5/13/2015

AACE
Post-Menopausal Osteoporosis
Guidelines 2015

Pauline Camacho, MD, FACE

Steven M. Petak MD, JD, MACE, FCLM

Educational Objectives
Discuss AACE guidelines related to the
prevention of osteoporosis
Review the approach to determining those
that can most benefit from osteoporosis
therapy in the AACE guidelines
Differentiate treatment options and initiate
individualized treatment regimens for
management of osteoporosis in the
guidelines

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It ain't what you don't know that gets you

into trouble. It's what you know for sure
that just ain't so.
Mark Twain

For full evidence based guideline see:

http://www.aace.com/pub/guidelines/

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Measures to Prevent Bone Loss

R1. Maintain adequate calcium intake
R2. Maintain adequate vitamin D intake
R3. Limit alcohol to 2 servings daily
R4. Limit caffeine intake
R5. Avoid or stop smoking
R6. Maintain active lifestyle including weight
bearing exercise at least 30 minutes daily

2015 Discussion Points: Bone Health PMO

Vitamin D
Measure 25-OH vitamin D in those at risk for insufficiency
Preferable range 25-OHD : 30 ng/ml to 60 ng/ml
Supplementation if needed: generally in range of 10002000 IU daily with higher amounts in some patients

Calcium
Counsel on adequate dietary intake of calcium about
1200 mg daily

Exercise
Active lifestyle, weight bearing and balance
exercises
Refer PT and OT as needed
www.iom.edu
www.aace.com (Petak SM and Watts NB)

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Does Type of Calcium Make a Difference?

Most preparations are calcium carbonate should
be taken with food for maximal absorption,
especially in elderly
Calcium citrate slightly better absorbed, can be
taken on an empty stomach but both carbonate and
citrate should take with food to reduce oxalate
absorption
Better to split doses as % calcium absorption
decreases with larger dose (limit about 500-600 mg
at at one time)
Side effects such as bloating, constipation, nausea
common especially in elderly (preparations with
magnesium can counteract constipation)
Food sources preferable

Does Calcium Increase Vascular Risk?

Calcium Supplements and Heart Events

Meta-analysis reported increased risk of MI & cardiovascular

events with calcium supplementation (Bolland, et. al, BMJ 2010)
Additional analysis including 16,718 women (46%) not taking
calcium supplements when WHI began found clinical MI or
revascularization increased
HR 1.16 (CI 1.01-1.34) p = 0.04

Analysis of data from 8 other trials plus WHI

28,072 patients (8 trials plus WHI subgroup)

Calcium with or without vitamin D versus placebo
Cardiovascular events (MI or stroke)
HR = 1.15 (1.03-1.27) p = 0.009
Bolland MJ et al. BMJ 2011;342:d2040

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A study of > 9000 participants followed for

10 years found that postmenopausal
women taking 500-1000 mg of
supplemental calcium had a survival
advantage (Langsetmo, JCEM 2013)
Other studies found no effect of calcium
supplements on CV risk (Lewis, JBMR
2011, Zhu, JBMR 2008, Hsia, Circulation
2007)

Nonpharmacologic Measures in
PMO Treatment
R7. Maintain adequate protein intake
R8. Use proper body mechanics
R9. Consider use of hip protectors in
individuals with high fall risk
R10. Take measures to reduce fall risk
R11. Consider referral to PT and OT

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PMO: Screening
R12. Women 65 years and older
R13. Younger postmenopausal women at
increased risk of fracture based on risk
factors
DXA to be considered based on fracture risk
considerations

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USPSTF 2010 Recommendations

The USPSTF recommends screening for
osteoporosis in women aged 65 years or
older and in younger women whose
fracture risk is equal to or greater than that
of a 65-year-old white woman who has no
additional risk factors.
Rating B: The USPSTF recommends the service.
There is high certainty that the net benefit is
moderate or there is moderate certainty that the
net benefit is moderate to substantial.
www.uspreventiveservicestaskforce.org/uspstf10/osteoporosis/osteors.htm

