2019 bone curriculum symposium - na-admin.eventscloud.com

Evelien Gielen, MD PhDDepartment of Geriatric Medicine & Centre for Metabolic Bone Diseases, UZ Leuven

Fracture prevention in the very elderly

2019 Bone Curriculum SymposiumLa Hulpe, 16th of March, 2019

2017

83.7 years

79.0 years

2060

88.8 years

86.2 years

https://statbel.fgov.be/nl/themas/bevolking/sterfte-en-levensverwachting/sterftetafels-en-levensverwachting

Life expectancy at birth in Belgium

Age-related exponential increase in fracture incidence

Sambrook. Lancet 2006; 367: 2010-2018

Age- and sex-specific incidence of hip, radiographic vertebral and distal forearm fractures

Epidemiology of fragility fractures in the very elderly

In ♀, 30% of all fragility fractures occur after 80 years 1

In ♀, 60% of hip fractures occur after 80 years 1,2

Prevalence of vertebral fractures in ♀

19% at 75-80y 22 % at 80-85y > 40% at ≥ 85y 3

By age 90 years, ~ 30% of ♀ and 17% of ♂ have had a hip fracture 4,5

Remaining lifetime risk at 80 years:

∙ Any fracture 6 ∙ Hip fracture 6

28.6% in ♀ 12.3% in ♀

9.6% in ♂ 3.7% in ♂

1Sanders. Med J Aust 1999; 170: 467-470; 2Chevalley. Bone 2007; 40: 1284-1289; 3Grados. Bone 2004;34: 362-367; 4Veronese. Injury 2018; 49: 1458-1460; 5Gallagher. Clin Orthop Relat Res 1980; 150: 163-71; 6Van Staa. Bone 2001. 29, 517-22

Age-related increase in osteoporotic fracture risk

Prevalence of osteoporosis increases with age

Kanis. WHO Scientific Group Technical Report 2007, University of Sheffield, UK

Estimated prevalence of osteoporosis (%) by age and gender,based on six population-based cohort studies in men and women.

Women

Men

Rate of falling increases with age

25%

15%

Rate of self-reported falling in the past 6 months by age, community-dwelling elderly > 65 years.Franse.

BMJ Open 2017; 7: e015827

Overview

1. Should all very eldery persons receive calcium and vitamine D?

2. Are antiresorptives and anabolics safe and effective at very high age?

3. Does it make sense to initiate OP treatment at very high age?

4. Which excercise therapy should we recommend to the oldest old?

5. Other issues in the very elderly with osteoporosis


Calcium Recommended dietary allowance (mg/day)

Upper level intake(mg/day)

51-70 years ♂51-70 years ♀

10001200

20002000

> 70 years 1200 2000

IOM Report 2011

Dietary reference intake for calcium and vitamin D

Vitamin D Recommended dietary allowance (IU/day)

Upper level intake(IU/day)

51-70 years ♂51-70 years ♀

600600

40004000

> 70 years 800 4000

Total = dietary + supplemental intake

= needed to achieve optimal serum 25OHD level (20 ng/ml = 50 nmol/l)

Age-related deficiency ofcalcium and vitamin D

Negative calcium balance in the elderly

Elderly are more vulnerable to calcium and vitamin D deficiency

A decrease in dietarycalcium intake

A decrease in intestinalabsorption of calcium

Less frequent exposure to sunlight

A decrease in thecapacity of the skin to

synthesize vitamin D

Lower circulating levels 1.25(OH)2D:- Reduced renal hydroxylation of

25OHD to 1.25(OH)2D in CKD- Increased catabolism of

1.25(OH)2D (↑ renal CYP24A1)

Veldurthy. Bone Research 2016; 4, 16041

Lower renal calcium reabsorption efficacy

Intestinal resistance to 1.25(OH)2D

Amorin. Eur J Clin Nutr 1996; 50: S577-S585; Lips. Endoc Rev 2001; 22: 477-501

Elderly are more vulnerable to calcium and vitamin D deficiency

Dietary Ca intake of elderly (75-80y) in 10European countries (in percentiles P10 and P90)

In 1/3: very low dietary Ca intake:- 300-600 mg/day in ♀- 350-700 mg/day in ♂

Serum 25(OH)D by age and functional status

Gradual decline of serum 25(OH)D from healthy adults to independent elderly, institutionalized elderly and

hip fracture patients

Thus, which very elderly should receive calcium and vitamin D?

