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Alastair R. McLellan MD, FRCPWestern Infirmary,
Glasgow
Core Medical Training
Osteoporosis &
fracture risk reduction
In UK >250,000 osteoporosis-related fractures per yearAnnual cost >£1.7 billion
• Osteoporosis & fracture epidemiology
• Treatment options & what’s new
• How to use treatments
• Treatment – emerging side effects
• Osteoporosis & the receiving physician
Osteoporosis & fracture risk reduction
• Osteoporosis & fracture epidemiology
• Treatment options & what’s new
• How to use treatments
• Treatment – emerging side effects
• Osteoporosis & the receiving physician
Osteoporosis & fracture risk reduction
Which site of fracture accounts for most clinical
fracture presentations in patients age ≥50yr?
FLS: 8yr WIG: 8668F & 2428M =11096
Which is the commonest site of new fracture in
patients age 50 & over?
North Glasgow FLS 1999-2007
22502 fracture presentations
Vertebral fractures: the paradox
Commonest fracture but
seldom identified
…….why?
Definition of vertebral fracture?
HEIGHT LOSSSHAPE
CHANGE
ENDPLATECHANGE
Definition of vertebral fracture
Definition of vertebral fractureused in the clinical trials
Height Loss % Absolute
Change in SQ Grading
ALENDRONATERALOXIFENECALCITONINIBANDRONATEZOLEDRONIC ACID
≥ 20% ≥ 4mm ≥ 1
RISEDRONATE ≥ 15% ≥ 4mm ≥ 1
1-34 PTH 0 to 1+
Vertebral fractures: the paradox
Why?
• Presentations of vertebral fractures
• Access to imaging
• Radiologists & reporting
McLellan et al: http://www.nhshealthquality.org/nhsqis
Vertebral Fractures
Vertebral fractures: under-diagnosed
Gehlbach et al.,Osteoporos Int 2000, 11:577
934 hospitalised women with a lateral chest x-ray
0
20
40
60
80
100
120
140
Patie
nts
(n)
132
65
23 25
Fractureidentified by studyradiologists
Fracturenoted in radiologyreport
Fracturenoted inmedical record
Receivedosteoporosistreatment
Prevalence of Vertebral Deformities : Age & Gender (EVOS study)
Ismail et al. O.I. 1999; 9: 206-213
Incidence rates for vertebral, wrist & hip fractures in women after age 50
Wasnich RD, Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 4th edition, 1999
Vertebral FracturesSemi-quantitative reading / visual scoring
Genant et al., J Bone Miner Res 1993, 8:137
Normal (Grade 0)
Wedge fracture Biconcave fracture Crush fracture
Mild fracture(Grade 1, ~20-25%)
Moderate fracture(Grade 2, ~25-40%)
Severe fracture(Grade 3, ~40%)
Epidemiology of Osteoporotic Fractures in UKDennison & Cooper BJCP 1996:50;33
Hip Spine Wrist
Lifetime Risk (%)Women (@50yr) 14 11 13Men (@50yr) 3 2 2
Mean Age (yr) 79 67 65
Mortality (relative survival)
MORBIDITY
MORTALITY
FRACTURES
Cumulative Survival Probability
Center JR et al., Lancet 1999, 353:878
Age
MEN
Surv
ival
pro
babi
lity
0.2
0.4
0.6
0.8
0
1.0
60 65 70 75 80 85
Dubbo PopulationVertebral/Major FracturesProximal Femur Fractures
Age
WOMEN
Surv
ival
pro
babi
lity
1.0
0
0.2
0.4
0.6
0.8
60 65 70 75 80 85
a fracture at any site is associated with 2-3x increased risk of
further fracture at any skeletal site
Among women with hip fracture:45% have had ≥1 previous fracture
18% will have ≥1 further fracture in next 2 yr
Previous fractures sinceage of 50 yr
Fractures during 1.8 (0.6) yr follow-up [0.5–3.1 yr]
45% 18%%
www.nhshealthquality.org/nhsqis
Risk factors for fracture&
opportunities to intervene?
