Prevalence, injury patterns, and clinical relevance

The incidence of lateral ankle sprains in the general population is approximately one injury per 10,000 people per day, with the lateral ligament structure affec­ted in 85 % of cases. Young adults aged 15 – 35 are particularly affected. This rate is significantly higher in physically active populations, particularly in sports with a high jumping and pivoting load profile, such as basketball, handball, volleyball, and soccer [2 – 4]. The classic injury pattern, consisting of a combination of supination / inversion trauma with combined plantar flexion, often leads to a tear of the lateral capsular ligament apparatus at the upper ankle joint (USG). The most common injury (approx. 85 %) is to the anterior talo­fibular ligament (ATFL), followed by the calcaneofibular ligament (CFL) (52 – 75%) and, less frequently (< 10 %), the posterior talofibular ligament (PTFL).

The lateral capsular ligament apparatus of the OSG not only serves as a stabilizer against anterior talar translation and inversion in the upper ankle joint. The anterior and posterior fibulotalar ligaments, together with the anterior and posterior portions of the deltoid ligament, form a firm ligamentous ring in the transverse plane of the malleolar fork (Fig. 1). Injury to the lateral structures thus leads to complex rotational instability. Epidemiological data show that 20 – 40 % of patients develop persistent symptoms such as pain, impingement syndromes, and functional and structural chronic instabilities after initial ankle sprain [5]. In athletes, a recurrence rate of up to 34 % has been reported if no targeted neuromuscular and proprioceptive rehabilitation is performed [6]. The risk of a repeat ankle injury is five times higher after a lateral ligament rupture [7]. Long-term clinical studies show that even seemingly “simple” lateral ligament ruptures significantly increase the risk of post-traumatic ankle osteoarthritis, especially in cases of residual instability or incomplete rehabi­litation. Microinstabilities and repeated subtle sprains lead to chondral damage, which can result in degenerative joint destruction [5, 6]. 

Fig. 1 Transverse view of the upper ankle joint. The deltoid ligament (D) forms a stable ligamentous ring together with the posterior tibiofibular ligament (PTL) and anterior tibiofibular ligament (ATFL) (LLC = lateral malleolus, MLC = medial malleolus). Rupture of the LFTA leads to a break in continuity with rotational instability in the upper ankle joint.

Diagnosis

Clinical examination forms the basis of the diagnosis. Targeted systematic palpation of the typical pain points (LFTA, LFC, anterior syndesmosis, peroneal tendons), the anterior drawer test, and the talar tilt test (inversion test) are used to test mechanical joint stability. Immediately after the acute event, swelling, pain, and muscle guarding significantly limit the informative value of these tests. A reevaluation after 3 – 4 days, as advocated by Niek van Dijk, enables a much more reliable assessment with improved diagnostic sensitivity and specificity [8].

Conventional X-ray diagnostics are not indicated if a fracture is not suspected. In particular, static images of the ankle joint do not provide reliable information in the acute injury situation. Ultrasound has proven to be a diagnostic tool for imaging ligament continuity, hematoma extent, and joint effusion volumes. Radiological studies have shown that the sensitivity of sonographic examination is significantly higher than that of MRI for imaging ruptured LFTA (94 – 100 vs. 67 – 87) and LFC (94 vs. 40 – 47) [9]. The specificity is approximately equivalent. Ultrasound thus enables rapid and cost-effective confirmation of the diagnosis and prompt initiation of treatment. Magnetic resonance imaging (MRI) remains indicated in cases of complex injury patterns, suspected concomitant pathologies such as osteochondral talus lesions, syndesmotic injuries, or in the absence of clinical improvement [10].

Conservative therapy and functional treatment concept

According to S2k guideline 187 – 025, conservative therapy is considered the gold standard for lateral ligament rupture without accompanying injury, provided that there are no complete ruptures of all three lateral ligaments with pronounced mechanical instability.

The main therapeutic goals are rapid pain reduction, edema reduction, restoration of physiological joint mobility, and regaining active-dynamic stability while minimizing the recurrence rate. Instead of complete immobilization and relief, early functional therapy with a semi-rigid ankle orthosis, which limits inversion and supination and reduces plantar flexion, is considered the standard. Several studies show that early functional treatment with early mobilization in the orthosis, full weight-bea­ring after pain and swelling have subsided, and accompanying physical therapy leads to a significantly faster return to sport, less muscle atrophy, and less joint stiffness than prolonged immobilization [11, 12]. Modular ankle orthoses have been available on the market for several years. The underlying concept of this treatment is the gradual reduction of the orthosis’s stabilization from the acute stage to the rehabilitation phase, adapted to the ligament healing phases. Modular systems allow for initially higher lateral guidance in the acute phase with a gradual reduction in stability over time, which supports early functional mobilization while protecting against renewed inversion trauma. This is intended to support improved alignment of the collagen fibrils in the regenerated tissue as well as improved proprioceptive stimulation [13].

