Michael Lewiecki, M.D.

Report
Update on Management of
Osteoporosis
E. Michael Lewiecki, MD
New Mexico Clinical Research & Osteoporosis Center
University of New Mexico School of Medicine
Albuquerque, NM
Faculty Disclosure
It is the policy of the American Society for Bone and Mineral Research
(ASBMR) and The France Foundation to ensure balance, independence,
objectivity, and scientific rigor in all its sponsored educational activities. All
faculty participating in this activity will disclose to the participants any
significant financial interest or other relationship with manufacturer(s) of any
commercial product(s)/device(s) and/or provider(s) of commercial services
included in this educational activity. The intent of this disclosure is not to
prevent a faculty member with a relevant financial or other relationship from
participating in the activity, but rather to provide participants with
information on which they can base their own judgments. The American
Society for Bone and Mineral Research (ASBMR) and The France Foundation
have identified and resolved any and all faculty conflicts of interest prior to
the release of this activity.
Disclosure
Grant / Research Support
Amgen, Eli Lilly, Merck, Novartis, Warner Chilcott
Consultant, Advisory Board, Speakers’ Bureau, or
Sponsored Speaking Events
Amgen, Eli Lilly, Merck, Novartis, Warner Chilcott
Learning Objectives
• Improve the ability to assess risk factors for osteoporosis and
apply evidence-based screening recommendations to these
at-risk patients within one’s practice
• Develop strategies to improve the treatment of patients with
osteoporosis
• Utilize the tools and other information provided within this
initiative, including patient education tools and systemsbased approaches to facilitate improving the assessment and
care being provided to patients with osteoporosis
Postmenopausal Osteoporosis in the
Primary Care Setting
•
•
•
•
What is osteoporosis?
Why you should care?
Whom to test and how?
Whom to treat and how?
Definition of Osteoporosis
• A skeletal disorder characterized by
– Compromised bone strength predisposing to
Normal Bone
– An increased risk of fracture
• Bone strength reflects the integration of
two main features:
– Bone density
– Bone quality
Osteoporotic Bone
2000 NIH Consensus Development Conference
Osteoporosis Is a Serious
Public Health Problem
• At age 50, lifetime risk of fracture is
– 1:2 women
– 1:5 men
• Affects 10 million Americans
– 8 million women
– 2 million men
• Additional 34 million have low bone mass
• 2 million fractures yearly*
• Direct cost $17 billion*
Distribution of Fractures
*Based on figures from 2005. Cost does not include lost
productivity, unpaid caregiver time, transportation and
social services
NOF Fast Facts. www.nof.org. Accessed February 2013.
Burge R, et al. J Bone Miner Res. 2007;22:465-475.
USDHHS. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD. 2004.
Identified Treatment Gap
NCQA HEDIS
HEDIS Measure
% Compliance*
Beta-blocker persistence after a heart attack
81.3%
Breast cancer screening
70.5%
Colorectal cancer screening
62.4%
Osteoporosis management after a fracture
22.8%
*2011 HMO Rates
NCQA State of Healthcare 2012 - HMO Statistics (Commercial or Medicare data from 2011).
http://www.ncqa.org/Portals/0/State%20of%20Health%20Care/2012/SOHC%20Report%20Web.pdf.
Accessed February 2013.
National Osteoporosis Foundation
2013 Guidelines
Major clinical recommendations
• Universal (risk, diet, vitamin D,