OSTEOPOROSIS
FRACTURES
RISK FACTORS FOR O
SKELETAL BONE MINERAL DENSITYHip geometry - HALU/S characteristicsMicroarchitectureBone turnover
SKELETAL/ FALL AGEGeneticMaternal hip #FRACTURE HISTORYHeightSmokingWeight change
FALLneuromuscular problemscognitionvisual impairmentdrug therapyfall mechanics
RISK
FACTORS
FOR
#
OSTEOPOROSIS
FRACTURES
RISK FACTORS FOR O
SKELETAL BONE MINERAL DENSITY
SKELETAL/ FALL AGEFRACTURE HISTORY
FALL
RISK
FACTORS
FOR
#
• Osteoporosis & fracture epidemiology
• Treatment options & what’s new
• How to use treatments
• Treatment – emerging side effects
• Osteoporosis & the receiving physician
Osteoporosis & fracture risk reduction
Anti-resorptive
Anabolic
‘Dual action’
Treatments & Efficacy
Vertebral Fx Non-vertebral FxOther Fx Hip Fx
OralHRT Yes Yes YesEtidronate* YesAlendronate* Yes Yes YesRisedronate* Yes Yes YesIbandronate* Yes [Yes]Raloxifene* Yes Calcitriol* YesStrontium Ranelate* Yes Yes [Yes]
Vertebral Fx Non-vertebral FxOther Fx Hip Fx
Subcutaneous Teriparatide* Yes Yes 1-84 PTH* Yes Denosumab* Yes Yes Yes Intravenous Pamidronate Ibandronate* Zoledronate* Yes Yes Yes Intranasal or Subcutaneous Calcitonin* Yes
Vertebral Fx Nonvertebral Fx
Other Fx Hip Fx
Alendronate* Yes Yes Yes
Risedronate* Yes Yes Yes
Zoledronic acid* Yes Yes Yes
PTH* Yes Yes ???
Strontium ranelate* Yes Yes ???
Denosumab* Yes Yes Yes
Appropriate use of appropriate treatments can halve the incidence of fractures
* plus calcium + vitaminD
The NEW ENGLANDJOURNAL of MEDICINE
Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis
Dennis M. Black, Ph.D., Pierre D. Delmas, M.D., Ph.D., Richard Eastell, M.D., Ian R. Reid, M.D., Steven Boonen, M.D., Ph.D., Jane A. Cauley, Dr.P.H., Felicia Cosman, M.D., Péter Lakatos, M.D., Ph.D., Ping
Chung Leung, M.D., Zulema Man, M.D., Carlos Mautalen, M.D., Peter Mesenbrink, Ph.D., Huilin Hu, Ph.D., John Caminis, M.D., Karen Tong, B.S., Theresa Rosario-Jansen, Ph.D., Joel Krasnow, M.D.,
Trisha F. Hue, M.P.H., Deborah Sellmeyer, M.D., Erik Fink Eriksen, M.D., D.M.Sc., Steven R. Cummings, M.D., for the HORIZON Pivotal Fracture Trial
2007 Volume 356:1809-1822
Study Population & Primary End Points
Inclusion
Women 65 to 89 years of age
Femoral neck T-score ≤–2.5 with or without fracture or ≤–1.5 with 2 mild or 1 moderate vertebral fracture
Primary Efficacy End Points
Reduction in vertebral fracture over 3 years
Reduction in time to hip fracture over 3 years
Black DM, et al. N Engl J Med. 2007;356:1809-1822
Values above bars are 3-year cumulative event rates based on Kaplan-Meier estimates. *P = .0024; †P < .0001; ‡P = .0002; relative risk reduction vs placebo §Hip fracture was not excluded from analysis of non-vertebral fracture.
41%*(17%, 58%)
77%†(63%, 86%)
25%‡(13%, 36%)
Clinical Vertebral Fracture
HipFracture
Non-vertebral Fracture§
1.4%(52/3875) 0.5%
(19/3875)
2.5%(88/3861)
2.6%(84/3861)
8.0%(292/3875)
10.7%(388/3861)
Cu
mu
lati
ve I
ncid
en
ce (
%)
of
New
C
lin
ical Fra
ctu
res O
ver
3 Y
ears
0
10
5
15
Zoledronic Acid Reduced Cumulative 3-Year Risk of Clinical Fractures (Hip, Clinical Vertebral, Non-vertebral)
ZOL 5 mg Placebo
Black DM, et al. N Engl J Med. 2007;356:1809-1822.
