Transcript Age Related Bone Loss and Osteoporosis PowerPoint

Age-related Bone
Loss and
Osteoporosis
Nahid Rianon, MD, DrPH
The University of Texas Health Science Center at Houston
Assistant Professor, Division of Geriatric and Palliative
Medicine,
Department of Internal Medicine
Dr. Nahid Rianon was a member of the Houston
Geriatric Education Center faculty. During her
time with the grant, she developed and
presented these slides to an interprofessional
audience.
Dr. Rianon is with The University of Texas
Health Science Center at Houston. She is an
Assistant Professor, Division of Geriatric and
Palliative Medicine, Department of Internal
Medicine.
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This project was funded by a grant from the
Health Resources and Services
Administration (HRSA) of the Department of
Health and Human Services. The grant was
initially funded in 2007 with renewed funding
for five years beginning in 2010. (Grant
#UB4HP19058). The grant was successfully
completed in June, 2015.
 Attendees will recognize osteoporosis and related
fractures as important health care problem of old
age
 Attendees will understand the patho-physiology of
age related bone loss
 Attendees will be able to calculate fracture risk in
geriatric patients and treat osteoporosis with an
individualized plan for each patient
 Attendees will be knowledgeable about prevention
of age related bone loss & related fractures
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 Fractures can decrease
quality of life:
 Physical: pain,
compressed abdomen,
spinal deformity
 Functional: decreased
mobility
 Psychosocial: depression
 Rate of recurrent
vertebral fracture after
the initial one: ~5-20%
NOF
 Hip fracture


~50% with hip
fractures will never
walk w/o assistance
~25% will require
long-term care
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 ~ $22 billion is spent annually for
osteoporosis and related fracture in the
Blume & Curtis, 2010
USA
 ~ $7 billion is spent annually for breast
State of Health Care Quality, 2007
cancer in the USA
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 ~10,000 baby boomers turn 65 everyday
 Number of elderly Americans (≥65 yrs)

34 million in 1998 to ~ 70 million in 2030
 Concerns of under-recognition and under-treatment


~20% f/u for treatment after fragility fractureOwn the Bone
Fracture- often first sign of presence of osteoporosis
 ~ half of the osteoporosis related office visits managed
by PCPs


5% in 2002 to 20% in 2008 (NHAMCS)Rianon et al., 2013
HTN, ↑ lipid, OA, DM & depression - common in them
 Barriers


For PCPs/Geriatricians: Competing chronic disease
priorities & lack of resources
Rapidly growing geriatric population – not enough trained
specialty care physicians
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
Osteoporosis & related fractures - important public
health problems of old age
 ~10 million Americans suffer from osteoporosis NOF
 ~ 34 million are at risk
 More than 2 million fractures in the USA in 2005
were attributable to osteoporosis

prevalent fractures 


vertebral fractures (most common)
hip fractures
wrist fractures
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For Women:
 Incidence of fractures
per year exceeds that of
stroke, MI & breast
cancer combined
For Men:
 Fracture risk is
higher than that of
prostate cancer
 ~1 in 2 Caucasian
women ≥50 years
experience a fracture in
their lifetime
 ~1 in 5 men ≥50
years will experience
a fracture
Osteoporosis affects men & women of all races/ethnicities
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 Compromised bone strength that
increases risk of fracture

Bone Strength is characterized by


Bone density &
Other bone qualities, e .g., micro-architecture
influenced by bone remodeling, bone turnover,
mineralization and other factors that are more
difficult to quantify, such as “damage
accumulation”
(NIH consensus conference 2000)
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Osteoporotic bone
Quantitative
& qualitative
changes
©2012 Multimedia Scriptorium, UTHealth
Trabecular bone
Mineral
loss
Cortical bone
Healthy femur
Fragility Fractures
Loss of mineral
& microstructure
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mg/cm2
ASBMR 2011
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Source: ASBMR using data from Looker A et al., 1998 Osteop. Intl
Types
 Trabecular
 20%
of skeletal mass
 Greater surface area
than cortical
 Provides supporting
strength to the ends
of weight-bearing
bones
 Cortical
 80%
of skeletal mass
 Solid outside shaft of
long bones
http://www.asbmr.org/default.aspx
Cells
 Osteoblasts

