Transcript Bone Health - Tackle Prostate Cancer

It takes more than
milk to improve bone
health!!
Lawrence Drudge-Coates
Urological Oncology Clinical Nurse Specialist & Hon Lecturer
King’s College Hospital NHS Foundation Trust, London, UK.
Functions of bone
Structural support
Production of blood cells
For heart, lungs and marrow
Red bone marrow produces blood
cells in a process known as
haematopoiesis
Protection of internal
organs
From mechanical damage,
particularly the brain, heart and
lungs
Attachment of muscles
Bones act as levers for muscles,
allowing voluntary movement
Storage of fatty acids
Yellow bone marrow contains a reserve
of fat for consumption during starvation
states
Acid-base balance
Bone buffers the blood against excessive
pH changes by absorbing or releasing
alkaline salts
Mineral storage
The skeleton is the largest depot for
minerals in the body; 99% of calcium,
85% of phosphorus and 50% of
magnesium are stored in the bones
EAUN E-learning course (2013): www.uroweb.org/nurses/educational-resources-for-nurses
Detoxification
Bone tissues can store heavy metals,
such as lead, which can be gradually
released and excreted
Normal Bone Health
For normal bone health – a process called
remodeling is required……
To cope with constant mechanical stress
To repair tiny fractures (Micro-fractures)
Ensures skeletal integrity
Maintains mineral homeostasis
Regulated by cytokines & systemic
hormones!!!
Continuous throughout life!!
EAUN E-learning course (2013): www.uroweb.org/nurses/educational-resources-for-nurses
Bone Remodeling……….
Maintained by tightly coupled programmed
balance between osteoblastic and osteoclastic
cellular activity.
Key cells …..
 Osteoblasts: cells that produce bone
 Osteoclasts: cells that break down bone
(Bone resorption)
Bone Remodeling - Maintaining the integrity of bone
“The Osteoblast & Osteoclast”
Resorption
30 - 43
days
Activation
Osteoclasts
Reversal
Resting
Apoptotic Osteoclasts
Stromal
Stromal
andand
bone
bone
lining
lining
cellscells
Formation
Preosteoblasts
Osteoblasts
90 -145
days
Mineralization
Osteoid
Adapted from Baron R. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 5th ed. 2003;1-8.
Raisz LG. J Clin Invest. 2005;115:3318-3325. Eriksen EF, Axelrod DW, Melsen F. Bone Histomorphometry. New York, NY:Raven Press; 1994:13-14.
Cancer Therapy Induced Bone
Loss (CTIBL)
In Prostate Cancer……………
ADT therapy in Prostate Cancer
Indications for ADT
Metastatic disease
Locally advanced disease
(T3-T4 stage)
• N+, M0 stage: Standard
adjuvant therapy in more than 2
positive nodes to radiation
therapy or radical prostatectomy
as primary local therapy
• Symptomatic patients
• M+ stage: Standard option;
mandatory in symptomatic
patients
• PSA-Doubling Time (DT)
<1 yr
• Extensive T3-T4 disease
• High PSA level
(>25-50 ng/mL)
• As concomitant/adjuvant
treatment (3 years) to radiation
treatment; shown to have a
survival advantage for risk
patients
Selected patients with
localised disease:
(T1a –T2c stage)
• Symptomatic patients, who need
palliation of symptoms, unfit for
curative treatment
• For high-risk patients,
neoadjuvant hormonal treatment
and concomitant hormonal
therapy plus radiotherapy result
in increased overall survival
ADT, androgen deprivation therapy; PSA, prostate-specific antigen
1 Mottet N et al. EAU guidelines on prostate cancer. 2014 . http://www.uroweb.org/guidelines/online-guidelines: (last accessed 4/2014)
So which treatments are we looking at ?
Prostate cancer
Androgen deprivation
therapy (ADT):
 LHRH injections
− Leuprolide
− Goserelin
− Triptorelin
 Orchidectomy
Pathophysiology of cancer treatment
induced bone loss – in Prostate Cancer
=
European Association of Urology Nurses : e-learning course: Bone Health and Urological Cancer 2012.
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The problem however exists before ADT is
started….
Prevalence of Osteoporosis at Baseline and Under ADT in Prostate Cancer: Cross-Sectional Data
Duration of ADT
(yr)
Patients (%)
Osteoporosis
Osteopenia
Normal
None
35.4
45.2
19.4
2
42.9
39.3
17.8
4
49.2
34.4
16.4
6
59.5
29.7
10.8
8
65.7
28.5
5.7
10
80.6
19.4
0
Morote J, et al. Urology. 2007;69:500-504.
