osteoporosisnew.ppt
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OSTEOPOROSIS
Kristen M. Nebel, DOMarch 10, 2010
OBJECTIVES Define Review Bone pathology Review risk factors, updated screening
recommendations, evaluation Male Osteoporosis Skilled care and osteoporosis Prevention and Treatment Vertebral Fracture management
OSTEOPOROSIS
Definition: A disease characterized by low bone mass and microarchitechtural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture incidence.
WHO: BMD T-score of -2.5 or less
STATISTICS
Effects approx. 8 million women in US22 million women with osteopenia
By 2020 14 million men and women Risk of fragility fractures
250,000 hip and 500,000 vertebral/ year in women
MORE trial: Risk of osteoporotic fracture > risk of CV event (MI or CVA) or breast CA
Risk of 2nd vertebral fracture within one year is 20%
STATISTICS
Impact of osteoporosis-related fractures: 2005 estimated Healthcare cost:$17 billion 432,000 hospital admissions 183,000 skilled care admissions (NOF.org)
BONE PATHOPHYSIOLOGY
Bone Strength Related to bone mass (measured by BMD) and
other factors, such as remodeling frequency (bone turnover), bone size and area, bone microarchitechture and degree of bone mineralization
BONE PATHOPHYSIOLOGY
Normal: Cyclic bone remodeling Osteoclasts: The mineral content of matrix is first
dissolved and the remaining protein components of the matrix (primarily collagen) are then degraded by proteolytic enzymes secreted into the resorption space.
BONE PATHOPHYSIOLOGY
Normal bone remodeling: Osteoblasts: Synthesize new bone by first laying
down a new protein matrix, principally composed of Type I collagen into the resorbed space. Individual collagen molecules become interconnected
by formation of pyridinoline cross-links to provide extra strength.
Bone mineralization occurs with deposition of hydroxyapatite.
BONE PATHOPHYSIOLOGY
Bone Turnover Markers Formation: bone-specific alkaline phosphatase
and osteocalcin
Resorption: carboxy terminal peptides of mature collaged (N-telopeptide and C-telopeptide) and deoxpyridinoline
SOMETHING SOMEWHERE WENT TERRIBLY WRONG
BONE PATHOPHYSIOLOGY
Abnormal: Imbalance of remodeling High bone turnover rate leads to weakening due
to weaker trabecular/ cancellous bone
BONE MASS CHANGES Peaks by mid-30’s Bone loss begins several years prior to
menopause Risk of fracture increases with BMD loss
Compared to younger women: odds of having OP in 65-69 y/o is 5.9x higher and in 75-79 y/o is 14.3x higher
Genetic factors contribute 80% to a women’s risk of osteoporosis BMD is likely to be lower in women with + FHX of
osteoporosis than those without. Risk of hip fx:
50% greater if 1st degree relative had + fx 127% greater if parent had hip fx
OSTEOPOROSIS: CONSEQUENCES Reduced QOL Increased mortality (20%) Failure to return to baseline (50%) Depression
RISK FACTORS FOR OSTEOPOROTIC FALLS: NOF Body weight
<70kg or BMI<21 Corticosteroids Personal history
of fractures as adult
First-degree relative with fragility fracture
Current smoking
Early menopause Nutrition Decreased activity ETOH Impaired vision Dementia Poor health Recent falls
FRACTURE RISK ASSESSMENT (FRAX) Introduced in 2008:
WHO’s new guide to identify an individual’s 10-yr risk of osteoporotic fracture
Goal: Ensure that those at high risk are treated Accounts for nine clinical risk factors +/- hip
BMD Allows for calculation even if no BMD available
Designed to decide who and when to newly treat (not for those currently on treatment)
Therapy indicated if 10-yr. risk of hip fracture >/= 3% or other major fracture risk >/= 20% Cut-off for therapy based on new cost-effective
treatment thresholds (Tosteson et al. Osteop. Int. 2007)
FRAX
FRAX
Does not apply to premenopausal women and men < 50 y/o