Horizon RFTPaldeep Atwal
Paldeep Atwal
OverviewEvent-driven, randomised, double-blind, placebo-
controlled clinical trial 2127 men and women from 148 clinical centres in
23 countriesTreatment
Annual infusion of either ZOL 5 mg or placeboLoading dose of vitamin D 75,000–125,000 IU/dCalcium 1000–1500 mg/d; vitamin D 400–1200
IU/dFollow-up visits at 6, 12, 24, and 36 months
Telephone interviews every 3 months starting at month 9
Primary and Secondary Efficacy End Points
Primary ObjectiveReduce the fracture rate of new clinical fractures
after surgical procedure for a low-trauma hip fracture
Secondary ObjectivesReduce the risk of clinical vertebral, hip, and non-
vertebral fractureIncrease BMD at the total hip and femoral neck of the
non-fracture hip at months 12 and 24Reduce subsequent hospitalisations
Study Population Inclusion
Male or female patients aged 50 years and older Randomised up to 90 days after surgical procedure for a
low-trauma hip fracture Ambulatory prior to hip fracture
Exclusion Use of oral bisphosphonates Calculated creatinine clearance <30 mL/min Hypercalcaemia (≥2.75 mmoL/L) Hypocalcaemia (corrected calcium <2.0 mmol/L) Primary hyperparathyroidism, hypoparathyroidism,
osteogenesis imperfecta, Paget’s disease Any prior use of IV bisphosphonate (within 2 years) Any prior use of parathyroid hormone and analogs for >1
week
Conclusions
In subjects treated within 90 days after surgical repair of a hip fracture, ZOL 5 mg: Reduced risk of overall clinical fractures by 35% (RR)
Multiple clinical fractures by 33% Clinical vertebral fractures by 46% Non-vertebral fracture by 27%
30% lower rate of hip fractures (NS vs placebo) Reduced mortality risk by 28% Increased total hip and femoral neck BMD at all time points Generally safe and well tolerated
Incidence of AEs and SAEs comparable to placebo Incidence of AEs and SAEs comparable to placebo No evidence of long-term effect on renal function 20% reduction in risk of atrial fibrillation/atrial flutter SAEs
Zoledronic acid reduced risk of all-cause mortality by 28% over time
0 120 240 360 480 600 720 840 960 1080
Time to death (Days)
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
0.18
Cu
mu
lati
ve in
cid
ence
Zoledronic acid (N=1054)Placebo (N=1057)
Hazard ratio, 0.72; (95% CI, 0.56-0.93)
P = 0.0117
ZOL N=1054 1029 987 943 806 674 507 348 237 144
PBO N=1057 1028 993 945 804 681 511 364 236 149
DenosumabAmanda Fitzpatrick
Denosumab (Prolia ™)• RANK (Receptor activator of nuclear factor kappa) receptors are found on
pre-osteoclasts. They are activated by binding of the RANK ligand (RANKL), allowing osteoclast maturation
• Osteoprotegerin (OPG) is a natural inhibitor of RANK-RANKL binding, so inhibits bone resorption. Found to stimulated in vivo by oestrogen.
• Denosumab, fully human monoclonal IgG antibody, binds RANK and prevents RANKL activation
FREEDOM trial• FREEDOM = Fracture REduction Evaluation
of Denosumab in Osteoporosis every 6 Months• Denosumab 60mg s/c injection 6 mthly for 3 years vs
placebo. Randomisation age-stratified.• 7868 patients, age 60 – 90yrs old, with T score
hip/lumbar spine between -2.5 to -4.0. • Primary aim: reduction in vertebral fractures• Exclusion criteria: bisphosphonates within past 12
months, more than 2 moderate or 1 severe vertebral fracture
• All subjects received calcium and vitamin D supplements
Results1. 68% reduction in relative risk of new vertebral fracture
2. 20% reduction in incidence of non-vertebral fractures, and 40% reduction in hip fracture
3. Increase over time in BMD lumbar spine (9%) and hip (6%)
3. Bone resorption reduced by 86% at 1 month (serum CTX) and maintained
• Short and long term AE’s: previous studies suggested ↑infections, ↑eczema, possible ↑malignancy however no evidence from FREEDOM study.
