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Michael R. McClung, MD, FACP, FASBMRProfessorial Fellow, Mary MacKillop Institute for Health Research

Australian Catholic University, Melbourne, VIC

Director, Oregon Osteoporosis CenterPortland, Oregon, USA

mmcclung.ooc@gmail.com

XXVII Congreso de Osteologia

Santiago de Chile

May 10, 2019

Reducing Fracture Risk in the Very Elderly

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Disclosures

I am disclosing financial relationships as follows:

Scientific Advisory Boards: Amgen

Honorarium for speaking: Amgen, Radius

Michael McClung, MD 2019

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Fracture Risk and Age

0

1000

2000

3000

<50 50-54 55-59 60-64 65-69 70-74 75-79 80-84 >85

Incidence per 100,000 person-

years

Hip

Clinical spine

Wrist

Melton et al, J Bone Miner Res 1992

Women

Age

Fracture type

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0

5

10

15

20

25

30

Age-Group (Years)

Perc

en

t

Minor Fractures

Other Major Fractures

Vertebral Fractures

Proximal Femur Fractures

60–69 70–70 > 80

Center J et al. Lancet 1999

Fractures by Age Dubbo Osteoporosis Epidemiology Study, 1989–1994

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Risk Factors for Fracture in Elderly Men

Advanced age

Low BMD

Prior fracture

Risk of falls

Co-morbidities

Cauley JA et al. J Bone Miner Res 2016;31:1810-19

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Osteoporosis Falls

Strategies for Reducing Hip Fracture Risk

Calcium and

Vitamin DPharmacological Therapy Injury prevention

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CS

Falls and Fractures

Orwoll ES et al. The relationships between physical performance, activity levels and falls in older

men. J Gerontol A Biol Sci Med Sci 2018. doi: 10.1093/gerona/gly248. [Epub ahead of print]

• Almost all hip fractures occur after a

fall to the side – not forward or

backwards.

• In older men and women, the risk of

falling is highest among those with low

activity/low performance, but most falls

(57-64%) and relatively high fall rates

(3.0-4.35/year) occurred in the other

groups (low activity/high performance,

high activity/high performance and high

activity/low performance; 70% were in

these groups).

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Reducing Fall Risk

• Exercise for strength and balance

• Vision correction

• Good nutrition

• Calcium and vitamin D

• correcting vitamin D deficiency improves muscle strength and reduces fall risk

• no evidence that elderly require more vitamin D or calcium than younger people

• but larger doses of vitamin D often given to elderly to ensure adequate intake

• Adequate protein

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Protein Requirements for Elderly Patients

• Older persons require more protein than their younger peers in order to maintain and

build up muscle.

• Between 1.0 and 1.2 g protein per kilogram body weight should be consumed daily.

• The anabolic threshold for the daily protein and amino acid intake is higher in older than

in younger adults, and should be set at approximately 25 to 30 g per meal, containing 2.5

to 2.8 g leucine.

• The source of protein and the amount of protein should be considered in all meals based

on these recommendations for optimal protein intake.

Bauer JM, Diekmann R. Protein and older persons. Clin Geriatr Med 2015;31:327-38

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BMD, Age and Hip Fracture Risk

0

5

10

15

20

-3 -2.5 -2 -1.5 -1 -0.5 0 0.5 1

Hip

fra

ctu

re r

isk

(% p

er

10 Y

ears

)

BMD T-score

Kanis et al, Osteoporos Int 2001

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BMD, Age and Hip Fracture Risk

The relationship between BMD and fracture risk varies with age.

0

5

10

15

20

-3 -2.5 -2 -1.5 -1 -0.5 0 0.5 1

Hip

fra

ctu

re r

isk

(% p

er

10 Y

ears

)

BMD T-score

Kanis et al, Osteoporos Int 2001

50

60

70

80

AGE

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Osteoporosis in the Very Elderly

1. Very elderly have most severe deficits in trabecular and cortical bone structure and strength

2. Fracture risk increases exponentially with advancing age

3. Consequences of fractures are most serious in the very elderly

4. There are questions about effectiveness of osteoporosis treatments in the very elderly

5. Many older patients have impaired renal function which may limit usefulness of bisphosphonates

BMD and Hip Fracture Risk in Elderly Women

EPIDOS Study: 7598 French women > 75 years of age

Schott et al. O.I. 1998

0

1

2

3

4

5

75-79 >80 >85

Age Groups

4.4 2.5 1.6

RR Hip Fracture:

OP vs no OP

0

5

10

15

20

<-2.5 >-2.5

Incid

en

ce/1

000

wo

man

-years

Femoral Neck T-score

• Osteoporosis is a risk factor for fracture in the elderly

• Absolute fracture risk increases with age

• BUT the proportion of risk attributable to osteoporosis decreases with advanced age

Age and Hip Fracture Risk

0%

5%

10%

50 55 60 65 70 75 80 85

5-y

ear

fractu

re r

isk

Age

National Osteoporosis Foundation, Osteoporos Int, 1998

Age and Hip Fracture Risk

0%

5%

10%

50 55 60 65 70 75 80 85

5-y

ear

fractu

re r

isk

Age

National Osteoporosis Foundation, Osteoporos Int, 1998

osteoporosis

falls

Drugs that treat osteoporosis will result in smaller reductions in relative risk but larger reductions in absolute risk in older vs younger patients.