BMD TESTINGRECOMMENDATIONS USPSTF/ NOF
ALL women 65+MEN >/= 70Younger postmenopausal women and men
50-70 with clinical RF’sAdults with fracture after age 50Adults with a condition or a medication a/w
low bone massPerimenopausal women with high-risk risk
factors (ie-meds, low BMI, h/o low-trauma fracture)
SCREENING METHODS
Dual-energy x-ray absorptiometry = preferred Femoral neck BMD is best predictor of hip fx Forearm BMD predicts non-hip fractures
Ultrasound densitometry (sahara screen)
SCREENING AND MEDICARECOVERAGE (ICD-9 CODES) Medicare covers BMD testing for the
following individuals 65 and olderEstrogen deficient women at clinical risk
for osteoporosis (627.2) Individuals with vertebral anomalies
(733.90) Individuals receiving, or planning to
receive, long-term glucocorticoid therapy of at least 5mg for 3 months (V58.69)
Individuals with primary HPTH (252.00) Medicare permits repeat BMD testing
every 2 years
OSTEOPOROSIS EVALUATION
“Silent fractures” Check for loss of height (>5cm) Up to 70% of vertebral fractures may be
asymptomatic In an evaluation of 2 primary care offices only
38% of patients with a history of vertebral fracture were evaluated for and treated for osteoporosis.
(Neuner et al. JAGS 2003)
MALE OSTEOPOROSIS Morbidity and mortality much higher in men
than women with osteoporotic fracture Secondary causes more common accounting
for 50% ETOH (15-20%), glucocorticoid (20%), and
hypogonadism (15-20%) Androgens may inhibit bone resorption
3-6% of men in US (NHANES III study) 28-47% with osteopenia
1/3 of men 60+ are likely to have an osteoporotic fracture
Average onset is 10 yrs later than in women Men often asymptomatic at onset
MALE OSTEOPOROSIS
Previously, no formal recommendations
Now, WHO recommends BMD forALL men >70Men 50-70 with risk factors
BMD should be compared to male references so that osteoporosis diagnoses are not missedBMD of hip is most reliable indicator due to
prevalence of spinal degenerative changes
OSTEOPOROSIS EVALUATION
When to suspect secondary causes: Premenopausal women Patient without risk factors Men <70 Multiple health problems Worsening osteoporosis despite therapy
SECONDARY CAUSES
Medications Renal insufficiency secondary HPTH Cushing’s Hyperthyroid Multiple myeloma Osteomalacia Paget’s Dz GI malabsorption / celiac Mets to bone
OSTEOPOROSIS EVALUATION
LabsCMP, phosphate, CBC, ESR, TSH/FT4Testosterone/ EstrogenSPEP24 hour urine for calcium and creatinine25-OH Vit. D Intact PTHBiochemical markers of bone turnover
ImagingX-rays not good for early detection: 20-
40% of BMD must be lost to detect
OSTEOPOROSIS AND SKILLED CARE: TO TREAT OR NOT TO TREAT? AMDA 2004 Quality Indicators:
Prevention: Within 1 month of admission all females to be offered Calcium, vitamin D, and weight-bearing exercises.
Mobilization: Attempted in bedfast individuals unless contraindicated
New Dx: Calcium and Vitamin D started within 1 month
New Dx: Therapy started within 3 monthsCorticosteroid tx for > 1 month: start calciumNew Dx: Evaluate meds for secondary
causesNew Osteoporotic fx in ambulatory resident:
Physical therapy should be started within 1 month
OSTEOPOROSIS AND SKILLED CARE: TO TREAT OR NOT TO TREAT? Osteoporosis present in up to 80% of
residents Most significant independent RFs for
fracture Low BMD and dependence for transfers (>3x
fracture risk of those w/o low BMD) (Duque et al. JAMDA ’06)
Dx in LTC BMD not always appropriate Quebec Symposium for LTCI: Diagnosis based on
patient risk factors, physical exam (kyphosis, fractures), x-ray and loss of height
Calcaneal BMD Vitamin D level
OSTEOPOROSIS AND SKILLED CARE: TO TREAT OR NOT TO TREAT? Studies estimate that therapy for
osteoporosis, including calcium and vitamin D, is prescribed in only 9-20% of residents with documented disease.