Proprioceptive and neuromuscular training – the focus of recurrence prevention

Proprioceptive and neuromuscular training is the most essential component of rehabilitation, as functional instability is not exclusively structural, but is also caused by disturbed afferent feedback and delayed peripheral muscle response patterns. Randomized controlled trials (RCTs) [3, 12, 14, 15] show that 8-12-week progressive proprioceptive programs (wobble board, balance pad, standing on one leg on unstable surfaces) reduce the recurrence rate of sprains by 35 – 41 % and significantly improve functional stability scores. Meta-analyses [16, 17] of more than 30 RCTs combined show a significant reduction in the risk of re-rupture by 39 – 47 % through structured sensorimotor training (level 1a evidence). The S2k guideline 187 – 025 recommends starting proprioceptive training as early as week 2 – 3 after the trauma, i.e., already in the orthotic treatment phase, with a progressive increase until week 12. The focus is on balance exercises, agility skills, reactive changes of direction, and sport-specific jump-landing sequences for high-level athletes. Effective exercises include standing on one leg on an unstable surface, the Star Excursion Balance Test (Fig. 2), lateral hop tests, and multi­directional jumps with defined landing patterns [18].

Biological regenerative adjuvants: PRP, hyaluronic acid, and ESWT

The use of platelet-rich plasma (PRP) in ligament ruptures aims to increase local growth factor concentrations to optimize ligament healing. Initial clinical studies report some positive effects on pain and subjective stability [19 – 21]. However, the current data are heterogeneous. Large-scale RCTs specifically on acute lateral OSG ligament ruptures are limited. The S2k guideline did not issue a strong recommendation for PRP in acute ligament injuries. Hyaluronic acid injections are mainly used to modu­late intra-articular inflammatory processes in soft tissue after an outer ligament rupture. Individual studies report faster pain reduction and a quicker return to sports [21, 22]. There is currently no consistent evidence of a benefit in accelerating ligament healing or reducing recurrent instability. At most, a complementary role may be considered in cases of associated chondral lesions. Preclinical models have demonstrated improved ligament regeneration, angiogenesis, and matrix remodeling with extracorporeal shock wave therapy (ESWT). No clinical data are available for this therapeutic measure in acute lateral ligament rupture, so there is no evidence-based recommendation. ESWT can be used as a selective option for reducing pain and swelling.

Conclusion

Consistent early functional therapy with adequate 6-week orthotic treatment, structured physical therapy, and intensive proprioceptive training form the main pillars of treatment. Proprioceptive training in the early phase and after removal of the orthosis is an essential factor in preventing functional instability and re-rupture.

