Transcript Osteoporosis

Osteoporosis
DeAnn Cummings, MD
January 12, 2012
Why Does it Matter?
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44 million people in U.S. with low bone mass
2 million osteoporotic fractures per year
$17 billion spent per year on osteoporotic fractures
and their complications
20% increased mortality over 5 years following a
vertebral fracture
10-30% increased mortality over one year following a
hip fracture
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17% for women
30% for men
Why Does it Matter?
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50% require nursing home care after hip
fracture
30% need assistance with daily activities
Only 20% return to previous level of
functioning
Definition
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A microarchitectural deterioration of bone
tissue resulting in decreased bone strength
which predisposes to an increased risk of
fracture
Bone strength = Bone density + Bone quality
Bone mineral density (BMD) is usually used
as a surrogate to assess bone strength
Bone Mineral Density
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Fracture risk increases 2-3 times for each
standard deviation below gender-matched
young adult mean
T score = #standard deviations from gendermatched young adult mean
Z score = #standard deviations from age and
gender-matched mean
T score best correlates with fracture risk
World Health Organization
Definitions
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Normal – T score greater than or equal to -1.0
Osteopenia – T score between -1.0 and -2.5
Osteoporosis – T score less than or equal to
-2.5
Established osteoporosis – T score < -2.5 and
at least one fragility fracture
Pathophysiology
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Balance between bone resorption and
formation (remodeling)
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Remodeling is in balance until about age 50
Osteoclasts resorb bone
Osteoblasts form bone
Estrogen inhibits osteoclastic bone resorption
Peak bone mass is established by age 20 for
the hip and during the early 30’s for the spine
Pathophysiology
Women have increased incidence of osteoporosis
compared to men due to:
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Lower peak bone mass
Greater bone loss after menopause (10% bone loss)
Men and non-white women have higher peak bone
mass than white women
Genetic factors – 70-80% of peak bone mass is
genetically determined
Pregnancy and lactation cause transient bone loss
Pathophysiology
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Bone quality
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Disruption of microarchitectural elements of
trabecular bone
Cortical thinning
Decrease in degree of mineralization
May be important in the future
Types of Osteoporosis
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Primary osteoporosis
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Related to aging and/or decreased gonadal function
Aging bone loss is slower than menopausal
Menopause related bone loss lasts about 10 yrs
Secondary osteoporosis
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Due to medications or chronic illnesses that
accelerate bone loss
Consider secondary osteoporosis if Z-score is low
Chronic Diseases
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Cushing’s syndrome
Hyperparathyroidism
Hyperthyroidism
Multiple myeloma
Lymphoma
Chronic liver disease
Chronic renal disease
Malabsorption syndromes
Paraplegics, quadriplegics
Hypogonadism
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Anorexia nervosa
Athletic amenorrhea
Diabetes mellitus
Hemochromatosis
Hyperprolactinemia
Osteogenesis imperfecta
Rheumatoid arthritis
Lupus
Psoriatic arthritis
Vitamin D and Calcium
deficiency
Medications
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Glucocorticoids
Lithium
Chemotherapy
GnRH agonist
Anticonvulsants
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Phenobarbital
Dilantin
Tegretol
Valproate
Methotrexate
SSRIs
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Prolonged heparin use
Coumadin (?)
Cyclosporine (?)
Aromatase inhibitors
Excess thyroid hormone
Medroxyprogesterone
Vitamin A
Proton pump inhibitors
Case #1
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70 year old female presents with a new
vertebral compression fracture after slipping
on the ice. She has never had BMD testing.
PMH
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HTN
Hyperlipidemia
GERD
Depression
Case #1
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MEDS
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Lisinopril
Zocor
Protonix
Celexa
Family hx – No hx osteoporosis known
Social hx – Non-smoker, no ETOH
Case #1
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Should her SSRI be stopped?
Should her PPI be stopped?
Should she have received BMD testing prior to
starting these meds?
SSRIs and Osteoporosis
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Canadian Multicenter Osteoporosis Trial –
2006
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Prospective cohort of 5008 adults 50 years old or
greater, followed over 5 years for fractures
137 were on SSRIs
Risk of fragility fracture was increased 2 fold for
pts on SSRIs
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Relative risk = 2.1 (1.3-3.4)
Relative risk for corticosteroids = 1.33-2.6
Study did not evaluate duration of SSRI use
PPIs and Osteoporosis
