Eccentric strengthening exercises and pacing

The therapy with the best data for degenerative tendinopathy or tendinosis is eccentric strengthening exercises. It is assumed that the main effect comes from the slow execution of the eccentric movement. An eccentric muscle contraction occurs when the muscle is lengthened while it is loaded with weights and contracted. An example of this would be slowly lengthening the biceps muscle with a dumbbell in the hand.(2) Another typical example is strengthening exercises on a staircase for the Achilles tendon, where the slow downward movement is the key component.

The effect of eccentric training for the treatment of tendon disorders can be partly explained by increased collagen synthesis by the tenocytes.(3) On the contrary, immobilization leads to atrophy of tendons, but due to the low metabolic rate and vascularity this happens rather slowly.(3) To emphasize it again for those affected, this means that absolute immobilization is not useful in most cases. Only in the case of a rupture or severe inflammation can short-term immobilization be useful.

Typically, chronic degenerative tendinopathy develops when stress and regeneration are out of balance, or the time for tendon regeneration is insufficient. As already described, fluoroquinolones lead to limited regeneration.(4) Consequently, the classic intervention with eccentric strengthening exercises unfortunately often does not lead to the desired result. In a small, self-conducted survey, around 70% of those affected described classic physiotherapy with eccentric training as counterproductive. It is very well documented that the production of new collagen fibrils is stimulated within a physiological framework. It can be shown more precisely that there is a simultaneous increase in collagen synthesis and degradation, with collagen synthesis persisting for longer.(5) Fluoroquinolone antibiotics, on the other hand, restrict collagen synthesis. The question therefore arises as to whether this is the reason for the lack of success of eccentric training in patients with fluoroquinolone-associated tendinopathies. Due to the limited regeneration, one can speculate that a significantly reduced intensity of eccentric exercises should be used, if at all.

Pacing

In our experience, pacing or “paced training” is more successful for fluoroquinolone-associated tendon disorders than traditional physiotherapy. After a temporary reduction in activity, the patient should first determine a “baseline” of stressful activities in relation to the affected tendon. Ideally, the activity should be measured objectively, for example by the total number of steps in the case of Achilles tendon complaints. The baseline is reached when there is no increase in pain with constant activity over a period of one month. It is also important to understand that pain often only occurs at night or 1-3 days after activity. A very slow increase in weight-bearing movements is necessary, preferably less than 5-10% increase in activity per month. Pacing is often difficult to implement. A high degree of mindfulness is required. There is a risk of progression of the tendon disease if the load is too high, which we unfortunately often see. The period of time during which the tendon should be handled with care is unknown, but significant structural changes have been shown in animal studies of up to 20 weeks after fluoroquinolone administration. It is recommended to be cautious with symptomatic patients and a gradual introduction to sporting activities should only take place after the pain has subsided.(6)

If the tendon is frequently pushed beyond its limits, a so-called “boom and bust” cycle occurs, whereby activity is often stopped completely during phases of increased pain, leading to a loss of fitness and muscle mass. The tendon tissue also becomes less resilient. As soon as the pain subsides, those affected begin their usual activity, which is often beyond the tissue’s limits. This then leads to renewed irritation of the tissue. This vicious circle is illustrated in the following picture:

Pacing is probably the most important measure to achieve a long-term improvement in tendon symptoms. We recommend working with a doctor, therapist or physiotherapist with knowledge of fluoroquinolone-associated tendon complaints and pacing for optimal implementation.

Cold Therapy

Cold causes short-term vasoconstriction, i.e. blood vessels contract and the blood vessel contracts. It is assumed to have an influence on the neovascularization described above, which is associated with the pain. Clinical experiments show that the short-term application of ice for 15-20 minutes per application several times a day is helpful for tendinosis.(2) If low-intensity eccentric training is used for treatment, cold therapy should not be performed immediately afterwards, otherwise the long-term adaptation of the tissue could be reduced.(7)

Shock Wave Therapy

Extracorporeal shock wave therapy, ESWT for short, shows activation of stem cells in tendons in vitro.8 Patients report positive results after repeated therapy. As with eccentric training, it should be noted that the intensity of the treatment should be reduced to a fraction of that used in the treatment of tendinosis due to pure chronic overload without the side effects of a fluoroquinolone antibiotic. As a rule, 8-12 sessions are required at intervals of approximately one week to assess the success of the therapy. If there is a deterioration after the first session, this is usually due to excessive intensity. Once it has subsided, the treatment can be repeated a second time at a lower intensity.