(Wright. JAMDA 2007)
Factors contributing to lack of prescribingComplianceTolerancePriceRisk vs. Benefit
Life expectancy, ambulation, time to efficacy
GENERAL TREATMENT AND PREVENTION RECOMMENDATIONS Nutrition
Calcium Dose increases with age due to decreased
absorption Decrease bone loss by 1%/ yr. Greatest benefit in elderly, late-menopausal, and
those with low baseline calcium intakeVitamin D
Recommended intake 800-1000 IU Meta-analysis (JAMA) showed reduced risk of hip and
non-vertebral fractures with 700-800 IU/day Natural sources: fatty fish, fish liver oils, and fortified
foods (milk = 400 IU /qt.)
GENERAL TREATMENT AND PREVENTION RECOMMENDATIONS Calcium and Vitamin D
Augmentation of other agents Studies of etidronate in individuals with Vitamin D > 40
showed greater increase in BMD measured at L-S and femoral neck compared with levels < 40
(Boonen et al. JAGS 2004)
Given to all on osteoporosis therapy Patients receiving corticosteroids
RA patients on prednisone lost 1-2% BMD/ yr. Those randomized to calcium (1000mg/d) and Vit. D (500IU/d) gained BMD at about 0.5%/yr.
Those with or at risk of deficiencies Secondary HPTH due to hypovitamin D showed improved
BMD on Alendronate and Vit. D compared with those only on Alendronate
(Baron et al. JAGS 2005)
GENERAL TREATMENT AND PREVENTION RECOMMENDATIONS Caffeine
Recommend < 4 cups/ d May reduce calcium absorption Some association with increased bone loss and
fracture rates
Vitamin K May help with bone metabolism and reducing
urinary calcium excretion No recommendations for supplementation
No association between Coumadin and fractures
GENERAL TREATMENT AND PREVENTION RECOMMENDATIONS Vitamin A
RDA of 700 micrograms High levels have been associated with increased risk of
hip fracture in 2 out of 3 studies Magnesium
Some epidemiologic studies showed correlation with increased BMD in elderly and females
Easily obtained in daily food intake Deficiencies may exist in elderly and those with GI
malabsorption ETOH
Can suppress osteoblasts Moderate intake (1-2 oz/week) in women 65+ is
associated with higher BMD and decreased risk of hip fracture
Heavy intake (>7oz/week) increases risks of falls and hip fractures
NON-PHARMACOLOGIC INTERVENTIONS Rehabilitation
Exercise Strengthening muscles: backs and legs Prospective 10-year study showed decreased risk of
vertebral fractures (Sinaki) Orthotics Gait training Pain Management
Avoiding substances of abuse
PHARMACOLOGIC OPTIONS Who to treat (NOF Clinician’s Guideline 2008)
Treatment: Postmenopausal women and men 50+ with BMD T-score of -2.5 or less Any hip or vertebral fracture BMD T-score of -1.0 to -2.5 AND prior fracture (new) BMD T-score of -1.0 to -2.5 AND secondary causes a/w
high risk of fracture BMD T-score of -1.0 to -2.5 AND 10-yr prob. of hip fx
>/= 3%, major fx >/= 20% Prevention
Women with BMD hip T-score of -2.0 or less and no risk factors
Women with BMD hip T-score of -1.5 with one or more risk factors and does not meet FRAX criteria
PHARMACOLOGIC OPTIONS
Antiresorptives Estrogens/HRT Selective-estrogen receptor modulators (SERMS) Calcitonin Bisphosphonates
Anabolic PTH
ESTROGENS/HRT Recommended for prevention only WHI: 5 years - 16K women ages 50-79 (mean
63) w/ uterus and no screening for osteoporosis
Increase in BMD Decrease in hip, vertebral, and other
osteoporotic fracture rates Increased risk of CV events, VTE, and Breast
CA; decrease in colon CA
SERMS: RALOXIFENE (EVISTA) Prevention and Treatment of
postmenopausal OP Vertebral fracture risk Daily oral dosing Modest increase in BMD of spine and hip;
decreases bone turnover Multiple Outcomes of Raloxifene Evaluation
(MORE): 3 year study of 7,700 women with OP Postmenopausal OP +/- previous vertebral fracture
Insignificant results: 30% and 50% reduction in risk of vertebral fracture
Side effects: hot flashes, leg cramps, increased VTE
