Assessment of Efficacy of Low Intensity Resistance Training in Men at Risk for Symptomatic Knee Osteoarthritis

Over 9.3 million adults over the age of 60 are afflicted with symptomatic knee
osteoarthritis (OA) characterized by radiographic findings and consistent knee pain or
stiffness. Furthermore, our research has indicated that reduced strength is a risk factor
for incident symptomatic knee OA and progressive knee OA in women.1, 3 In light of this
finding, there is a need to increase quadriceps strength to attenuate worsening of this
disease. Studies and practice have long indicated that high intensity resistance training is
the most efficient means of eliciting skeletal muscle hypertrophy and strength gains.2, 4
The American College of Sports Medicine as well as the National Strength and Conditioning
Association have indicated that a resistance training intensity of greater than 65% of the
one-repetition maximum (1 RM) is the minimum intensity needed to achieve desired muscle
hypertrophy and strength gains.2, 4 This is problematic for those suffering from symptomatic
knee OA. Loading an already painful joint at 65% of (1 RM) would be poorly tolerated and
possibly injurious for an individual already suffering knee pain and stiffness during
activities of daily living. With the inability to perform the exercises prescribed to elicit
the necessary strength gains, knee OA sufferers find themselves unable to alleviate
debilitating pain that can result in significant decreases in quality of life. Fortunately,
a method of training, called partial blood flow restriction (PBFR), may offer older adults
and particularly those with knee OA, the ability to develop the strength gains necessary to
attenuate disease progression without requiring deleterious joint loading. There is mounting
evidence that this training modality serves as a stimulator of muscle growth even when
performed at relatively low intensities.

PBFR was developed in Japan. Its basic principles involve the restriction of blood flow to
the exercising muscle with the purpose of increasing muscle mass. However, participants are
able to elicit similar strength gains performing exercises at, for example, only 30% of 1RM
to those attained through conventional high intensity resistance training. Current PBFR
training methods are the result of 40 years of research and development.5 Recent studies
have demonstrated efficacy and some mechanisms for the effect of PBFR training eliciting
significant isometric and isokinetic strength gains as well as increasing ability of adults
to perform functional tasks.6 Exercising at only 30% 1RM, PBFR training may benefit older
adults suffering from knee OA by enabling development of the strength necessary to protect
against disease worsening while avoiding the need to load the joint at deleterious levels.

This study is a follow-up study to IRB#201101711 that we completed earlier this year. That
study demonstrated tolerance and safety of the protocol. However, the increases in strength
were of a smaller magnitude than we hoped to elicit. The protocol for this follow-up study
is very similar to the prior study. We have made some changes in an effort to maintain
tolerability and safety, while hopefully eliciting a greater clinical benefit. Specifically,
we have reduced the study duration from 9 to 4 weeks and have selected a more efficient
exercise protocol that will both reduce subject burden while also halving the length of time
that the PBFR cuffs will be worn for each exercise session. The prior study was too gentle
to strengthen the quadriceps muscles, so we have increased the resistance from 15% of their
maximum to 30% of their maximum. This is still low intensity compared with usual weight
lifting that would be at >65%. We believe that these changes will increase benefit to
participants while reducing the time burden.

Literature cited

1. Segal NA, Torner JC, Felson D, Niu J, Sharma L, Lewis CE et al. Effect of thigh
strength on incident radiographic and symptomatic knee osteoarthritis in a longitudinal
cohort. Arthritis Rheum 2009;61(9):1210-7.

2. Abe T, Kearns CF, Sato Y. Muscle size and strength are increased following walk
training with restricted venous blood flow from the leg muscle, Kaatsu-walk training. J
Appl Physiol 2006;100(5):1460-6.

3. Segal NA, Glass NA, Torner J, Yang M, Felson DT, Sharma L et al. Quadriceps weakness
predicts risk for knee joint space narrowing in women in the MOST cohort.
Osteoarthritis Cartilage 2010;18(6):769-75.

4. Abe T, Kearns CF, Manso Filho HC, Sato Y, McKeever KH. Muscle, tendon, and somatotropin
responses to the restriction of muscle blood flow induced by KAATSU-walk training.
Equine Vet J Suppl 2006(36):345-8.

5. Sato Y. The history and future of KAATSU Training. Int J KAATSU Training Research
2005;1:1-5.

6. Fry CS, Glynn EL, Drummond MJ, Timmerman KL, Fujita S, Abe T et al. Blood flow
restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in older
men. J Appl Physiol;108(5):1199-209.

7. Takarada Y, Takazawa H, Ishii N. Applications of vascular occlusion diminish disuse
atrophy of knee extensor muscles. Med Sci Sports Exerc 2000;32(12):2035-9.

8. Takano H, Morita T, Iida H, Asada K, Kato M, Uno K et al. Hemodynamic and hormonal
responses to a short-term low-intensity resistance exercise with the reduction of
muscle blood flow. Eur J Appl Physiol 2005;95(1):65-73.

9. Fujita S, Abe T, Drummond MJ, Cadenas JG, Dreyer HC, Sato Y et al. Blood flow
restriction during low-intensity resistance exercise increases S6K1 phosphorylation and
muscle protein synthesis. J Appl Physiol 2007;103(3):903-10.

10. Iida H, Kurano M, Takano H, Kubota N, Morita T, Meguro K et al. Hemodynamic and
neurohumoral responses to the restriction of femoral blood flow by KAATSU in healthy
subjects. Eur J Appl Physiol 2007;100(3):275-85.

11. Cook SB, Clark RC, Ploutz-Snyder LL. Effects of Exercise Load and Blood-Flow
Restriction on Skeletal Muscle Function. Med Sci Sports Exerc 2007.

Inclusion Criteria:

- male

- ≥ 45 years

- has at least one of the following: BMI≥25, frequent knee symptoms on most of the last
30 days, history of knee injury which rendered individual unable to walk without
assistance for at least 2 days, history of knee surgery, diagnosis of knee
osteoarthritis

Exclusion Criteria:

- Resistance training at any time in the last 3 months prior to study

- Bilateral knee replacement

- Lower limb amputation

- Lower limb surgery in the last 6 months that affects walking ability or ability to
exercise

- Back, hip or knee problems that affect walking ability or ability to exercise

- Unable to walk without a cane or walker

- Inflammatory joint or muscle disease such as rheumatoid or psoriatic arthritis or
polymyalgia rheumatica

- Multiple sclerosis

- Known neuropathy

- Self-report of Diabetes

- Currently being treated for cancer or having untreated cancer

- Terminal illness (cannot be cured or adequately treated and there is a reasonable
expectation of death in the near future)

- Peripheral Vascular Disease

- History of myocardial infarction or stroke in the last year

- History of deep venous thrombosis

- Chest pain during exercise or at rest

- Use of supplemental oxygen

- Inability to follow protocol (e.g. lack of ability to attend visits or understand
instructions)

- Staff concern for subject health (such as history of dizziness/faintness or current
restrictions on activity)

- Concurrent study participation

- Unable to attend more than 2 days within any 1 week or unable to attend 4 or more
sessions during the study