Age 70 85

Fracture risk 1.5% 3%

Relative reduction 50% 30%

Absolute reduction 0.75% 1%

BMD and Fracture Risk in the Elderly

Conclusions:

• BMD is predictive of fracture risk in elderly women

• The relationship between BMD and fracture risk is strongly influenced by age

• Other risk factors (previous fractures, bone turnover, frailty) also affect fracture risk

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Strategies to Reduce Fracture Risk

• General measures

• Exercise

• Vision correction

• Good nutrition

• Calcium and vitamin D

• Adequate protein

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Therapy to Reduce Hip Fracture Risk

Calcium and vitamin D

• older adults are increasingly dependent upon adequate calcium and vitamin D intake

• vitamin D deficiency is very common among elderly, especially in those with hip fracture

• vitamin D deficiency is associated with muscle weakness and increased fall risk and well as accelerated bone loss

OOCChapuy MC et al. N EngI J Med 1992;327:1637-42

0

40

80

120

0 6 12 18

Number with New Fractures

PBOCa-D

3270 mobile elderly women (mean age

84±6 years) living in nursing homes

were randomly assigned to receive

1200 mg calcium daily in the form of

tricalcium phosphate plus vitamin D3

800 IU daily or double placebo

Most were vitamin D deficient

30% reduction in hip fractures at 18

months (43% in compliant subjects)

Months

P = 0.02

Calcium and Vitamin D

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Osteoporosis: Calcium and Vitamin D

• USA Institute of Medicine

• Calcium intake: 1200 mg total intake daily

• Vitamin D: Recommended intake: 800 IU daily

• For vitamin D, RDAs of 600 IU/d for ages 1–70 yr and 800 IU/d for ages 71 yr and

older, corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50

nmol/liter), meet the requirements of at least 97.5% of the population.

Ross AC et al. J Clin Endocrinol Metab 2011;96:53–8

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Strategies to Reduce Fracture Risk

• General measures• Exercise• Vision correction• Good nutrition

• Calcium and vitamin D• Adequate protein

• Pharmacological therapy for patients at high fracture riskIs this effective?

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Group 1

Low Bone Density

70-79 years old

Fem. Neck T-Score < -4**

or

Fem. Neck T-Score < -3**

plus >1 Risk Factor *

Group 2

Clinical Risk Factor

> 80 years old

no BMD requirement

> 1 Risk Factor *

or

Fem. Neck T-Score < -4**

HIP Trial: Inclusion Criteria

** based on manufacturer’s database

maternal hip fracture poor tandem gait

previous hip fracture difficulty standing

smoking recent falls

poor psychomotor skills

*

McClung et al, N Engl J Med 2001;344:333-40

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Patients Age 70-79 with low BMD

Number 5445Risk reduction % (CI) 40% (10, 60) p=0.009

0

2

4

6

% Patients with Hip Fracture

McClung M et al, NEJM 2001

Risedronate Therapy and Hip Fractures

Age >80 with Clinical Risk factors for Hip Fracture

3886

20% (-20,40) P = 0.35

70-79 80 and older

Placebo

Risedronate

HIP Study

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BMD: 3 Year Results in Hip

Control Risedronate 5mg

Femoral Neck BMD

Age 70-79 Age 80 and older-1

0

1

2

3

4%

ch

an

ge f

rom

baselin

e

McClung M et al, NEJM 2001

BMD responses were similar in younger and older patients

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Osteoporosis Status of Elderly HIP Subjects

FN BMD T-score

0

5

10

<-2.5 >-2.5 Unknown

These data suggest that most women in Group 2 did not have

osteoporosis.

