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Trial registered on ANZCTR


Registration number
ACTRN12614001230640
Ethics application status
Approved
Date submitted
31/07/2014
Date registered
24/11/2014
Date last updated
4/02/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
A pilot study to assess bone mineral density (BMD) by digital X­ray radiogrammetry (DXR) in women undergoing mammography, and comparison with BMD by dual energy X­ray absorptiometry (DXA)
Scientific title
Investigating postmenopausal women over the age of 50 with digital X-ray radiogrammetry (DXR) at the time of mammography to determine bone mineral density (BMD) and comparison with BMD determined by dual energy X-ray absorptiometry (DXA).
Secondary ID [1] 284699 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoporosis 292042 0
Condition category
Condition code
Musculoskeletal 292378 292378 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Digital X-ray Radiogrammetry (DXR)

Participants will undergo digital x-ray radiogrammetry (DXR) at the time of mammography. This involves women placing their hand on the x-ray plate of the mammogram machine and having a simple x-ray of their hand taken. This x-ray image is then deidentified and digitally analysed to determine the individuals BMD.
Intervention code [1] 289479 0
Early detection / Screening
Comparator / control treatment
Dual energy X-ray absorptiometery (DXA):

Patients will be required to undergo a DXA scan (current gold standard for BMD assessment) for the purpose of comparison after they are assessed with DXR. This will involve participants travelling to the designated DXA facility in Chatswood in order to be scanned. The process of DXA scanning involves the participant lying supine on the imaging bed and being imaged at the head and neck of femur, wrist, lumbar spine.
Control group
Active

Outcomes
Primary outcome [1] 292248 0
The primary objective of this pilot study is to determine the correlation between BMD assessed by hand DXR and DXA of the spine hip and forearm, using a local Australian population attending for follow up mammography.
Timepoint [1] 292248 0
At the conclusion of the study (200 participants enrolled and followed up)
Secondary outcome [1] 308532 0
To determine the sensitivity and specificity of DXR for DXA determine low BMD (current gold standard).
Timepoint [1] 308532 0
At the conclusion of the study (200 participants enrolled and followed up)
Secondary outcome [2] 308533 0
To determine the ease with which DXR can be performed in conjunction with routine mammography, including patient and staff satisfaction with the technique.

In order the assess these parameters, patients and radiographers will complete a questionnaire, designed specifically for the study, addressing their perceived satisfaction with the imaging process. In the case of patients this will be done at the end on the DXR imaging process. For radiographers, this will be done at the conclusion of the study.
Timepoint [2] 308533 0
At the conclusion of the study (200 participants enrolled and followed up)

Participants will complete a brief survey, designed specifically for the study, at the end of their procedure that addresses their satisfaction with the imaging technique. This will also be undertaken for the radiographers involved to ascertain the ease of use of DXR, in this case they will be surveyed at the end of the study.
Secondary outcome [3] 308534 0
To utilise DXR T-scores and questionnaire responses, to assess how closely fracture risk is predicted by DXR compared to DXA using the validated fracture risk prediction tools; FRAX and the Garvan fracture risk calculator.
Timepoint [3] 308534 0
At the conclusion of the study (200 participants enrolled and followed up)

Each patient will complete a brief questionnaire in the waiting room before the DXR assessment is performed. DXR data will be available after the scan has been completed. The comparative DXA data will be available after the DXA assessment has been performed in Chatswood.

Eligibility
Key inclusion criteria
All participants included will be women who are postmenopausal and over the age of 50
Minimum age
50 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Male, premenopausal, less than 50 years old, physically unable to meet the criteria required for the study

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
200 participants will be recruited for the study. Participants will be post-menopausal women, aged over 50, who provide informed consent and who are attending for a diagnostic mammogram at the Breast Cancer Institute (BCI) at Westmead Hospital. For women who have had a hysterectomy and may not know their menopausal status, women aged 55 and over will be eligible for inclusion.