Calcium and vitamin D supplementation is recommended for 1,2:

• Patients at high risk of calcium and vitamin D deficiencyo Institutionalized, frail or functional dependent elderly

• Patients with osteoporotic fractures

1Harvey. Osteoporos Int 2017; 28: 447-62; 2Kanis. Osteoporos Int 2019; 30: 3-44

Overview







Evidence of anti-fracture efficacy of OP treatment comes mainlyfrom RCTs in women with a mean age of 70-75 years

Evidence in (very) elderly is mostly based on post-hoc subgroupanalyses* of the landmark osteoporosis trials in postmenopausal♀

Evidence for the efficacy of osteoporosis treatment in the very elderly

* (4) Ensrud. Arch Int Med 1997; 157: 2617-2624; (5) Hochberg. J Bone Miner Res 2005; 20: 971-973; (6) Axelsson. ASBMR Annual Meeting; Atlanta 2016; (8) McClung. 2001; 344:333-340; (9) Boonen. JAGS 2004; 52: 1832-1839; (12) Boonen. JAGS 2010; 58: 292-299; (14) Boonen. J Clin Endocrinol Metab. 2011; 96: 1727-1736; (15) McClung. J Bone MinerRes 2012; 27: 211-218; (18) Seeman. J Bone Miner Res 2006; 21: 1113-1120; (19) Seeman. Bone 2010; 46:1038-1042; (21) Boonen. JAGS 2006; 54: 782-789.

Summary of efficacy of osteoporosis treatment in the very elderly

Gielen. Calcif Tissue Int. 2017; 101: 111-131; Gielen. Encyclopedia Endocrine Disease, 2nd Edition, p748-757

Vertebral fractures Hip fracturesNon-vertebral

fracturesConclusion

Alendronate RR = 0.62 (4)

RR 0.55 (constant RR) (5)

HR = 0.72 (6)


- - Proven hip and vertebralfracture reduction- ↑ ARR with ↑ age

Risedronate HR = 0.56 (9) RR = 0.8 (8) 10.8% (Ris) vs. 11.9%; NS (8)

14.0% (Ris) vs. 16.2%; NS (9)

≠ Vertebral vs. hip/non-vertebral:- BP do not impact on non-skeletal RF for # (impaired gait,...)- Insufficient power in older age

Zoledronic acid HR = 0.34 (12) HR = 0.82; pinteract age SS (12) HR = 0.73 (12) No effect on hip #:

- Greater influence of non-

skeletal RF for hip # with ↑ age

- Sample size not powered to

detect hip # RR in older age

Denosumab RR = 0.36 (15) 0.9% (Dmab) vs. 2.3% (14) RR = 0.84; pinteract age NS (15) Effective treatment in elderly

~ distinct effect on cortical bone?

(Strontium

ranelate)

RR 0.68 (18)

RR 0.69 (19)

RR 0.68 (18)

RR 0.76 (19)

RR 0.69 (18)

RR 0.73 (19)

↑ cardiac events => withdrawel

August 2017

Teriparatide RR = 0.35 (21) - RR = 0.75 (21) Not powered to show SS RR in

non-vertebral fracture in old age

(4) Ensrud. Arch Int Med 1997; 157: 2617-2624; (5) Hochberg. J Bone Miner Res 2005; 20: 971-973; (6) Axelsson. ASBMR Annual Meeting; Atlanta 2016; (8) McClung. 2001; 344: 333-340; (9)Boonen. JAGS 2004; 52: 1832-1839; (12) Boonen. JAGS 2010; 58: 292-299; (14) Boonen. J Clin Endocrinol Metab. 2011; 96: 1727-1736; (15) McClung. J Bone Miner Res 2012; 27: 211-218; (18)Seeman. J Bone Miner Res 2006; 21: 1113-1120; (19) Seeman. Bone 2010; 46:1038-1042; (21) Boonen. JAGS 2006; 54: 782-789.

