Transcript Osteoporosis - Health Sciences Center

Top 10 Questions About
Bobo Tanner MD
Director, Osteoporosis Clinic
Division of Rheumatology & Allergy
Vanderbilt University Medical Center
Nashville TN
April 21, 2016
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1. Describe the evaluation of osteoporosis
2. Formulate a patient-centered and evidencebased treatment plan
3. Focus on issues of particular importance to
the PCP such as prevention, therapeutic
lifestyle changes and health maintenance
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70 yo w female
Fell at home ( tripped over dog)
Left femur fracture
Hospitalized: open reduction, internal fixation
2 weeks rehab hospital
3 months home care, walker, forgetful
4 months assisted living, does not recognize
family
Hospitalized, UTI, pneumonia, sepsis
expired
Defining Osteoporosis:
Most common metabolic bone disease in adults
Normal Bone
Functional definition: A systemic skeletal
disease characterized by low bone mass and
micro-architectural deterioration of bone tissue
with a consequent increase in bone fragility
and susceptibility to fracture (fragility
fracture).1
Fragility fracture: Fracture after fall from a
standing height
Quantitative Definition: WHO T-score <-2.5 2
Osteoporotic Bone
1Consensus
Development Conference: Diagnosis, Prophylaxis, and Treatment of
Osteoporosis. Am J Med 1991;90:107-110
2 Kanis JBMR 1994
Death2,6
1.
Mortality rate same as breast cancer
Disability1,2
2.
50% incapacitation
3.
Dependence1,2
20% of females need assisted living or
nursing home
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Delirium & dementia3,4,5
40% to 60% risk of delirium
41% higher rate of dementia
1www.share.iofbonehealth.org/WOD/2012
2Cooper
C, et. al., Am J Epidemiol 1993;137:1001
et al. . J Am Geriatr Soc 1988;36:525–530.
3Givens et al J Am Geriatr Soc. 2008 Jun;56(6):1075-9
4Tsai C et al, Medicine 2014 93(26) :1-7
5Marcantonio et al J Am Geriatr Soc. 2011 Nov;59 Suppl 2:S282-8
6Panula et al BMC Musculoskeletal Disorders 2011, 12:105
3Gustafson
Phone survey: ~800 older US adults in 2007
What do you fear most?
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Loss of independence: 26%
Moving out of home into nursing home: 13%
Giving up driving: 11%
Loss of family/friends: 11%
Death: 3%
www.slideshare.net/clarityproducts/clarity-2007aging-in-place-in-america-2836029
Diagnosis & Treatment Goal:
Reduce the Risk of Fracture
The Osteoporotic Event: Hip Fracture
Prevention: Understand the Causes
…trending on Twitter
#osteoporosis
Haddad JG, Kaplan FS
Journal of Clinical Rheumatology
2(1):33-40 1996
#1. When Should Bone Density
Testing Be Performed?
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Multiple sites
 Spine
 Hip
 Forearm
 Total body
Considered the
clinical standard
“Gold Standard”
Osteoporosis : T-score
World Health Organization (WHO) Classification
Postmenopausal Caucasian with DXA measure
T-score
Normal
³ -1
Osteopenia
< -1 and > -2.5
Osteoporosis
£ -2.5
Severe
Osteoporosis
£ -2.5 with Fracture
WHO Study Group JBMR 1994
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Women with estrogen deficiency
Spine x-ray evidence of fracture or OP
Glucocorticoid therapy (3mos, >5mg/d)
Primary Hyper-PTH
Follow-up treatment (23 months unless
medical reason for sooner e.g. steroids)
Which Woman is at Higher Fracture Risk?
54 year old smoker with a T-score of -2.0
10
oryear risk of hip fracture = 2.5%; major osteoporotic fracture = 10%
81 year old with no prior fracture with a Tscore of -1.4
10 year risk of hip fracture = 3.2%; major osteoporotic fracture = 26%
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Frequency of falls
Inability to arise from sitting w/out hands
Bifocals
Diabetes mellitus
Chronic use of PPI
Chronic Use of SSRI
Chronic use of anti-seizure medications
#2. Which Lab tests should you order ?
1. CBC
2. Liver Function Tests
3. Creatinine
4. Calcium
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6.
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8.
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Phos
TSH
PTH
25-OH Vitamin D
(24 hr. urine calcium, magnesium, phos,
creatinine)
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In 664 peri/postmenopausal♀, T-score < –2.5
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53% had secondary osteoporosis by history
With lab testing:
 12% had previously unrecognized factors including
low vitamin D ( < 20 ng/ml)*
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Conclusion: Previously undiagnosed disorders are
common
Tannenbaum C. J Clin Endocrinol Metab. 2002;87(10):4431. *Luckey, personal communication
20
#3. Reducing the Risk of Fracture:
Is estrogen therapy effective
after age 65?
