Download Preventing Breaking Bad - American Osteopathic Association

PREVENTING BREAKING BAD:
OSTEOPOROSIS
MANAGEMENT
Dr. Edward Warren
Chair, Geriatrics
Carolinas Campus
May 6, 2012 12:45 pm
Disclaimer
I have no relevant financial relationships that
would bias my opinions on this topic.
Meet me afterward to make offers!
Objectives
1. Define osteoporosis.
2. Apply knowledge of causes of osteoporosis to
patient evaluation and management.
3. Apply knowledge of sequellae of osteoporosis to
patient evaluation and management.
4. Treat osteoporosis optimally.
5. Prevent osteoporosis effectively.
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Osteoporosis
• A reduction in bone mass with an
increased risk and ease of fractures
• Loss of bone tissue results in a
deterioration of skeletal microarchitecture
Osteoporosis
• Increased “porosity” of bone
• Prevalence = 10,000,000 in the US
only a minority of these are diagnosed
and treated
Osteopenia
• Osteopenia = low bone density
• “penia” from Greek “penes”, related to
“penury” meaning “poor”.
• Osteopenic women have more than 50%
of the fractures postmenopause.
• Prevalence = 18,000,000 in the US
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Prevalence
Underdiagnosed & Undertreated in ALL!
• Osteopenia in Caucasians & Asians
– Women
– Men
52%
35%
• Osteoporosis in Caucasians & Asians
– Women
– Men
20%
7%
• Hispanic women are catching up fast!
• Blacks have 40% less fractures, but more
fatalities!
Bone Remodeling
• Bone repairs itself by constant, active remodeling
– bone reabsorption (osteoclasts)
– bone formation (osteoblasts)
• The remodeling cycle may become unbalanced
– after menopause
– with aging in both men and women
– bone reabsorption rate exceeds bone formation rate:
weeks vs months
– net bone loss is predominantly cancellous
(trabecular) bone.
Lifetime Changes in Bone Mass
Age
Women
Men
Up to mid-20s & 30s
Bone mass increases rapidly, reaching peak bone mass
Mid-30s to 40s
A few years of stability, then slow
bone loss
No risk factors
yearly bone loss 1%
Mid-40s to 50s
Menopause leads to rapid yearly
bone loss  7% for  7 years
With risk factors
Yearly bone loss  6%
Mid-50s to late life
Continuing yearly bone loss of 1% to 2%
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Risk Factors
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Personal fracture
1° relative fracture
Female gender
Advanced age
Caucasian/Asian
Low Ca intake
Vitamin D deficiency
Low hormone levels
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Tobacco abuse
Alcohol Abuse
Sedentary Lifestyle
Frailty
Ectomorphic
Certain medications
Certain diseases
Risk Factors: Medications
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Anticonvulsants
Warfarin
Glucocorticoids
Lithium
Neuroleptics
Medroxyprogesterone
Excess levothyroxine
Excess Vitamin A
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Cushing’s Disease
Addison’s Disease
1° Hyperparathyroidism
Hyperthyroidism
Hypogonadism
Multiple myeloma
Leukemias
Sickle Cell
Osteomalacia
• Excess Vitamin D
• PO4 binding antacids:
Aluminum hydroxide
• Aromatase Inhibitors &
GnRH Antagonists (for
CA prostate)
• Immunosuppressants &
Cytotoxins (i.e. MTX)
Risk Factors: Diseases
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Paget’s Disease
COPD
Vitamin D deficiency
Malabsorption
syndromes
Malnutrition
RA, Lupus
Diabetes Mellitus
Renal Failure
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Risk Factors: Ca & Vitamin D
• Calcium, vitamin D & parathyroid hormone
maintain bone homeostasis.
• Low Ca in diet or malabsorption of it leads to 2°
hyperparathyroidism.
• PTH is excreted when serum Ca is low, leading to
increased bone resorption, decreased renal Ca
excretion, and increased renal production of 1,25
dihydroxy-vitamin D.
• Vitamin D increases absorption of Ca and P from
the gut, and inhibits PTH synthesis.
Clinical Manifestations
• Hip fractures
• Vertebral and other Osteoporotic Fractures
• Wrist fractures
• Most any fracture you can think of
– pelvis, head of the humerus, etc.
