Dr Claire Higham 11.9.19 - PowerPoint Presentation

Slide1

Dr Claire

Higham

11.9.19

Consultant

Endocrinologist,

The

Christie Hospital NHS FTHonorary Senior Lecturer, University of Manchester

Can we prevent fractures in patients with cancer?

Slide2

Hormonal influences

o

estrogen

testosterone

growth hormoneglucocorticoids

Dietary influences

BMIcalciumvitamin Dmagnesium Microenvironmentgeneticscellular processesvascular supply

Macroenvironmentweight bearing exercisemuscle strength/torsionfalls risk

radiotherapy

t

umour cells

a

norexia and

cachexia

h

ormone antagonists

chemotherapy

Other Risk Factors

s

moking

a

lcohol

FHx

hip fracture

o

ther conditions

(

eg

RA/DM/IBD/OI)

Slide3

Hormonal influences

o

estrogen

testosteronegrowth hormone

glucocorticoids

Dietary influences

BMIcalciumvitamin Dmagnesium Microenvironmentgeneticscellular processesvascular supply Macroenvironment

weight bearing exercisemuscle strength/torsionfalls risk

radiotherapy

t

umour cells

a

norexia and

cachexia

h

ormone antagonists

chemotherapy

radiotherapy

chemotherapy

glucocorticoids

hormone

antagonists

anorexia/

cachexia

t

umour

cells

Slide4

Bone Mineral Density

Bone Mineralisation

Skeletal Growth and

DevelopmentFractures

Slide5

Not all fractures are the same !

Osteoporotic

Fragility Fracture

Pathological

Fracture

Pelvic InsufficiencyFracture

Slide6

Primary prevention

20% of people suffering a hip fracture will die within 12 months

50% of people suffering a hip fracture will not live independently

# in those >60 years account for 2 million hospital bed days in UK

Can we prevent a first fracture?

Slide7

Secondary prevention

prior vertebral fracture leads to 5x increase in future fracture

prior fracture (any site) leads to 2x increase in future fracture

Can we prevent further fracture?

Slide8

Primary and Secondary Prevention

Osteoporotic

Fragility Fracture

Cummings et al JAMA 2002: 288: 1889-1897

Slide9

Primary and Secondary Prevention

Osteoporotic

Fragility Fracture

Alendronate

FIT trialRisedronate

VERT trialIbandronate

BONE trialZoledronateHORIZON trialplacebobisphosphonate47%41%62%70%% patients with VF

Post menopausal femalesDenosumabTeriparatideBisphosphonate therapy

Slide10

Primary and Secondary Prevention

Osteoporotic

Fragility Fracture

Limitations of current data:

few studies have fracture as outcome

few studies in men, older frail, osteoporosisis exercise safe in osteoporosis ?is exercise safe following fracture?

does exercise prevent fracture ?Lifestyle : - exercise

Slide11

Primary and Secondary Prevention

Osteoporotic

Fragility Fracture

Limitations of current data:

few studies have fracture as outcome

few studies in men, older frail, osteoporosisis exercise safe in osteoporosis ? YESis exercise safe following fracture? YES

does exercise prevent fracture ? POSSIBLYLifestyle : - exercise

Slide12

Exercise and Fracture

Strong

Steady

Straight

exercise reduces falls risk

most NVF caused by falls

promoting bone strengthphysical activity: hip # risk BMD loss*Lack of evidence in elderly*reduce the risk and help symptoms of VF*Don’t know if exercise reduces the falls that cause fractures!*

STRONGSTEADYSTRAIGHT

Slide13

(8) Think about maximising bone health

Exercise, cancer and bone

BMD in ALL did not improve with 2 yr exercise program- poor compliance (Hartman et al 2009; 53(1):64-71) BMD in ALL improved with low magnitude high frequencymechanical stimulation

(Mogil et al 2016; 2(7): 908-914)

randomised, placebo controlled (n=48 completed)> 5yrs from diagnosis of childhood ALLZ-scores BMD <-1stim

placebo

Meanchange

SD

Mean

change

SD

P

Total body BMD

0.25

0.78

-0.19

0.79

0.05

QCT tibia

4.89

10.3

0.64

10.5

0.08

Slide14

(8) Think about maximising bone health

DXA femoral neck

DXA lumbar spine

Adults with OsteopeniaBreast Cancer all on AI/SERM’s

mean ages 46-62 yrs

Prostate Cancermean age 67-70 yrs

Exercise program 6- 24monthsresistance and impact exerciseaerobic exercisecombination (football!)87% retention“trend” for beneficial effect(resistance/impact exercise)FOOTBALL IS DANGEROUS (5 injuries) Exercise, cancer and bone

