD) of “young normal”
Osteopenia = T-score between –1 and –2.5 =BMD between 1 and 2.5 SD less than “young normal”
Osteoporosis = T-score ≤ –2.5 = BMD 2.5 or more less than “young normal”
Established osteoporosis = T-score ≤ –2.5 plus history of fragility fracture
BMD Measurement Techniques
Dual x-ray absorptiometry (DXA)
Central DXA – spine, hip, or wrist(diagnosis & monitoring)
**** Spine or hip central DXA is the standard diagnostic technique ****
Peripheral DXA – forearm, finger, heel (screening)
Single-energy x-ray absorptiometry (SXA) – forearm, finger, heel (screening)
Quantitative computed tomography (QCT)– central or peripheral(diagnosis & monitoring)
Ultrasound densitometry– heel, tibia, patella, or other peripheral sites.
Not as precise as DXA or SXA, but good prediction of fracture risk (screening)
BMD testing should be performed on:
All women ≥ 65
Postmenopausal women < 65 with one or more risk factors (other than race, gender, postmenopausal)
Postmenopausal women with fractures (confirm diagnosis, determine disease severity)
Treatment to reduce fracture risk is recommended for women with
T-scores < –2.0 by hip DXA without risk factors
T-scores < –1.5 by hip DXA plus ≥ 1 risk factors
prior vertebral or hip fracture
Desired Therapeutic Outcomes* / Osteoporosis prevention goals*
  1. Optimize skeletal development and maximize peakbone mass at skeletal maturity
  2. Prevent age-related and secondary causes of bone loss
  3. Preserve the structural integrity of the skeleton
  4. Prevent fractures
Osteoporosis treatment goals*
  1. Prevent fractures
  2. Stabilize or achieve an increase in bone mass
  3. Relieve symptoms of fractures and skeletal deformity
  4. Maximize physical function
*American Associationof Clinical Endocrinologists Medical Guidelines For Clinical Practice Forthe Preventionand Treatment of Postmenopausal Osteoporosis: 2001 Edition,withselectedupdatesfor 2003
Treatment Options**
**See Treatment Options Table / Non-pharmacologic
  1. adequate calcium/vitamin D intake and good nutrition in general
    calcium ~1000-1200mg daily
    vitamin D ~400-800 IU daily
  2. regular weight bearing exercise
  3. fall prevention – vision, hearing, neurological defects, medication side effects, home safety, walking aids
  4. fall protection – hip protective garments
  5. alcohol moderation and tobacco abstinence
Pharmacologic
therapeutic class generic drug (Brand)
  1. bisphosphonates alendronate (Fosamax),ibandronate (Boniva), risedronate (Actonel)
  2. calcitonin (Miacalcin, Fortical)
  3. estrogen therapy (Climara, Estrace, Estraderm, Ogen, Ortho-Est, Premarin, Vivelle)
  4. hormone therapy (Activella, Femhrt, Premphase, Prempro)
  5. parathyroid hormone teriparatide (Forteo)
  6. selective estrogen raloxifene (Evista)
receptor modulator
Monitoring / Efficacy
DXA every 1-2 years (note that fracture risk may decrease without noted increase in BMD)
Height yearly
Patient reported fall, fracture, bone pain monthly or weekly
Toxicity
Bisphospinates
Alendronate – serum calcium and phosphorus
patient reported dyspepsia, heartburn, acid reflux, dysphagia
physical exam for GERD, esophagitis, esophageal ulcer, gastritis, gastric ulcer
Ibandronate – serum creatinine before each IV dose, serum calcium, phosphorus, and magnesium,
patient reported dyspepsia
physical exam for esophagitis, gastritis, ulcer
Risedronate – alkaline phosphates, serum calcium, phosphorus, and potassium
patient reported dyspepsia, heartburn, acid reflux, dysphagia
physical exam for esophagitis, gastritis, ulcer
Calcitonin
serum calcium
patient reported rhinitis, nosebleeds, sinusitis
physical exam for nasal ulceration
Estrogen
patient reported chest pain, SOB, hemoptysis, cardiac awareness, one-sided weakness, sudden visual or speech problems, sudden confusion or dizziness, sudden severe headache, claudication, leg warmth/ redness/ swelling
Hormone therapy
mammogram yearly
patient reported chest pain, SOB, hemoptysis, cardiac awareness, one-sided weakness, sudden visual or speech problems, sudden confusion or dizziness, sudden severe headache, claudication, leg warmth/ redness/ swelling
patient reported unusual vaginal bleeding
Teriparatide
calcium, BP, uric acid
Raloxifene
CBC, lipid profile
patient reported claudication, leg cramps, leg warmth/ redness/ swelling of the leg, hot flashes, leg cramps

References

American Associationof Clinical Endocrinologists Medical Guidelines For Clinical Practice Forthe Preventionand Treatment of Postmenopausal Osteoporosis: 2001 Edition, withselectedupdatesfor 2003

Physician’s Guide to Prevention and Treatment of Osteoporosis, National Osteoporosis Foundation, 2003

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Marie Meyer, PharmD Candidate 2007Pharmacotherapy Presentation – Pharmaceutical Care Rotation

University of MarylandSchool of PharmacyHappy Harry’s PharmacyPatientCareCenter, Perryville, MD