• Effectiveness is similar to that of zolendronate, and greater than oral bisphosphonates
• Cost: £1000 per patient/year, compare to alendronate £50/year, zolendronate £250/year
• Other positive trials of Denosumab– Reduced vertebral #s by 62% prostate Ca patients receiving
hormone deprivation therapy (n= 1468) – Smaller studies in bone metastases related to prostate, breast
and other malignancies– Benefits to cortical bone (radius) in PM women– In RA: two randomised trials demonstrate increase in hand
bone mineral density, total around 300 patients
Adverse Events
Cummings SR et al. N Engl J Med 2009;361:756-765
Drugs Cost (£)
Alendronic acid (generic) 70mg weekly 3.66
Raloxifene (Evista®) 60mg daily * 17.06
Risedronate (Actonel®) 5mg daily 19.10
Risedronate (Actonel®) 35mg weekly 20.30
Ibandronic acid (Bonviva®) 150mg monthly * 21.45
Alendronic acid (Fosamax®) 70mg weekly 22.80
Alendronic acid 70mg & Vit D3 2800 i.u.(Fosavance®) * 22.80
Alendronic acid (Fosamax®) 10mg daily 23.12
Alendronic acid (generic) 10mg daily 23.15
Strontium ranelate (Protelos®) 2g daily 25.60
Teriparatide (Forsteo®) 20mcg daily 271.88
Table 1: Cost for 28 days treatment (Scottish Drug Tariff May 2007 / BNF March 2007)
• Osteoporosis & fracture epidemiology
• Treatment options & what’s new
• How to use treatments
• Treatment – emerging side effects
• Osteoporosis & the receiving physician
Osteoporosis & fracture risk reduction
When is treatment required?
Future fracture risk
determines need for treatment
DXA
FRAXCathy Anderson
FRAX in osteoporosis treatment
Dr Cathy AndersonCT2
28/09/10
FRAX
• WHO developed, computer driven, calculation tool (www.sheffield.ac.uk/FRAX/index.jsp)
• Predicts the 10 year probability of both hip fracture and all major osteoporotic fracture
• Based on clinical risk factors with the option of including Bone Mineral Density at femoral neck to increase the accuracy
• Developed on individual patient models and allows selection based on gender and nationality.
FRAX ToolSelect Tool appropriate to nationalityEnter: Age, sex, weight (kg), height (cm)Answer ‘yes/no’ to
Previous fracture? Parent fracture?Current smoker?Glucocorticoid use? (current or > 3 months)RA diagnosis?Secondary osteoporosis?
Alcohol intake > 3 units/dayEnter Femoral Neck BMD g/cm2 if known
Interpretation
Tool calculates – BMI– 10 year hip # probability– 10 year major osteoporotic # probability
Links to the National Osteoporosis Guidelines Group (NOGG) website where it plots your result on a risk stratification graph that advises low, intermediate or high risk.
Problems
• Doesn’t allow for multiple previous fractures (increased risk) or for specification of site of previous fracture.
• Doesn’t specify dose of glucocorticoid• Doesn’t allow for uncertainty as to whether
patient has a risk factor or not• Doesn’t include falls risk• Doesn’t account for ethnic minorities
Treatment Decisions
• Only intended as an aid to treatment decisions• Low – reassure, lifestyle advice and repeat in 5
years• Intermediate – measure BMD and recalculate• High – Consider treatment• Treatment will depend on local factors linked to
cost effectiveness – take into account cost of fracture, cost of risk factor management, cost of treatment, health care allowance locally.
• 55yr female
• Colles’ fracture
• Smoker 20cigs
• Maternal hip fracture age 75yr
Should she receive treatment for fracture secondary prevention?
