Evaluation of the prevalence, incidence and progression of bone erosions in rheumatoid arthritis (RA) by high-resolution peripheral quantitative computer tomography (HRpQCT) compared to standard imaging techniques

High resolution peripheral quantitative computed tomography (HRpQCT) is a novel
in-vivo imaging technique to assess cortical and trabecular bone structure in 3
dimensions (3-D) with a resolution of 82 micrometer. It has been demonstrated
that HRpQCT enables to identify cortical defects (bone erosions) in small hand
joints up to 20-40 times more frequently than on conventional hand X-rays. Bone
erosions in the small hand joints on X-rays are the standard method to evaluate
bone destruction in rheumatoid arthritis (RA), cross-sectionally and
longitudinally. This study aims to assess whether it is possible to identify
3-D bone erosions in patients with RA at an earlier time and with higher
sensitivity than with conventional 2-D X-ray, magnetic resonance imaging (MRI)
and ultrasound (US). If confirmed, HRpQCT could become a new and more sensitive
method of choice to detect bone erosions in RA. Detection of small erosions
earlier in time may have direct implications since treatment is more aggressive
in more severe and erosive RA.

The primary objective is to study 1/ cross-sectionally the prevalence of bone
erosions and 2/ longitudinally the progression of bone erosions in the 2nd and
3rd proximal interphalangeal (PIP) joints and metacarpophalangeal (MCP) joints
of the hands bilaterally in patients with RA, and healthy controls only the
dominant hand 2nd and 3rd PIP, MCP joints and including the 2nd and 3rd DIP
joints, by using the HRpQCT (Total of 800 RA + 480 healthy control joints in
the study). Secondary objectives are to compare the number of joints with
erosions detected by HRpQCT with 1/ the number of joints with erosions detected
by X-rays, MRI and US and 2/ the number of joints with osteitis by MRI; to
explore possibilities to quantify the 3-D joint space volume occupied by
cartilage; and to correlate the prevalence and progression of erosions with
serum bone turnover markers.

Exploratory, single-centre cohort study

Blood 2x 4ml EDTA and 2x 10 ml serum.
HRpQCT and radiography, in total 80 microSv for RA patients and 68 microSv for
healthy controls and females with handosteoarthritis .

After screening, there will be 2 study visits in a 1-year period. Each visit
takes approximately 2 hours, thus 4 hours in total. During the visits, X-rays,
ultrasound (not applicable for females with handosteoarthritis), HRpQCT and MR
(not applicable for females with handosteoarthritis)I of the hands will be
performed. In total 28mL blood will be collected ( 20ml Serum and 4ml EDTA),
which will be combined with routine laboratory assessments for outpatient
clinical care. Clinical information on disease activity will be collected from
medical charts. The effective dose the patient will be exposed to during an
X-ray measurement is around 10 µSv (2 measurements during the study, total 20
µSv). Adding up to the radiation dose from the HRpQCT device (60 µSv), the
total radiation dose on patients during the entire study will be around 80 µSv
for RA patients, and 62µSv for healthy controls and females with
handosteoarthritis because of the reduction to dominant hand including DIP
joints, which is equivalent to 1.5 week background irradiation in the
Netherlands.
There are no direct benefits for the subjects who participate in this study.
However, the knowledge which will be gained by this study may have potential
benefits for RA patients in the future.