Literature

1. Vuurberg G, Hoorntje A, Wink LM, van der Doelen BFW, van den Bekerom MP, Dekker R, van Dijk CN, Krips R et al. Diagnosis, treatment and prevention of ankle sprains: update of an evidence-based clinical guideline. Br J Sports Med 2018, 52(15); doi: 10.1136/bjsports-2017-098106
2. Junge A, Engebretsen L, Mountjoy ML, Alonso JM, Renström PA, Aubry MJ, Dvorak J.Sports injuries during the Summer Olympic Games 2008. Am J Sports Med 2009, 37(11):2165-72; doi: 10.1177/0363546509339357
3. Doherty C, Delahunt E, Caulfield B, Hertel J, Ryan J, Bleakley C. The incidence and prevalence of ankle sprain injury: a systematic review and meta-analysis of prospective epidemiological studies. Sports Med 2014, 44(1):123-40. doi: 10.1007/s40279-013-0102-5
4. van den Bekerom MP, Kerkhoffs GM, McCollum GA, Calder JD, van Dijk CN.Management of acute lateral ankle ligament injury in the athlete. Knee Surg Sports Traumatol Arthrosc 2013, 21(6):1390-5. doi: 10.1007/s00167-012-2252-7
5. Valderrabano V, Hintermann B, Horisberger M, Fung TS.Ligamentous posttraumatic ankle osteoarthritis. Am J Sports Med. 2006, 34(4):612-20. doi: 10.1177/0363546505281813
6. van Rijn RM, van Os AG, Bernsen RM, Luijsterburg PA, Koes BW, Bierma-Zeinstra SM.What is the clinical course of acute ankle sprains? A systematic literature review. Am J Med 2008, 121(4):324-331.e6. doi: 10.1016/j.amjmed.2007.11.018
7. McKay GD, Goldie PA, Payne WR, Oakes BW.Ankle injuries in basketball: injury rate and risk factors. Br J Sports Med 2001, 35(2):103-8. doi: 10.1136/bjsm.35.2.103
8. van Dijk CN, Lim LS, Bossuyt PM, Marti RK. Physical examination is sufficient for the diagnosis of sprained ankles. J Bone Joint Surg Br 1996, 78(6):958-62. doi: 10.1302/0301-620x78b6.1283
9. Gribble PA.Evaluating and Differentiating Ankle Instability. . J Athl Train 2019, 54(6):617-627. doi: 10.4085/1062-6050-484-17. Epub 2019 Jun 4
10. Crema MD, Krivokapic B, Guermazi A et al. MRI of ankle sprain: the association between joint effusion and structural injury severity in a large cohort of athletes Eur Radiol 2019, 29(11):6336-6344. doi: 10.1007/s00330-019-06156-1
11. Kerkhoffs GM, Rowe BH, Assendelft WJ, Kelly K, Struijs PA, van Dijk CNImmobilisation and functional treatment for acute lateral ankle ligament injuries in adults. . Cochrane Database Syst Rev 2013, 28(3): CD003762. doi: 10.1002/14651858.CD003762
12. Rivera MJ, Winkelmann ZK, Powden CJ, Games KE.Proprioceptive Training for the Prevention of Ankle Sprains: An Evidence-Based Review J Athl Train 2017, 52(11):1065-1067. doi: 10.4085/1062-6050-52.11.16
13. Best R, Böhle C, Schiffer, T, Petersen W, Ellermann A, Brüggemann GP, Liebau C. Early functional outcome of two different orthotic concepts in ankle sprains: a randomized controlled trial. Arch Orthop Trauma Surg 2015, 135(7):993-1001. doi: 10.1007/s00402-015-2230-x
14. Grimm NL, Jacobs JC Jr, Kim J, Amendola A, Shea KG.Ankle Injury Prevention Programs for Soccer Athletes Are Protective: A Level-I Meta-Analysis. J Bone Joint Surg Am 2016, 98(17):1436-43. doi: 10.2106/JBJS.15.00933
15. Emery CA, Owoeye OBA, Räisänen AM, Befus K, Hubkarao T et al. The „SHRed Injuries Basketball“ Neuromuscular Training Warm-up Program Reduces Ankle and Knee Injury Rates by 36% in Youth Basketball. J Orthop Sports Phys Ther 2022, 52(1):40-48. doi: 10.2519/jospt.2022.10959
16. van der Wees PJ, Lenssen AF, Hendriks EJ, Stomp DJ, Dekker J, de Bie RA.Effectiveness of exercise therapy and manual mobilisation in ankle sprain and functional instability: a systematic review. Aust J Physiother 2006, 52(1):27-37. doi: 10.1016/s0004-9514(06)70059-9
17. Otsuka S, Papadopoulos K, Bampouras TM, Maestroni L.What is the effect of ankle disk training and taping on proprioception deficit after lateral ankle sprains among active populations? – A systematic review. J Bodyw Mov Ther 2022, 31:62-71. doi: 10.1016/j.jbmt.2022.04.001
18. VBG Fachwissen. Return-to-Competition. Testmanual zur Beurteilung der Spielfähigkeit nach akuter lateraler Bandverletzung am Sprunggelenk. Stand Juni 2022. https://www.vbg.de/cms/sport/return-to-competition/rtc-sprunggelenk
19. Ding Q, Wang X, Liu Y, Li Y, Zhang D, Wang H, Ma S, Han Q, Zhuang W.The efficacy of platelet-rich plasma in ankle disease: a systematic review and meta-analysis. . J Orthop Surg Res 2024, 31;19(1):895. doi: 10.1186/s13018-024-05420-5.
20. Zhang J, Wang C, Li X, Fu S, Gu W, Shi Z.Platelet-rich plasma, a biomaterial, for the treatment of anterior talofibular ligament in lateral ankle sprain. . Front Bioeng Biotechnol. 2022, 22(10):1073063. doi: 10.3389/fbioe.2022.1073063
21. Chen YT, Wu WT, Lee RP, Yu TC, Chen IH, Yeh KT.Platelet-rich plasma and hyaluronic acid in the treatment of acute ankle sprains: A review. Biomol Biomed 2025. doi:10.17305/bb.2025.13327.
22. Petrella RJ, Petrella MJ, Cogliano A.Periarticular hyaluronic acid in acute ankle sprain. Clin J Sport Med 2007, 17(4):251-7. doi: 10.1097/JSM.0b013e3180f6169f