• 55yr female• Colles’ fracture• Smoker 20cigs• Maternal hip fracture age 75yr
FRAX major fx = 19%, hip fx = 2.8%
Fracture Risk if
FN T-score = +2
FN T-score = +1
FN T-score = 0
FN T-score = -1
FN T-score = -2.5
FN T-score = -3
FRAXPros• Quantitation of fracture
risk facilitates communication & understanding
• Easy to use
Cons• FRAX fracture risk doesn’t
imply that treatment can modify that risk
• Non-vertebral fracture risk can only be reduced in those <70 when T-score <-2.
• Doesn’t work if lowest T-score is at spine
• Underestimates fracture risk if >1 previous fracture
ALN only prevents nonvertebral fractures in osteoporotic women
Cummings et al JAMA 1998; 280: 2077-2082FITII: Pre-planned analysis: 2214 ALN v 2218 PBO, 4.2yr follow up
Only in those with osteoporosis 63 clinical fractures (incl 12 hip) prevented per 1000 women yrs’ Rx
plus 27 radiographic vertebral fractures prevented
PBO PBOALN ALN
FN T-score
n
HRT ?BZD 43 IBAN ?CLO 18ALN 19 FOSITRIS 22 (12hip) HIPALN 63 (12hip) FITII
CLO 5RIS ?
HRT 3
Guidelines &
treatment decisions
http://www.sign.ac.uk/guidelines/fulltext/71/index.html
Prevalence of Osteoporosis in Women & Men with Fractures I
%
• Osteoporosis & fracture epidemiology
• Treatment options & what’s new
• How to use treatments
• Treatment – emerging side effects
• Osteoporosis & the receiving physician
Osteoporosis & fracture risk reduction
ONJ - BONJ
First reported 2003, now 500+ casesRisk in osteoporosis with oral BPs
1:10,000 to <1:100,000 patient-treatment yr
Risk in cancer with high dose IV BPs 1:10 to 1:100 patient-treatment yrBut true incidence maybe higher!!
Khosla et al JBMR 2007:22:1479-1491
Migliorati 2003; Marx 2003; Ruggiero et al 2004
Atypical ‘simple with thick cortices pattern’ of femoral diaphyseal fractures associated with ALN
Lenart et al NEJM 2008; 358: 1304-6
1. Simple transverse pattern
2. Beaking of cortex on one side
3. Hypertrophied diaphyseal cortices
4. Results from minimal or no trauma
BPs & Oesophageal CaAllan Drummond
?oesophageal ca
Exposure to Oral Bisphosphonates and Risk of Esophageal Cancer Chris R. Cardwell, PhD; Christian C. Abnet, PhD; Marie M. Cantwell, PhD; Liam J. Murray, MD JAMA. 2010;304(6):657-663. doi:10.1001/jama.2010.1098
Oral bisphosphonates and oesophageal cancerDiane K Wyskowski, epidemiologistBMJ 2010;341:c4506
Multiple case reports – suggesting multiple types of oesophageal injury
Number of studies suggested possible link to oesophageal ca – inadequate methods for definitive link
Green study – similar to JAMA paper but suggested > risk oesophageal ca with > prescriptions (longer f/u)
Most recently – JAMA paper (note neither study validated diagnoses by medical records or looked at whether drugs taken correctly)
Data from UK GP research database 96-06 Bisphosphonate & control cohorts Main outcomes – oesophageal/gastric ca Approx 4½ year mean follow-up 41,000 per cohort 0.48/1000 bis, 0.44/1000 control Statistically no significant increased risk
Evidence inconclusive proving link between bisphosphonates and oesophageal ca
Clear instructions due to known risks eg oesophagitis/ulcers
Check for any previous swallowing problems and report any new problems early
Should still prescribe with caution Weigh up risk/benefit ratio
Doesn’t apply to calcium PLUS vitamin D
7+ trials – didn’t consider CVSRFs e.g weight,
smoking, HBP, diabetes, IHD & lipid disorders
No dose-relationship seen
51yr Male, JA• Ex-policeman, now drug enforcement agency• 13th Nov – fell over with motorbike, sustained
back pain (lumbar to lower thoracic spine)• Persistent ache since, with pain upto 5/10
Spine X-ray report
• Generalised osteopaenia• LV1, TV12, TV5 & TV6 – grade 3 wedge fx
PMH: Back pain since 1987 – noted to have VFx at LV1 assoc with RTA~1997, another back injury assoc
with RTA & noted to have VFx at TV3 & TV4
Mild oesophagitis 1992DU 1993
Rx: VenlafaxineNSAIDDiazepam
SH: lives with wife & 2 childrenNon-smoker8U alcohol / wDietary Ca2+: ≥ 1000mg/dExercise – daily yoga or swimming
RF: Paternal hip fx age 83yrMother acq’d kyphosis with aging
- associated height loss of 6ins- confirmed osteoporosis
O/E: Spine configuration – normalRange movements – sl. all directionsNo focal tenderness
• ‘Radiological osteopaenia’– plain X-rays not sensitive for bone loss– the need for DXA?