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Prospective trial – (Roux 1/09)
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Need more studies
FDA recommends considering shorter duration or
lower dose of PPI
PPI may interfere with calcium absorption
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1211 post-menopausal women
For women on omeprazole the relative risk for vertebral
fractures was 3.5 (1.14-8.44)
Consider calcium citrate supplementation
No studies on initial BMD testing prior to starting
med
Case #2
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16 year old female presents for discussion of
birth control options.
PMH – None
Family hx – No hx osteoporosis
Social hx – No smoking, ETOH or drugs
Pt really wants Depo Provera but her Mom is
concerned about side effects – she has heard
that it weakens bones.
DepoProvera
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Cross-sectional studies show decreased BMD
in Depo users
No studies have shown increased fracture risk
with depo-users
Bone mass increases with cessation of Depo
FDA recommends stopping Depo after 2 years
unless no other viable birth control options
FDA suggests evaluating BMD for use greater
than 2 years
History – Risk Factors
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History of fractures, esp. vertebra, hip or wrist
Family history of osteoporosis or fragility fxs.
Menstrual history – history of estrogen
deficiency
Nutrition
Exercise
Habits – tobacco, alcohol and caffeine use
History and Physical Exam
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No reliable history or physical findings to
identify patients with osteoporosis
Look for risk factors and signs of occult
vertebral fractures
Look for possible secondary causes of
osteoporosis
Consider further laboratory tests only if signs
of a secondary cause
History – Vertebral Fractures
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Back pain – acute or chronic
Loss of height (>1 inch)
Restrictive lung disease symptoms (exertional
dyspnea, decreased exercise tolerance)
Symptoms of reduced abdominal cavity (early
satiety)
Symptoms of depression, anxiety and fear
Physical Exam
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Measure height and body weight
Look for spinal tenderness and deformities
(dowager’s hump)
Look for tooth loss
Look for protuberant abdomen
Signs of secondary osteoporosis
Consider home visit to assess risk for falling
Risk Factors for Osteoporosis
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Non-modifiable
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Female gender
Increased age
White or Asian race
Family history of osteoporosis
Personal history of fracture
Previous hyperthyroidism
Rheumatoid arthritis
Secondary osteoporosis
Risk Factors for Osteoporosis
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Modifiable
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Tobacco use
Sedentary lifestyle
Caffeine use (tea is OK)
Low calcium and vitamin D intake
Alcohol use (> 2 drinks per day)
Hormone deficiency states
Low weight (BMI<21)
Elevated homocysteine levels
Corticosteroid use (5 mg prednisone daily for 3 months)
Risk Factors for Fractures
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History of falling
Poor physical condition
Neurological disorders
Impaired vision and hearing
Certain meds – sedatives, anti-hypertensives
Environmental hazards
Environment Modification
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Remove throw rugs
Decrease clutter
Handrails on stairs
Improve lighting, night lights
Handrails in tubs and showers, non-skid surfaces
Cane or walker if needed
Consider hip protectors
Wear supportive, low-heeled shoes
Tape down electric cords
Case #3
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63 year old female presents for a physical
PMH
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HTN
GERD
Anxiety
Meds
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Metoprolol
Omeprazole
Case #3
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Social hx – smokes 1ppd, minimal ETOH
Family hx – No osteoporosis or hip fractures
BMI = 23, Ht = 5-4
Should she be screened for osteoporosis?
Screening – Who to Screen?
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No studies showing decreased fracture risk
with screening
However:
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Good evidence for increasing risk of osteoporosis
and fracture with age
Good evidence that bone mineral density
accurately predicts fracture risk (RR=2.6 for -1SD)
Good evidence that treating asymptomatic women
with osteoporosis decreases fracture risk
Screening – Who to Screen?
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US Preventive Services Task Force
recommendations based on current evidence
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Screen all women > or equal to 65 years
Screen women 60-65 yrs. if at increased risk
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Lower body wt. is best predictor of low BMD
Consider using FRAX
Grade B recommendations – fair to good evidence
to support recommendation, benefits outweigh
risks
Screening – Who to Screen?
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USPSTF recommendations continued
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No recommendations for or against routine
screening in women <60 yrs. or women 60-64 yrs.
with no increased risk
Screening women at lower risk for osteoporosis