Professional sports are undergoing a profound transformation through the integration of precision medicine, also known as personalized medicine. By tailoring training, nutrition, recovery, and injury prevention strategies to the individual genetic, physiological, and subjective profiles of each athlete, precision medicine aims to enhance performance, reduce the risk of injury, and ultimately extend athletic careers. This article examines the current applications, benefits, and future directions of precision medicine in professional sports.

Individualization as a new paradigm in sports medicine

Precision medicine has established itself in many areas of medicine as an individualized approach to tailoring therapy and prevention strategies more specifi­cally to the biological, genetic, and environmental characteristics of the athlete. In sports medicine, this approach is still in its infancy – but the change is noticeable: with the use of high-resolution diagnostics and modern technologies, the need for tailor-made care for athletes is growing. These technologies support the necessary shift towards individualized, data-supported care concepts that is resulting from the development of professional sports. 

The aim is to tailor training management, regenerative and preventive measures, and therapeutic interventions more closely to individual needs in order to specifically promote performance and identify injury risks at an early stage. Precision medicine provides the metho­dological basis for making data-­driven and individually informed decisions – beyond blanket recommendations. 

Fields of application and challenges

The implementation of precision medi­cine in sports medicine requires a deep understanding of individual resilience and adaptability. A central aspect is the close integration with performance diag­nostics, which makes relevant parameters measurable and interpretable. The focus is on the athlete as a complex system with numerous interconnected influencing factors.

Looking at the concepts of performance components in training science literature, the structural and functional complexity of athletic performance becomes clear – and with it the challenges associated with precision medicine [1]. Training and regeneration processes must be designed in such a way that they both promote performance deve­lopment and improve stress tolerance. Precision medicine provides the framework for collecting and analyzing data in a targeted manner and translating it into concrete measures.

This results in key areas of application:

• Prevention Analysis and targeted reduction of injury risk
• Rehabilitation Optimizing and shortening return processes and preventing relapses
• Regeneration Individualizing and accelerating recovery processes to increase stress tolerance and training effectiveness
• Injury cause analysis Better understanding injury mechanisms and using this knowledge for prevention
• Performance optimization Achieving maximum performance in a sustainable manner
• Increasing longevity Reducing cell age and optimizing function ultimately lead to a higher life expectancy for athletes

The following section explains the key aspects of the aforementioned areas of application for personalized sports medicine in more detail. 

Genetic profiling and personalized approaches

Advances in www.dnathlete.li have enabled the identification of specific mar­kers related to muscle building, endurance, injury susceptibility, and recovery rates. When coaches and medical teams know an athlete’s genetic predisposition, they can design training and prevention programs that are tailored to the athlete’s innate strengths and take potential weaknesses into account. For example, certain genetic profiles may indicate a predisposition to muscle, ligament, or tendon injuries, allowing targeted and additional preventive measures to be taken. Or another genetic predisposition may enable higher levels of performance when consuming caffeine, beta-alanine, or creatine, while this is not the case for others [2]. A study published in the World Academy of Science Journal highlights the integration of genetic profiles with traditional biochemical and physiological assessments to optimize performance and ensure longevity in sports [3].

The great potential of epigenetics – understanding and utilizing molecular individuality

Epigenetic processes add a dynamic component to this perspective: they control which genes are activated or deactivated under certain conditions – influenced by training, nutrition, stress, or environmental stimuli. 

These adjustments are reversible and make it possible to achieve long-term positive changes at the cellular level through targeted stimuli. Epigenetic age clocks are complex biomarkers based on DNA methylation patterns that usually reflect biological age more accurately than chronological age, thus providing insights into an individual’s health and aging process.

