Botulinum toxin injections may rebalance calf muscle forces.
Rebalancing may reduce knee joint forces to benefit osteoarthritis conditions.
Clinically significant improvement of a patient’s condition observed.
Added insight from a musculoskeletal simulation model.
The results support further investigation by randomized trials.
Knee osteoarthritis is a progressive disease that may require management for years before knee arthroplasty can be considered. Previously reported musculoskeletal models suggest that rebalancing the strength of the triceps surae muscles can reduce the joint loads.
A single patient diagnosed with mild/moderate medial left knee osteoarthritis was treated with botulinum toxin injections in the gastrocnemius muscle of the calf, based on the hypothesis that this would rebalance the triceps surae load distribution and reduce tibiofemoral joint loads. Tests were performed before and 4 weeks after injection to record functional clinical scores and to obtain lower limb joint kinematic and kinetic data of walking, which were subsequently analyzed with a musculoskeletal simulation model.
The patient experienced a clinically relevant improvement in self-reported pain levels in activities-of-daily-living, stair climbing, 6 minutes’ treadmill test, range-of-motion, and in the functional knee questionnaire, KOOS. No improvement was seen when performing lunges. The musculoskeletal simulations showed the expected shift in loads between the muscles, reduced knee loads, and improvement of the load symmetry between the legs.
The case corroborates the hypothesis, and this suggests further tests by randomized controlled trials. If confirmed, this simple and reversible medical intervention can improve the management of early-stage knee osteoarthritis.
). KOA limits activities-of-daily-living and reduces quality-of-life. Reduced ability to engage in social and physical activities can lead to isolation, depression, sedentary lifestyles, and obesity.
), so there is a strong interest in non-surgical management strategies to postpone or avoid surgery, especially for young KOA patients (
). Weight loss reduces the load on the joint proportionally and has beneficial effects on KOA symptoms (
). Muscle forces contribute a dominant part of the tibiofemoral joint loads (
). Weight loss and exercise therapies with potential influence on muscle strength are therefore considered as the “first choice” of non-surgical intervention (
quantified the contribution of the gastrocnemius to the knee compressive force, mainly in the second peak of the stance phase of walking gait.
devised a biofeedback training system to reduce the activation of the gastrocnemius in favor of the soleus and reported a reduction of the simulated internal joint forces by 12%. All things equal, rebalancing of the calf muscle forces would offload the joint corresponding to a significant weight loss.
) based on the idea that pain can be a result of prolonged contraction of the adductor muscles.
Here, we build on the biomechanical arguments for load rebalancing referred above and hypothesize that BT intervention in the gastrocnemius muscle will offload the tibiofemoral joint, primarily in the second peak of the stance phase, and that this will lead to an improvement of the patient’s condition. We report on a KOA patient case with subject-specific musculoskeletal models based on motion data pre and post-intervention to take possible changes in the motion pattern and ground reaction forces into account. This offers a simulation-based insight that is not dependent on an all-things-equal presumption.
The experimental protocol was approved by the Regional Ethical Review Board of Capital Region of Denmark, Journal no. H-19072203.
This study included a female patient, 55 years of age, body weight 66.3 kg, stature 153.2 cm, and BMI 28.3 with bilateral knee pain, which was more severe in the left knee. The pain was activity-related as well as at rest. The patient reported a declining ability for distance walking and participation in leisure activities such as cycling and recreational dancing.
Radiological examination of the knee showed bilateral incipient medial KOA (Ahlbeck grade 1), and 6.0/6.4 degrees varus in the left/right knees respectively. The patient was initially referred to municipal strength training but experienced a deterioration in her functional and pain status. She was then treated with an arthrocentesis with steroid injections in both knees without effect, after which an arthroscopic housecleaning of the left knee was performed. This showed grade 3 osteoarthritis in the medial femoral condyle including the patellofemoral joint. The medial tibial surface had significant grade 3 osteoarthritis. Normal cartilage was found in the lateral joint compartment. The arthroscopy initially relieved symptoms, which returned after 3 months.
The patient was referred for evaluation since she wanted an alternative to surgical treatment with knee arthroplasty. The patient signed a written informed consent form according to local guidelines.
Table 1Summary of the experimental procedure.
VAS: Visual Analog Scale. KOOS: Knee Injury and Osteoarthritis Outcome Score. GRF: Ground Reaction Force.
). The patient walked with preferred speed along the pathway without regard for the force plates, until five complete hits on the force plates were obtained for each leg. Knee extension and plantar flexion strength were subjectively assessed by a trained clinician on a scale from 0 to 5 according to
Botulinum toxin A injections were performed ultrasound-guided and without anesthesia with 150 ie Dysport (300 ie Dysport/1.5 ml NaCl) into both heads of m. gastrocnemius in the left calf, following an established clinical procedure. The drug reaches maximum effect after approximately 4 weeks and gradually wears off after 12–24 weeks.
). The model was built on the Twente Lower Extremity Model ver. 2 (
), which is accessible in open source via the AnyScript Managed Model Repository (
). The model was driven by the gait marker data, which also created a subject-specific scaling of segment dimensions (
), and loaded by the force plate data. The post-trials assumed 20% reduced strength in both heads of the left m. gastrocnemius to account for the effect of the injections.
Table 2Test results pre and 4 weeks post-injection.
Pains scores are on the VAS scale. Knee range-of-motion is in degrees as max extension-max flexion. Ankle range-of-motion is reported in degrees as max dorsi flexion-max plantar flexion. Range-of-motion and strength pertain to the left side, while the VAS scores are not side-speciic. *The patient was exhausted and could not perform the test.
The average daily pain reduction was 3 on the VAS scale, and reductions of 2.5–3 were recorded for the treadmill test. Stair climbing VAS was reduced by 4, while there was no difference for the lunges. The knee range-of-motion was improved by 35 degrees due to reduced swelling around the joint. The ankle range-of-motion was unaffected, and so were the joint strengths, except that the patient did not report pain during the post test.
The patient reported a reduction of her pain 1 week post injection, improving gradually until the evaluation after 4 weeks. She had resumed her previous level of recreational activities and her walking distance had improved, but problems with stair climbing and squats remained. The patient reported muscle pain consistent with delayed onset of muscle soreness (DOMS) in the soleus in the weeks after the injection. After 2 months, she experienced difficulties sleeping due to knee pain and requested another injection treatment.
The patient experienced a gradual and considerable improvement of clinical scores following the injections. The results indicate that the inflammation-related excitation of the pain system was reduced, while the KOA problem persisted and caused pain in high-load situations. Reduced inflammation was documented by the increase of the knee range-of-motion by 35 degrees. There were no side effects reported except for temporary DOMS.
In the interest of patient compliance, the pharmaceutical approach described here is clinically attractive compared with training regimes aimed at strengthening m. soleus. The patient’s experience of post injection DOMS in m. soleus indicates that the weakening of m. gastrocnemius may strengthen m. soleus. A combined treatment protocol with injections followed by targeted soleus exercise could therefore be considered.
The results, when combined with the biomechanical basis of the hypothesis, are promising and suggest further investigation by a randomized study. If confirmed, this simple and reversable medical intervention can improve the management of early-stage knee osteoarthritis.
Christian Wong protocolled the project, treated, and performed patient evaluations.
John Rasmussen performed computer simulations to recover the effect of strength balancing on knee compressive loads and processed data.
Jesper Bencke performed clinical tests and gait analysis.
All authors contributed to the discussion of the results and the preparation of the manuscript.
The authors have no competing interests.
This work was supported by Innovation Fund Denmark .
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Published online: April 20, 2022
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