Treatment effect of Alendronate from a geriatric perspective

Vertebral fractures

All Age < 75y Age ≥ 75y

Post hoc analysis FIT Vertebral Fracture ArmN = 2027; 55-82 years (n = 539; 75-82 years)

Ensrud. Arch Intern Med 1997; 157: 2617-2624; Hochberg. J Bone Miner Res 2005; 20: 971-973

0

0.4

0.2

0.8

0.6

1.0

Rel

ativ

eri

sk

RR 0.53 RR 0.49; RR 0.6295% CI 0.35-0.68 95% CI 0.41-0.94

NNT = 9 NNT = 8pinterteract < 75 and ≥ 75y > 0.48

RRR 47% RRR 51% RRR 38%

Pooled analysis FIT I and IIN= 3658; 55-80 years

Even

ts p

er 1

0.0

00

PYR

50

100

150

200

Vertebral fractures

55 65 75 85

PlaceboRisedronate

RR 0.55; 95% CI 0.37-0.83 (constant over age groups)

ARR (♀ with fractures per 10.000 PYR)[55- < 65y] = 15 [75-85y] = 75

PlaceboZoledronic acid

HR = 0.82; 95% Cl 0.56-1.20

3

0

1

2

4

2.8%3.6%

NS; p = 0.297

Boonen. J Am Geriatr Soc 2004; 52: 1832-1839; Boonen. J Am Geriatr Soc 2010; 58: 292-299

Even

t ra

te(%

) o

f n

ew f

ract

ure

s

Treatment effect of Risedronate & Zoledronic acid from a geriatric perspective

Post hoc pooled analysis of HORIZON-PFT & Horizon-RFTN = 3888; ≥ 75 years mean age 79.4 years

p interact < 75 and ≥ 75y < 0.04

Hip fracturesNon-vertebral fractures

15

0

5

10

20NS; p = 0.66

Inci

den

ce(%

) o

f n

ew f

ract

ure

s

16.2% 14.0%

Post hoc pooled analysis of VERT-NA, VERT-MN & HIPN = 1392; ≥ 80 yearsmean age 83 years

PlaceboRisedronate

Summary of efficacy of osteoporosis treatment in the very elderly

Gielen. Calcif Tissue Int. 2017; 101: 111-131; Gielen. Encyclopedia Endocrine Disease, 2nd Edition, p748-757

Vertebral fractures Hip fracturesNon-vertebral

fracturesConclusion

Alendronate RR = 0.62 (4)


HR = 0.72 (6)


- - Proven hip and vertebralfracture reduction- ↑ ARR with ↑ age

Risedronate HR = 0.56 (9) RR = 0.8 (8) 10.8% (Ris) vs. 11.9%; NS (8)

14.0% (Ris) vs. 16.2%; NS (9)

≠ Vertebral vs. hip/non-vertebral:- BP do not impact on non-skeletal RF for # (impaired gait,...)- Insufficient power in older age

Zoledronic acid HR = 0.34 (12) HR = 0.82; pinteract age SS (12) HR = 0.73 (12) No effect on hip #:

- Greater influence of non-

skeletal RF for hip # with ↑ age

- Sample size not powered to

detect hip # RR in older age

Denosumab RR = 0.36 (15) 0.9% (Dmab) vs. 2.3% (14) RR = 0.84; pinteract age NS (15) Effective treatment in elderly

~ distinct effect on cortical bone?

(Strontium

ranelate)

RR 0.68 (18)

RR 0.69 (19)

RR 0.68 (18)

RR 0.76 (19)

RR 0.69 (18)

RR 0.73 (19)

↑ cardiac events => withdrawel

August 2017

Teriparatide RR = 0.35 (21) - RR = 0.75 (21) Not powered to show SS RR in

non-vertebral fracture in old age

(4) Ensrud. Arch Int Med 1997; 157: 2617-2624; (5) Hochberg. J Bone Miner Res 2005; 20: 971-973; (6) Axelsson. ASBMR Annual Meeting; Atlanta 2016; (8) McClung. 2001; 344: 333-340; (9)Boonen. JAGS 2004; 52: 1832-1839; (12) Boonen. JAGS 2010; 58: 292-299; (14) Boonen. J Clin Endocrinol Metab. 2011; 96: 1727-1736; (15) McClung. J Bone Miner Res 2012; 27: 211-218; (18)Seeman. J Bone Miner Res 2006; 21: 1113-1120; (19) Seeman. Bone 2010; 46:1038-1042; (21) Boonen. JAGS 2006; 54: 782-789.