Women will be broadly informed of an opportunity to participate in this research before their appointment at the Breast Cancer Institute (BCI).

They will then be approached on the day of their appointment and provided with additional information regarding the study. They will then be able to make a decision as to whether they would like to participate in the study. At all times there will be a member of the research team available to answer and questions.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will not be randomised. All women included in the study will undergo both BMD assessment using DXR and DXA for comparison.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
All data will be entered into the Statistical Package for the Social Sciences (SPSS) and analysed using descriptive statistics.

Linear correlation modelling will be used to compare DXR-BMD measurements with BMD measurement obtained using DXA at the forearm, hip and spine.

The relationship of BMD measurements by DXA and by DXR to postmenopausal risk factors, such as self-reported fracture, use of glucocorticoids and other risk factors assessed in the study questionnaire, will be analysed using logistic regression models.

Receiver operator characteristic curve analysis will be used to determine DXR cut-offs that define 90% sensitivity and 90% specificity to have or not have reduced DXA-derived BMD (defined as T-scores less than or equal to -1 in the osteopaenic range and T-scores less than or equal to -2.5 in the osteoporotic range) at the forearm, hip or spine. This will indicate the percentage of the study participants who would require additional DXA evaluation to ascertain whether they have a low BMD, and will provide an indication of the practical, clinical utility of DXR screening.

Where there is a discrepancy between the DXR and DXA T-scores equal to 1 SD, the individual hand X-rays will be reviewed. A post hoc analysis of these patients will be undertaken to determine the characteristics of this group and to potentially highlight the cause of any discordance.

A cost analysis will be undertaken in order to determine the additional cost (including commercial costs quoted by Sectra and radiographer time) of using DXR as an addition to standard mammography screening.

Fracture risk, using the FRAX and the Garvan calculators (that are validated for DXA), will be calculated using T-scores derived from both DXR and DXA in conjunction with questionnaire data. The FRAX for DXA will be calculated on site in Chatswood after the completion of the DXA and included in the patient report. These calculators provide 5 and 10-year risks for any fracture and hip fracture. Because the Garvan calculator is only valid for women aged 60 years and over, not all data will be appropriate for that risk calculator. Australian population data will be used for the calculation of the FRAX.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 2515 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 8155 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 289318 0
Other Collaborative groups
Name [1] 289318 0
Sydney West-Translational Cancer Research Centre (SW-TCRC)
Address [1] 289318 0
Crown Princess Mary Cancer Centre Westmead
PO Box 533 Wentworthville
Westmead Hospital
Westmead NSW 2145
Country [1] 289318 0
Australia
Primary sponsor type
Hospital
Name
Breast Cancer Institute (Westmead Hospital)
Address
Level 1, Westmead Hospital Cnr Hawkesbury & Darcy Roads
Westmead
NSW
2145
Australia
Country
Australia
Secondary sponsor category [1] 287989 0
None
Name [1] 287989 0
Address [1] 287989 0
Country [1] 287989 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291081 0
Western Sydney Local Health District HREC
Ethics committee address [1] 291081 0
Westmead Research Office,
Room 1072,
Level 1 Education Block,
Westmead Hospital
Hawkesbury Road
Westmead 2145, NSW
Ethics committee country [1] 291081 0
Australia
Date submitted for ethics approval [1] 291081 0
15/10/2013
Approval date [1] 291081 0
06/03/2014
Ethics approval number [1] 291081 0
HREC2013/12/2.5(3851) AU RED HREC13/WMEAD/365

Summary
Brief summary
This project is a pilot study that aims to evaluate the accuracy of digital X­ray radiogrammetry (DXR) in determining bone mineral density (BMD), as compared to BMD by dual energy X­ray absorptiometry (DXA). Participants will be women aged fifty years or older who are postmenopausal and are attending for a follow up mammogram.