PRP

Platelet-rich plasma injections are also frequently used by patients. The idea behind this is to use the growth factors from platelets for faster regeneration. Platelet-derived growth factors stimulate the proliferation of fibroblasts and tenocytes as well as the synthesis of collagen.(5)

A study on PRP and tendon regeneration in general showed that the injection is only effective in the early stages of tendinopathy. This could be the reason for the contradictory results of PRP for the treatment of tendinopathies in clinical studies.(9)

Some patients report improvement, but there are also many reports of no improvement after multiple treatments. Due to the low risk of the therapy, the good availability and the lack of alternatives, it seems worth a try for non-healing fluoroquinolone-associated tendinopathy with proven degeneration.

Falls eine PRP Therapie durchgeführt wird, sollte man sich an einen Experten wenden. Häufig wurde von Injektionen in die eigentliche Sehne berichtet. Gerade im Bereich der Achillessehne kann dies zu einer zusätzlichen Verringerung der Elastizität führen. Am erfolgreichsten scheint die Therapie zu sein, wenn das PRP ins umliegende Gewebe von Sehnen gespritzt wird. Bei der Achillessehne könnte das PRP beispielsweise in den Kager-Fettkörper gespritzt werden. Die Wachstumsfaktoren diffundieren dann zum Sehnengewebe. Häufig ist eine repetitive Therapie notwendig.

Near infrared light therapy (NIR) / low level laser therapy (LLLT)

Therapy with near-infrared light, also known as low-level laser therapy, promotes the formation of collagen tissue and mitochondrial energy production.(10-13) We have received several reports from patients who have been able to improve tendon complaints as well as experience positive changes to their skin, for example. For the best possible outcome, it is critical to apply the therapy correctly. The operating instructions often recommend a therapy duration that is far too long. As near-infrared light increases oxidative stress in the short term (hormetic stimulus), it could lead to relapses if the intensity is too high.(14) We therefore recommend a consultation with the attending physician or therapist with good knowledge of NIR therapy before starting therapy. Regular treatment at intervals of approx. 15-20 cm (6-8 inch) over 2-3 minutes seems ideal. However, this depends on the characteristics of the device used and the localization of the targeted tissue. The deeper the tissue is located, the longer the site must be irradiated so that the effective dose in joules penetrates to the target structure.

Massages

Massages promote blood circulation and cell activity of the fibroblasts for the formation of new collagen. There is also a reduction in the overactive sympathetic nervous system. Myofascial techniques and trigger point treatments can also lead to stretching of the muscle and therefore reduce strain on the tendon.(2)

Sclerotherapy

Another therapy to reduce pain is sclerotherapy, i.e. the destruction of blood vessels of the neovascularization and the accompanying nerve fibers. Studies have shown that this therapy can reduce pain and restore function in advanced stages of tendinopathy.(5) We have not yet had any direct experience with sclerotherapy in FQAD patients. This form of therapy is only listed here for the sake of completeness.

Diet and Supplements

In addition to physical therapies, an appropriate diet and certain substances are important for the regeneration of tendon tissue. Among other things, vitamin C, manganese and zinc are important for collagen production. In this section, we discuss the most important substances and present our personal experience we gained from our clients.

Antioxidant therapy

Current literature recommends the use of antioxidants such as vitamin C, coenzyme Q10 and/or magnesium to prevent or reduce the toxic effects of fluoroquinolone antibiotics.(6)

We have already described the connection between oxidative stress and the induction of MMPs in the article on the causes of tendon diseases. Reducing oxidative stress in the tenocytes as quickly as possible therefore appears to be particularly important. Although anecdotally reported, there is currently no evidence for the treatment of persistent symptoms with infusions of antioxidants such as glutathione.(6) We generally advise against infusion therapies for fluoroquinolone-associated symptoms, as we have often been told of negative experiences by those affected. Furthermore, the current evidence does not justify the financial costs for the patient.

Vitamin C

The efficacy of vitamin C in non-fluoroquinolone-associated tendinopathy is well documented in the literature. Vitamin C increases collagen synthesis and leads to better tendon regeneration.(17) Vitamin C is also the most important free radical scavenger in collagenous tissue.(18) Since fluoroquinolone antibiotics lead to oxidative stress as described in the article Cause of tendinopathy (Crosslink Article 5: Cause of tendinopathy) and this has also been observed in tendon cells after exposure, vitamin C is of particular importance in the treatment of fluoroquinolone-associated tendinopathy. It is likely that vitamin C is consumed more quickly and is therefore deficient. In numerous urine tests, we have regularly found a severe vitamin C deficiency.