can identify additional women who might benefit
from treatment but would prevent smaller #
fractures.
Grade C recommendation – balance of benefits to
harms is too close to make recommendation
Screening – Who to Screen?
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USPSTF guidelines agree with guidelines of
the National Osteoporosis Foundation and the
American Association of Clinical
Endocrinologists
All recommend screening only if results will
influence treatment
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If patient not in favor of treatment, DON’T
SCREEN!
Screening in Men
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National Osteoporosis Foundation
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Recommends screening all men over age 70
regardless of risk factors
Evaluate for risk factors and discuss calcium and
vitamin D intake in all men >50
Screen men ages 50-69 with risk factors
However, very little evidence for or against
screening men
Screening Disadvantages
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Cost
Potential radiation exposure
Potential unnecessary treatment for false
positive or misinterpreted results
Increased anxiety and perceived vulnerability
– can lead to increase in sedentary habits
Risk Factor Assessment
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Which are best at predicting osteoporotic
fractures?
May help decide who to screen
Risk Factor Assessment
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Age, weight and history of previous fracture
correlate the best with low BMD
FRAX = Fracture Risk Assessment tool
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Developed by WHO – 2008
Estimates 10 year probability of major
osteoporotic fractures and hip fracture
www.shef.ac.uk/FRAX/
Risk Factor Assessment
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FRAX
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Age
Gender
Prior fracture
Low BMI
Oral steroids
Rheumatoid arthritis
Secondary osteoporosis
Parental hx of hip fracture
Smoking
ETOH
Case #3
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Decision is made to screen this patient
Which test is the best test?
Screening – Which Test?
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Conventional x-rays – osteopenia not detected
until bone mass 40% decreased
Bone turnover markers – experimental,
expensive and no good evidence to support use
(human osteocalcin, bone alkaline
phosphatase)
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High false positive rate
Screening – Which Test?
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All tests below have equivalent fracture risk
predictability
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Dual-energy x-ray absorptiometry (DEXA)
Quantitative CT
Calcaneal ultrasonography
Screening – Which Test?
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Calcaneal ultrasonography
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Usually tests calcaneus only
Reflects other aspects of bone quality
More portable test
No radiation
Low cost
Low precision
Difficult to apply measurements to treatment
protocols
Screening – Which Test?
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Quantitative CT
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Usually tests spine and hip
High radiation
High cost
Good precision
Screening – Which Test?
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DEXA
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Best validated test in studies and therefore
considered gold standard
Results vary by 6-15% when using machines from
different manufacturers
Usually test spine, hip or wrist (lateral spine)
Low radiation
Intermediate cost
Excellent precision – best if same machine is used
and same technician
Screening – Which Test?
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DEXA
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HOWEVER……
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DEXA identifies fewer than half the people that go on
to have an osteoporotic fracture
Case #3
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Her DEXA reveals a T-score = -1.5
When should she be retested if at all?
Screening – How Often?
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Screening more often than every 2 years will
not show accurate change in BMD
Repeat screening more likely to be beneficial
in older women and women with risk factors
No evidence about follow-up BMD testing
after initiation of treatment
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NOF recommends follow-up BMD every 2 years
on treatment
Screening Summary
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Screen all high risk women
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Women > 64
Women < 65 with significant risk factors
Men with risk factors
Screen every 2 years
Consider using risk assessment tools to
determine high risk
DEXA scan is best test (BUT not perfect)
Case #3
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She gets repeat screening with DEXA in two
years and the T-score is now -2.5
Does she need evaluation for secondary causes
of osteoporosis?
Evaluating for Secondary
Osteoporosis
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AACE
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CBC
CMP
Ca, Phos
24 hour urine for Ca, Na, creatinine excretion
25-hydroxyvitamin D level
Above eval detects 90% of secondary
osteoporosis
Case #4
