The effect of low-dose radiotherapy on pain in mild osteoarthritis of the hip

Osteoarthritis (OA) is a degenerative disorder of articular joints leading to a
gradual loss of articular cartilage. This disease can give rise to pain, joint
effusion, locking phenomena and a limited range of motion. The increase in life
expectancy, change in life-style habits as well as a growing number of obese
patients lead to a growing number of patients suffering from painful OA. Above
the age of 65 years, 17% of the male population and 29% of the female
population has some degree of OA. Although it is well known that there is a
large discrepancy between radiologic findings and pain, the percentage of
patients suffering from pain increases with the radiologic grade of OA.

Initial management of osteoarthritis is usually conservative. This may include
analgesics and non-pharmacological therapy such as weight loss, physical
therapy and ambulatory aids. Non-steroidal anti-inflammatory drugs (NSAIDs) and
corticosteroid injections are considered to be preferred agents for the
pharmacological management of OA. However, many of the NSAIDs, both the COX-2
selective inhibitors and the traditional NSAIDs, are associated with a
moderately increased risk of cardiovascular events and gastro-intestinal
problems. Local treatment with intra-articular injections can be effective, but
longer-term benefits have not been confirmed. If conservative treatment fails,
surgical options are considered, of which joint arthroplasty is most effective.
In the older patient, especially when severe comorbidity is present, surgery
may be considered too risky. Therefore effective non-invasive treatment options
are urgently needed for patients with a painful OA, who cannot be operated
because of their comorbidity, or are not willing to undergo surgery.
Furthermore, in early stages of OA, other conservative treatments options are
needed to relieve pain, postpone operative intervention and minimize
analgesic-related side-effects.

Currently, radiotherapy for pain reduction in OA is an accepted and frequently
used treatment in Germany and in Central and Eastern European countries. It is
not commonly practised in other parts of the world due to conflicting
literature on this topic and fear of tumour induction. Even though some studies
show excellent results regarding this treatment, the quality of the available
literature is not convincing and level I evidence is still missing.

The main objective of this prospective randomized study is to examine the
effect of low-dose radiotherapy on pain sensation in patients with early OA of
the hip.

Our hypothesis is that radiotherapy can achieve a pain-reducing effect of at
least 20% after 6 months.

Clinical, prospective, randomized study.

Low-dose radiotherapy provides for a low-risk, non-invasive treatment modality
for patients with painful osteoarthritis. It could potentially lower the need
for medication with its related side-effects, and possible postpone or prevent
surgical intervention.
Directly following radiation, the joint might be slightly more painful, but
this effect normally disappears in the first weeks after radiation. The
reported life-time risk of cancer induction due to LDRT is about 0.2%.

Cancer induction due to radiotherapy
There is ongoing discussion about the risk of cancer induction due to low-dose
radiotherapy. Dose distribution in the body is not homogeneous during radiation
therapy, which together with the different susceptibilities for
radiation-induced carcinogenesis in the different organs exposed, makes it
difficult to properly estimate the risk. The concept of *effective dose
delivered to tissues* introduced by the International Commission on
Radiological Protection (ICRP) contributes to a more accurate estimation of
this risk.
The effective radiation dose which is delivered to tissues is dependent on the
weighing factors of the tissue.These factors represent the susceptibility of
the tissue to radiation. The effective radiaton dose is measured in Sievert
(Sv), whilst the overall administered dose is measured in Gray (Gy).

During irradiation of the hip joint, the exposed tissues include bone marrow,
bone, skin and muscle. We estimate that the hip joint will consist of at most
3% of the total body tissue. An estimate of the total effective dose of 6 Gy
radiotherapy of the hip joint can be calculated as follows:

E = 0.12 (weighing factor red bone marrow) x 6 (6 Gy) x 0.03 (3% of tissue) +
0.01 (weighing factor skin) x 6 x 0.03 + 0.01 (weighing factor bone) x 6 x 0.03
+ 0.05 (weighing factor other tissues) x 6 x 0.03 = 34 mSv

This number can be used to make a rough estimation of the risk of cancer
induction, specifically the life-time risk of developing a fatal tumour. For
the general population, this risk has been set on 5% per Sv. Thus, in the case
of 6 Gy radiotherapy, the added life- time risk for developing a fatal tumour
would be 0.2%. It needs to be noted that the average time for developing an
hematological malignancy is between 5 and 10 years. For solid tumours, this
time is around 15-20 years. We will estimate that our patient population will
have an average age of around 70 years, which makes the risk of tumour
induction by 6 Gy radiotherapy extremely low.

For reference, the annual background radiation in The Netherlands is about 2
mSv whilst a trans-Atlantic flight from Amsterdam to New York amounts to about
0.04 mSv. For further reference, patients with head/neck carcinomas are
irradiated with 70 Gy (35 fractions), lung carcinomas up to 69 Gy (42
fractions) and oesophagus carcinomas up to 41.4 - 50.4 Gy.