Osteoporosis

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Osteoporosis

• Capital Conference 2007
• Marc Childress, MD

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Osteoporosis

• Epidemiology
• Risk Factors
• Prevention
• Screening
• Diagnosis
• Treatment
• Osteoporosis in Men
• Management
• Falls
• Acute Complications

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Osteoporosis

• Average female bone mineral density peaks at age
  35, slow decline thereafter
• Density loss is accelerated post-menopausally

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Epidemiology

• 1.3 million osteoporotic fractures in U.S. every
  year
• 40 of women over 50 have osteopenia
• 7 of women over 50 have osteoporosis
• Presence of osteoporosis carries 4-fold increase
  in fracture rate (over 50 years old)

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Epidemiology

• Among those who live to 90 years old, 1/3 of
  women and 1/6 of men will have sustained
  osteoporotic fracture
• Hip fracture mortality at 1 year is approaching
  25

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Risk Factors

• Female Gender
• 3X more likely to have hip or vertebral fracture
  than men
• 6X more likely to have forearm fracture
• Caucasian Race
• Higher than African-American, Asian race
• Smoking
• Low Body Weight (less than 58 kilos)

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Risk Factors (contd)

• Sedentary Lifestyle
• Excessive Alcohol Intake
• Ample suggestion that moderate alcohol intake may
  be protective
• No clear threshold
• Nursing Home Residents
• 10X more likely to experience hip fracture than
  age-matched non-residents

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Predisposing Medical Conditions

• Estrogen Deficiency
• Inflammatory Bowel Disease
• Type 2 Diabetes Mellitus
• Celiac disease
• Cystic fibrosis
• Hyperthyroidism
• Hyperparathyroidism

• Hypogonadism
• Liver Disease
• Corticosteroid use
• Heparin use
• Cyclosporine use
• Depo-Provera use
• Vitamin A (systemic retinoid) use

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Risk Factors (contd)

• No clear increase in risk with carbonated
  beverages
• Although unclear risk association with excessive
  caffeine

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What they want you to know

• Chronic excess thyroid hormone replacement over a
  number of years in post-menopausal women can lead
  to
• diffuse nontoxic goiter
• osteoarthritis
• osteoporosis
• hyperparathyroidism

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What they want you to know

• A 31-year-old white female presents with her
  third stress fracture of a lower extremity in the
  past 4 years. Her history and examination are
  otherwise unremarkable except for a controlled
  seizure disorder.
• The most likely cause of her bone problem is
• Addisons disease
• Hypothyroidism
• Osteogenesis imperfecta
• Anticonvulsive medication

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Prevention

• Adequate total dietary calcium
• 1500 mg/day for postmenopausal without HRT
• 1000-1200 mg/day premen, postmen with HRT
• Vitamin D
• 800 IU/day for postmenopausal
• 400 IU/day premen, postmen with HRT
• Regular weight-bearing exercise
• Additional protective factors increased BMI,
  African-American ethnicity, moderate EtOH intake

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What they want you to know

• Which of the following antihypertensives agents
  may help preserve bone mineral density?
• Atenolol (Tenormin)
• Doxazosin (Cardura)
• Enalapril (Vasotec)
• Hydrochlorothiazide
• Nifedipine (Procardia, Adalat)
• Which one of the following is associated with a
  reduced risk of post-menopausal osteoporosis?
• Corticosteroid use
• Cigarette smoking
• Diuretic use
• Low BMI
• Asian Ethnicity

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Screening

• USPTF/AAFP routine screening above the age of
  65, consider between 60-65 for increased risk
• National Osteoporosis Foundationrecommend
  screening above 65, or in younger with risk
  factors
• Difficulty with recommendations
• Cost issues
• Time interval of screening examination

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Screening Options

• Single Photon absorptiometry
• -can only be used at radius or calcaneus (unclear
  attenuation source)
• Dual Photon absorptiometry
• -can be used at deeper sites (spine,hip)