In addition to its antioxidant effect, vitamin C is one of the most important cofactors in the hydroxylation of the amino acid proline to hydroxyproline, which is restricted by fluoroquinolone antibiotics. A lack of vitamin C, on the other hand, leads to reduced procollagen synthesis and hydroxylation of the amino acids proline and lysine, which can lead to inhibition of tendon regeneration.(17) Finally, vitamin C is responsible for the reduction of oxidized vitamin E.(19) As already noted, there are studies that show that a good supply of vitamin E can protect, at least partially, against fluoroquinolone-induced tendinopathy.

Magnesium

In an animal study with juvenile dogs, a magnesium deficiency led to symptoms similar to those caused by exposure to ciprofloxacin.(26) Magnesium is also a cofactor in the hydroxylation of the amino acid proline to hydroxyproline. Magnesium is part of the standard therapy for FQAD and should also be given for tendon pain.

Collagen hydrolysate

Studies show that exposure to a fluoroquinolone antibiotic leads to reduced hydroxylation of proline to hydroxyproline. It therefore seems reasonable to take collagen hydrolysate, a protein powder with a high proportion of the amino acids hydroxyproline and proline.(15) In animal studies, the intake of 15g collagen hydrolysate leads to increased synthesis of collagen.(16) Whether the additional supply of hydroxyproline is actually used for the production of collagen in tenocytes is, however, questionable. If we again take the word of those affected, there is a wide spectrum from not effective at all to a clear improvement after continuous intake. As an alternative to animal products, there are now also vegan preparations containing hydroxyproline. Lastly, we have to be careful, as some FQAD Patients suffer worsening of symptoms with supplementing Collagen, probably due to metabolizing hydroxyproline and glycin into oxalates.

Cissus quadrangularis

So far we have had good experience with Cissus quadrangularis, a plant used in Ayurvedic medicine for the regeneration of bones and for the treatment of joint complaints and inflammation.(20, 21) In our experience, around 1/3 of those affected with tendon complaints respond to Cissus quadrangularis, with moderate to good improvement occurring within a few months. It can be useful to test different preparations and different dosages.

Inhibition of matrix metallo-proteinases (MMPs)

Although speculated as a promising therapy, we have had little success with natural MMP inhibitors for the treatment of fluoroquinolone-associated tendinopathy. In addition to a large number of natural MMP inhibitors (22), there are also synthetically produced inhibitors of matrix metalloproteinases. One of the known substances is the tetracycline antibiotic doxycycline.(23) Apart from this, studies have been conducted with the MMP inhibitor apronitin in non-fluoroquinolone-associated tendinopathies. Injection with apronitin had an effect in the treatment of patellar tendinopathy when injected in non-fluoroquinolone-associated tendinopathy, but mixed results in Achilles tendinopathy.(24) Our conclusion: Due to the good side effect profile of natural MMP inhibitors such as ashwaghanda or propolis, there is certainly nothing wrong with trying them.

Tendon pain without evidence of degenerative or inflammatory tendinopathy

In most cases, neither an MRI nor an ultrasound scan can detect a pathological change in the affected person. Sometimes minimal inflammation is found around the tendon, which does not correspond to the extent of the pain experienced by those affected. Therefore, this type of tendon pain is often, unfortunately, classified as psychosomatic. As already mentioned in the article on the question of how tendon pain develops, it must be assumed that the pain in these patients is caused by an interaction between the tendon tissue and the peripheral nervous system. In these cases, too, therapy with paced training, magnesium and Cissus quadrangularis can be helpful. In addition, shock wave and cold therapy can lead to pain reduction.

In this situation, treatment with PRP injections does not appear to make sense. However, some patients have had success with neural therapy, which modulates the peripheral nervous system by injecting a local anesthetic (usually procaine). We also recommend regular massage in this situation to reduce the overactive sympathetic nervous system. So-called “mind-body” interventions to modulate the perception of pain are also important. Mindfulness-based pain management (crosslink to MBPM page) or pain reprocessing therapy (PRT), for example, should be tried. Drug-based pain therapy with gabapentin or pregabalin, for example, was also found to be helpful by some patients. However, the benefits of the therapy must be carefully weighed up against the side effects by the attending physician.

Conclusion

Overall, optimal conditions are required for tendon regeneration. These include sufficient recovery time, avoidance of renewed overloading as well as a good metabolism and blood supply.(5) The necessary building blocks for collagen synthesis must be supplied to the body. Ultimately, a continuously increasing therapeutic stimulus is required, but this should be below the threshold at which the symptoms become more severe. All of this is easier said than done, which is why we recommend working with an expert. If you cannot find anyone in your area who is familiar with pacing in fluoroquinolone-associated tendinopathies, we recommend that you contact us for an individual consultation and/or exchange ideas with other sufferers in our self-help group.