• When osteoporosis confirmed at young age – careful hx essential– circumstances of fx– growth & development– systematic hx – gi, renal, haem, endo, – Rx– FH
• What examination is essential?exclude Cushing’s syndromeassess for hypogonadism – incl testicles, gynaecomastia etc.
• What tests are necessary?Precautions re timing
The Clinical Problem
Osteoporosis - under-recognized in men, & untreated in most men with fractures.
60yr male - 25% risk of osteoporotic fx during lifetime Nguyen et al. Am J Epidem 1996; 144: 255-63
1/3 of all hip fractures occur in men Gullberg et al. Osteoporos Int 1997;7:407-413.
Mortality after hip, vertebral & other fx is higher in men Center et al. Lancet 1999; 353: 878
After hip fracture 4.5% men v 49.5% women undergo assessment or receive antiresorptive RxKiebzak et al Arch Int Med 2002; 162: 2217
Mortality After All Major Types of Osteoporotic Fracture in Men & Women: An Observational Study
Center et al Lancet 1999; 353: 878-882
Mortality Rates for Fracture Patients v General Population
The Clinical Problem – Diagnosis
• WHO thresholds for diagnosis of osteoporosis & osteopaenia in postmen. women, also apply to men.
• For any given spine or hip BMD, risk of fracture is
similar among men & women of the same age.
• But men with hip fracture have higher BMD than women, (? other factors e.g. microarchitecture or trauma, may contribute more to risk of fracture in men
• For diagnostic purposes, sex-specific T score is used
EPOS. J Bone Miner Res 2002;17:2214-2221. de Laet et al J Bone Miner Res 2002;17:2231-2236.
Johnell et al Calcif Tissue Int 2001;69:182-184.
Spine & hip BMD & T- scoresin men & women with NVFx
Male Female p
Age 65.2 (10) 68.2 (10.3) 0.0001Spine (L1-4)
BMD(g/cm2) 0.921 (0.16) 0.834 (0.152) 0.0001
T-score -1.54 (1.45) -1.94 (1.38) 0.0001
Total hip
BMD(g/cm2) 0.798 (0.174) 0.706 (0.159) 0.0001
T-score -1.29 (1.09) -1.6 (1.23) 0.0001
FLS: Prevalence of Osteoporosis inMen with Fractures (all sites)
Sharma,S., Fraser, M., Lovell, F., Reece, A., McLellan A.R. JBJS 2008;90: 72-7
n 344 369 310 289 295 234 139 75
Prevalence of Osteoporosis in Women & Men with Fractures
Sharma,S., Fraser, M., Lovell, F., Reece, A., McLellan A.R. JBJS 2008;90: 72-7
%
60% have secondary osteoporosis
15%85%
The Clinical Problem - Hypogonadism
• in 66% of elderly male nursing-home residents with hip fractures.