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Screening Options

• Dual X-ray absorptiometry (DEXA)MOST POPULAR
• Pros
• -precise measurements at clinically relevant
  sites (hip and spine)
• -minimal radiation
• Cons
• -not portable
• -expensive

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Screening Options

• Quantitative CT
• Pros
• -similar accuracy to DEXA
• -may have slightly better predictive value in
  risk of vertebral fracture
• Cons
• -more expensive (than DEXA)
• -less reproducible (bigger variance)
• -higher radiation

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Screening Options

• Ultrasound
• Pros
• -studies thus far have suggested similar
  predictive ability of fracture to DEXA
• -No radiation
• -Portable
• Cons
• -unable to provide true Bone Density Measurements
  (less applicable to current diagnostic standards
  and treatment goals based on BMD)
• current role in identifying high risk
  individuals, not in pervasive screening

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Diagnosis

• 2 Methods
• 1) Radiographic determination of Bone Mineral
  Density to be
• -1 Standard Deviations below young adult
  reference mean-OSTEOPENIA
• -2.5 Standard Deviations below young adult
  reference mean-OSTEOPOROSIS
• 2) Presence of fragility fracture (no signif
  trauma hx, and absence of osteomalacia or bone
  tumor)

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Treatment

• Bisphosphonates- most appropriate initial
  treatment for women with osteoporosis
• Alendronate (10 mg/day or 70 mg weekly),
• -best when taken on empty stomach with 8 oz.
  water, standing upright for 30 minutes, risk of
  esophagitis
• - contraindicated in patients with active upper
  GI disease
• Risedronate (5 mg/day or 35 mg weekly)
• -less apparent GI risk than alendronate

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Treatment

• SERMS (Selective Estrogen Receptor Modulators)-
• Raloxifene-best data among 2 in class, approved
  for both prevention and treatment of osteoporosis
• Tamoxifennot FDA approved, but some data to
  suggest bone benefit

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Treatment

• PTH (Teriparatide)-daily injections. Currently
  limited to those at very high fracture risk or
  those unresponsive to bisphosponate therapy due
  to high cost (20/day) and risk of osteosarcoma
• Calcitonin- nasal spray. Less effect on bone
  than bisphosphonates, risk of tachyphylaxis.
  Unique role in acute treatment of osteoporotic
  fracturemay be switched to alternate therapy
  once pain diminished.

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Treatment

• Estrogen / Progestin therapy
• No longer first line, but still an option in
  women who may be contraindicated from or
  intolerant to bisphosponates or raloxifene.
• Combination therapy- there are demonstrable gains
  in using bisphosponates in combination with
  SERMs, and estrogen therapy if no
  contraindications and less than desired benefit
  on single osteoporosis therapy

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What they want you to know

• Raloxifene (Evista)
• is used to manage hot flashes
• increases bone density
• stimulates breast tissue
• stimulates endometrial proliferation
• raises LDL and total cholesterol levels

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Osteoporosis in Men

• --1.5 million men in U.S. with osteoporosis, 3.5
  million at risk
• --1 in 6 men at 90 years of age will experience
  hip fracture. Mortality with hip fracture higher
  in men than in women.
• --Treatment includes testosterone therapy (unless
  contraindicatedsee question) as first line, as
  well as bisphonate therapy (works equally well in
  mensee question). Likely role for recombinant
  PTH and possibly SERMs (raloxifene).
• --Must assure adequate calcium and vitamin D
  intake, although these are not sufficient for
  treatment of osteoporosis
• --Diagnosis best made with DEXA, still compared
  to standard of young woman

