osteoporosis and fracture risk reduction comep oct 2010

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

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

#

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)

When is treatment required?

Future fracture risk

determines need for treatment

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

%

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+

osteoporosis and fracture risk reduction comep oct 2010

Health & Medicine

fracture opportunities

yr fractures

site of fracture accounts

osteoporosisrelated

inradiology report fracture

yr previous fractures

osteoporosis treatment

wrist hip fractures