seminair 22-11-2014 - prof. dr. p. geusens- osteoporose en mortaliteit

Osteoporosis and mortality

Prof Dr Piet Geusens Reumatoloog en Revalida8earts

MUMC & UHasselt Prof

. Dr. P

. Geu

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MUMC & UHasselt Arras, France

OLL Maastricht 2012

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Only post-‐mortem fractures: a long way to go


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Mortality aJer fractures


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•  What are causes of mortality? •  How much the risk of mortality is increased aJer fracture, and why?

•  Mul8-‐outcome compe8ng risk analysis (re-‐fracture + mortality)

•  Can we influence post-‐fracture mortality?

MUMC & UHasselt

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www.index.mundi

Death rate Europe (/1000)

Nl: 8.4 Be: 10.6

MUMC & UHasselt

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MUMC & UHasselt

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MUMC & UHasselt WHO website ASDR: age-specic death rate

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MUMC & UHasselt WHO website

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IS THE RISK OF MORTALITY INCREASED AFTER FRACTURE?

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Independent effects of vertebral deformity (yes/no) and femoral neck BMD T score (osteoporosis; low/normal) on mortality

(bars).

Pongchaiyakul, J Bone Miner Res 2005;20:1349

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Cumula8ve mortality over 5 years

Center JR et al., Lancet 1999, 353:878 Dubbo Population Australia Vertebral/Major Fractures Proximal Femur Fractures

Age

MEN

Surv

ival

pro

babi

lity

0.2

0.4

0.6

0.8

0

1.0

60 65 70 75 80 85

Age

WOMEN

Surv

ival

pro

babi

lity

1.0

0

0.2

0.4

0.6

0.8

60 65 70 75 80 85

Vertebrall#

Hip#

Population

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Kaplan–Meier survival analysis in males and females with a fragility hip fracture in 2004–2005

Diamantopoulos, Clinical Interventions in Aging 2013:8 817

Women

Men

MUMC & UHasselt

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Mortality following hip fracture compared with general popula8on values

Abrahamson, Osteoporos Int (2009) 20:1633

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Mortality aJer second HFx stra8fied according to sex compared with the mortality of the background popula8on

MUMC & UHasselt

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Kaplan-‐Meier survival curves for women with osteoporo8c fractures aged 60–74 yr (A), aged 75+ yr (B).

MUMC&UHasselt Center, JCEM, 2011,1006

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Standardized mortality ra8o among 2901 Olmsted County, MN, USA, residents following a fracture due to no more than moderate trauma in 1989–1991, adjusted for

age, by fracture site, and sex

Melton, Osteoporos Int. 2013 May ; 24(5): 1689

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Bliuc, JAMA, February 4, 2009—Vol 301

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Cameron, JBMR, 2010, pp 866 MUMC & UHasselt

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Adjusted* hazard ra8os of death among par8cipants with incident hip fracture and death

Ionnaidis, CMAJ 2009

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Fractures and mortality: literature review of prospective studies

A. Leboime et al. / Joint Bone Spine 77 (2010) S107

Population/cohort studies Osteoporosis cohort

Prevalent vertebral fracture Prof. D

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Paiern of mortality in the general popula8on and following hip fracture

Kanis, Bone 32 (2003) 468 MUMC & UHasselt

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MULTI-‐OUTCOME COMPETING RISK ANALYSIS (RE-‐FRACTURE + MORTALITY)

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•  Mul8-‐outcome compe8ng risk analysis – Compe88ef risicomodel

•  CBO 2011 •  Opsporingsbeleid

– Case finding •  Opvolging

– Follow up Prof

. Dr. P

. Geu

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Cumula8ve incidences of refracture and mortality following ini8al osteoporo8c fracture

Bliuc, JBMR, 2013, pp 2317 MUMC & UHasselt

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Schema8c illustra8on of various outcome states during 8me-‐to event analysis of fracture

Leslie, Osteoporos Int (2013) 24:681

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Mutis, Leukemia , 2010, 1388

Competing risk model in cancer patients

Effect of HA-1 disparity on all outcome parameters, depending on the aGVHD status. All curves estimated in a competing risks framework; the four panels arise from fitting a competing risk model on each of the four subgroups separately (that is, four univariate analyses without further model assumptions apart from the competing risks framework). RFS: relapse-free survival; NRM: non-relapse-related mortality.