Critical to bone
formation
 Osteoclasts

Reabsorb bone
 Osteocytes

Exact role is still
under investigationinvolved in bone
turnover
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Physiology- Normal State
Osteoclast
Osteoclast
Precursor
Osteoblast
Precursors
Osteoblast
LEGEND: LC = Lining Cells
CL = Cement Line
OS = Osteoid
BRU = Bone Remodeling Unit
Normal Bone Remodeling Sequence
Resorption = Formation
No change in bone mass
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Pathogenesis of age-related bone loss:
Unbalanced Remodeling
Net bone loss
Resorption > Formation
Inadequate
calcium or
vitamin D
Menopause
Aging
Medications
or diseases
Osteoporosis
Normal
Bone Structure
Osteoporotic
Bone Structure
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DXA scan - Left hip
DXA scan - Lumbar spine
 Osteoporosis = A T- score of <-2.5 for BMD
 Osteopenia = A T-score of -1 to -2.5 for BMD
 Usual sites for DXA are lumbar spine and left hip
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Who should we screen: USPSTF
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Screening: other organizations
Organization Recommendations
Women
men
NOF
BMD for all ≥65 y &
BMD for all ≥70 y
postmenopausal <65 y, & 50-69 y, based
based on risk profile
on risk profile
WHO
Indirect evidence
supports screening for
≥65 y, but no direct
evidence for widespread
screening
ACP
ACOG
Older men at high
risk & candidate
for therapy
BMD for all ≥65 y &
postmenopausal <65 y
who have ≥1 risk factor
Ann Intern Med. 2011;154:356-364
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 Age (40-90), gender,
height & weight,
race/ethnicity
 Previous fracture
 Rheumatoid arthritis
 2ndary Osteoporosis


 Hip fracture in parents
 Current smoking

 Alcohol

 Glucocorticoids (oral)≥
3 months @ dose 5mg
daily or more –


or equivalent doses of
other glucocorticoids
DM-I, OI in adults,
Untreated Hyper or
Hypothyroidism,
Premature Menopause
(<45 yrs),
Chronic malnutrition or
malabsorption &
Chronic liver disease
 Bone mineral density
(BMD)
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 T-score between -1.0 to  Hx of hip fracture
2.5 @ fem. neck, total hip
 Other prior fractures &
or spine AND 2ndary
T-score between -1.0 to
cause ↑ risk of fracture
-2.5 @ fem. neck, total
 Steroid use, total
hip or spine

Height loss (vert. frac.)*
immobilization, men
w/androgen deprivation
therapy
 T-score ≤-2.5 @ fem.
neck, total hip or spine  T-score between -1.0 to
-2.5 @ fem. neck, total
hip or spine AND 10-yr
probability of hip fracture
≥ 3% or any major
osteoporosis-related
www.nof.org/professionals/clinical-guidelines fracture ≥ 20% (FRAX)
* Hannan et al., 2012 JBMR
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 Bisphosphonates

Oral
Alendronate 10 mg daily
or 70 mg wkly
 Risedronate 5 mg daily
or 35 mg weekly or 150
mg/mo
 Ibandronate 150 mg/mo
Intra-venous
 Zoledronic acid 5 mg/yr
 Teriparatide

Recombinant human
PTH (not >2 yrs)
 Contra-indicated in
cancer patients)


20 mcg sq daily

 Denosumab

60 mcg sc/q 6

Humanized monoclonal
antibody
 Calcium (1200-1500 mg) + Vitamin D (800-1000 IU daily)
www.nof.org/professionals/clinical-guidelines
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 SERM

Raloxifene – not
commonly used
because it increases
risk of DVT &
increased hot flashes
 Testosterone


If hypogonadism is the
cause of osteoporosis
Caution if history of
prostate cancer
 Estrogen/Progestin

Not encouraged due to
increased risk of
breast cancer, stroke,
DVT and coronary
diseases
www.nof.org/professionals/clinical-guidelines
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 Calcium
 1000-1500 mg
daily
 Consider intake
with diet
 Formulation:
 Carbonate (with
meal)
 Citrate (fasting
state)
www.nof.org/professionals/clinical-guidelines;
IOM & Endocrine society guidelines
 Vitamin D



Screen at-risk patients
Check 25 hydroxy
vitamin D total
Recommended level
30 ng/dl
 Ergo/Chole-calciferol
800-1000 IU daily
 Unless <30 – then
50000 IU q weekly for
8-12 wks