FREEDOMN = 7808

60-90 y, mean age 72.3 y

Overall population

2.3%

0.7%0.9%

1.2%

Inci

de

nce

of

frac

ture

s (%

)

0

1

2

3

RRR 40%p = 0.04

RRR 62%p = 0.007

High risk criterion: ≥ 75 years

Placebo

Denosumab

Cummings. N Engl J Med 2009; 361: 756-765; Boonen. J Clin Endocrinol Metabol 2011; 96:1727-1736

Post hoc analysis of FREEDOM N = 2471

≥ 75 y, mean age 78.2 y

Treatment effect of Denosumab from a geriatric perspective

p interact < 75 and ≥ 75y = NS

Hip fractures

RR = 0.60; 95% CI 0.37-0.97 RR = 0.38

29-year old woman 63-year old woman 90-year old woman

Cortical porosity increases with age after menopause

Zebaze. Lancet 2010:9727:17291736

Summary of safety of osteoporosis treatment in the very elderly

Gielen. Clin Interv Aging 2017; 12: 1065-1077(9) Boonen. JAGS 2004; 52: 1832-1839; (12) Boonen. JAGS 2010; 58: 292-299; (14) Boonen. J Clin Endocrinol Metab. 2011; 96: 1727-1736; (21) Boonen. JAGS 2006; 54: 782-789.

Adverse eventRisedronate (9) Zoledronic acid (12) Denosumab (14) Teriparatide (21)

Placebo RIS p-value Placebo ZOL p-value Placebo Dmab p-value Placebo TPT p-value

≥ 1 adverse event 89.7% 90.9% NS 91.8% 92.6% .34 93.0% 93.4% .86 91% 83% NSNausea 8.3% 9.4% NS 5.9% 7.5% .05 9% 8% NSDyspepsia 6.8% 6.8% NS 5% 4% NSAbdominal pain 7.7% 8.2% NS 13% 6% NSDiarrhea 5.6% 6.8% .11 3% 10% NSConstipation 9.1% 8.2% .46Oesophagitis 1.3% 1.7% NSStomach ulcer 1.0% 1.4% NSAE’s within 3 days 25.7% 41.5% <.001Pyrexia 4.0% 12.1% <.001Myalgia 3.1% 8.6% <.001Influenza-like illness 2.1% 5.2% <.001Bone pain 1.5% 4.3% <.001Chills 0.6% 3.5% <.001Arthralgia 19.7% 20.3% .63 10% 8% NSBack pain 21.4% 21.6% .94 25% 15% SSLeg cramps 2% 2% NSHeadache 6.1 7.7 .07 5% 6% NSDizziness 7.1% 7.2% >.99 8% 9% NSHypertension 12.4% 12.8% .70 11% 9% NSCataract 5.7% 6.8% .16 10% 2% SSDeafness 3% 1% NSPruritus 5% 0% SSWeight loss 5% 2% NSIncrease creatinine > 0.5 mg/dl 3.5% 4.7% .08Atrial fibrillation 3.3% 3.5% .72Any serious AE 37.9% 37.5% .82 30.2% 30.0% .76Death 7.1% 5.7% .276 7.5% 7.0% .58 4.1% 3.2% .18Withdrawals due to AEs 20.3% 20.6% .947Dermatitis, eczemaDVTSeizures disorders

Specific issues in the (very) elderly

Comorbidity (CKD, dementia, …)

Polypharmacy

Low compliance

Thus, are antiresorptives and anabolics safe & effective at very high age?

Yes, osteoporosis treatment in the very elderly• reduces the risk of fractures, at least in older individuals with documented

osteoporosis, and for vertebral fractures and possibly also for hip fractures

• may be even more effective in frail elderly who have a higher baseline risk

• appears relatively safe

However• specific issues should be taken into account in the elderly and may influence

the choice of therapy (comorbidity, polypharmacy, non-compliance)

Overview







Anti-fracture efficacy Type of vertebralfracture

% RRR

1 yearfracture rate

(R/ vs placebo)

RR; 95% CI

Alendronate (FIT I+II) clinical 59% n.a. 0.41

Risedronate (Vert-NA) morphometric 65% 2.4% vs 6.4% 0.35; 95% CI 0.19-0.62

Zoledronic acid (HORIZON) morphometric 60% 1.5% vs 3.7% 0.40

Denosumab (FREEDOM) morphometric 61% 0.8% vs 2.2% 0.39

Black. J Clin Endocrinol Metab 2000; 85: 4118-4124; Harris. JAMA 1999; 282: 1344-1352;Black. N Engl J Med 2007; 356: 1809-1822; Cummings. N Engl J Med 2009; 361: 756-765http://statbel.fgov.be