Slide15

(8) Think about maximising bone health

c

hildren and young adults poorly compliant to exercise studies

likely benefit to BMD from high frequency mechanical stimulationprior to attainment of peak bone mass – ? benefit in older adultsresistance and impact exercise likely most beneficial in adults - ? pre menopausal women benefit moreno fracture data (except that football increases the risk! - safety)no data beyond 48 months

data needed outside ALL, breast and prostate cancer

Exercise, cancer and bone

Slide16

Not all fractures are the same !

Osteoporotic

Fragility Fracture

Pathological

Fracture

Pelvic InsufficiencyFracture

Slide17

Pelvic Insufficiency Fractures

Slide18

Pelvic Insufficiency Fractures

Pain

Slide19

Pelvic Insufficiency Fractures

Pain

Anxiety

Slide20

Pelvic Insufficiency Fractures

Pain

Anxiety

Immobility

Slide21

20

4

0

6080100 %

PIF1992

19941996

200020022000200020052006200820082009

20102010201120122012

20132014

2014

2017

2017

2017

2018

2018

2019

2015

>

1020 PIF described

Pelvic Insufficiency Fractures are common

following pelvic radiotherapy

cervical/uterine

a

ll pelvic

rectal

prostate

chordoma

Higham CE, Faithfull

S.

Clin

Oncol

(R

Coll

Radiol

). 2015 Nov;27(11):

668-78 – updated 2019

Slide22

Pelvic Insufficiency Fractures

: hypothetical mechanisms

? benefit of lifestyle intervention – exercise (

prehabilitation)/nutrition/address risk factors

Slide23

p

rior to surgery

c

ancer n= 63prior to surgery non-cancer n= 55

Prehabilitation clinical trials

Slide24

p

rior to surgery

c

ancer n= 63prior to surgery non-cancer n= 55

n= 3

HSCT n= 3radiotherapy n= 1chemotherapy

Slide25

p

rior to surgery

c

ancer n= 63prior to surgery non-cancer n= 55

n= 3

HSCT n= 3radiotherapy n= 1chemotherapy n= 1pelvic radiotherapy

Slide26

p

rior to surgery

c

ancer n= 63prior to surgery non-cancer n= 55

n= 3

HSCT n= 3radiotherapy n= 1chemotherapy n= 1pelvic radiotherapy

recruitingcompleted

active, not recruitingnot yet recruiting

unknown

s

uspended/terminated

Slide27

Exercise

Nutrition

Psychological Interventions

Slide28

Exercise

Nutrition

Psychological Interventions

But :acceptable :

burden of responsibility burden of informationpatient experienceequitable

cost- effective safe

Slide29

Clinical Academic Research Partnership

Bone Toxicity following Pelvic Radiotherapy:

u

nderstanding, predicting and preventing radiotherapy related insufficiency fracturesrandomised

controlledfeasibility StudyMusculoskeletal Health Package

women undergoing pelvic radiotherapycervical and uterine cancer

Slide30

Clinical Academic Research Partnership

Bone Toxicity following Pelvic Radiotherapy:

u

nderstanding, predicting and preventing radiotherapy related insufficiency fracturesacceptability

safetyePROMs and

ePREMshealth economics

power for multicentre RCT

Slide31

Clinical Academic Research Partnership

Bone Toxicity following Pelvic Radiotherapy:

u

nderstanding, predicting and preventing radiotherapy related insufficiency fracturesfracture incidence

BMD and body composition6 minute walk test

stability and grip strengthbone turnover

Slide32

Summary

Multiple causes of poor bone health in cancer patients

Low BMD predisposes to fragility fracture

- post-menopausal women and older men - increased morbidity and mortalityNot all fractures are the same

- osteoporotic fragility fractures vs radiotherapy PIF Exercise can improve BMD, reduce falls risk, improve confidence

Prehabilitation studies mainly relate to surgery - 1 study concerning pelvic radiotherapy

- no bone outcomes in any prehab studyIs a musculoskeletal bone health package feasible, acceptable, cost-effective ?