The effect of high-resistance muscle strength training and vitamin D supplementation in persons with knee osteoarthritis

As there is currently no cure for OA, conservative treatment is the cornerstone
of OA management. Muscle strengthening in particular is a key-target in the
conservative treatment of knee OA. In all major international treatment
guidelines, exercise therapy (with a dominant role for muscle strengthening) is
recommended. However, the optimal training intensity of muscle strengthening
exercises in knee OA is not known to date and this is important to maximize
patient outcomes from exercise therapy. Based on research in non-OA populations
it is expected that high-resistance strength training is more effective than
low-resistance strength training to improve muscle strength, without causing
serious side effects.
Also, it has been hypothesized that vitamin D supplementation could enhance the
effects of exercise therapy on muscle strength, since low serum 25-hydroxy (OH)
vitamin D level, which is common in older adults, is associated with impaired
muscle cell function. In healthy subjects, indications for a beneficial effect
of vitamin D supplementation plus exercise on muscle strength have been found.
To improve the effectiveness of strength training in patients with knee OA
vitamin D supplementation has the potential to be a useful adjunct.

To determine (1) whether high-resistance strength training (70-80% of
one-repetition maximum (1RM)) is more effective in improving muscle strength
compared to low-resistance strength training (40-50%% of 1RM) and (2) whether
vitamin D supplementation enhances the effect of muscle strength training on
muscle strength in knee OA patients with vitamin D deficiency.
The ultimate goal of the intervention study is to optimize strength training in
knee OA, thereby increasing the beneficial effect on pain and activity
limitations.

We will conduct a randomized controlled trial with a 2x2 factorial design
(n=220). Participants will be randomized into four groups: 1) high resistance
strength training and vitamin D3 supplementation, 2) high resistance strength
training and placebo, 3) low resistance strength training and vitamin D
supplementation, 4) low resistance strength training and placebo. Measurements
will be performed at baseline (start of vitamin D supplementation or placebo),
at 3 months (start of strength training), at 6 months (post-intervention), and
at 12 months (6 months post-intervention).

Addendum:
In addition, 68 knee OA patients with normal vitamin D levels will be included
in order to study the effect of high versus low resistance strength training.
The larger sample size (n=288) will lead to more statistical power (0.90).
Patients with normal vitamin D levels will be randomized into either high or
low resistance training, without supplementation with vitamin D or placebo.
These patients will have 3 measurement points instead of 4 measurement points:
measurements on T1 will be their baseline measurement, as they will start with
resistance training without a previous period of supplementation.

The total intervention period will be 6 months. In the first 3 months, vitamin
D tablets (1200IU daily) or placebo tablets will be taken in order to increase
the 25(OH) vitamin D level (in case of vitamin D tablets). In the second 3
months, patients will additionally receive a strength training program,
including exercises that are primarily aimed at improving quadriceps and
hamstrings strength. Both the high-resistance strength training group and the
low-resistance strength training group will exercise 3 times per week (2
supervised sessions at Reade and 1 home exercise program). In the
high-resistance group exercises will be performed with a load of 70-80% of 1
repetition-maximum (1RM) compared to a load of 40-50% of 1RM in the
low-resistance group.

Potential participants will be screened with an internet-based (or postal if
applicable) questionnaire and by telephone, followed by a screening visit
(short physical examination, questionnaire and blood draw). If they pass the
screening visit they will be invited to come to Reade for a visit with the
rehabilitation physician and rheumatologist for diagnosis and final decision on
eligibility. Participants will be measured four times: at baseline, after 3, 6
and 12 months. Participants have to complete questionnaires and perform
physical performance tests and blood and urine will be collected.
The total intervention period will be 6 months. In the first 3 months, vitamin
D tablets (1200IU daily) or placebo tablets will be taken. In the second 3
months, patients will additionally receive a strength training program. The
risk of the vitamin D treatment is negligible. Strength training is an
effective and recommended treatment in patients with knee OA. Risks are
minimal, due to supervision of experienced physical therapists and wide
experience of the research group in conducting exercise trials in knee OA.