MUMC & UHasselt

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Cumula8ve incidences of refracture and mortality following ini8al osteoporo8c fracture

Kaplan-‐Meyer

Bliuc, JBMR, 2013, pp 2317

At 5 yrs: 26% died 24% re-fracture

At 5 yrs: 37% died 20% re-fracture

MUMC & UHasselt

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Stacked graph of cumula8ve incidences of refracture, mortality following ini8al osteoporo8c fracture, and mortality following

refracture


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Stacked graph of cumula8ve incidences of refracture and mortality aJer one osteoporo8c fracture and aJer refracture compared with

an age-‐matched general popula8on

excess deaths after refracture

expected mortality excess deaths after initial fracture

refracture and alive alive, no fracture

Bliuc, JCEM, 2014

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Stacked graph of cumula8ve incidences of mortality following ini8al osteoporo8c fracture in black and

following refracture


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Pa8ents with hip fracture: risk of subsequent fracture and mortality

azMaastricht & UHasselt

Re-fracture risk Mortality Re-fracture risk in all in survivers

Von Friessendorf, JBMR, 2008

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Mortality and fractures aJer ini8al hip or hand/foot fracture Maastricht model

56%

8%9%

27%

1st Hip n=469Died, no 2nd fracture

Fracture + died

Fracture + alive

Alive, no 2nd fracture

Absolute fracture risk during survival: 39% 20%

Maastricht UMC UHasselt Huntjens, Osteoporos Int (2010) 21:2075

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WHY IS THE RISK OF MORTALITY INCREASED AFTER FRACTURE?

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Absolute mortality rates and age-‐adjusted standardized mortality ra8os according to BMD and ini8al fracture type

Bliuc, JBMR, 2014 MUMC & UHasselt

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Popula8on-‐aiributable risk/frac8on (PAR/PAF)

PAR

•  18% in women and 25% in men, similar for all types of ini8al NVNH fracture –  Bliuc, JCEM, 2014

•  a minority of deaths following hospitaliza8on for vertebral fracture are aiributable to the fracture itself –  Kanis, OI, 2004

PAF •  mortality associated with hip fracture during the first two years

contributed in men 4.2% and in women 5.1% to the total popula8on mortality (cigarie smoking and high blood pressure contributed to 8% and 7%) –  Omsland, Bone, 2014

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Excess deaths over 5 years in Dubbo popula8on by sex and age-‐group

For all fracture patients, 9·5% of deaths were listed as directly due to fracture, almost all of which were of the hip. The other causes of death for the fracture patients included causes secondary to cancer (21·9%), cardiac disease (33·3%), and stroke (18·1%),

Center, Lancet, 1999

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Bliuc, JBMR, 2014

11% of deaths in women and >30% of deaths in men could be attributed to low-trauma fractures

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Survival with Kaplan-‐Meier analysis during 22-‐yr follow-‐up

Von Friessendorf, JBMR, 2008 MUMC & UHasselt

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Black, JBMR, 2014

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Prevalence of cardiovascular risk factors and diabetes mellitus type 2 according to the center classifica8on

Wyers, BioMed Research International, 2014

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azMaastricht & UHasselt

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Kristensen, Medical Care, 2014 Prof

. Dr. P

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Kaplan–Meier survival analysis aJer hip fracture

I—independent community ambulator II—community ambulatory with cane

Group Ia: previous vertebral fracture at the time of hip fracture Group Ib: no vertebral fracture at the time of hip fracture

Ha, J Bone Miner Metab, 2014 MUMC & UHasselt

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Frost, Bone, 2011 MUMC & UHasselt

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The main causes of the excess mortality in the first 9 months were: - infections (HR: 6.66, 95% CI 1.95–22.77, p<.002) for females - cardiac disease (HR: 2.68, 95% CI 1.39–5.15, p<.003) for both males and females. Bisphosphonate use was associated with a reduction in mortality after hip fracture (p<.002).