CALCITONIN (MIACALCIN) Treatment of postmenopausal OP (at least 5
yrs.) only Patients unable to tolerate other agents Daily dosing as nasal spray, SC injection, and
oral Minimally inhibits bone resorption; possible
analgesic effect for acute vertebral fx PROOF trial: At 5 yrs 33% reduced risk of new
vertebral fx (200 mcg). After 5 yrs, increased dose (400 mcg) required to perpetuate BMD increase
Side effects: nasal irritation, nausea, local inflammation and flushing
BISPHOSPHONATES: ALENDRONATE (FOSAMAX) Prevention and Treatment of Male and
Postmenopausal OP, Treatment of Glucocorticoid-induced OP
Daily or weekly dosing; oral form (tab or liquid) Inhibits osteoclasts, Increases BMD + h/o spine fx: Reduces risks of all osteoporotic
fractures by 50% over 3 yrs. (NOF) - h/o spine fx: Reduces incidence of spine fx by 46%
over 3 yrs. Side effects: Gastric irritation and ulcers, CrCl <35,
hypocalcamia, ONJ
OSTEONECROSIS OF THE JAW American College of Rheumatology
position paperCase review found 60% of cases to be following
oral surgery or dental extraction. 94% of the cases occurred with IV bisphosphonates (Pamidronate or Zoledronic acid) and 85% had MM or metastatic breast CA to bone.
Non-cancer patients and oral meds not considered risk factors
Recommendations to avoid ONJ: treating infections and obtaining routine dental care prior to therapy
Appearance of intraoral lesion with exposed bone +/- painful ulcers, ragged
RISEDRONATE (ACTONEL) Prevention and Treatment of
Glucocorticoid-induced, male, and Postmenopausal OP
Daily, weekly, or monthly (75mg on 2 consecutive days) dosing, oral form only
+ h/o spine fracture reduces risk of spine fracture by 41-49% and hip fractures by 36% over 3 yrs. (NOF)
Polled data of VERT and HIP trials for women 80+ with OP showed NNT = 12 to prevent 1 new vertebral fracture after 1 year of therapy. After 3 years of therapy NNT = 16
IBANDRONATE (BONIVA) Prevention and Treatment of
Postmenopausal OP Dosing: IV q 3 months or orally daily or
monthly Decreases risk of vertebral (not hip) fracture
by 50% over 3 yrs. RCT by Delmas et al: Comparison of oral and
IV dosing 1400 women with OP of lumbar of lumber spine
At 1 year lumbar/ femur BMD greater in IV group greater than PO
Side effects: flu-like illness with 1st infusion, GI upset, arthralgias
ZOLEDRONATE (RECLAST)
Treatment of Postmenopausal OP Dosing: 5mg IV yearly Reduces incidence of spine fracture by
70%, hip fractures 41%, and non-vertebral fx 25% over 3 yrs.
Side-effects: Acute phase reactants (arthralgia, HA, myalgia, fever)- may pretreat with TylenolRisk of side effects tapers with
subsequent dosing
BISPHOSPHONATES AND ATRIAL FIBRILLATION
Conflicting reports from population-based case controlled studies Reanalysis of several trials did not show
increased risk of atrial fibrillation. Current recommendations are not to withdraw
therapy
PTH (1-34): TERIPERATIDE (FORTEO)Treatment of high risk
postmenopausal and male OPT-score of -3.5, fractures + T-score -2.5,
and those who fail 2 yrs of bisphosphonate therapy
Daily SC injections (only approved for 2 years duration)
Anabolic: Stimulates osteoblast activity-> increased trabecular bone density
PTH (1-34): TERIPERATIDE (FORTEO) Side effects: dizziness, leg cramps,
osteosarcoma seen in rat trials Contraindications: Paget’s disease of bone,
prior radiation therapy of the skeleton, bone metastases, hypercalcemia, or a h/o skeletal malignancy
PTH (1-34): TERIPERATIDE (FORTEO) “Fracture Prevention Trial”: 20mcg/d reduced
vertebral and non-vertebral fractures by 65% and 53%, respectively Review of FPT to assess safety and efficacy in women
75+ compared with younger women found that lumbar and femoral neck BMD both increased significantly and new vertebral fractures risk NNT =11 (Boonen et al. JAGS 2006)
Limitation of study: Subjects were ambulatory w/o significant comorbidities.