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71 year old female presents for a review of her
DEXA results which reveal a T-score of -2.0.
She has no hx of fractures and no family hx of
fractures. She does not smoke. Her BMI=25.
Do you tell her she has osteoporosis?
Are her results normal?
Do you recommend treatment for osteoporosis
and if so what?
Who to Treat?
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Definite reduction in fractures for treatment of
BMD <-2.5 and for pts with history of fragility
fractures
Is there any benefit in treating anyone else?
What About Osteopenia?
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T score between -1.0 and -2.5
RCTs show no reduction in fracture risk for
patients with T scores -1.6 to -2.5
Individualize management
Decrease modifiable risk factors
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Increase calcium and vitamin D intake
Increase exercise
Decrease tobacco, alcohol and caffeine use
What About Osteopenia?
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Use FRAX calculator
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If assessed risk of hip fracture is >3% for the next
ten years, consider treatment
If risk of major osteoporotic fracture (wrist,
vertebral, hip or proximal humerus) is >20% for
the next ten years, consider treatment
Using this calculator most pts with osteopenia will
not be treated
No actual studies on outcomes using FRAX
www.shef.ac.uk/FRAX/
Treatment Options
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Exercise
Calcium and Vitamin D
Estrogen
Bisphosphonates
Raloxifene
Calcitonin
Parathyroid hormone
Case #5
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65 year old, very healthy female has just found
out she has osteoporosis. She does not want to
“pollute her body with chemicals” and will
only use “natural remedies”
What do you recommend?
Exercise
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Weight-bearing activity – walking, running,
aerobics, stair-climbing, strength training,
dancing, court and field sports
No data on cycling, skating or skiing
Exercise 3x/week for 30-60 minutes duration
Strength training reduces risk of falling also
Short term exercise increases BMD by 2% in
meta-analysis of 16 trials
Exercise
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Cochrane review 2002
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18 RCTs of BMD in postmenopausal women
Increased BMD of spine with any exercise
Increased BMD of hip with walking
Meta-analysis 4/2004 (Kelley, et al)
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143 premenopausal women
Resistance exercise did not increase or maintain
BMD
Calcium and Vitamin D
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Randomized controlled trials show improved
BMD and decreased fractures with combo
NNT = 48 to prevent one hip fracture after 1.5
years of treatment
Need 1200 mg Ca/day and 800 IU vit. D/day
Calcium better absorbed if taken with food and
600 mg or less at a time
Cost = $5/month
Calcium and Vitamin D
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Calcium citrate is slightly better absorbed than
Ca carbonate
Consider using Ca citrate if patient on acid
blocker med
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Ca carbonate – Oscal, Caltrate, Tums, Viactiv
Ca citrate - Citracal
Calcium and Vitamin D
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Side effects of calcium include dyspepsia, gas,
bloating and constipation(10%)
May interfere with absorption of tetracycline or
quinolones
If history of kidney stones evaluate for hypercalciuria
prior to giving calcium
Recent meta-analysis based on WHI showed slight
increase in MI and stroke in pts taking Ca with or
without vitamin D (Bolland 4/11)
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RR of MI = 1.24 (1.07-1.45)
Calcium
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Cochrane review – 2004
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15 RCTs, 1806 subjects
Small improvement in bone density after 2-3 yrs
Trend toward decrease in vertebral fractures
Unclear if calcium alone decreases non-vertebral
fractures
Vitamin D
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Vitamin D deficiency
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Decreased calcium absorption
PTH-mediated increase in bone resorption
Decreased muscle strength and increased falls
Vitamin D
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Cochrane review – April 2009
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Vitamin D alone showed no sig. effect on hip or
vertebral fracture rate
Vitamin D with calcium slightly reduced nonvertebral fractures, but no effect on vertebral
fractures
No evidence that analogs of vitamin D offer any
advantage over native vitamin D
Vitamin D2 and vitamin D3 equally effective
Vitamin D
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National Osteoporosis Foundation
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Recommends 800 – 1000 IU daily
Consider testing in pts at risk for deficiency
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Elderly
Malabsorption diseases
Chronic kidney disease
Housebound patients
Test serum 25(OH)D level should be between 3060 (toxicity > 100)
Folate and Vitamin B12
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RCT (Sato – 3/2005)
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628 pts, s/p stroke
5 mg folate and 1500 mcg of B12 vs placebo