Bone loss in men and women at 1 year
Bone loss due to hormone
ablation therapy
10
Bone loss at 1 year (%)
8
6
7.4%
7.7%
♂
Naturally occurring bone
loss
4.6%
4
♂
2.6%
2%
2
0.5%
1%
0
Normal men
Postmenopausal
women
Menopausal
women
AI therapy
postmenopause
Androgen
deprivation
therapy in men
AI therapy +
GnRH agonist
premenopause
Higano CS. Nat Clin Pract Urol 2008;5:24-34; Eastell R, et al. J Bone Miner Res 2006;21:1215-23; Maillefert JF, et al.J
Urol 1999;161:1219-22; Gnant M, et al. Lancet Oncol 2008;9:840-9; Shapiro CL, et al. J Clin Oncol 2001;19:3306-11.
Premature
menopause
secondary to
chemotherapy
Fracture rate per person per year (%)
ADT consistently increases fracture risk in
men with prostate cancer
19.4
20
17.2
18
16
14
12
12.7
12.6
10
No ADT
ADT
7.9
8
6.5
6
4
2
0
Shahinian 20051
(1–5 year)
Smith 20062
(> 12 year)
Alibhai 20103
(6.7 year)
1.
Shahinian VB et al. N Engl J Med 2005;352:154–64. 2. Smith MR et al. J Clin Oncol
2005;23:7897–903. 3. Alibhai SMH et al. J Urol 2010;184:918–24.
ADT, androgen-deprivation therapy
Effects of osteoporosis:
Vertebral and hip fractures
Osteoporotic
compression
fractures
Osteoporotic
compression
fracture with
‘wedge’ deformity
EAUN e-learning bone health course 2013.
Available at: http://www.uroweb.org/nurses/educational-resources-for-nurses/
Osteoporotic
fracture of the
left femur
Hip Fractures Impact Mortality and Life
Expectancy
• 1-2 yr mortality in men is ~ 30% to 38% [1-3]
• Hip fracture affects life expectancy
dramatically[4,5]
• Aged 60-69 yrs: 11.5 yrs of decreased life expectancy
• Aged 70-79 yrs: 5.0 yrs of decreased life expectancy
1. Forsen L, et al. Osteoporosis Int. 1999;10:73-78. 2. Schurch MA, et al. J Bone Miner Res. 1996;11: 1935-1942. 3.
Soderqvist A, et al. Gerontology. 2009;55:496-504. 4. Cree M, et al. J Am Geriatr Soc. 2000;48:283-288. 5. Center JR, et al.
Lancet. 1999;353:878-882.
NICE Guidelines (2014) :
Prostate cancer: diagnosis and management
Osteoporosis 1.4.12:
Do not routinely offer bisphosphonates to prevent osteoporosis in men
with prostate cancer having androgen deprivation therapy.
1.4.13
• Consider assessing fracture risk in men with prostate cancer who are
having androgen deprivation therapy, in line with Osteoporosis (NICE
clinical guideline 146) Consider measuring BMD with DXA before starting treatments that may
have a rapid adverse effect on bone density (for example, sex hormone deprivation for treatment for
breast or prostate cancer).
1.4.14
• Offer bisphosphonates to men who are having androgen deprivation
therapy and have osteoporosis.
1.4.15
• Consider denosumab for men who are having androgen deprivation
therapy and have osteoporosis if bisphosphonates are contraindicated or
not tolerated.
Clinical guideline Published: 8 January 2014 nice.org.uk/guidance/cg175. www.nice.org.uk/guidance/cg175/resources/prostate-cancer-diagnosisand-management-35109753913285 - access 3/11/2015.
Metabolic changes from ADT….
• Weight gain (2.4% gain)
• More fat Mass (10% up)
• Muscle loss (3% decline)
• Insulin resistance (26-65% higher fasting)
• Triglycerides (26% increase)
• Cholesterol (10% increase)
Choi M . Korean J Urol. 2015 Jan; 56(1): 12–18.
Assessment tools
Establish patient
history
Bone mineral
density (BMD)
WHO/Fracture Risk
Assessment
Dual energy X-ray
absorptiometry
(DEXA) scanning
FRAX: 10-year
fracture probability
WHO Fracture Risk Assessment tool. Available at:
http://www.shef.ac.uk/FRAX (Accessed Aug 2014).
Assessment and monitoring
Nurses have a key role
in fracture risk assessment
Comorbidities
Fracture
history
Medications
Lifestyle
Detailed
patient
history
Assessment tools
Referral
Tanna N. Nurs Times 2009;105:28−31.