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What they want you to know

• A 79-year old white male with a previous history
  of prostate cancer has a lumbar spine film
  suggesting osteopenia. Subsequent bone density
  studies show a T score of -2.7. Which one of the
  following is appropriate first line therapy for
  this patient?
• A) Testosterone
• B) Calcitonin nasal spray (Micalcin)
• C) Raloxifene (Evista)
• D) Alendronate (Fosamax)
• Which one of the following is true regarding the
  use of Alendronate (Fosamax) for the treatment of
  osteoporosis in men?
• A) Its effectiveness is similar to that
  seen in women
• B) It is ineffective in patients with
  Pagets disease
• C) It is contraindicated in patients
  taking NSAIDs
• D) It causes a decrease in height

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Chronic Management

• --No advantage of remeasuring BMD within 1 year
• --Recommendations for remeasurement in 1 or 2
  years once therapy has been started
• --If evaluated, and no change at one year, not
  indicative of eventual benefit. Recommend
  ensuring adequate calcium Vit D, and additional
  risk factor reduction (smoking cessation,
  deacreased EtOH, etc.)If significant worsening,
  likely unresponsive to therapy. If improvement,
  continue regimen and follow long term.

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What they want you to know

• A 70-year-old female had a lumbar vertebral
  fracture 3 years ago. At that time she had a
  dual-energy absorptiometry (DEXA) scan, with a T
  score of -2.6, and was placed on alendronate
  (Fosamax), calcium, and vitamin D. She recently
  quit smoking. Her BMI is 21. A DEXA scan today
  shows her bone mineral density to be -2.1.
• Which one of the following would be most
  appropriate in the management of this patient?
• Replace alendronate with raloxifene (Evista)
• Stop alendronate, but continue calcium and
  vitamin D
• Add raloxifene to her regimen
• Add teriparatide (Forteo) to her regimen
• Make no change to her regimen

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Falls

• --Fracture risk is still significantly linked to
  risk of fall
• --Ability to safely transfer is independent risk
  factor
• --Vitamin D has been shown in numerous studies to
  decrease risk of falls independent of the
  structural bone benefit

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What they want you to know

• Which one of the following has been shown to
  reduce the risk of falls in the elderly?
• Vitamin D
• Amityriptyline (Elavil)
• Haloperidol (Haldol)
• Lorazepam (Ativan)

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Acute Complications

• Remember that Calcitonin has additional benefit
  of pain reduction in acute course of compression
  fracture
• A 70-year-old white female with osteoporosis sees
  you for follow-up a few days after an emergency
  room visit for an acute T12 vertebral compression
  fracture. The fracture was suspected clinically
  and on plain films the diagnosis was confirmed
  with a bone scan. The emergency department
  physician prescribed oxycontin and NSAIDs, but
  the patient is still experiencing considerable
  discomfort.
• In addition to increasing the dosage of
  oxycodone, which one of the following
  interventions would you suggest now to reduce the
  patients pain?
• Calcitonin (Miacalcin)
• Raloxifene (Evista)
• Alendronate (Fosamax)
• Physical therapy, including dexamethasone
  iontophoresis
• Vertebroplasty
• A 78-year-old white female presents with a 3-day
  history of lower thoracic back pain. She denies
  any antecedent fall or trauma, and first noted
  pain upon arising. Her description of the pain
  indicates that it is severe, bilateral, and
  without radiation to the arms or legs.
• Her past medical history is positive for
  hypertension and controlled diabetes milletus.
  Her meds include HCTZ, enalipril, metformin, and
  MVI. She is a previous smoker but does not drink
  alcohol. She underwent menopause at age 50 and
  took estrogen for a few months for hot flashes.
  Physical exam reveals her to be in moderate pain
  with a somewhat stooped posture and mild
  tenderness over T12-L1. She has negative
  straight leg raising and normal lower extremity
  sensation, strength, and reflexes.
• Which of the following is true regarding this
  patients likely condition?
• An MRI or nuclear medicine bone scan should be
  performed
• Prolonged (approximately 2 weeks) bed rest will
  increase the chance of complete recovery
• Investigation for an underlying malignancy is
  indicated
• Subcutaneous or intranasal calcitonin (Calcimar,
  Miacalcin) may be very helpful for pain relief

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Questions?