Decreased hip fractures in treated group
NNT = 14
Magnesium
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Often taken by patients
No studies show decrease in fracture rate or
increase in BMD
Phytoestrogens
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Act as weak estrogens but also have antiestrogen effects
Primary source of phytoestrogens is
isoflavones which are found in soybeans(less
in tofu) and lignans (flaxseed; some cereals,
fruit, vegetables, and legumes)
Secondary sources are black cohosh and red
clover
Phytoestrogens
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Small studies show some decrease in hot
flushes and vaginal dryness
No human studies showing effect on bone
Dosage, purity, and adverse effects unknown
Estreven and Remifemin are combinations of
isoflavones, black cohosh and red clover
Estrogen Replacement Therapy
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WHI (Women’s Health Initiative Study)
NNT = 2000 to prevent one hip fracture after 5
years of treatment
Not as effective for treatment but has definite
benefit for prevention
Strongest benefit for ERT is for women < 60
HERS showed no sig. decrease in fracture rate
over 4 years
FDA approved only for prevention
ERT
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Transdermal and oral forms equally effective
MUST use progesterone with estrogen if
patient has intact uterus
Estrogen with or without progesterone is
equally as effective
Cost = $14-28/month
Secondary benefit of decreasing menopausal
symptoms
ERT - Harms
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WHI study
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Small increased risk of 22% for cardiovascular
events (7 additional cases/10,000/yr)
26% increased risk of invasive breast cancer (8
additional cases/10,000/yr)
41% increased risk of stroke (8 additional
cases/10,000/yr)
2-fold increased risk of pulmonary embolism
SE’s – Vag. Bleeding, nausea, headache, mood
alterations, breast tenderness, bloating
Bisphosphonates
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Work by inhibiting osteoclastic activity
RCT’s show significant and rapid reduction in
fracture risk for women with previous fracture
and osteoporosis
Evidence not as good for women without
previous fracture
Alendronate (Fosamax)
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NNT = 34 to prevent one vert. fx over 3 yrs.
NNT = 86 to prevent one hip fx over 3 yrs.
Dose = 5-10 mg/day or 35-70 mg/week
Forms – oral solution, Fosamax with D weekly
Cost = $95/month
SE’s – nausea, dyspepsia, esophageal ulcer,
esophagitis
Weekly dosing showed equivalent increase in BMD
to daily dosing (no data on fractures)
Alendronate
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Meta-analysis of RCTs – (Papapoulos – 5/05)
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Post-menopausal women
Dose = 5-10 mg/day for 1-4.5 yrs
Overall risk reduction for hip fractures of 55% in
pts with osteoporosis
Clinically sig decrease in hip fractures
Risedronate (Actonel)
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NNT = 15 to prevent one vert. fx over 3 yrs.
NNT = 91 to prevent one hip fx over 3 yrs.
Dose = 5 mg/day, 35 mg/week, 150 mg/month
Cost = $150/month
SE’s – abdominal pain, nausea, diarrhea but
not sig. different from placebo
No sig. GI adverse events even in patients with
history of ulcers, GERD, or taking NSAIDS
Risedronate
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Cochrane systematic review – 8/2003
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8 RCTs
Postmenopausal women received 5 mg/day,
compared to Ca or placebo
Increased BMD after 3 yrs
Decreased vertebral and non-vertebral fractures
No difference in side effects compared to placebo
Ibandronate (Boniva)
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BONE study – (Delmas – 9/2003)
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Large multi-national RCT
Oral Ibandronate Osteoporosis Vertebral Fracture
Trial in N. America and Europe
2946 post-menopausal women
Daily or intermittent ibandronate vs placebo
Decreased risk for vertebral fractures by 50-62%
NO decreased risk of non-vertebral fractures
Zoledronic Acid (Reclast)
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Given IV every 12 months
Decreases both vertebral and hip fractures
Expensive
Consider only in certain high risk pts
Bisphosphonates
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Less than 1% of each dose is absorbed
Optimize absorption by taking with full glass
of water and 30 mins prior to breakfast
Avoid GI problems by standing or sitting for
30 mins after taking med
Do not use in patients with creatinine
clearance <30 ml/min or hypocalcemia
Accumulates in bone – long term effects
unknown
Bisphosphonates
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Does one work better than another?
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Head to head RCT of alendronate 70 mg/week and
risedronate 35 mg/week (Rosen-1/2005)
Total of 1053 postmenopausal women with
osteoporosis, studied over 12 months
Alendronate showed greater increase in BMD
compared to risedronate
Fracture rate not assessed
Both drugs tolerated equally well
Case #6
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72 year old female with T-score = -2.7 and no
hx fracture.
You have recommended starting a
bisphosphonate but she has heard that these
drugs cause cancer and a jaw problem.
What do you say?
Bisphosphonates

