The treatment of medial tibial stress syndrome with Biphosphanates

Introduction

Medial tibial stress syndrome (MTSS) is one of the most common causes of exercise induced leg pain¹. Incidences in training programs varying from 4-35% are reported, with both extremes being derived from military studies^2,3. A recent systematic review reported a lack of good quality studies on the treatment of MTSS despite these high incidences⁴. Only three randomized studies were found and they were all of poor quality^2,5,6. The review reported that no treatment has been shown superior to rest alone. It was suggested that clinical trials should be performed on the treatment of MTSS. The same review proposed that MTSS is a problem of bony overload4. Different imaging studies provided evidence for the bone overload theory^{7,8,9,10,11,12}. These findings suggest that the pathology of MTSS has similarities with tibial stress fractures. In the seventies Roub et al already suggested a continuum between stress reaction of bone and stress fractures¹³.
Since bony overload has been shown the underlying problem in MTSS, possibly treatment options for bone overload/resorption of the bony cortex could apply to MTSS. In the last decade few studies have been conducted, which examined the role of biphosphanates in bone overload. These studies, in humans, consisted of some case series about treatment of stress fractures and localized transient osteoporosis^14,15. More commonly it has been used in the treatment of osteoporosis^16,17. Bisphosphanates inhibit bone resorption by being selectively taken up and adsorbed to mineral surfaces in bone, where they interfere with the action of osteoclasts. In this way osteoclast activity is reduced and apoptosis of the osteoclast may occur¹⁸.
So far, no publications were found that treated MTSS with biphosphanates. This case report describes two cases in which biphosphanates were started in MTSS patients.

Case 1

A 27 year old male rugby player from Sri Lanka presented with bilateral shin pain for more than two years. The pain was present on the posteromedial side of the tibia. The complaints worsened during training and matches and persisted for several days after severe exercise. He insisted on playing the key matches of the season and did not take adequate rest. On examination he walked with an antalgic gait. On inspection he was found to have pronated feet with lowering of the medial arch. Inspection of his shins revealed no swelling or erythema. The medial borders of the middle third of the tibiae were painful on palpation. Resistance testing for the muscles of the lower leg was not painful. Examination of the ankles and knee joints was normal and also the neurovascular examination of the lower leg. X-rays of the tibiae showed periosteal reaction on both sides. MRI revealed bone marrow oedema and periosteal reaction of the tibia. Based on his history, findings on examination and imaging the diagnosis of MTSS was made.
As first phase of conservative treatment, taping of the shins was performed and the athlete was prescribed a shin support (sleeve). He did not train for four weeks, apart from light jogging and crosstraining. Also orthosis were prescribed. After four weeks he was re-evaluated and the pain was reduced, but still he experienced pain on the posteromedial border of the tibia after 700 meters jogging.
Then, Sodium Alendronate 10mg with Calcium lactate 500mg daily was started for three months. The athlete was advised to start cross training, running in a pool, swimming and cycling. After three weeks, the shin pain decreased gradually so that he could start his normal training program after eight weeks. Eleven weeks after the Sodium Alendronate was started he was able to compete at his pre-injury level. There were no side effects reported from the medication.

Case 2

An 18 year old female high-level athlete from Sri Lanka who ran 800, 1500 and 400 meters relay, presented to a sports medicine clinic with bilateral shin pain for more than 18 months. The pain was located along the posteromedial border of the tibia and started after 300-400 meters of running. On stopping, the pain gradually decreased over the course of the next few hours. She trained 5 times per week for two hours. She did not report menstrual disorders or a changed pattern of the menstrual cycle. No treatment was performed before the consultation. Inspection of the legs was normal with a neutral alignment and feet. Tenderness of both tibiae along the posteromedial border over the middle one third was present on palpation. X-rays of both tibiae showed evidence of periosteal reaction on the middle third. An isotope bone scan revealed a longitudinal uptake pattern on both tibiae, the right more marked than the left, which excluded a stress fracture.
The athlete was advised to refrain from weight bearing sporting activity. Though she was advised to commence a cross training program, which she was not able to do so due to lack of facilities in the vicinity.
Assessment after four weeks of relative rest, revealed only a moderate improvement. Although she did not participate in running training, she had practiced some volleyball. Due to the only moderate improvement of the load reduction she was prescribed Sodium Alendronate 10mg daily with supportive Calcium lactacte 600mg daily for three months.
During the first three weeks she did not take part in any sports activities. Assessment of her condition at three weekly intervals, showed a significant improvement of her condition. She was advised to start brisk walking in week six, jogging in the 8^th week and moderate speed running in the 9^th week. She could perform her normal running training at the 10th week after initiating the Alendronate therapy. There were no side effects reported from the medication.

Discussion

Few treatment options for MTSS exist at present despite of the high incidences found in athletes¹⁹. Most likely, new treatment strategies should be focussed on bony overload instead of a traction induced periostitis since the nature of the MTSS condition⁴. Biphosphanates are currently used for osteoporosis, transient osteoporosis and stress fractures^14,15,16. Treatment with oral biphosphanates may lead to stomach upset20, and oesophagus ulcera²¹. Cases of osteonecrosis of the jaw have been described²², but treatment with biphospanates seems safe even in the long term^23,24.

This report aimed at describing the additional effect of biphosphonates in patients with MTSS added to our usual care. Normally standard treatment consists of rest followed by graded activity²⁵. The two cases described were able to practise and compete in their sports, rugby and running, 10-11 weeks after starting biphosphanates. Worth mentioning is that the second patient did have an altered loading pattern after the initiation of the biphosphanates. She decreased the volume of her volleyball activities, although she was a runner. This could have influenced the time to return to sport. However, we think this influence was minimal, because the volume of volleyball was low and the running volume was not changed after the biphosphanates. In the literature few reports adequately describe the time to return to sport. In the randomized trial by Andrish et al² military personnel was treated for MTSS after 1-4 days of shin pain. They reported an average of 10 days lost to running. The second randomized trial was also conducted in the military. Follow-up in this study was only 14 days⁵. The third most recent randomized study was conducted by Johnston et al in the US Army⁶. Their criteria for completion of the study was to run 800 meters (0,5 mile). Half of the subjects that started the study did complete the study. On average the treatment group completed the 800 meters after 14,4 days and the control group after 17,2 days.
These data can hardly be compared to the athletes in this case report. The two cases reported here had a much longer duration of symptoms prior to the start of treatment. One other MTSS treatment study (a retrospective controlled study) reported follow-up better and was conducted among athletes²⁶. They compared exercise therapy (stretching and strengthening of the calves) and shockwave therapy with exercise therapy. The shockwave therapy in addition to the standard care improved a Likert activity scale more than the control group. However, after 4 months none of the control group were completely recovered and only 24% of the combined treatment group. Preliminary data of Moen et al (2010) revealed in the follow-up of 50 MTSS patients that in different treatment groups the time to return to sport (being able to train at the desired level) was 90-100 days.
When compared to the athletes reported here, they were able to train at their desired level after 10-11 weeks (=70-77 days). This seems promising but the fact that it is a case report means no solid conclusions can be made. This case report raises the possibility that biphosphanates could decrease the time to return to sport in MTSS patients. To gain more information on the possible effect size of the biphosphanates therapy and assess possible complications a larger prospective case series should be performed. After this a double blinded prospective randomised controlled clinical trial can be considered. The duration and dosage of the treatment is not yet known and should also be studied further.

Conclusion

This case report described two patients with MTSS treated with biphosphanates after other conservative treatment failed. The results seem promising, but further research
is needed.