DXR is a method that can be used to estimate BMD from plain digital hand X­ray images. It assesses BMD from images of the mid 2nd, 3rd and 4th metacarpals. The data is then transmitted in deidentified fashion to Sectra, a Swedish company that has developed the ‘OneScreen’ technology, that combines both mammography and digital X­ ray radiogrammetry. A BMD in g/cm2, a T­score and a Z­score are then transmitted back within minutes. A number of studies have demonstrated that T and Z­scores derived from such DXR examinations correlate closely to values derived by DXA, which is considered the gold standard for screening or follow up bone densitometry. BMD by DXR has been shown to predict fracture risk, similarly to DXA.

Women over the age of 50 who are postmenopausal may already have low BMD and are at risk of further BMD reductions. Women who attend for follow up mammography are, in addition, a group who may require breast surgery and possibly aromatase inhibitors that eliminate sex steroid production and increase fracture risk. The addition of a digital hand X­ray for DXR analysis to the mammography examination requires no additional equipment and takes only a few seconds. If DXR is shown to correlate closely to DXA in our local population, it has potential to be used in osteoporosis screening for women who may require aromatase inhibitors. If cost effective, it might even be considered as a screening tool when women attend for routine mammography, because women screened for breast cancer are the same group who may benefit from awareness of low BMD.

After ethical approval of this study and after participants have provided informed consent, data will be collected from women over the age of 50 who are post­menopausal and who present for a second mammogram after having a positive screening mammogram in the community. The women will complete a short questionnaire following which DXR of the hand will be performed immediately after mammography and the DXR images will be transmitted for analysis. This de­identified data is generally returned within 5 minutes with BMD Z and T­scores.

Participants will also undergo a DXA examination of the forearm, hip and spine to allow a comparison of the DXR measurements. Participants with results by DXA that indicate a BMD in the osteopaenic range will be provided with a letter which can be taken to their general practitioner for further discussion. Any participant with a BMD in the osteoporotic range will be given a letter for their general practitioner who will also be informed of the result by telephone. For participants with T­scores less than ­3 (indicating osteoporotic­range BMD at or greater than 3 standard deviations below the mean), referral to a specialist will also be suggested. While physicians associated with this study will be available to discuss any result with a participant, they will not be involved in ongoing management for ethical reasons.

To date, DXR using the Sectra system has not been used in Australia, but has undergone evaluation at single sites in the UK, Sweden and the USA. If the technique proves accurate for BMD evaluation in this pilot study, wider application for BMD evaluation in women undergoing mammography might be considered. Compared to DXA, it would be more simple and convenient, is lower radiation and may be cost effective enough to consider as a screening tool in either specific circumstances (such as follow up mammography) or for general postmenopausal evaluation.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 60 60 0 0

Contacts
Principal investigator
Name 38086 0
A/Prof Grahame Elder
Address 38086 0
Department of Renal Medicine,
Westmead Hospital,
Cnr Hawkesbury and Darcy Roads,
Westmead, NSW, 2145
Country 38086 0
Australia
Phone 38086 0
+61 2 98456962
Fax 38086 0
Email 38086 0
g.elder@garvan.org.au
Contact person for public queries
Name 38087 0
Dr Elisabeth Elder
Address 38087 0
Breast Cancer Institute
Westmead Hospital
Cnr Hawkesbury and Darcy Roads,
Westmead, NSW, 2145
Country 38087 0
Australia
Phone 38087 0
+61 2 98455555
Fax 38087 0
Email 38087 0
elisabeth.elder@bci.org.au
Contact person for scientific queries
Name 38088 0
A/Prof Grahame Elder
Address 38088 0
Department of Renal Medicine,
Westmead Hospital,
Cnr Hawkesbury and Darcy Roads,
Westmead, NSW, 2145
Country 38088 0
Australia
Phone 38088 0
+61 2 98456962
Fax 38088 0
Email 38088 0
g.elder@garvan.org.au

No information has been provided regarding IPD availability
Summary results
No Results