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Medication
Fracture outcome
Side Effects
Bisphosphonates
Reduces risk of vertebral,
non-vertebral & hip (except
ibandronate) fracture
•Gastro-intestinal irritation
•Myalgia & arthralgia
•Renal toxicity
•Atypical fracture
•Osteonecrosis of jaw
Teriparatide
Reduces risk of both vertebral •Osteosarcoma observed in
& non-vertebral fracture
rats (contra-indicated in
patients with history of cancer)
Denosumab
Reduces risk of vertebral,
non-vertebral & hip fracture
Silverman & Christiansen, 2012, Osteop Intl
•Dermatitis
•Hyporcalcemia
•Osteonecrosis of jaw
•Pancreatitis
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 For Bisphosphonates:
 Alternate options
 Atypical fracture
 Switch to other
 Jaw necrosis
agents
 Severe GERD/gastritis or
 Teriparatide: up to
GI bleed
2 years
 Unimproved BMD despite
treatment
 Fracture while being on tx
 Intervention
 Drug holiday
 Monitor with DXA/1-2 yrs
 Monitor bone markers/yr
*Rianon N et al., 2011
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DXA Acquired BMD
 Stable or improved
BMD
 Loss of BMD <%CV
showing no
significant change
over mechanical
drift from QA report
for DXA machine
Carey J, 2005; Delmas P et al., 2009; ASBMR
Bone Markers
 Suppression of Bone
markers
 Both formation and
resorption markers
 not a standard
practice yet
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 Fracture Liaison Services (FLS)
 Goal:
Bringing patients back for DXA
Improve rates of f/u
 Results:
Improved follow up and prevention
Increased continuity and quality of care
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 ↑case identification,diagnosis,treatmentBogoch et al.,2006, JBJS-Am
 Increased BMD test (3-45%)Inderjeeth et al., 2010 MJA
 Liaison between orthopedics & discharge destination
health care team (including PCP)
 ↑ provider awareness & treatmentSwitzer et al.,2009 JortTrau
 ↑ treatment with documentation & f/uWard et al., 2007 Osteop Int
 Fracture prevention algorithm
Kaiser Permanente, 2009
 No information on BTM
 Inter-professional team worked together
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Formation
 Serum bone specific
alkaline phosphatase
(BAP) (5.6-29 mcg/L)
 Serum pro-collagen
type 1 aminoterminal propeptide
(P1NP) (20-108 mcg/ml)
 Osteocalcin (8-32 ng/ml)
Resorption
 Serum C-terminal
cross-linking
telopeptide of type I
collages (CTX)
 Urine N-terminal
cross-linking
telopeptide of type I
collagen (NTX)
 2nd
void sample in the
AM (4-64 nmol
BCE/mmol
creatinine)
ASBMR: http://www.asbmr.org
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85 year old CF, BMI 21, lost about 4” since age 30s, no
hx of cancer/previous fx/other 2ndary risk of osteop, no
FHx of osteop or hip fx in parents, former smoker, social
drinker, exercises regularly, hx of tx for osteoporosis w/
bisphosphonates for 14 yrs w/o much improvement in
BMD. DXA acquired femur neck T scores since 1997
were:
T score Fem Neck
Year
-2.1
1997
-2.2
2006
-2.1
2008
-2.0
2010
Change from baseline was +2.0%
DXA was done using the same machine at the same place
U-NTX 18, P1NP 11, Vit D, Calc, PTH, Mg & Phos WNR.
What would you do at this point?
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• Patient had osteopenia: In a patient with osteopenia –
treatment is indicated if FRAX score indicates
treatment or she has a history of fragility fracture

FRAX not valid for her due to history of treatment with
bisphosphonate
• Also has a long history (>5 years of bisphosphonate
use)
• Bone markers are suppressed
• Stop bisphosphonate – start drug holiday, monitor in
a year
• Continue calcium and vitamin D supplementation and
weight bearing exercise
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http://www.surgeongeneral.gov/library/bonehealth/chapter_6.html#NutritionsImpacto34
nBoneHealthAReviewoftheEvidence
 Weight bearing
exercise


Stimulates bone
formation
2.5 to 4 hours/wk of
moderate to severe
intensity physical
activity
 Non-skeletal
Environmental/Behavioral

Fall prevention

Improve balance & gaitPT/OT
Smoking cessation
 Avoid risk level alcohol
use
 Avoid flexion in patients
with risk of or hx of
 Calcium and Vitamin D
vertebral fracture
 Regular supplemental
 FLS (Fracture Liaison Services)
required dose
 Network within the clinic,
or group of providers
Chodzko-Zajko WJ et al., 2008 & ASBMR

(2ndary prevention)
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 Osteoporosis is a progressive & chronic
metabolic bone disease that decreases bone
density with deterioration of bone structure.
 Clinical Diagnosis = T- score of <-2.5 for BMD
 Prevention & treatment with a comprehensive
and individualized approach.
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 * Hannan et al., 2012 JBMR
 Ann Intern Med. 2011;154:356-364
 ASBMR: http://www.asbmr.org
 Bogoch et al.,2006, JBJS-Am
 Chodzko-Zajko WJ et al., 2008 & ASBMR
 http://www.asbmr.org/default.aspx
 http://www.surgeongeneral.gov/library/bonehealth/chapter_6.html#NutritionsImpactonBon
eHealthAReviewoftheEvidence
 Inderjeeth et al., 2010 MJA
IOM & Endocrine society guidelines
 Kaiser Permanente, 2009
 (NIH consensus conference 2000)
 Rianon N et al., 2011
 Silverman & Christiansen, 2012, Osteop Intl
 Source: ASBMR using data from Looker A et al., 1998 Osteop. Intl
 Switzer et al.,2009 JortTrau
 Ward et al., 2007 Osteop Int
 www.nof.org/professionals/clinical-guidelines
www.shef.ac.uk/FRAX

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?
Questions?
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