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Bone benefit occurs even late in life
10-20% non-responders
But “wash out” effect when discontinued
Overshadowed by Women’s Health Initiative
results : risks of C-V dz, breast cancer
#4. Since the FDA recommends
estrogens for short term use only,
what are the options for osteoporosis
and osteopenia treatment?
Osteoclast
Lining cells precursors
Activated
Osteoclasts
Lining cells
Osteoblasts
Bone remodeling unit
Resting
Stage
Activation Resorption
2–4 weeks
Reversal
Phase
Formation
Remodeling
Completed
3–4 months
1. Marcus R. In: Hardman JG et al. Goodman & Gillman’s The Pharmacologic Basis of Therapeutics.
10th ed. McGraw-Hill; 2001:1715–1743.
2. Tanaka Y et al. Curr Drug Targets Inflamm Allergy. 2005;4:325–328.
3. Rosen CJ. Available at: http://www.endotext.org/parathyroid/index.htm. Accessed March 15, 2006.
Drug
Post Menopausal OP
Prevention
Treatment
Risedronate
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Ibandronate
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Zoledronic acid
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Alendronate
Raloxifene
Estrogen
Calcitonin*
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Denosumab
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Teriparatide
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Steroid OP
Male OP
Prevention
Treatment
Treatment
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*
Under review
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#5. How long should a patient stay on
treatment?
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Monitor with repeat DXA scans q 1-2 years
Monitor Bone Turnover Markers
(N-telopeptide , Procollagen 1 N-terminal Peptide
(P1NP) Osteocalcin, Alkaline Phosphatase)
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7-10 year bisphosphonate data:
 “ Drug Holiday” after 5 yrs?
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10 year Denosumab data
3 year Teriparatide data
Safety Concerns with bisphosphonates & denosumab:
 Osteonecrosis of the jaw (ONJ)?
 Atypical subtrochanteric fractures?
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Signs &Symptoms:1
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Asymptomatic or
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Facial pain, jaw pain
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Soft-tissue swelling,drainage
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Exposed,necrotic bone
Cultures: actinomyces2
Risk factors
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Cancer & concomitant therapies
Poor oral hygiene
Smoking
Pre-existing dental disease, anemia, coagulopathy, and infection
Ruggiero SL, Hehrotra B, Rosenberg TJ, et al. J
Oral Maxillofac Surg. 2004;62:527-34.
Management
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Povidone-iodine & 0.12% chlorhexidine mouthwash
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Oral antibiotics and anti-inflammatory drugs
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Conservative debridement for necrotic tissue
Melo MD, Obeid G. J Can Dent
Assoc 2005;71: 11-3.
1. Expert Panel Recommendations for the Prevention, Diagnosis, and Treatment of Osteonecrosis of the Jaws:
June 2004
2. Naveau A. Joint Bone Spine 2005.
Any Fragility Fracture (1)
2668
Hip Fracture (1)
387
Anaphylaxis from Penicillin Shot
32
Death by MVA
11
Death by Murder
6
ONJ- Osteoporosis Patient
0.7
Death by Lighting Strike
0.6
(1) Women age 65-69 (from Swedish
National Bureau of Statistics and
database of Olmsted County, MN, USA.)
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10
20
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50
60
70
80
90 100
Risk per 100,000 People per Year
Kanis JA et al. Osteoporos Int. 2001;12:417-427. Pharmcoepidemiol Drug Saf.
2003;12:195-202. National Center for Health Statistics. JADA. 2006;137:1144-1150.
www.nssl.noaa.gov/papers/techmemos/NWS-SR-193/techmemo-sr193-4.html
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Rare
Low energy or spontaneous
Subtrochanteric ,arbitrarily 5cm below l. troch
Thickened lateral cortex (often bilat.)
Transeverse or spiral fracture
“beak” assoc. with stress fracture
Thigh pain before fracture
Often 5-10 years of bisphos. use
Goh JBJS 2007, Nevaiser J Ortho Truama 2008, Somford JBMR 2009, Capeci JBJS 2009,
Lenart Osteoporosis International 2009, Koh J Ortho Trauma 2010
Bukata S ISCD Ann Mtg San Antonio 2010
Goh SK. JBJS 2007;89:349
Goh SK. JBJS 2007;89:349
#6. What should be done if a patient does
not respond to treatment?