Osteonecrosis of the jaw (ONJ)
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Canadian Consensus Practice Guidelines (6/2008)
ONJ has been clearly associated with use of high
dose IV bisphosphonates in the treatment of cancer
ONJ has NOT been clearly linked with low-dose
bisphosphonates used for osteoporosis
Advise good oral hygiene and regular dental visits
Consider holding drug for non-emergent dental
surgery
Bisphosphonates

Atrial fibrillation

Systematic review – (Loke – 2009)
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Results of studies were mixed
There may be a link with bisphosphonates and atrial fib
but data was too heterogeneous to make a determination
No increase in stroke risk or cardiovascular mortality
FDA fells this is a chance finding
Bisphosphonates
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Subtrochanteric fracture
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Esophageal cancer
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Occur after minimal or no trauma
Direct etiologic relationship not yet substantiated
Incidence went from 1 case per 1000 in untreated
pts to 2 cases per 1000 in those treated with
bisphosphonates for 5 years or more
Consider drug holiday of 1-2 years after 3-5
years of therapy
Case #7
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
75 year old female with hx osteoporotic
vertebral fx cannot tolerate the
bisphosphonates. She has hx of severe GERD
and peptic ulcer disease.
What do you recommend?
Selective Estrogen Receptor
Modulators
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Raloxifene (Evista)
Blocks action of cytokines which stimulate
bone resorption
RCT’s show sig. decrease in new vertebral
fractures for women with previous history of
fracture and osteoporosis
NNT = 29 to prevent one vert. fx over 3 yrs.
NO evidence of decrease in hip fractures
Raloxifene
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Dose = 60 mg/day
Cost = $150/month
Secondary benefit may be reduction of breast
cancer risk
SE’s – leg cramps(3%), hot flashes(6%), risk
of venous thromboembolism (1 in 465
women/yr)
Does not increase risk of endometrial
hyperplasia or cancer
Salmon Calcitonin
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Calcitonin nasal spray (Miacalcin)
Large RCT showed decreased new vertebral
fractures in women with previous history of
osteoporotic vertebral fx.
No effect reported for hip fractures
No definite effect for women with no previous
osteoporotic fx.
Increased BMD less than that seen with
bisphosphonates or estrogen
Salmon Calcitonin
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
Dose = 200 IU/day, 1 spray in 1 nostril qd
Cost = $112/month
SE’s – rhinitis(5%), epistaxis, sinusitis
Alternate nostrils to decrease SE’s
Secondary benefit of decreased pain from
vertebral fractures
Parathyroid Hormone

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Stimulates bone formation
Teriparatide (Forteo) – recombinant PTH
RCT shows 1/3 decreased incidence of vert. fx and ½
decreased incidence of non-vert. fx
Dose = 20 mcg SC qd
Less convenient
More expensive - $1000/month
SEs – nausea, headache, hypercalcemia, dizziness,
leg cramps, ? risk osteosarcoma
Measure Ca, vitamin D and PTH levels prior to
treatment
Parathyroid Hormone

FDA black box warning


Teriparatide caused osteosarcoma in rats using
much higher doses of the drug
Drug is contraindicated in pts at risk for
osteosarcoma

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Pagets disease of bone
Hx of irradiation involving the skeleton
Unexplained elevation of alkaline phosphatase
Safety after 2 years duration is unknown
Parathyroid Hormone

RCT – (Neer – 5/01)
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1637 post-menopausal women with prior vertebral
fractures
Average T-score = -2.6
20 or 40 mcg PTH vs placebo
NNT = 11 to prevent one vertebral fracture
40 mcg dose worked a little better but had more
side effects (hypercalcemia)
Parathyroid Hormone