% w

ith

Hip

Fra

ctu

re

McClung et al. N Engl J Med. 2001

70% of cohort

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Risedronate: Group 2 Subgroups

0

2

4

6

8

10

<-2.5 >-2.5 or Unknown

Incid

en

ce (

%)

Placebo

Relative Risk Reduction: 26% -8%

p value 0.37 NA

NNT 38

McClung et al. NEJM 2001BMD at Baseline

30/311 44/622 19/1002 38/1951

9.7%

7.2%

3.8% 4.0%

Women ages >80 with

> 1 RF for hip fracture

Retrospective analysis

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Zoledronic Acid and Fracture RiskPost-hoc Analyses in Patients Age 75 and Older

0

2

4

6

8

10

12

14

16

18

Clinical Fracture Non-vertebral Hip

Overall ≥75 Overall ≥75 Overall ≥75

28%

(-20%, 44%)

P = 0.297

Incid

en

ce a

t M

on

th 3

6 (

%)

41%

(17%, 58%)

P = 0.002

33%

(23%, 42%)

P < 0.001

35%

(22%, 46%)

P < 0.001

25%

(13%, 36%)

P <0.001

27%

(10%, 30%)

P = 0.002

Black DM et al. N Engl J Med 2007;356:1809-22Boonen S et al. J Am Geriatr Soc 2010;58:292–99

Placebo

Zoledronic acid

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Denosumab and Fracture RiskAnalyses in Patients Age 75 and Older

0

2

4

6

8

10

Vertebral Non-vertebral Hip

Overall ≥75 Overall ≥75 Overall ≥75

62%

(22%, 82%)

P = 0.0065

Incid

en

ce a

t M

on

th 3

6 (

%)

40%

(3%, 63%)

P = 0.04

68%

(59%, 74%)

P <0.001

64%

(47%, 75%)20%

(5%, 33%)

P = 0.01

16%

(-12%, 37%)

Pre-planned

Post-hoc

McClung MR et al. J Bone Miner Res. 2012;27:211-18.Boonen S, McClung M et al. J Clin Endocrinol Metab. 2011;96:1727-36

Placebo

Denosumab

Denosumab effective in subgroup

aged 75 years and older

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Denosumab FREEDOM StudyIncidence of Vertebral and Hip Fracture

RRR 61%

P < 0.0001

2.2% 0.9%

0

1

2

3

4

5

6

7

8

9

0-12 Months

Inc

ide

nc

e a

t M

on

th 3

6 (

%)

Placebo

Denosumab

0-24 Months 0-36 Months

5.0% 1.4% 7.2% 2.3%

RRR 71%

P < 0.0001

RRR 68%

P < 0.0001

Cummings SR, McClung MR et al. N Engl J Med 2009;361:756-65

Hip FractureVertebral Fracture

Cu

mu

lati

ve

in

cid

en

ce

-%

Month

Effect of fracture protection seen with in first 12 months of therapy

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Teriparatide and Abaloparatide in the Elderly

Boonen S et al. J Am Geriatr Soc 2006;54:782-9

Marcus R et al. J Bone Miner Res 2003;18:18-23

McClung MR et al. Menopause 2018;25:767-71

• Subgroup analyses suggest that the effectiveness of teriparatide and

abaloparatide on BMD or fracture risk is not affected by age

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Osteoporosis Treatment Among Nursing

Home Residents

Loh FE et al. Sr Care Pharm. 2019;34:109-26

• Among 96,408 women with osteoporosis in a Medicare database, with

osteoporosis, prevalence of evidence-based medication use was 42.3% in

2006 and dropped slightly to 40.4% in 2008.

• Long-term care residents were significantly less likely to use any

osteoporosis medication compared with community dwellers (40.6% vs.

53.1%).

• Bisphosphonates were the top choice among medication users, but were

prescribed much less often to long-term care residents (RR = 0.79, 95% CI

0.75-0.83) compared with community residents

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Osteoporosis Treatment Among Nursing

Home Residents

Zarowitz BJ et al. J Am Med Dir Assoc 2015;16:341-8

• Retrospective cohort analysis of nursing home residents in the Omnicare

Senior Health Outcomes (OSHO) data repository during the time period of

October 1, 2011, to September 30, 2012.

• A total of 23,666 (13.5%) had a coded diagnosis of osteoporosis

• mean age was 82.5 years

• 85.1% were female

• 89% met criteria for “high risk” based on age and history of falls or fracture

• 10.8% had hip fracture, and 15.8% had other fracture.

• Only ~1/3 of patients with osteoporosis received active treatment

• Treatment rates were similar between those with (31.7%) and without

(32.0%) a hip fracture

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Reducing Fracture Risk in the Oldest Old

• Fracture risk is high among very elderly patients

• General measures and fall prevention are important

• There is strong evidence that treatment with bisphosphonates

or denosumab is effective in these patients

• Few older patients receive osteoporosis therapy

• In ambulatory, functional elderly patients at high fracture risk

with life expectancy of > 6 months, pharmacological therapy

to reduce fracture risk should be a very high priority

McClung M. Personal opinion 2019

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Thank you

Michael R. McClung, MD, FACPOregon Osteoporosis Center

Portland, Oregon, USA

mmcclung.ooc@gmail.com