Onset of anti-fracture efficacy vs life expectancy

Remaining life expectancy in Belgium

Birth 55 years 65 years 75 years 85 years 95 years

Men 77.94 25.19 17.26 10.42 5.17 2.34

Women 82.93 29.29 20.68 12.72 6.29 2.88

n.a. = not available

Black. J Clin Endocrinol Metab 2000; 85: 4118-4124; Harris. JAMA 1999; 282: 1344-1352;Black. N Engl J Med 2007; 356: 1809-1822; Cummings. N Engl J Med 2009; 361: 756-765http://statbel.fgov.be

n.a. = not available

Onset of anti-fracture efficacy vs life expectancy

Anti-fracture efficacy Type of fracture % RRR

fracture rate(R/ vs placebo) at 18 or 36 months

RR; 95% CI

Alendronate (FIT I+II) Hip 63% 18 months; n.a. 0.37

Risedronate (Vert-NA) Non-vertebral 39% 3y; 5.2% vs 8.4% 0.6; 95% CI 0.39-0.94

Zoledronic acid (HORIZON) Hip 41% 3y; 1.4% vs 2.5% 0.59; 95% CI 0.42-0.83

Denosumab (FREEDOM) Hip 40% 3y; 0.7% vs 1.2% 0.60; 95% CI 0.37-0.97

Remaining life expectancy in Belgium

Birth 55 years 65 years 75 years 85 years 95 years

Men 77.94 25.19 17.26 10.42 5.17 2.34

Women 82.93 29.29 20.68 12.72 6.29 2.88

Thus, does it make sense to initiate OP treatment at very high age?

Yes, if life-expectancy is > 1 year and certainly when > 3 years

Blain. J Nutr Health Agin 2016. 20: 647-652

Overview



3. Who should receive osteoporosis (OP) treatment?




Physical exercise therapy in adults > 50 years

Daly et al. Climacteric 2017; 20: 119-24

(Mild to moderate) impact training• can preserve or improve LS and FN BMD• impact ~ gait speed > 6.14 km/h

Progressive resistance training• conflicting results• target muscles attached

to/near spine/hip• loads < 80% of 1 RM:

generally ineffective

Exercise group (EG) Control group (CG) Mean change (%)

(in-groupdifference)

P-value(in-groupdifference)

P-value(betweengroupdifference)

De Jongh 2000

N=143mean age: 79y17 weeks

Supervised strength, endurance, coordinationand flexibility training2x/week, 45 min

No exercises BMD total bodyEG: 0.000%CG: -0.003%

NRNR

0.99

Santin-Medeiros2015

N=37mean age:

82.3y (EG) 82.2y (CG)

8 months

WBV training2x/week

No exercises BMD FNEG:-1.75%CG: -2.71%

BMD total hipEG: -2.88%CG: -4.32%

0.3430.162

0.3150.152

NR

NR

Verschueren 2011

N=113mean age: 79.6y6 months

-WBV training3x/week, 15 min-Vit D

-No exercises

-Vit D

BMD total hipEG: +0.75%CG: +0.88%

<0.001NR

0.949

Villareal2004

N=112mean age: 83y9 months

-Supervised resistanceand endurance exercises3x/week, 90-120 min-Ca/D

-Home-exercises(flexibilitly, balanceand coordination)-Ca/D

BMD FN: NRBMD total hip: NR

BMD LS: NR

NRNRNR

0.080.580.65

De Jongh. Am J Public Health 2000; 90: 947-954; Santin-Medeiros. Nutr Hosp 2015; 31: 1654-1659; Verschueren. JBMR 2011; 26: 42-49; Villareal. Am J Clin Nutr 1991; 53: 1304-1311

WBV = whole-body vibration; NR = not reported

Efficacy of physical exercise therapy in the very elderly

Efficacy of physical exercise therapy in the very elderly

8 wks PRT in 10 elderly > 90y• 3x/week, 3 sets of 8 repetitions, 80% of 1 RM

o 9% ↑ quadriceps sizeo 150% ↑ muscle strengtho 50% ↑ gait speed

8 wks PRT in 40 elderly > 90y (90-97y)• 3x/week, 2-3 sets of 8-10 repetitions, load

gradually increased from 30% 70% of 1 RMo 1 RM leg press ↑ with 10.6 kg (CI 4.1-17.1; p=.01)

Fiatarone. JAMA 1990; 263: 3029-34; Serra-Rexach. JAGS 2011; 59: 594-602

Thus, which exercise therapy should we recommend to the oldest old?

