Transcript Osteoporosis update - Bon Secours Hospitals

Osteoporosis
Catherine Molloy
Cons Rheumatologist
MD MSc FRCP CCD
Sept 2015
Osteoporosis (OP)
• A systemic skeletal disease
characterised by
• low bone mass
• microarchitectural
deterioration of bone
Compromised bone strength
Fracture
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Whom to suspect?
How to diagnose
Lifestyle, Exercise
Medication
• Side-effects
• When to review
Whom to suspect of OP…?
Mrs M O’S, 55yo
• Postmenopausal, no fracture history
• Family history hip #
• Routine DEXA
2015
T score L1-4
T score L fem neck
-2.4
-2.6
Risk factors/history
• Postmenopausal
• Family history OP
• Coeliac, Infl bowel disease,
malabsorption
• Thyroid, parathyroid
disease
• Steroid use
• Antiepileptic meds
How to diagnose osteoporosis
1. Presence of a fragility fracture
2. DEXA
• T-score ≤-2.5 only hip and L1-4 (IOS, ISCD, NOS)
3. Bone biopsy
DEXA
• Radiation= ambient daily dose
• Only C/I pregnancy,
widespread metalwork
• WHO 1994 criteria use the Tscore for classification into
three main groups:
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1. Normal BMD: T-score
≥ -1.0
2. Osteopenia: T-score
-1.0 to -2.49
3. Osteoporosis: T-score
≤ -2.5 , e.g. -3.5
With prevalent fragility fractures and Tscores <-2.5 ‘severe OP’
FRAX calculator www.shef.ac.uk/FRAX
Screening for secondary causes
• FBC, CRP
• UE LFT, ferritin
• TFT, Ca, PO4, Alk phos, PTH
• TTG
• SPEP
• Testosterone, SHBG
• Oestradiol, prog
Management
Osteoporosis therapies
• Compliance
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Nature of condition (silent)
Nature of medication,
mode of admin
• Ca, Vit D
• HRT/ Raloxifene
• Bisphosphonates
• Denosumab (Prolia)
• PTH (Forsteo)
• Strontium
Daily Ca+2 requirements
 Adults
1000mg/d
 Teens, pregnant 1200mg/d
 Breastfeeding
1500mg/d
Each of following 250- 300mg:
o 1 glass fortified milk
o 1 matchbox size of cheese
o 1 carton yoghurt
Vitamin D deficiency
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Ireland: 74% adults, 88%
primary school children have
<50% recommended daily intake
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 Risk in
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elderly
obese
darker skinned
malabsorption incl. coeliac
Hepatic or renal disease
All adults over 50
IOF Recommendations, 2013
Universal guidance
• Counsel on the risk of osteoporosis and related fractures
• Advise on a diet rich in fruits and vegetables, includes adequate amounts of total calcium
intake (1,000 mg/d for men 50-70; 1,200 mg/d for women ≥ 51 and men ≥ 71)
• Advise on vitamin D intake (800-1,000 IU per day), including supplements if necessary for
individuals ≥ 50
• Recommend regular weight-bearing and muscle-strengthening exercise to improve
agility, strength, posture and balance and reduce the risk of falls and fractures.
• Assess risk factors for falls and offer appropriate modifications (e.g. home safety
assessment, balance training exercises, correction of vitamin D insufficiency, avoidance of
certain medications and bifocals use when appropriate).
• Advise on cessation of tobacco smoking and avoidance of excessive alcohol intake.