exercise, smoking, monitoring)
• Diagnosis (BMD, vertebral imaging,
causes of secondary osteoporosis)
• Monitoring (BMD)
• Treatment (initiation criteria, options,
duration)
http://www.nof.org/hcp/practice/tools. Accessed March 2013.
Who Should Have a Bone Density Test?
•
•
•
•
AAFP1 and NOF2
Women age 65 and older and men age 70 and older
Younger postmenopausal women and men ages
50–69 with clinical risk factors
Adults who have a fracture after age 50
Adults with a condition (e.g., rheumatoid arthritis)
or taking a medication (e.g., glucocorticoids)
associated with low bone mass or bone loss
1. Sweet MG, et al. Am Fam Physician. 2009;79(3):193-200.
2. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis.
www.nof.org. Accessed February 2013.
Reimbursement for DXA
Final Rule
Since 2006, Medicare covers bone
densitometry for five indications
• Estrogen-deficient women at clinical risk for osteoporosis
• Patients with vertebral abnormalities
• Patients receiving long-term glucocorticoids (prednisone
≥ 5 mg/d or equivalent for 3+ months)
• Patients with primary hyperparathyroidism
• Patients being monitored to assess the response to an
approved drug
Federal Register. 2006;71(231):67783-67784.
WHO Criteria for
Postmenopausal Osteoporosis
The T-score compares an individual’s BMD with the
mean value for young adults and expresses
the difference as a standard deviation score.
Category
T-score
Normal
-1.0 and above
Low bone mass
(osteopenia)
Between -1.0 to -2.5
Osteoporosis
-2.5 and below
Kanis JA, et al. J Bone Miner Res. 1994;9:1137-1141.
NOF Treatment Guidelines 2013
Women ≥ 65 and men ≥ 70
(younger with risk factors)
DXA
T-score ≤ -2.5 in the lumbar spine, total hip,
or femoral neck
or
Hip or spine (clinical or radiographic) fracture
YES
Candidate for
TREATMENT
YES
http://www.nof.org/hcp/practice/tools. Accessed March 2013.
T-score between -1.0 and -2.5
and high fracture risk
FRAX
10-y fracture risk
≥ 3% for hip fracture
or
≥ 20% for major osteoporotic fracture
Web Version 3.4
Clinical Benefits of FRAX
• Derives 10-year probability of clinical event from
measurable parameters
• Internationally recognized and validated
• Based on data from multiple cohorts
• Easily accessible on the Internet or DXA software
• Helps identify patients who need treatment
Limitations of FRAX™
WHO Fracture Probability Tool
• Not valid in patients on treatment
• Only hip BMD is considered
• Risk is “yes/no” – there is no consideration of “dose”
(e.g., fractures, glucocorticoids, smoking, alcohol)
• Not all risk factors are included (e.g., falls)
• “Major osteoporotic fracture” is not the same as all
osteoporotic fractures
• Clinical judgment is required
Watts NB, et al. J Bone Miner Res 2009;24:975-979.
Patient Care Goals
• Identify patients at risk of fractures
• Reduce incidence of fractures
• Maintain quality of life
– Activity
– Independence
– Health
Universal Recommendations
• Counsel on the risk of fractures
• Calcium intake as follows, ideally through diet, with
supplements if necessary
– 1000 mg per day for men 50-70
– 1200 mg per day for women ≥ 51
– 1200 mg per day for men ≥ 71
• Vitamin D intake should be 800-1,000 IU per day,
supplemented if necessary (age ≥50)
• Regular weight-bearing and muscle-strengthening exercise
• Fall prevention evaluation and training
http://www.nof.org/hcp/practice/tools. Accessed March 2013.
FDA-approved Medications
Indications
Postmenopausal
Osteoporosis
Drug
Estrogen
Prevention
Treatment
Prevention
Men
Treatment