RCT – (Body–10/02)
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14 months duration
Compared PTH to alendronate
PTH increased BMD in hip and spine more than
alendronate (12.2% vs 5.6%)
Non-vertebral fracture rate was lower in the PTH
group
Denosumab
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Monoclonal antibody against RANKL
Decreases osteoclastic activity
Brand name – Prolia
60 mg SQ every 6 months
Studies show reduced fractures of the hip,
spine and non-vertebral sites
SEs – Skin infections, dermatitis, ?
osteonecrosis of the jaw
Combination Therapy

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No studies demonstrating reduction in fracture
risk
More improvement in BMD with combined
estrogen and alendronate
RCT of combined PTH and alendronate
showed no improvement over PTH alone
(Finkelstein-2003)
AACE does not recommend combined therapy
Treatment Monitoring

AACE guidelines

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DEXA every 1-2 years until stable
BMD should be stable or increasing and there
should be no fractures
If this is not the case consider different treatment
Osteoporosis in Men


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30% of hip fractures occur in males
1.5 million men >65 have osteoporosis
May have higher mortality rate compared to
females
2/3 have secondary osteoporosis

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Hypogonadism, glucocorticoid use, etc.
Risk increases with age but later than in
women
Osteoporosis in Men

Treatment

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1000 mg/day calcium and 800 IU/day vitamin D
Exercise
If hypogonadism, consider testosterone
Bisphosphonates – RCT of alendronate 10 mg/day
showed sig increase in BMD and decrease in
vertebral fractures (Orwoll – 8/2000)
PTH – RCT of PTH 20mcg/day showed increased
BMD (Orwoll – 1/2003)
Prevention Summary


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

Start adequate calcium and vitamin D intake in
childhood
Encourage exercise
Decrease risk factors for osteoporosis
Decrease risk factors for falling
Consider bisphosphonate for prevention if
high risk
Treatment Summary

AACE recommendations





1st line – alendronate, risedronate, zoledronic acid,
denosumab
2nd line – ibandronate, raloxifene
Last line – calcitonin
Teriparatide only for pts that fail above
No combination therapy
References

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Prevention and Treatment of Osteoporosis in Postmenopausal Women.
JFP October 2002
Screening for Osteoporosis in Postmenopausal Women: Recommendations
and Rationale, US Preventive Services Task Force. Ann. Intern. Med. 17
Sept. 2002
Radiologic Bone Assessment in the Eval. of Osteoporosis. AFP April 2002
Cauley, JA. Effects of HRT on clinical fractures and ht loss(HERS). Am J
Med. 2001.
Papapoulos, SE. Meta-analysis of the efficacy of alendronate for the
prevention of hip fractures in postmenopausal women. Osteoporosis Int.
2005 May.
Delmas, PD. Daily and intermittent oral ibandronate normalize bone
turnover and reduce vertebral fracture risk: results from the BONE study.
Osteoporosis Int. 2004 April.
References
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Calcium Supplements. The Medical Letter April 3, 2000
Osteoporosis: Parts I and II AFP March 2001
Cochrane Database
Petitti, DB. The WHO Study of Hormonal Contraception and Bone Health.
Ob-Gyn. 2000 May.
Orr-Walker, BJ. The effect of past use of the injectable contraceptive depot
medroxyprog. acetate on bone mineral density in normal post-menopausal
women. Clin Endocrinol. 1998 Nov.
Kelley, GA. Efficacy of resistance exercise on lumbar spine and femoral
neck BMD in premenopausal women: a meta-analysis. J Womens Health.
2004 April.
Sato, Y. Effect of folate and mecobalamin on hip fractures in pts with
stroke: a RCT. JAMA. 2005 March.
References
Bauer, DC. Use of statins and fracture: results of 4 prospective studies and
cumulative meta-analysis of observational studies and controlled trials.
Arch Intern Med. 2004 Jan.
Neer, RM. Effect of PTH on fractures and BMD in postmenopausal women
with osteoporosis. N Engl J Med. 2001 May
Body, JJ. A randomized double-blind trial to compare the efficacy of
teriparatide with alendronate in postmenopausal women with osteoporosis.
J Clin Endocrinol Metab. 2002 Oct.
Orwoll, E. Alendronate for the treatment of osteoporosis in men. N Engl J
Med. 2000 Aug.
Orwoll, ES. The effect of teriparatide therapy in men with osteoporosis. J
Bone Miner Res. 2003 Jan.
AACE Guidelines for Diag and Treatment of Osteoporosis - 2010