CONCURRENT THERAPY
Synergism: Teriperatide and Alendronate?Small RCT 83 men: Spine and femoral neck
BMD increased greatest in PTH only group Alendronate impaired PTH anabolic activity
(Finkelstein et al. NEJM 2003)
Recommended that bisphosphonate therapy follows PTH (Teriperatide).
Simultaneous use of bisphosphonate and other not generally recommended
EVALUATING TREATMENT EFFICACY
Repeat BMD testing every 1-2 years while patient on therapy
Step-up therapy Ensure compliance Evaluate for secondary causes if no
improvement
STOPPING THERAPY No real guidelinesStudy to compare stopping Alendronate
after 5 years vs. continuing x 10yrs.Discontinuing Alendronate after 5 years
showed moderate decline in BMDNo significant change in nonvertebral
fracturesSlight increase in clinical vertebral fracture
risk Stopping for up to 5 years does not significantly
increase fracture risk Patients with very high fracture risk may benefit
from continued therapy(JAMA. 2006;296:2927-2938)
FUTURE THERAPIES
Denosumab Monoclonal Ab against RANKL: inhibits
osteoclasts FREEDOM trial (NEJM 2009:361:756-65)
3 year study, >7500 postmenopausal women (60-90) with low BMD received med vs placebo
Improved BMD of LS (10%) and total hip (4%) Reduced biochemical markers Reduced incidence of new vertebral, hip, and nonvertebral
fractures
Vs. Alendronate Slight increase BMD with Denosumab (NEJM 2006;354:821)
Similar side effects
BMD gain is reversal with stopping medication
FUTURE THERAPIES Strontium ranelate
Decreases osteoclast/ increases osteoblasts ? Antiremodeling effect
Cochrane Review: Daily treatment x 3 years vs placebo- Decrease in vert fx (37%), nonvert fx (14%). NNT=9
Tibolone Synthetic steroid with estrogenic, androgenic, and
progestagenic properties increase BMD Growth Hormones
MANAGEMENT OF VERTEBRAL FRACTURES Limited clinical occurrences Conservative
Oral pain management Physical therapy
Surgical Kyphoplasty Vertebroplasty
KYPHOPLASTY
Balloon creates a cavity in vertebral body in which to inject cementRestores vertebral body height in 70%Reduces fracturePartially corrects kyphosis
Complications: nerve damage and bleeding
Pain relief in 80-90% Studies vs. conservative treatment
show benefit in short-term f/u but not long-term (Lancet. 2009 Mar 21;373(9668):1016-24)
VERTEBROPLASTY Fluoroscopic procedure where cement is
injected into vertebral body Prevents further collapse, does not restore
height Pain relief within 48 hours generally, effective
in 75-90% Complications: fracture of pedicle, psoas
muscle hemorrhage, cement leakage, ARDS
VERTEBROPLASTY
Indications: Painful osteoporotic fractures Painful vertebrae secondary to invasion of tumor Painful fracture a/w osteonecrosis Any fracture where inflammation/ edema present on
imaging (at least 2 weeks old).
Contraindications: Asymptomatic vertebral compression fracture Ongoing local/ systemic infection Retropulsed bone fragment causing myelopathy Uncorrectable coagulopathy Physical obstruction of spinal canal (JVIR 2003)
VERTEBROPLASTY
2 recent studies showed no significant improvement in pain or function following vertebroplasty vs. sham procedures
(NEJM 2009:361:569-79, NEJM 2009: 361:557-568)
THE END
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