Jc- Risedronate in Osteogenesis Imperfecta

8/13/2019 Jc- Risedronate in Osteogenesis Imperfecta

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RISEDRONATE IN CHILDREN WITH OSTEOGENESIS

IMPERFECTA: A RANDOMISED, DOUBLE-BLIND, PLACEBO-

CONTROLLED TRIAL

Nick Bishop, Silvano Adami, S Faisal Ahmed et al..

The Lancet Oct2013;382:1424-32


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Introduction

Osteogenesis imperfecta (OI) also known as brittle bone disease is the mostcommon heritable bone disease with an osteoporotic phenotype.

Prevalence 1- 2 per 20000 population.

Affected children sustain recurrent fractures, bony deformity and bone pain.

Bisposponates are an established treatment , they areal bone mineraldensity

!isedronate an 3rd generation orally administered bisphosphonate was welltolerated and significantly B"# and reduced lon bone bowin deformities andfractures in mild to moderate disease state.


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Objective

!o investiate the safety and efficacy ofrisedronate in children with osteoenesisimperfecta ,most of whom had mild disease state.


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Inclusion criteria

"hildren with osteoenesis imperfecta aed 4-1$ years%

#ith h$o at least one non traumatic fracture or a lowimpact fracture alon with age ad&usted or se' ad&ustedareal B"# ( score of -0%1 or less for either total body orlumbar spine sites, or

An ad&usted areal B"# ( score of -0%2 or lessirrespective of history of fracture.


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Exclusion criteria

Patients who)eiged *10 +gs.

Patients with o cancerwithin the previous % yrs.

!hose with untreated ric+ets durin previous yrs.

erum 2$-ydro'y .it # conc *20nmol/%

&ad used treatmentsthat could affect interpretation of study findings%

&ad disease that was se.ere enouh that in their country of oriin they would normallyhave been offeredi%. bisposponates treatment%


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Study design

Prospective, parallel, double'blind.

andomied * placebo' controlled trail.

+ulti centre study, - hospitals of / different countries

0tudy period' / years

#ritten Informed consent was obtained from the patients1 parents or their leal

representatives.

Protocols were approved by the institutional ethics committee and review boards.


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Methodology -Trial profile

/ pts were screened, of which 23 met studycriteria and were assined randomly

43 in risedronate roup

%- in placebo roup

1$ )itdra)als


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Methodology

23 patients ,aed between 2'% yrs with OI were included in the study

elepone randomisation systemwas used to assin the patients under tworoups in 5 ratio.

roups of 43 * %- respectively (43'in risedronate roup * %-' in placebo roup)

!hese roups received daily risedronate (.%m for those who weihed -'/-ks

and %m for those who weihed 6 /- ks) or placebo for yr.

fter 1st yr all the patients were iven risedronate (open label pase).


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Methodology

7urin nd and /rd year of study patients received open labelresidronate daily dependin on their wt at the end of st yr.

0tudy treatment was iven, alon with 120ml )aterwas asked to take

at least /- mins before st food $drink of the day andremained uprihtfor /- mins after dosin.

All patients received daily calcium(%--'---m) and .itamin #(--' 8-- I9)appropriate to their weiht.


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Methodology

Patients visited study centers on screenin, baseline, and months/,8,,%,:,2,/- and /8 for clinical review.

+easurement of heiht and lateral lumbar spine radioraphswere donefor assessment of vertebral fracture status at screenin and annually

7ual enery ;ray absorptiometry scans of lumbar spine * total body

were ac


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Methodology.

0erum * urine analysis forbone turn o.er mar+erswere done at baseline * months/,8,,2 * /8.

9rinary ='terminal crosslinkin telopeptide oftype 1 collagenwas measured by /

5rinary creatininewas measured by std colorimetric assay.

0erum bone specific al+aline pospatasewas measured by immuno

chemiluminescence assay.

0erum chemistry, eamatology, tyroidand paratyroid function tests, .it #analysis, urineanalysis * radiograp of left and and )ristwere done periodicallyto assess bone ae.


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Statistical analysis

!he primary efficacy analysis was done by67Oand (test with treatment, ae roup * pooled centre as fi;edeffects and baseline as covariate.


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Results

>umbar spine areal B"# ( score were similar in bot the roup atbaseline.

"ean total body areal B"# ( score

risedronate roup ? '.2

placebo roup ? '.:

"ean B"# at the end of te placebo controlled pase wasobserved to be greater in risedronate group (2.2':.) than inplacebo roup(%.3' .3) withp*0%0001. (table')


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Results

able 2: chanes frombaseline in areal B"# ( scorefor lumbar spine* total body.

9igure 2: shows mean canges in areal bone mineral density.('areal @+7 of lumbar spine B' areal @+7 for total body)

able 35 incidence of vertebral collapses

9igure 4,$ : canges in urine 6' creatinine serum bonespecific al+aline pospatase conc%

able 45 Adverse effects,


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discussion

!he study shows sinificantly reater increase in lumbar spine areal@+7 at 8 * monthsin children with osteoenesis imperfecta treatedwith oral risedronate than in those iven placebo.

!he study of alendronate in /4 children with moderate to severeosteoenesis imperfecta, did not show a reduction in fracture incidencedespite an increase in lumbar spine areal @+7.


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Discussion !ise in lumbar spine areal B"# in children who recei.ed only

.itamin # calcium was steeper in first = monts tan insecond8months of placebo' controlled phase, this implies an effect ofsuch supplementation on fillin of the remodellin space.

=ew morpometric .ertebral collapses occurred in botgroups durin both placebo'controlled * open' label phases.


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Conclusion

Oral risedronate increased areal B"# * reduced te ris+ offirst * recurrent clinical fractures in children with osteoenesisimperfecta

!he dru was)ell tolerated.

>ess sinificant adverse effects with no deats%

isedronateshould be regarded as a treatment option for childrenwith osteoenesis imperfecta.


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merits

Prospective , parallel * double' blind

andomied * placebo controlled

+ulti centre study


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Demerits

!he study doesn1t include asian population.


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limitations

7onfirmatory radiograps )ere not obtained and sent to centralfacility.

=o patient sufferin from moderate to se.ere disease state wereconsidered.

=o child with se.ere .itamin # deficiencywere considered.


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Critiue of the paper Is the title suitable for the study doneB

Is the study hypothesis presented clearlyB

Is the review of literature appropriate * ade


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Jc- Risedronate in Osteogenesis Imperfecta