For athletes, these biomarkers have significant potential as they provide a personalized assessment of how training load, recovery, nutrition, and lifestyle affect long-term health and performance. Monitoring biological age can help optimize training plans, avoid over- or under-training, and take measures to prolong peak performance and reduce the risk of injury. In addition, epigenetic insights can provide information about personalized recovery strategies and serve as a valuable tool for planning the longevity of athletes [4, 5]. 

Biomarkers and their potential for performance optimization

Laboratory markers provide crucial insights into an athlete’s physiological state and are therefore a cornerstone of precision medicine in sports. Biomarkers, such as creatine kinase (CK), help monitor muscle damage and recovery and enable individual training adjustments that optimize performance while minimizing the risk of overtraining and injury. Elevated CK levels, for example, may indicate excessive muscular stress or insufficient recovery, allowing timely measures such as modified training load, nutritional support, or rest periods to be initiated. Regular monitoring of such markers ensures a data-driven approach to athlete care and enables tailored strategies that increase resi­lience, improve performance, and support long-term athletic development. Regular communication with the athlete is crucial in interpreting these values in order to integrate subjective assessments into the decision-making process and avoid misinterpretations.

Biomechanics – objectively analyzing and individually adapting movement patterns

Biomechanical analyses provide important insights for the individualized care of athletes. Every person moves differently, influenced by muscle control, joint structure, coordination, and movement experience. These individ ual movement patterns influence both the risk of injury and performance ability. Modern technologies such as motion capture systems, force plates, and electromyography (EMG) enable these patterns to be recorded as objectively as possible. Based on the data obtained, targeted analyses can be carried out and adjustments to technical training and load design can be derived with the aim of making movements more efficient, avoiding overload, and better meeting sport-specific requirements. EMG diagnostics provide valuable information on muscular control and enable early identification of neuromuscular deficits in prehabilitation and targeted correction using biofeedback-­based activation. Biomechanical analyses thus make an important contribution to performance optimization and injury prevention and are an essential component of personalized sports medicine concepts.

Wearable technology and real-time monitoring

The integration of wearable devices with built-in sensors enables the continuous recording of vital parameters, movement patterns, and stress data. These wearables provide real-time information on variables such as heart rate variability (HRV), oxygen saturation, and biomechanical efficiency. These insights enable immediate adjustment of training intensity and technique to optimize performance while minimizing the risk of injury. Recent developments include AI-driven smart sportswear that uses integrated sensors to monitor muscle activation and breathing patterns, for example, and provide real-time feedback on the quality of training execution [6].

Precision strategies for hydration and nutrition

Individualized hydration and nutrition plans are key components of precision medicine in sports. By analyzing individual sweat composition and metabolic responses, nutritionists can tailor electrolyte replacement and diet plans to the specific needs of each athlete.

This personalized approach ensures optimal energy availability, improves reco­very, and supports overall health. Genetic testing also plays a role in determining nutritional needs, as certain gene variants can influence nutrient metabolism, leading to more effective nutritional strategies. 

Pharmacogenomics and injury management

Pharmacogenomics – the study of how genes affect an individual’s response to medication – enables the customization of medication regimens for injury treatment and pain management. Understanding genetic variations in drug metabolism helps in selecting the most effective medications with minimal side effects, improving recovery outcomes and reducing downtime.

This approach ensures that medications and recovery programs are tailored to each athlete’s genetic predisposition, improving performance and reducing the risk of injury [7]. 

Neurocognition

Improving neurocognition offers significant benefits to athletes by enhan­cing mental processing speed, attention, reaction time, and decision-making under pressure, which are key components of peak athletic performance.

As part of a precision medicine approach, these interventions are tailored to the cognitive profile of the individual athlete, enabling customized strategies that complement physical training.

Cognitive improvements can help athletes better anticipate plays, adapt to changing environments, and focus in critical situations, which can lead to a competitive advantage in performance. This holistic strategy ensures that athletes are optimally prepared for success, not only physically but also mentally.

Numerous scientific studies have shown that any peripheral injury can be accompanied by changes in different parts of the brain. These findings also call for new, individualized prevention and rehabilitation strategies and allow for individualized preparation of athletes even before surgical interventions as prehabilitation. Tools such as SkillCourt are an example of the integration of neurocognitive training into precision sports medicine. SkillCourt uses interactive, data-driven technology to measure, analyze, and train visual perception, cognitive agility, and motor coordination in real time. By analyzing an athlete’s performance on these tasks, coaches and physicians can identify cognitive strengths and deficits and take targeted measures to improve overall game performance. Integrating such tools into an athlete’s training program supports injury prevention, rehabilitation, and sustained peak performance, bridging the gap between brain function and physical execution in sports [8 – 10].