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The International Osteoporosis Foundation recommends
changing treatment if :
1. Two or more incident fragility fractures occur
2. One fracture occurs, there is a significant decrease in
Bone Density and/or no reduction in Bone Turnover
Markers (BTMs)
3. Both a significant decrease in Bone Density and no
significant decrease Bone Turnover Markers (BTMs)
BTMs = serum P1NP or C-Telopeptide
Diez-Perez, et. al, Osteoporos Int, 23:2769-, 2012
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Stable BMD or BMD is a good response
Review compliance /adherence
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Review the diagnosis
 Lab work : CBC, Chemistry, Phos, TSH, PTH, 25-OH
Vitamin D, 24 hr. urine calcium,magnesium,phos,protein
immunoelectropheresis
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Switch treatment : IV? subcutaneous? anabolic?
New agents under study:
 anti-cathepsin K ( odanacatib)
 anti- sclerostin (romosozumab )
RANKL
RANK
Denosumab
CFU-M
Prefusion
osteoclast
Multinucleated
osteoclast
Active Osteoclast
BONE
Adapted from Boyle et al. Nature. 2003;423:337.
Anabolic agent
Daily injection for two years
Safety issues:
2-year rat study: developed osteosarcomas
Teriparatide not for patients with:
1.
Paget’s disease
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Prior radiation therapy
3.
Immature skeleton
#7. When should combination
therapy be used?
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2 antiresorptive drugs may be additive (BMD)
 Alendronate + estrogen
 Alendronate + raloxifene
 Risedronate + estrogen
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Caveat
 No fracture data
 Increased cost
 Possible increased side effects
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Combination of antiresorptive and anabolic agents theoretically
attractive: but data is specific for certain agents
 No advantage to alendronate + teriparatide combination
 Synergy with denosumab + teriparatide combination
Black DM, et al. New Engl J Med. 2003;349:1207.
Leder BZ, et al. J Clin Endocrinol Metab 2014; 99: 1694–700.
#8. What is the role of Calcium
supplementation?
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Evidence suggests that calcium + vitamin D
supplementation reduces bone loss and fractures
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Some studies suggest that calcium supplements
(not dietary) may increase vascular disease risk
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Effects on vascular disease are controversial and
expert opinion is divided
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Calcium is a simple first step in promoting bone
health;
 consume 1000-1200 mg daily preferably from food sources,
 supplements should be used when an adequate dietary
intake cannot be achieved
Institute of Medicine. 1997. Washington, DC, Academy Press
4.0%
2.30%
2.0%
0.0%
Change in Spine BMC -2.0%
at 2 yrs.
-4.0%
Ettinger Annals Int Med 1988
Untreated
Calcium
Alone
Conjugated
Estrogens +
Calcium
-6.0%
-8.0%
-10.0%
See also
N Engl J Med
Volume 354;7:669-683
February 16, 2006
-12.0%
-9.00%
-10.50%
Calcium is necessary but not sufficient for treatment of Post
Menopausal Osteoporosis
#9. What is the role of Vitamin D
supplementation?
• Critical for normal calcium absorption &
mineralization of osteoid (type I collagen)
• Storage form measured as 25-OH Vitamin D
• Goal : 32ng/ml: ↓ PTH, ↑ calcium absorption
• Also affects muscle strength
• Risk factors for deficiency:
– Inadequate diet, sunlight, high BMI
– Anticonvulsant therapy, liver dz,
– Malabsorption (celiac disease)
Storage form
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Aging
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skin less effective as a source
dietary intake reduced
GI tract less effective absorption
Renal activation declines
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Replenish with 50,000 International Units once a week for 8 weeks
Maintenance with 1,000 units daily
Vitamin D 3 is more ”potent” than D2
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Other vitamins and minerals may be helpful; Magnesium, K, B12
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but excessive Vitamin A appears to increase fracture risk
Bischoff-Ferrari H. et al. JAMA. 2005;293(18):2257-2264
Janssen HCJP, et al. Am J Clin Nutr. 2002;75:611
#10. How does one treat an
elderly patient with severe,
established osteoporosis?
Control
% of Patients
with Fractures
2.0
Risedronate
69%
1.0
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*
0.0
0
3
6
Months
.
Watts N, et al. J Bone Miner Res. 2001;16(suppl 1):S407.
.
9
12
Insert needle into
vertebral body
 Inflate balloon
 Create a cavity, deflate
& withdraw balloon
 Inject methyl
methacrylate
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Hip Protectors
1801 elderly men and women in long stay or supported home care
0.12
Control 67 fx
0.10
Cumulative
Hazard of
Hip
Fractures
0.08
Protectors 13 fx
54% reduction*
0.06
0.04
0.02
0.00
0
*P=0.008
6
12
Months
18
24
Kannus P, et al. N Engl J Med 2000; 343:1506-1513
1. Early death is associated with fragility fractures
DXA scans predict fracture risk & monitor
response to treatment
3. Therapeutic intervention can reduce fracture
risks & mortality
4. Calcium & Vitamin D are essential but may not
be sufficient
2.