Calcitonin*
(Miacalcin®, Fortical®)

Raloxifene (Evista®)


Ibandronate (Boniva®)


Alendronate (Fosamax®)


Risedronate (Actonel®)











Risedronate (Atelvia®)
Zoledronate (Reclast®)
Glucocorticoid-induced
Osteoporosis


Denosumab (Prolia™)

Teriparatide (Forteo®)

*FDA advisory board found that evidence did not support calcitonin salmon for the
treatment of osteoporosis (March 5, 2013)



Evidence for Fracture Reduction
Vertebral
Fracture
Nonvertebral
Fracture
Hip
Fracture
Calcitonin
(Miacalcin®, Fortical®)

No effect
demonstrated
No effect
demonstrated
Raloxifene (Evista®)

No effect
demonstrated
No effect
demonstrated
Ibandronate (Boniva®)

No effect
demonstrated
No effect
demonstrated
Alendronate (Fosamax®)



Risedronate (Actonel®, Atelvia®)



Zoledronic acid (Reclast®)



Denosumab (Prolia™)



Teriparatide (Forteo®)


No effect
demonstrated
Drug
Adapted from Murad MH, et al. J Clin Endocrinol Metab. 2012;97(6):1871-1880.
Bisphosphonates
Side Effects/Safety Concerns
•
•
•
•
May cause esophageal irritation (oral)
Can cause acute phase response (IV and high-dose oral)
Contraindicated in patients with hypocalcemia
Limited to patients with good kidney function (GFR > 30
or 35 mL/min)
• Musculoskeletal pain?
• Osteonecrosis of the jaw?
• Atypical femur fractures?
•
•
•
•
•
Bisphosphonates
“Side Benefits”
Decreased risk of breast cancer1-5
Decreased risk of colorectal cancer6
Decreased risk of stroke7
Reduced risk of gastric cancer8
Decreased overall mortality9,10
1. Chlebowski RT, et al. J Clin Oncol. 2010;28:3582-3590.
2. Dreyfuss JH. CA Cancer J Clin. 2010;60:343-344.
3. Newcomb PA, et al. Br J Cancer. 2010;102:799-802.
4. Rennert G, et al. J Clin Oncol. 2010;28:3577-3581.
5. Vestergaard P, et al. Calcif Tissue Int. 2011;88:255-262.
6. Rennert G, et al. J Clin Oncol. 2011;9:1146-1150.
7. Kang JH, et al. Osteoporos Int. 2012;23(10):2551-2557.
8. Abrahamsen B, et al. J Bone Miner Res. 2012;27:679-686.
9. Center JR, et al. J Clin Endocrinol Metab. 2011;96:1006-1014.
10. Sambrook PN, et al. Osteoporos Int. 2011;22:2551-2556.
Bisphosphonates
How Long Should Treatment Last?
• Bisphosphonates have a long residence time in
bone
• When long-term therapy is stopped, is sufficient
drug available to exert a continuing benefit?
• Does long-term treatment create safety concerns
that limit the duration of treatment?
Porras AG, et al. Clin Pharmacokinet. 1999;36(5):315-328.
Watts NB, et al. J Clin Endocrinol Metab. 2010;95(4):1555-1565.
Long-term Experience with Alendronate
Fit Long-term Extension (FLEX) Study
• Patients who received ~5 years of alendronate in the
Fracture Intervention Trial signed up for a second 5-year
study
• Re-randomized to stay on alendronate (n = 662) or
changed to placebo (n = 437)
• For those who had 10 years of alendronate compared with
stopping after 5 years
– Clinical vertebral fractures were reduced by 55% overall
– Nonvertebral fractures were reduced by 50% in women
with T-scores -2.5 or below at the start of FLEX
Schwartz AV, et al. J Bone Miner Res. 2010;25:976-982.
Clinical Vertebral Fractures
in the FLEX Study
Cumulative Incidence
of Fractures (%)
6
5.3%
ALN 5 years  Placebo 5 years
Alendronate 10 years
5
4
RR  55%
P = 0.013
3
2.4%
2
1
0
0
ALN/PLB 437
ALN/ALN 662
1
428
659
Black DM, et al. JAMA. 2006;296:2927-2938.
2
3
Years Since FIT
429
421
657
654
4
5
417
650
414
646
Suggestions for Bisphosphonate Duration
• Long-term treatment (e.g., 5–10 years) appears to be
safe for most patients
• For lower risk patients, after 3–5 years of treatment,
“drug holidays” can probably be taken without a
major sacrifice of efficacy
• Higher risk patients should probably continue
treatment for at least 10 years
• No evidence beyond 10 years
Watts NB and Diab D. J Clin Endocrinol Metab. 2010;95(4):1555-1565.
Denosumab
• Fully human monoclonal antibody to RANKL;
decreases osteoclast differentiation, function and
survival
• Reduces risk of spine, hip and nonvertebral fractures
• For treatment of osteoporosis, SQ dosing every 6
months
• Does not require dose adjustment for decreased
kidney function