Artificial intelligence and predictive analytics

The use of artificial intelligence (AI), especially machine learning techniques, enables sports medicine to precisely analyze large, complex data sets to predict injury risks and performance trends.

By processing data from various sources, such as wearables, training logs, and medical records, AI models can identify patterns and provide actionable insights that facilitate proactive interventions and strategic planning. Predictive analytics and machine learning are transforming injury prevention strategies in sports medicine by analyzing large amounts of data to identify patterns and trends that indicate an increased risk of injury. A well-thought-out data strategy is essential, because it is not the quantity, but the relevance, quality, and targeted use of data that determine the success of precision medicine applications. 

Conclusion

The integration of precision medicine into professional sports represents a paradigm shift in athlete care and performance optimization. Through individualized approaches based on genetic insights, real-time monitoring, and personalized analysis, sports organizations can sustainably improve the longevity, performance, and overall well-being of athletes. All of the technologies mentioned are already available today and should be used in a targeted manner as part of a basic sports medical examination in order to comprehensively assess the initial situation and identify individual deficits at an early stage. On this basis, tailor-made intervention programs can be developed, which can be adapted through regular re-testing in order to respond dynamically to changes. With advancing technological development, the potential of precision medicine to revolutionize athletic performance and health management is becoming increasingly tangible.

Literature

[1] Blobel, T. (2022). Sportinformationssysteme – Systemarchitektur, Anwendungsfälle und Marktanalyse. Dissertation. München: Technische Universität München. https://mediatum.ub.tum.de/doc/1639907/1639907.pdf

[2] Panagiotou, N., Sagonas, A., Salata, E., Fotis, T., & Ntoumou, E. (2025). Athlegenetics: Athletic characteristics and musculoskeletal conditions (Review). World Academy of Sciences Journal, 7, 44. https://doi.org/10.3892/wasj.2025.332

[3] Pfab, F., Sieland, J., Haser, C., Banzer, W., & Kocher, T. (2023). Genetische Faktoren bei Muskelverletzungen im Sport [Genetics in sports-muscle injuries]. Orthopadie (Heidelberg, Germany), 52(11), 889–896. https://doi.org/10.1007/s00132-023-04439-6

[4] Brooke, R. T., Kocher, T., Zauner, R., Gordevicius, J., Milčiūtė, M., Nowakowski, M., Haser, C., Blobel, T., Sieland, J., Langhoff, D., Banzer, W., Horvath, S., & Pfab, F. (2024). Epigenetic age monitoring in professional soccer players for tracking recovery and the effects of strenuous exercise [Preprint]. medRxiv. https://doi.org/10.1101/2024.11.28.24317877

[5] Gibbs, W. Biomarkers and ageing: The clock-watcher. Nature 508, 168–170 (2014). https://doi.org/10.1038/508168a

[6] Tang, C., Yi, W., Zhang, Z., Occhipinti, E., & Occhipinti, L. G. (2025). AI-driven smart sportswear for real-time fitness monitoring using textile strain sensors (arXiv Preprint No. 2504.08500). arXiv. https://arxiv.org/abs/2504.08500

[7] Roden, D. M., McLeod, H. L., Relling, M. V., Williams, M. S., Mensah, G. A., Peterson, J. F., & Van Driest, S. L. (2019). Pharmacogenomics. Lancet (London, England), 394(10197), 521–532. https://doi.org/10.1016/S0140-6736(19)31276-0

[8] Friebe, D., Hülsdünker, T., Giesche, F., Banzer, W., Pfab, F., Haser, C., & Vogt, L. (2023). Reliability and Usefulness of the SKILLCOURT as a Computerized Agility and Motor-Cognitive Testing Tool. Medicine and science in sports and exercise, 55(7), 1265–1273. https://doi.org/10.1249/MSS.0000000000003153

[9] Friebe, D., Sieland, J., Both, H., Giesche, F., Haser, C., Hülsdünker, T., Pfab, F., Vogt, L., & Banzer, W. (2024). Validity of a motor-cognitive dual-task agility test in elite youth football players. European journal of sport science, 24(8), 1056–1066. https://doi.org/10.1002/ejsc.12153