USPSTF 2010 Recommendations

Based on the U.S. FRAX tool, a 65-year-old
white woman with no other risk factors has a
9.3% 10-year risk for any osteoporotic fracture.
Although the USPSTF recommends using a
9.3% 10-year fracture risk threshold to screen
women aged 50-64 years, clinicians should also
consider each patients values and preferences
and use clinical judgment when discussing
screening with women in this age group.

www.uspreventiveservicestaskforce.org/uspstf10/osteoporosis/osteors.htm

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What Does 9.3% Look Like?

50 year old, smoker, BMI < 21 kg/m2, daily ETOH,
parental history of hip fracture
55 year old with parental history of fracture
60 year old with BMI < 21 kg/m2 with daily ETOH
60 year old smoker with daily ETOH

PMO: Diagnosis
R14. Use central DXA measurements
R15. In absence of fracture, osteoporosis
defined as a T-score -2.5 or below at
spine, femoral neck, or total hip
R16. Osteoporosis defined as presence of
hip or spine fracture in absence of other
bone conditions

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2015 Discussion Point:

Definition of Osteoporosis
Definition to include: High fracture risk
using FRAX country-specific threshold in a
person with low bone mass or osteopenia?

PMO: Evaluation
R17. Evaluate for secondary osteoporosis
R18. Evaluate for prevalent vertebral fractures
Lateral spine imaging with x-ray studies or
vertebral fracture assessment in patients with
unexplained height loss, kyphosis, or suspected
spine fractures

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Secondary Causes: Often Occult

Drugs

Chronic
Diseases

Nutritional
Conditions

Endocrine Diseases
or Metabolic Causes

Glucocorticoids
GnRH agonists
Aromatase
inhibitors
Medroxyprogest
erone acetate
Phenytoin
Excess thyroid
Heparin
Phenobarbital
Lithium
TZDs
PPIs
SSRIs

Rheumatoid
arthritis
Myeloma and
cancers
COPD
Organ
Transplantation
Renal tubular
acidosis
Mastocytosis
Thalassemia
Immobilization
HIV

Vitamin D
deficiency
Malabsorption
Hypercalciuria
Calcium
deficiency
Alcoholism
Gastric/obesity
surgery
Chronic liver
disease
Malnutrition
Homocysteine

Hypogonadism
Hyperparathyroidism
Cushing syndrome
Thyrotoxicosis
Anorexia nervosa
Hyperprolactinemia
Porphyria
Hypophosphatasia
Type I DM
Acromegaly

Prevalence of Occult Secondary Osteoporosis

No large, population-based studies; studies from referral
centers vary by criteria for inclusion, extent of testing and
definition of vitamin D deficiency

Prevalence in studies which assessed urinary

calcium and vitamin D:
Women & men, varying ages1-4 37-63%
Post-hip fracture patients5 60-80%
Bone loss on pharmacologic therapy6,7 > 50%
1Deutschman

H J Intern Med 252:389

ST Calcif Tissue Int 64:275
CS 2008 ASBMR abstract
4Gabaroi DC 2010 Menopause 17:135
5Edwards BJ 2008 Osteoporos Int 19:991
6Lewiecki EM. J Bone Miner Res 2002;17(Suppl 1):S367
7Geller JL, Endocr Pract 2008 Apr;14(3):293
2Hayden

3 Ryan

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Common Medications Possibly Associated With

Increased Fracture Risk
Proton-pump inhibitors (PPIs)
hip fracture after long-term, high-dose therapy in
observational studies1

Selective-serotonin reuptake inhibitors (SSRIs)

2x risk fragility fracture seen with daily use2

Thiazolidinediones (TZDs)
risk peripheral fractures in post-menopausal women
with type 2 diabetes on rosiglitazone compared to
metformin or glyburide3
1Yang

YX et al. JAMA 2006;296:2947-2953

JB et al. Arch Int Med 2007;167:188-194
3Kahn SE et al. Diabetes Care 2008;31:845-851, Loke YK et al CMAJ 2009;180:32-9
2Richards

What Testing Should be Done?