• Effect is reversible within 6–12 months of stopping
Cummings SR, et al; FREEDOM Trial. N Engl J Med. 2009;361(8):756-765.
Jiang X, et al. Menopause. 2013;20(2):117-119.
Differences Among Antiresorptive Agents
• Pharmacology – mechanism of action, onset and offset of
effect, skeletal retention
• Route of administration – oral (fasting or with food) or
parenteral
• Frequency of administration – daily, weekly, monthly,
quarterly, twice yearly, once yearly
• Side effects/tolerability – depends on agent and patient
• Non-skeletal effects – breast cancer reduction (raloxifene)
• Cost/insurance coverage – generic oral; drugs “administered
by health professional” covered by Medicare Part B
Teriparatide
• Recombinant human PTH (rhPTH [1-34])
• Mechanism of action different from other agents
(anabolic)
• Daily SC injection
• Indicated for patients at high risk for fracture
– Postmenopausal women with osteoporosis
– Men with primary or hypogonadal osteoporosis
– Men and women with osteoporosis associated with
sustained systemic glucocorticoid therapy
• Treatment limited to 2 years, follow with antiresorptive
agent
Forteo PI. http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021318s012lbl.pdf. Accessed Feb 2013.
Han SL, Wan SL. Int J Clin Pract. 2012;66:199-209.
Monitoring
• Monitor with DXA every 1–2 years
– Do not "over-interpret" change
– Be happy when BMD is stable OR increasing
• Why do some patients lose BMD on treatment?
– Poor adherence
– Malabsorption
– Underlying disorders that need to be addressed
• Some patients may respond to therapy yet still have
unacceptably high fracture risk – consider change in
therapy
Fall Prevention
•
•
•
•
•
•
Improve lighting
Remove loose rugs
Add grab bars near bathtubs, toilets and stairways
Formal home safety evaluation
Physical therapy for core strength and balance
Eliminate medications that can affect alertness and
balance
• Assistive device evaluation and training
Sweet MG, et al. Am Fam Physician. 2009;79(3):193-200.
Where Are We Now?
The Good News
• Improved awareness
• Excellent diagnostic tools available
• Fracture risk assessment using BMD and/or clinical
risk factors
• Safe and effective individualized treatment
• Better understanding of pathogenesis
• Federal initiatives to improve care
Where Are We Now?
The Bad News
•
•
•
•
•
•
Declining numbers of patients on therapy
Under-recognition of patients at risk for fracture
Poor primary and secondary adherence
Poor patient understanding of risk/benefit
Decreasing access to DXA
Increasing patient concerns about side effects
Secondary Fracture Prevention
• A fracture is a sentinel event
• A fracture in a person over 50 is the most powerful
risk factor for a future fracture
• Many high risk patients have the fracture successfully
treated but do NOT receive subsequent medical
assessment and treatment to prevent the next
fracture
What can I Do as a PCP?
Practical Steps
• Patient dialog
– Risk communication
– Shared decision making
• Decision aids
– Handouts
– Web resources
– Brochures
What can I Do as a PCP?
Practical Steps
• Identify patients who are at high risk
– Use EHR decision tools
– Flag patients with risk profile
– Use checklist of risk factors
• Identify patients who are not adherent
– Pharmacy refill data if available
– Ask questions
Patients who are nonadherent to one therapy are often
nonadherent to others
Performance-improvement CME
and MOC Part IV Approved (ABFM)
https://achsos.community360.net/default.aspx. Accessed April 2013.
Update on Management of Osteoporosis
• What is osteoporosis?
– Decreased bone strength predisposing to an increased risk of
fracture
• Why you should care
– Common, significant cost, morbidity and mortality
• Whom to test and how
– DXA for all women by age 65, higher risk women earlier; FRAX is a
useful tool
• Whom to treat and how
– Individuals at high risk of fracture; approved agents are safe and
effective; treatment decisions must be individualized
Questions
or Comments?
WILL YOUR BONES LAST AS LONG AS YOU DO?

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