• 1,500,000 fractures yearly in the US
HIP Fractures
• Incidence doubles q5 years after age 70.
• 300,000 hip fractures yearly in the US
• Likelihood for a 50 year old Caucasian to
fracture a hip is: 14% women, 5% men
– African Americans are half as likely.
• Only ⅓ have a full recovery.
• 20% live in a nursing home lifelong.
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HIP Fractures
Complications:
• Deep venous thrombosis
• Pulmonary embolism
• 5 – 20% mortality rate
• 66% suffer permanent mobility loss
• Doubles risk of future fractures.
Vertebral Compression Fractures
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700,000 yearly in the US
Many are asymptomatic
Height loss
Kyphosis
Back pain
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Vertebral Compression Fractures
• Thoracic compression fractures
– Restrictive lung disease
• Lumbar compression fractures
– abdominal distention
– early satiety
– constipation
PEARL
THE MOST
IMPORTANT PART
OF TREATMENT
IS DIAGNOSIS.
Evaluation
• Comprehensive H&PE as ALWAYS!
• Measure bone mineral density: BMD
• Assess for secondary causes of bone loss:
UGH!
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H&PE
• FH: fractures, especially at early age
• SH: tobacco, ethanol, activity, diet
• PMH: prior fractures, risk factors, fragility
fractures (with minimal force), vitamin D &
calcium use
• Elderly fall risk: balance, orthostatic
hypotension, debility, poor vision, poor
hearing, poor cognition
H&PE
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BMI < 20
kyphoscoliosis
vertebral point tenderness
height loss
Bone Mineral Density
• Dual-energy X-ray Absorptiometry (DEXA, DXA)
– highly accurate, standard in most centers
• Single-energy X-ray Absorptiometry (SEXA, SXA, SEX?)
– less accurate, less available
• Quantitative CT
– expensive, more radiation, less reproducible
– gives true density
• Ultrasound
– cheap and mobile
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Bone Mineral Density: DXA
• Preferred method of measurement
• Can measure hip, anterior-posterior spine,
lateral spine, and wrist
• Cost = $200 to $300
• Covered by Medicare and Medicaid at 24
month intervals on anyone
Bone Mineral Density: DXA
• Two dimensional technique.
• Two x-ray energies are used to measure the
mineralization in an area. The mineral
content is divided by this area.
• Small people are rated spuriously low.
• Machines vary from each other = problem
Bone Mineral Density: DXA
• STASTICS TO THE RESCUE
– A Bell-shaped curve is formed for each
population by age, gender, and race.
– T-score compares one to 30 year olds matched
for gender and race.
– Z-score compares one to age, gender, and race
matched controls.
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T-score graph
The WHO has defined the
following categories based on
bone density in white women:
Normal bone: T-score > -1
Osteopenia: -1 > T-score > -2.5
Osteoporosis: T-score < -2.5
National Osteoporosis Foundation
Recommendations for DXA
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Women > age 65 & Men > age 70
Estrogen-deficient women with clinical risks
Osteopenia or vertebral fracture on x-ray
Fragility fractures
Patients with illness or medication that imparts risk > age 50
Glucocorticoid treatment ≥ 7.5 mg of prednisone duration of
therapy > 3 months
• Primary hyperparathyroidism
• Monitoring response to an FDA-approved medication for
osteoporosis
Monitoring with DXA
• Repeat BMD evaluations at > 2 year intervals
since years are needed for any changes
• Significant changes are 4% in spine and 6% in
hips
• Treatments do not often produce changes large
enough to detect reliably
• In those below age 50, use Z-scores. If < -2.0,
then they are “below expected range”, and would
need additional clinical criteria for a diagnosis.
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FRAX
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This is the WHO fracture risk algorithm
www.shef.uk/FRAX/
Enter clinical data and get a fracture risk.
The National Osteoporosis Foundation
advises treatment for 3% risk of hip
fracture or 20% risk of osteoporotic
fractures.