Cameron, JBMR, 2010, pp 866 MUMC & UHasselt

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Frost, Bone, 2011 MUMC & UHasselt

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HR for mortality by number of dysmobility condi8ons and age

Looker, OI, 2014 MUMC & UHasselt

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Shortt, J Orthop Trauma 2005;19:396

MUMC & UHasselt

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Pre-‐opera8ve indicators for mortality following hip fracture surgery

Smith, Age and Ageing 2014; 43: 464 MUMC & UHasselt

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CAN WE INFLUENCE POST-‐FRACTURE MORTALITY?

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Watts, NEJM, 1990, 73

Can we decrease the risk of fractures? A shocking question before 1990

MUMC & UHasselt

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Agents for the preven8on of fragility fractures compared against placebo (combined direct and indirect es8mates).

Murad, JCEM, 2012, 1871

Network meta-analysis of 116 trials (139,647 patients; median age, 64 yr; 86% females)

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Can we decrease mortality after fractures? A shocking question now?

MUMC & UHasselt

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•  2.6% of incident fractures would be prevented if no women had heart disease

•  7.2% of incident fractures would be prevented if no women had osteoarthri8s

•  1.5% of incident fractures would be prevented if no women had COPD

•  0.4% of incident fractures would be prevented if no women had mul8ple sclerosis and 0.4% of incident fractures would be prevented if no women had Parkinson's disease.

Dennison, Bone 50 (2012) 1288

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5-‐year mortality rate aJer fracture and in the general popula8on according to femoral neck T-‐score stra8fied according to age (>75

and ≤ 75 years) and gender (women and men)

Bliuc, JBMR, 2014 MUMC & UHasselt

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Survival rate of pa8ents with interval from injury to surgery of >5 and ≤5 days

Li et al. Journal of Orthopaedic Surgery and Research 2014, 9:37 MUMC & UHasselt

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Hip fracture mortality

Thomas, Bone Joint J 2014;96-B:373 MUMC & UHasselt

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Mortality aJer recent hip fracture

Lyles, N Engl J Med 2007;357:1799- MUMC & UHasselt

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HR for reduc8ons in death by 8ming of first study drug infusion

Erikson, Bone Miner Res 2009;24:1308 MUMC & UHasselt

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Sattui, Nat. Rev. Endocrinol. 2014,10, 592

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Sattui, Nat. Rev. Endocrinol. 2014,10, 592 MUMC & UHasselt

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Kaplan-‐Meier survival curves according to osteoporosis medica8on for women with osteoporo8c fractures aged 60–74 yr (A), aged 75 yr (B).

MUMC&UHasselt Center, JCEM, 2011,1006

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Mortality incidence within 2 years aJer baseline fracture between the

interven8on and pre-‐interven8on group

Hazard ratio’s were calculated by multivariable Cox regression analysis with adjustment for age, sex and baseline fracture location

Huntjens, Injury, Int. J. Care Injured 42S (2011) S39

Before–after impact analysis in consecutive patients older than 50 years who were admitted In the same hospital with a NVF during 2 periods: 1/ pre-intervention group (n = 1,920, enrolled in 1999–2001) 2/ intervention group (n = 1,335, enrolled in 2004–2006).

MUMC & UHasselt

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Cumula8ve survival rate with mortality as the event for the pa8ents in the FLS group (black line) and the no-‐FLS group (gray line).

Huntjens, J Bone Joint Surg Am. 2014;96:e29(1-8)

Hospital with (MUMC) and without FLS (VieCuri) Years 2005-2006

MUMC & UHasselt

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Mechanisms of decreased post-‐fracture mortality

•  Decrease of subsequent fracture risk? –  Explains only 8% of zoledronate effect

•  Treatment of secondary osteoporosis, other metabolic bone diseases and co-‐morbidi8es?

•  Adequate calcium and vitamin D supply? •  …..?

MUMC & UHasselt

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Conclusions

•  The risk of mortality is increased aJer fracture •  Mul8-‐outcome compe8ng risk analysis (re-‐fracture + mortality) is the analysis of choice

•  We probably can influence post-‐fracture mortality: –  Decrease of subsequent fracture risk –  Treatment of secondary osteoporosis, other metabolic bone diseases and co-‐morbidi8es

–  Adequate calcium and vitamin D supply

–  And …..

MUMC & UHasselt

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It’s 8me now, Have a good and safe WE and winter holidays

MUMC & UHasselt

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seminair 22-11-2014 - prof. dr. p. geusens- osteoporose en mortaliteit

Health & Medicine