Detailed patient history
Major risk factors
 Hypogonadism (hormone ablation therapy)
 Prior fragility fracture (after age 40 yrs)
 Age (> 65 yrs)
 Low bone mineral density (T-score < -2.5)
 Family history of fracture
 Vertebral compression fracture
 Osteopaenia apparent on X-ray
Saad F, et al. J Clin Oncol 2008;26:5465−76;
Tanna N. Nurs Times 2009;105:28−31.
Most major risk
factors result from:
 Medications
 Comorbidities
Less likely
to be
modifiable
Detailed patient history
Minor risk factors
 Rheumatoid arthritis
 Low dietary calcium and vitamin D
 Smoker
Most minor risk
factors result from
lifestyle choices
 Excessive alcohol intake (> 2 units per day)
 Excessive caffeine intake (> 4 cups/day)
 Weight (< 57 kg)
 Weight loss (> 10% of weight at age 25 yrs)
Saad F, et al. J Clin Oncol 2008;26:5465−76;
Tanna N. Nurs Times 2009;105:28−31.
More likely
to be
modifiable
Measuring
Bone Mineral Density (BMD)
• DEXA scanning provides an estimate of BMD
• low BMD scores can accurately predict the risk of
future fracture*
• Axial DEXA - Gold standard
Measures spine - Most sensitive to early bone loss
Hip :
- Best predicts hip fracture and fracture at other
skeletal sites
- Preferential for decision making
T-score: interpreting DEXA results
T-score
The number of standard deviations that separate the patient from
the mean value of a healthy population − every unit decrease is
associated with 10−12% loss of bone density
World Health Organization. Guidelines for preclinical evaluation
and clinical trials in osteoporosis, 1998.
Non-pharmacological treatment options:
Diet and lifestyle modification
Calcium and
vitamin D
Addressing
modifiable
risk factors
Weight-bearing
exercise and
falls prevention
Limit alcohol
and caffeine
consumption
Smoking
cessation
Hadji P, et al. Ann Oncol 2008;19:1407–16.
Daily sources of calcium and vitamin D
Calcium
Vitamin D
Yogurt, plain, low fat
Cod liver oil
Sardines, canned in oil, with bones
Salmon (sockeye), cooked
Cheddar cheese
Mackerel, cooked
Milk, non-fat
Tuna fish, canned in water
Milk, low fat
Milk, vitamin D-fortified
Yogurt, fruit, low fat
Orange juice, vitamin D-fortified
Orange juice, calcium-fortified
Sardines, canned in oil
Salmon, pink, canned, with bones
Liver, beef, cooked
Cottage cheese, 1% milk fat
Egg (vitamin D in yolks)
Spinach, cooked
Cheese, Swiss
Recommended intake: 1.2–1.5 g/day
Recommended intake: 800 IU/day
Supplementation may be needed
Adapted from NIH. Dietary supplement factsheet: calcium; vitamin D.
Available at http://dietary-supplements.info.nih.gov/factsheets/calcium.asp; http://ods.od.nih.gov/factsheets/vitamind.asp (Accessed Sept 2014);
Boehnke Michaud L and Goodi S. Am J Health Syst Pharm 2006;63:534−46.
Exercise recommendations
 Aim to increase …. muscle strength safely, decrease immobility-related
complications, and prevent fall and fracture
 To help reduce the risk of falls and fractures the following exercises are
recommended:
 Weight-bearing
 Muscle-strengthening
 Aerobic exercise does not support its role for improving BMD, although
aerobic exercise can improve overall health
 Therapeutic exercise should also address osteoporosis-related deformities of
spinal posture, which can increase risk of fall and fracture.
 The effect of strengthening exercise is augmented by proper intake of
Calcium & Vitamin D
 As with pharmacological interventions, therapeutic exercise programmes
should be individualised
Exercises for people at high risk of fracture and
who may have broken bones already
• Strength-training exercises (exercises using body weight
as resistance).
- Wrist curls inc weights, Leg lifts.
• Weight-bearing aerobic activities
-walking, stair climbing
• Flexibility exercises - stretching
• Stability and balance exercises to reduce the risk of falling.
Exercise and osteoporosis (2014) www.nos.org.uk/~/document.doc?id=770
Exercises to avoid
• High-impact, fast - moving exercises such as jumping,
running, jogging or skipping
- increase compression in your spine and lower extremities.
•
Exercises in which you bend forwards and twist your waist,
such as touching your toes or doing sit-ups
- These movements put pressure on the bones in your
spine.
