Consultant Endocrinologist The Christie Hospital NHS FT Honorary Senior Lecturer University of Manchester Can we prevent fractures in patients with cancer ID: 908939
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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?
Slide2Hormonal 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)
Slide3Hormonal 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
Slide4Bone Mineral Density
Bone Mineralisation
Skeletal Growth and
DevelopmentFractures
Slide5Not all fractures are the same !
Osteoporotic
Fragility Fracture
Pathological
Fracture
Pelvic InsufficiencyFracture
Slide6Primary 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?
Slide7Secondary 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?
Slide8Primary and Secondary Prevention
Osteoporotic
Fragility Fracture
Cummings et al JAMA 2002: 288: 1889-1897
Slide9Primary and Secondary Prevention
Osteoporotic
Fragility Fracture
Alendronate
FIT trialRisedronate
VERT trialIbandronate
BONE trialZoledronateHORIZON trialplacebobisphosphonate47%41%62%70%% patients with VF
Post menopausal femalesDenosumabTeriparatideBisphosphonate therapy
Slide10Primary 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
Slide11Primary 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
Slide12Exercise 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
Slide16Not all fractures are the same !
Osteoporotic
Fragility Fracture
Pathological
Fracture
Pelvic InsufficiencyFracture
Slide17Pelvic Insufficiency Fractures
Slide18Pelvic Insufficiency Fractures
Pain
Slide19Pelvic Insufficiency Fractures
Pain
Anxiety
Slide20Pelvic Insufficiency Fractures
Pain
Anxiety
Immobility
Slide2120
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
Slide22Pelvic Insufficiency Fractures
: hypothetical mechanisms
? benefit of lifestyle intervention – exercise (
prehabilitation)/nutrition/address risk factors
Slide23p
rior to surgery
c
ancer n= 63prior to surgery non-cancer n= 55
Prehabilitation clinical trials
Slide24p
rior to surgery
c
ancer n= 63prior to surgery non-cancer n= 55
n= 3
HSCT n= 3radiotherapy n= 1chemotherapy
Slide25p
rior to surgery
c
ancer n= 63prior to surgery non-cancer n= 55
n= 3
HSCT n= 3radiotherapy n= 1chemotherapy n= 1pelvic radiotherapy
Slide26p
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
Slide27Exercise
Nutrition
Psychological Interventions
Slide28Exercise
Nutrition
Psychological Interventions
But :acceptable :
burden of responsibility burden of informationpatient experienceequitable
cost- effective safe
Slide29Clinical 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
Slide30Clinical 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
Slide31Clinical 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
Slide32Summary
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 ?