FRAX
Screening for Secondary Causes
Disease
Recommended Laboratory Tests
Cushing’s disease
Electrolytes (low K)
Hyperthyroidism
TSH (low)
Multiple myeloma
CBC, Total serum protein (high globulin)
Osteomalacia
Alkaline phosphatase, 25(OH) vitamin D (< 32
ng/ml), 24 hr urine calcium
Paget’s disease
Alkaline phosphatase, x-ray of painful bones
Primary hyperparathyroidism
Calcium (high), Phosphorus
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Screening for Secondary Causes
• ↑ Ca  hyperparathyroidism or malignancy
– ↑ iPTH  hyperparathyroidism
– ↓ iPTH  malignancy (↑ PTHrP suggests humoral
hypercalemia of malignancy)
• ↓ Ca  osteomalacia, malnutrition, or
malabsorption
Screening for Secondary Causes
• Cushing’s suspected  dexamethasone
suppression test
• Malnutrition suspected  albumen, prealbumen,
cholesterol, CBC, vitamin B12, folic acid, Fe, TIBC
 if low, then further evaluation needed
• Myeloma suspected  serum protein
electrophoresis, urine electrophoresis for light
chains, and bone marrow exam
• X-rays are for fracture documentation only.
Preventing and Treating Osteoporosis
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Weight-bearing exercise: lifelong
Smoking cessation: lifelong
Ethanol moderation: lifelong
Calcium and vitamin D: dietary, sunlight, lifelong
Estrogen replacement
Bisphosphonates
Selective estrogen receptor modulators
Calcitonin
Others
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Treatment Criteria
• T-score < -2.5
• Any postmenopausal woman with risk
factors regardless of T-score
Risk Factor Reduction
• Glucocorticoids can be titrated to
minimal effective doses.
• Thyroid hormone doses need to be as low
as needed to normalize TSH.
• Smoking cessation.
• Ethanol moderation.
Fall Risk Factor Reduction
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Ethanol avoidance.
Reduce or eliminate sedating medications.
Protect against orthostatic hypotension.
Address nocturia.
Fix environmental hazards: wires, rugs,
furniture, socks
• Vision correction
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Exercise
• Decrease in physical activity or immobilization
 decline in bone mass
• Walking, a weight-bearing exercise, can be
recommended for all adults
• Exercise  2% bone mass increase at best. NNT =
1600
• Start slowly and gradually increase the number of days
and time spent walking each day (at least 3 days
weekly)
• Improves coordination, balance, and strength.
DOE’s vs POE’s
• DOE = disease oriented evidence
– 2% increase in bone mineral density
• POE = patient oriented evidence
– how many fractures are prevented
NNT
• Alendronate reduces vertebral
compression fractures 44%: relative risk.
• Shun, reject, ignore relative risk.
• Liars figure and figures lie.
• At worst relative risk is used to fool you
into believing something is better than it
really is.
• At best it is being presented by someone
who does not know any better.
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NNT
• Alendronate reduces vertebral compression
fractures 44% in 3 years
• Placebo 3.9% fractures: alendronate 2.2%
• Number Needed to Treat
• 1.7% absolute reduction
 1.7/100 patients  reciprocal
 NNT of 59 patients to prevent 1 fracture/3 years
NNT
• “NNT” is well ensconced in the medical parlance
and can be searched for on the internet with a drug
name to find the value easily.
• Bisphosphonates reduce hip fractures about 40%,
relative risk.
• About 1% of people over 65 have hip fractures
yearly
• Absolute reduction is thus 0.4% or 4/1000
• The reciprocal of 0.004 is NNT = 250
• Is it worth $250,000 to prevent one hip fracture a
year?
Calcium & Vitamin D
• Calcium and vitamin D maintain or increase bone density
in postmenopausal women & help prevent hip and
nonvertebral fractures in all older adults.
• Calcium has no benefit on fracture rate used alone.
• Vitamin D: NNT = 45 to prevent a hip fracture over 3 years.
• 1200 mg / day of calcium: men 65 years and older &
postmenopausal women.
• 1000 IU / day of vitamin D3: regardless of sunlight exposure
to offset skin changes that  efficient use of UV light to
synthesize vitamin D precursors. (I start with 4000 units qd.)
• Calcium has no harmful cardiac effects.
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Estrogen Replacement
• Estrogen produces bone loss protection.
• All benefit is lost in 10 years if stopped.