Exercise and osteoporosis (2014) www.nos.org.uk/~/document.doc?id=770
Bone targeted therapies
Bisphosphonates
• Bisphosphonates exert their effects by specifically
inhibiting osteoclast activity (bone resorption) and
inducing apoptosis (cell death)
• Bisphosphonates have been shown to increase bone
mineral density in clinical trials
• It has not been determined if the use of bisphosphonate
reduces the rate of fractures in men who receive ADT
• Supplementation with calcium and vitamin D is essential
Denosumab
•
Denosumab is a human monoclonal antibody that inhibits
RANK Ligand, preventing osteoclast formation, function and
survival
•
Denosumab is indicated for treatment of:
• Men with prostate cancer receiving hormone ablation
therapy, and who are at increased fracture risk
•
Administration is subcutaneous, at a dose of 60 mg every 6
months (for both post-menopausal women and CTIBL in
prostate cancer)
•
Supplementation with calcium and vitamin D is essential
Cancer Induced Bone Loss
(CIBL)
Bone Metastases…………
Common sites of bone metastases
• Spine
• Pelvis
• Ribs
• Skull
• Upper arm
• Long leg bones
Red areas show sites
of highest blood flow
Yellow areas show
sites of medium blood
flow
Scan of a person with
metastatic bone disease.
Light areas show tumour
metastasis in the bone
tissue
American Academy of Orthopaedic Surgeons. Metastatic bone disease. http://orthoinfo.aaos.org/topic.cfm?topic=A00093
Mundy GR. Cancer 1997;80(8 Suppl):1546-1556.
Goals of management
Pain control
Prevent fractures and
spinal cord compression
Optimise
quality of life
Prevent hypercalcaemia
of malignancy
Reich CD. Clin J Oncol Nurs 2003;7:641-6.
Maintain and
promote mobility
Assessing men with bone metastases
History and physical
assessment
Skeletal
complications
Signs and
symptoms
Pain
Assessment
tools
Imaging
Common
techniques
EAUN E-learning course (2013): www.uroweb.org/nurses/educational-resources-for-nurses
The concept of Skeletal-related events, or bone
complications
ADT-induced bone
loss  fractures
Bone metastases
Skeletal-related
events (SREs)
Radiation
to bone
Pathological
fracture
Spinal cord
compression
Surgery
to bone
Increased
cancer burden
Increased pain
Decreased HRQoL
Increased
health resource
utilisation
SREs can have serious consequences
Bone
metastasis
SREs
Cost
of SREs
Decreased mobility
Increased pain
Increased hospitalisation
rate and duration
Decreased quality of life
Increased mortality
Pain should always be assessed!!
 Assessment is the key to providing effective pain control
 Repeat assessments are necessary as pain evolves
Medical
diagnosis
Psychological
assessment
Pain
diagnosis
& treatment
Cleary JF. Cancer Control 2000;7:120−31;
Payne R. J Pain Symptom Manage 2000;19(1 Suppl):S12−5.
Presentation of bone pain
Bone issue
Type of pain
Bone metastasis/
bone lesions
 Usually dull and constant with increased intensity
at night or with weight bearing
 Tends to develop gradually and becomes more
severe within weeks to months
Pathological fracture
 Acute and sharp with a specific focal point
Spinal cord
compression
 Initially localised, and typically increases in
intensity over time
 May become more radicular if lumbosacral
spine involved
 Bilateral, gripping girdle discomfort if thoracic
epidural lesions
Reich CD. Clin J Oncol Nurs 2003;7:641−6;
Prasad D and Schiff D. Lancet Oncol 2005;6:15−24.
Management Options for Bone Pain
Type of Pain
Treatment Options
Weight bearing
Surgery
Palliative radiotherapy
Pain medications (NSAIDs, narcotics)
Neuropathic
Surgery
Palliative radiotherapy
Pain medications (gabapentin, pregabalin, duloxetine);
narcotics often less helpful
Diffuse bone pain
Palliative radiotherapy
Pain management (NSAIDs, narcotics, muscle relaxants,
radiopharmaceuticals, bone-modifying agents)
Vertebral fracture
Kyphoplasty/vertebroplasty
Palliative radiotherapy
Pain management (NSAIDs, narcotics, muscle relaxants)
NCCN. Clinical practice guidelines in oncology: adult cancer pain. v.2.2012.
Radium-223 Targets Bone Metastases
radium-223 reduced the risk of death by 30% and prolonged time to
first symptomatic skeletal event by 5.8 months.
Range of α-particle
Radium-223
Bone surface
• Limited penetration of α emitters (~ 2-10 cell diameters) results in highly
localized killing of tumour cells with minimal collateral damage to normal
tissue in surrounding area
Parker C, et al. 2012 ASCO GU Cancers Symposium. Abstract 8.
Thank you for your
attention!