ASBMR Recommendations
Basic: CBC, chemistry panel, TSH, 25(OH)D, 24
hour urine calcium/creatinine
Additional: E2, LH, FSH, prolactin, PTH, 1,25OHD, 24 hour urine free cortisol,
Iron/TIBC/ferritin, celiac testing, SPEP/UPEP,
ESR/CRP, tryptase, bone turnover markers,
transiliac bone biopsy (if low trauma fracture and
negative evaluation)
Cohen Adi, Shane E. Primer ASBMR 2009;289-293

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Importance of 24-hour Urine Calcium

Effectively identifies both hypercalciuria and malabsorption when
results fall outside normal values (60-300 mg/day1)

Both disorders associated with higher rates of bone loss1,2

Calcium deficiency associated with diminished or absent BMD

response to therapy2

Each condition requires a specific intervention for optimal

patient management

Spot urine calcium does not detect malabsorption3

38% of new diagnoses would have been missed without 24 hour
urine calcium results14
1Heaney

RP, et al. Osteoporos Int 1999;9:13-18

2Nieves JW 1998 Am J Nutr 67:182
3Ciacci C, et al. Am J Gastroenterol. 1995;90:1480-4
4 Tannenbaum C, et al. J Clin Endocrinol Metab. 2002;87:4431-7

Who Needs Pharmacologic Therapy?

R19. Those patients with a history of a
fracture of the hip or spine
R20. Patients without a history of fractures
but with a T-score of -2.5 or lower
R21. Patients with a T-score between -1.0
and -2.5 if FRAX 10 year major
osteoporosis related fracture probability at
20% or more or hip fracture probability at
3% or more

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US/NOF Thresholds:
Major osteoporosis related fracture: 20%
Hip fracture: 3%

Apply clinical judgment!!

http://www.shef.ac.uk/FRAX/

What Drugs Can Be Used to Treat PMO?

Use Drugs with Proven Antifracture Efficacy
R22. Use alendronate, risedronate, zoledronic acid,
and denosumab as first line therapy
R23. Use ibandronate as a second line agent
R24. Use raloxifene as a second or third line agent
R25. Use calcitonin as the last line of therapy
R26. Use teriparatide for patients with very high
fracture risk or patients in whom bisphosphonate
therapy has failed
R27. Advise against the use of combination therapy
Cost, improved efficacy not documented, safety

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FDA-Approved Medications
Drug

PMO
Prevention

Estrogen

GIO

Treatment

Men

Prevention

Treatment

Ibandronate

Zoledronic
acid

Raloxifene

Calcitonin
Alendronate
Risedronate

Denosumab
Teriparatide

Fracture Risk Reduction in PMO

Medication
Estrogen
Alendronate
Risedronate
Ibandronate
Zoledronic
acid
Calcitonin
Raloxifene
Denosumab
Teriparatide

Spine

Hip

Nonvertebral

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2015 Discussion Points: Osteoporosis

Medication Options
Broad spectrum
Alendronate, risedronate, zoledronic acid,
denosumab

Parenteral options if needed

Denosumab, zoledronic acid, teriparatide

Spine specific efficacy

Ibandronate, raloxifene

Combined denosumab and teriparatide

achieves improved BMD response vs
either agent alone but data for fracture risk
are lacking.
Strongly recommend antiresorptive
therapy following teriparatide therapy

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How is Treatment Monitored?