With increasing age, the emphasis of exercise shouldswitch gradually from bone loading to muscle loading

Exercises to improve balance and coordination

Avoid explosive or high-impact loading

https://www.iofbonehealth.org/exercise-recommendations; Pfeifer. JBMR 2004; 19: 1208-1214

Overview



3. Who should receive osteoporosis (OP) treatment?




Falls and fall prevention in the very elderly with osteoporosis

“The fall prevention program was successful, but then she slippedon the tube of supplements that had fallen on the ground”

• Every year, 30% of community-dwelling elderly > 65y falls 50% in those > 80y

• Institutionalized elderly are 3x likely to fall than those in the community

• 10% of falls result in a fracture; 2% in a hip #

• 90% of hip fractures are the result of a fall

Franse. BMJ Open 2017; 7; e015827; Blain. J Nutr Health Aging 2016; 20: 647-652

FRAX Garvan Qfracture-2016

Age Yes, 40-90y Yes, 50-96y Yes, 30-99y dementia

cancer

astma/COPD

heart attack, angina, stroke, TIA

chronic liver disease

chronic kidneydisease (stage 4/5)

Parkinson’s disease

malbsorption (Crohn, CU, …)

endocrine problem(hyperT,, Cushing, hyperparaT.)

Gender Yes Yes Yes

Height Yes Yes Yes

Weight Yes Yes Yes

Previous fracture Yes Yes, since 50y

(0, 1, 2, ≥ 3 #)

Yes, fracture of wrist, hip,

spine or shoulder

Parenteral hip fracture Yes No Yes, or osteoporosis

Smoking Yes, current No Yes, non-smoker, ex-smoker,

light (< 10), medium(10-19), heavy (≥ 20)

Glucocorticoid use Yes, currently or previously

prednisolone ≥ 5mg/d > 3mo

No Yes, taking steroid tablets

regularly

Rheumatoid arthritis Yes No Yes, or SLE

Secondary osteoporosis Yes No

Alcohol Yes, > 3 units daily No Yes, none, < 1 unit/d,

1-2, 3-6, 7-9, > 9/d

epilepsy or takinganticonvulsants

takingantidepressants

taking oestrogen onlyHRT

Femoral neck BMD Yes Yes No

History of falls No Yes, last 12 mo

(0, 1, 2, ≥ 3 falls)

Yes

Living in nursing home No No Yes

HR for fractures Major osteoporotic #

Hip fracture

Falls, adj. for FRAX 1.51 (1.29-1.77) 1.54 (1.21-1.95)

Falls, adj. for FN BMD 1.58 (1.35-1.85) 1.64 (1.29-2.08)

• Data are hazard ratios (95% CI) adjusted for age and time since baseline• Meta-analysis of MrOS (N=7857, ≥ 65y)

Falls predict fractures independently of FRAX and BMD

Harvey. J Bone Miner Ras 2018; 33: 510-516; Yu . J Am Dir Assoc 2014; 15: 551-558

Elderly at high risk of future falls:

• previous fall in the last 12 months

• fear of falling or significant gait, muscle strength or balance problems

Should receive CGA to determine their individual medical, functional and psychosocial concerns that contribute to fall risk

Multifactorial treatment plan should be initiated

Blain. J Nutr Health Aging 2016; 20: 647-652

Fall and fracture prevention in the very elderly with osteoporosis

Combination of fracture liaison services (FLS) and geriatric medicine services


Conclusion

In the very elderly,

1. Calcium and vitamin D supplementation is recommended in frail orinstitutionalized patients and patients with osteoporotic fractures

2. Osteoporosis treatment reduces the risk of fractures, at least forvertebral fractures and possibly also for hip fractures

3. Osteoporosis treatment should be initiated when life expectancy > 1 year

4. Emphasis of exercise therapy lies on muscle loading and balance training

5. Fracture prevention in very elderly with OP and high fall requires FLStogether with mutifactorial interventions based on CGA

~ postmenopausal population Extra/different in (very) elderly

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