• Measure height annually, preferably with a wall mounted stadiometer
Exercise
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30 minutes weight-bearing
exercise > 3 times a week
Up and down a flight of
stairs 10 times is 1/3 daily
requirement
Dancing best of allconstant changes of
direction and intensity
Pharmacologic Treatment
recommendations (IOF)
1. hip or vertebral # (clinical/asymptomatic)
2. T-scores < -2.5 at the femoral neck (FN), total hip
(TH) or lumbar spine (LS)
by DXA, after appropriate evaluation
3. postmenopausal women and men ≥ 50 with osteopaenia (DXA, FN/TH/LS) and a
10-year hip fracture probability > 3% or a 10-year major osteoporosis-related
fracture probability > 20%
based on the (Irish-)adapted WHO absolute fracture risk model (FRAX)
• Not indefinite
After 3-5 year treatment period, reassess
OP drug overview
Bisphosphonates
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Inhibitory effect on osteoclasts
Decrease bone resorption and risk of # vert and hips
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Alendronate (Fosamax, Fosavance with 5600IU VitD)
Risedronate (Actonel, Actonel plus calcium and D) and SIOP
Zoledronic acid (Aclasta)- annual IVI; Pagets and SIOP
Ibandronate (Bonviva)- 3mg IV per 3/12
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Contraindications:
• GORD, hiatus hernia, gastritis, impaired renal function,
hypocalcaemia, pregnancy
Osteonecrosis of jaw (ONJ)
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Exposed bone and slow healing
Infection+ trauma + poor healing (+/immunocompromise)
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Chemotherapy > OP doses
Oral hygiene critical
? Pre therapy dental review
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Cave dental implants/ extractions
Atypical femoral fractures (AFFs)
• located in the subtrochanteric region and diaphysis of the femur
• reported in patients taking BPs and denosumab, also occur with no meds
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Risk of AFF
• 1000 females treated with BP for 5 years
• Prevents 35-50 nonvert, 50-115 vert #= 85-165 typical #
• Versus ‘causing’ 5 AFF
• Relative risk of patients with AFFs taking BPs is high,
but the absolute risk is low, from 3.2 -50 per 100,000 pt-yrs
• Duration of treatment:
• long‐term use may be associated with higher risk (100 per 100,000 pt‐yrs)
• when BPs are stopped, risk of an AFF may decline
JBMRes 2014 ASBMR
ONJ and AFF
• Increased risk with
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Malignancy (disease and higher doses)
Poor oral hygiene
Steroid use
Prolonged BP use (>5-7 years)
Denosumab (Prolia)
• Human monoclonal
antibody against RANKL
which is a member of the
TNF superfamily of ligands
and receptors
• inhibits maturation of
osteoclasts, reduces bone
breakdown
• 60mg sc every 6 months x 4
• Compliance
• # risk reduction = IV bisphos
Denosumab ctd
• Increases spine BMD by 9% and hip BMD by 6%
• RR for vertebral fracture 0.32 and for hip fracture 0.6
• Potential infectious complications but no significant
difference in serious adverse events compared to
placebo
• Recent reports AFF and ONJ
Cummings S, et al "A Phase III Study of the Effects of Denosumab on Vertebral,
Nonvertebral, and Hip Fracture in Women With Osteoporosis: Results from the
FREEDOM Trial" JBMR 2008; 23: Abstract 1286
Parathyroid hormone (teriparatide)
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Bone-FORMING
High-tech prescription
100mcg od sc x 24 months
Serum Ca at 1, 3 and 6 months
Repeat DEXA at 18-24 months
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C/I severe renal disease, Ca
BF, pregnant, met bone other than OP
Summary of Drug Therapies
Therapy
Mode and
Frequency of administration
Increase in
Spine BMD
Increase in
Hip BMD
RR for
vert #
RR for
non-vert #
Bisphosphonate
s
Oral, IV
Daily, Weekly, Monthly,
Yearly
6.2%*
4.7%*
0.53*
0.49*
Strontium
Ranelate
Oral, Daily
14%$$
8%$$
0.59
0.64
PTH
S/C, Daily
9.7%**
2.8%**
0.35**
0.47**
SERMS
Oral, Daily
2.6%
2.1%
0.7
N/S
HRT
Oral, Daily
6.8%
4.1%
0.66
0.87$
Denosumab
s/c 6 monthly
9%
6%
0.32
0.6
Calcitonin
Intranasal, S/C or I/M Daily
1.5%
N/S
0.67
N/S
•* Data for Alendronate, ** Data for Teriparatide, $ Hip fracture data
•$$ Strontium content can account for up to 50% change in BMD
Monitoring patients (IOS)
• Perform BMD testing 1 to 2 years after initiating therapy
to reduce fracture risk and every two years thereafter.
• More frequent testing may be warranted in certain clinical
situations.
• The interval between repeat BMD screening may be
longer for patients without major risk factors and who
have an initial T-score in the normal or upper low bone
mass range.
When to stop or change therapy..
•Intolerant of meds
•Questionable compliance
•After 5years of bisphosphonates
•Declining T-scores
• ?? new #
Conclusion
• Prevalent silent disease, suspect everyone!
• # = fall + quality + density
• Information, Calcium and Vit D, exercise
• DEXA
• Drug compliance esp BP
• ONJ, AFF
• Screen for secondary causes
• Follow-up essential
Steroid-induced OP (SIOP)
treatment guidelines
• Lifestyle, etc
• Postmenopausal F and M> 50
• treat ALL patients on pred ≥ 7.5/d
• treat those on pred < 7.5/d, if FRAX 10Y risk major #>10%
• Premenopausal F and M <50
• Only if # history
• Males, non-childbearing F if ≥ 5mg/d
• Childbearing F ≥ 7.5/d
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ZART (Zol, alend, rised, teriparatide)
ACR criteria Grossmann, 2010