R28. Obtain a baseline DXA, and repeat DXA
every 1-2 years until stable. Continue follow-up
every 2 years or at a less frequent interval
R29. Monitor changes in spine or total hip BMD
R30. Follow-up of patients should be in the
same facility, with the same machine, and if
possible, the same technologist
R31. Bone turnover markers may be used at
baseline to identify patients with high bone
turnover and can be used to follow the response
to therapy

What is Successful Treatment of

Osteoporosis?
R32. BMD is stable or increasing and no fractures
are present
R33. For patients taking antiresorptive agents,
bone turnover markers at or below the median
value for premenopausal women are achieved
R34. One fracture is not necessarily evidence of
failure. Consider alternative therapy or
reassessment for secondary causes of bone loss
for patients who have recurrent fracture while
receiving therapy

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How Long Should Patients be Treated?

R35. For treatment with bisphosphonates, if
osteoporosis is mild, consider a drug holiday
after 4-5 years of stability. If fracture risk is high,
consider a drug holiday of 1-2 years after 10
years of treatment
R36. Follow BMD and bone turnover markers
during a drug holiday period and reinitiate
therapy if BMD declines substantially, bone
turnover markers increase, or a fracture occurs

2015 Discussion Points

Consider a drug holiday after 3-5 years
of stability in lower-risk patients and after
6-10 years in higher risk-patients.
Teriparatide or raloxifene may be used
during the bisphosphonate holiday in
higher risk patients
End of the holiday is based on individual
patients

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2015 Postmenopausal Osteoporosis Treatment Algorithm

Lumbar spine or femoral neck or total hip Tscore of 2.5, a history of fragility fracture, or
high FRAX score**

Screen for causes of secondary osteoporosis

Correct calcium/vitamin D deficiency and
address secondary causes

Initiate pharmacologic therapy

Education on lifestyle measures, fall
prevention, benefits and risks of drugs

No prior fragility fractures or

Lower fracture risk **

Prior fragility fractures or higher fracture risk **

Alendronate, risedronate, zoledronic

acid, denosumab
Alternate therapy: Ibandronate,
raloxifene, teriparatide

Teriparatide, denosumab, zoledronic acid

Alternate therapy: Alendronate, risedronate,
ibandronate, raloxifene

To page 3

To page 2

Continued from page 1

No prior fractures or
Lower fracture risk

Alendronate and risedronate,

zoledronic acid, denosumab
Alternate therapy:
Ibandronate, raloxifene,
teriparatide

Reassess at least yearly for response to therapy and fracture

risk
Increasing or stable BMD and no fractures, T
score better than -2.5

Consider a bisphosphonate holiday in 3-5

years
Resume therapy when a fracture occurs, BMD
declines beyond LSC, or patient meets initial
treatment criteria

Progression of bone loss or recurrent fractures

Assess compliance, re-evaluate for causes of

secondary osteoporosis and factors leading to
suboptimal response to therapy

Switch to injectable antiresorptive if on oral

agent; switch to teriparatide if on injectable
antiresorptive or at very high risk of fracture

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Continued from page 1

Prior fragility fractures or indicators of higher
fracture risk

Teriparatide , denosumab, zoledronic acid

Alternate therapy: Alendronate, risedronate,
ibandronate, raloxifene

Reassess at least yearly for response to therapy and fracture

risk
Teriparatide for up to 2 years

Sequential therapy with oral or

injectable antiresorptive agent

Denosumab and zoledronic

acid

Continue therapy or switch

to teriparatide if with
progression of bone loss or
recurrent fractures

*10 year major osteoporotic fracture 20% and hip fracture risk 3% or above
country specific threshold
**Indicators of higher fracture risk: advanced age, frailty, prior fractures, glucocorticoids,
very low T-scores. See table

When Should Patients Be Referred

to Clinical Endocrinologists?
R37. When a patient with normal BMD sustains a
fracture without major trauma
R38. When recurrent fractures or continued bone
loss occurs in a patient receiving therapy without
obvious treatable causes of bone loss
R39. When osteoporosis is unexpectedly severe or
has unusual features
R40. When a patient has a condition that
complicates management (for example: renal failure,
hyperparathyroidism, malabsorption)

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Additional Questions

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