• 10,000 treated women in 1 year
– 8 extra MI’s
18 extra DVT’s
– 8 extra CVA’s
6 fewer CA colon
– 5 fewer hip fractures
44 fewer fractures
– neutral death rate (voided by progesterone)
• NNT 385 for hip fractures over 3 years
Estrogen Replacement
• SERMS (selective estrogen response
modulators)
• Tamoxifen reduces bone turnover and CA
breast, but it increases uterine CA.
• Raloxifene reduces vertebral collapse as well
as CA breast. NNT is 22 in 4 years for a
vertebral fracture.
Bisphosphonates
• Structurally related to pyrophosphates which are
incorporated into bone matrices where resorption is
active.
• Impair osteoclast function.
• Poorly absorbed: bioavailability only 5%.
• Reduce osteoclast number by apoptosis
• NNT for hip fracture 77 – 91 in 3 years
• NNT for vertebral fracture 13 – 20 in 3 years
• Side effects: dyspepsia & esophageal perforation
• Incapacitating bone pain, arthralgia, and myalgia can
occur any time.
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Bisphosphonates: Alendronate
• In comparison with placebo:
–  bone density of spine (8%) & hip (3.5%) – DOE’s
–  vertebral & hip fracture rate by 50% at 2 years
• NNT 37 for vertebral fractures in 3 years – POE
• Dosing for Prevention: Once-weekly 70 mg po: $102/month
• Side effects
– GI: abdominal pain, dyspepsia, esophagitis, nausea,
vomiting, diarrhea
– Musculoskeletal pain
Bisphosphonates: Zoledronic Acid
• Most potent. Given by yearly IV infusion.
• In comparison with placebo:
–  bone density of spine (5.1%) & hip (3.5%) – DOE’s
–  vertebral & hip fracture rate by 70% and 41%
respectively at 3 years
• NNT 107 for vertebral fractures in 3 years – POE
• NNH (number needed to harm) = 100
• Cost $1250/year
• Side effects
– GI: abdominal pain, dyspepsia, esophagitis, nausea,
vomiting, diarrhea
– Musculoskeletal pain
Other Bisphosphonates
• Risedronate
– Approved for osteoporosis: 35 mg po weekly: $130/month
– In comparison with placebo:
•  bone density of spine (5.4%) & hip (1.6%) – DOE’s
•  new vertebral & hip fracture rate of 50% – relative risk
– GI side effects
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Ibandronate: similar: $470/3 months
Benefits lost 1 year after stopping
NNT = 13 – 20 over 3 years for vertebral fracture
Death rates equal in drug and placebo groups
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Instructions for Taking
Bisphosphonates
• Take first thing in the morning before eating or drinking
anything else.
• Take with at least 8 oz of plain tap water.
• Take while upright in a chair or standing, and remain
upright for 30 minutes after ingestion.
• Do not eat or drink anything for 30 minutes after ingestion.
Calcitonin
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Hormonal suppressor of osteoclasts
It has minimal effect on bone strength and fractures.
NNT = 10 in 5 years
Possible analgesic effect in women with painful vertebral
compression fractures
• Dosing
– Subcutaneous injection: frequent nausea & flushing
– Nasal spray (fewer reported side effects, greater patient
acceptance, may be less effective): $145/month
Denosumab
• Human monoclonal antibody to RANKL
receptor activator of nuclear factor kappa-B ligand
• This inhibits the formation of mature
osteoclasts
• 60 mg sc q6 months: $1200/6 months
• NNT = 56 in 3 years vertebral fracture
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Teriparatide
• An exogenous PTH analogue
• In 3 years reduces vertebral fracture 65%
and nonvertebral fractures 54%
• Give a single daily injection for 2 years
• NNT = 11 in 1½ years
• $600/month
Fluoride
• Increases bone mass 10% -- DOE
• Has no influence on reducing fractures
• May increase fractures
Hip Pads
• Worn over the greater trochanters
• Prevents hip fractures
• NNT = 7
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Hip Pads
Citations
• Lindsay Robert, Cosman Felicia, "Chapter
354. Osteoporosis”. Fauci AS, Braunwald E,
Kasper DL, Hauser SL, Longo DL, Jameson
JL, Loscalzo J: Harrison's Principles of
Internal Medicine, 18e:
http://www.accessmedicine.com/content.aspx
?aID=9143360
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