• in 20% of men with spinal fractures
• in most cases - asymptomatic
Abbasi et al. Am J Med Sci 1995;310:229-234
Labs JA, 51yr M
• U&Es, LFTs, TFTs – all normal• Adj Ca2+ 2.41mmol/L, ALP 94U/L• LH 2.4U/L, FSH 4.5U/L• Testosterone 12.1(range 10-36)
SHBG 65nmol/LFree testo 151pmol/L (range >200)
• TTG• IGS & EP
0
5
10
15
20
25
30
35
Previous fx Smoking Seldom on feet Recurrent falls FHosteoporosis
Alcohol XS Hx maternalhip fx
Height loss
Male
Female%
p<0.0001
NS
p=0.003
P<0.0001
p<0.0001
p<0.0001
NS
p<0.0001
Prevalence of the major risk factors for osteoporosis & for fracture
Efficacy of Rx in Men (DBRPCTs)Rx VFx Non-VFx Hip Fx
ALN Yes ND ND
RIS ND ND ND
ZOL ? ? ND
1-34PTH ND ND ND
TESTO ND ND ND
Orwoll et al NEJM 2000; 343: 604 n=241, VFx 0.85 (ALN) v 7% (PBO), p0.02Boonen et al JBMR 2009; 24: 719 n=284Lyles et al NEJM 2007; 357: 1799 n=508 men of 2175Orwoll et al JBMR 2003; 18: 9 n=437, 11mo f/u only
Alendronate for the Treatment of Osteoporosis in Men
Orwoll et al. NEJM 2000; 343: 604-610
Double-blind placebo controlled RCT over 2yr241 men; 31-87yr, average age 63yr
FN T-score -2 + LS T-score -1 orFN T-score -1 + 1 vertebral deformity or hx of osteoporotic fracture
Alendronate 10mg/d + 500mg Ca/d + 400IU vitD/d OR PBO + 500mg Ca/d + 400IU vitD/d
Alendronate for the Treatment of
Osteoporosis in MenOrwoll et al. NEJM 2000; 343:
604-610
Incidence of morphometric vertebral fractures
ALN 7.1%PBO 0.8%
p=0.02
1+ Vertebral fracture
Osteoporosis & fracture risk assessment
Fracture secondary prevention as per protocol
Check for history of warning symptomsPast history of cancer in last 10yr
Unexplained weight lossWorsening pain associated with VFx over last 3 months
Blood testsESR, FBC, U&Es, LFTs, Ca, PO4, IGS&EP, vitD, TFTs
& in males- testo, LH/FSH
WARNING SYMPTOMS or SIGNIFICANT ABN BLOODS?
Yes No
Other testsIf male - PSA
If past bowel ca – CEAIf past ovarian ca – CA125
CXR ( if not done in last 3/12)MRI / CT spine if appropriate to excl tumour
If strongly suspect neoplasmor
if otherwise unwell or
Severe pain / pain management problem
Yes No
Urgent admission E3/4Urgent new Bone
Clinic appointment2-4 weeks
DADS follow-up @ 2yr incl morphometry
IF PAIN – ENSURE OPTIMAL PAIN MANAGEMENT
How many vertebral fracturesare present?
3+ 1-2
HIP FRACTURE – Female Age 75 and overGive single oral dose 100,000 IU vitaminD @ as soon as feasible post hip fracture & start 1000mg
CaCO3+800IU vitaminD asap, (if on this already – continue)
Already on a BP(bisphosphonate)?
No
YesGood prognosis & eGFR 30 or over
Duration of treatment?Yes No
1. Patient or resident carer understand concepts of osteoporosis, fracture risk reduction & protocol for ingesting oral BPAND2. No contraindications to oral BPs [dysphagia / oesophageal stricture / achalasia /hypocalcaemia].
Yes
Oral ALN 70mg / wk
No
Patient suitable for IV BP& eGFR 35 or over
Yes No
Arrange IV zoledronic acid 5mg infusion (over at least 15min),
4-6/52 after hip fracture
Consider oral BP or, if at risk equivalent to that of fracture
plus T-score -2.4 or less, consider strontium ranelate.
Continue b.d. calcium + vitaminD
Continue b.d.oral calcium + vitaminD
More than 2yr 2yr or less
Optimal compliance with / adherence to BP & BP well tolerated
YesNo
Continue oral BPIF eGFR is 30 or moreOtherwise continue
b.d. calcium + vitaminD
GREATER GLASGOW & CLYDE PROTOCOL FOR FRACTURE SECONDARY PREVENTION AFTER HIP FRACTURE IN WOMEN AGE 75+