[10] Hülsdünker, T., Friebe, D., Giesche, F., Vogt, L., Pfab, F., Haser, C., & Banzer, W. (2023). Validity of the SKILLCOURT® technology for agility and cognitive performance assessment in healthy active adults. Journal of exercise science and fitness, 21(3), 260–267. https://doi.org/10.1016/j.jesf.2023.04.003

Muscle cramps are a temporary but intense and painful involuntary contraction of the skeletal muscles that can occur in many different situations. There is evidence that some cases are related to water and salt imbalances, while others appear to be triggered by persistent abnormal spinal reflex acti­vity as a result of fatigue in the affected muscles. This has led to alternative explanations, such as the theory of neuromuscular fatigue – i.e., impaired signal transmission between the brain and muscles after prolonged exertion.

Studies show that dehydration has no effect on the stimulation frequency required to trigger a cramp and confirm the involvement of spinal mechanisms. However, it is questionable to what extent these models are relevant to spontaneous cramps that occur during (exercise-associated muscle cramps (EAMC)) or after exercise. It has therefore been hypothesized that cramps are caused by persistent abnormal spinal reflex acti­vity, which appears to be secondary to muscle fatigue. In particular, EAMC has been attributed to a disturbance in the sustained activity of alpha motor neurons, which is based on a dysregulation of alpha motor neurons at the spinal level. Muscle fatigue was considered to be a triggering factor, as it increases the afferent activity of the muscle spindles (type Ia and II) and simultaneously inhibits the afferent activity of the type Ib Golgi tendon organs. Indirect evidence supporting this theory comes from the observation that passive stretching of the affected muscle during a cramp can alleviate the symptoms – presumably through autogenic inhibition via the tendon organ reflex. Nevertheless, this does not explain why cramps are not an inevitable consequence of every strenuous activity, why they occur more frequently in environments with high heat stress, or why some people are affected while others are spared.

In the human model of electrically induced cramps, it has been reported that pickle juice effectively shortens the duration of cramps. Miller et al. found that the duration of cramps was reduced by an average of about 37 % when 1 mL of pickle juice was consumed two seconds after the onset of cramps, compared to an experiment in which water was drunk. This did not affect the intensity of the cramp. Ingesting small amounts of pickle juice had no measurable effect on plasma concentrations of sodium, potassium, magnesium, or calcium, nor on plasma osmolality or plasma volume. Since the pickle juice did not cause any changes in circulating electrolytes, the authors suggested that the shortened cramp is mediated by the activation of receptors in the oropharynx, leading to a reduced discharge rate of the alpha motor neurons that innervate the affected muscle. However, it is important to emphasize that this was not a study of EAMC, but rather cramps triggered by electrical stimulation during a maximal voluntary contraction of a small foot muscle. In a randomized study (2023) involving 82 patients with liver cirrhosis and a history of more than four muscle cramps in the previous month, 1 tablespoon of pickle juice taken at the onset of a cramp improved cramp intensity without causing any adverse side effects.

Literature

1. Miller, K.C. Electrolyte and Plasma Responses After Pickle Juice, Mustard, and Deionized Water Ingestion in Dehydrated Humans. J Athl Train. 2014 May-Jun;49(3):360–367. doi: 10.4085/1062-6050-49.2.23
2. Elliot B Tapper et al. Pickle Juice Intervention for Cirrhotic Cramps Reduction: The PICCLES Randomized Controlled Trial. Am J Gastroenterol. 2022 Apr 13;117(6):895–901. doi:10.14309/ajg.0000000000001781
3. Ronald J Maughan, Susan M Shirreffs. Muscle Cramping During Exercise: Causes, Solutions, and Questions Remaining. Sports Med. 2019 Nov 6;49(Suppl 2):115–124. doi: 10.1007/s40279-019-01162-1.
4. Miller KC, Mack GW, Knight KL, et al. Reflex inhibition of electrically induced muscle cramps in hypohydrated humans. Med Sci Sports Exerc. 2010;42(5):953–961. doi: 10.1249/MSS.0b013e3181c0647e.
5. Miller KC, Mack G, Knight KL. Electrolyte and plasma changes after ingestion of pickle juice, water, and a common carbohydrate-electrolyte solution. J Athl Train. 2009;44(5):454–461. doi: 10.4085/1062-6050-44.5.454.
6. Kevin C Miller. Electrolyte and plasma responses after pickle juice, mustard, and deionized water ingestion in dehydrated humans. J Athl Train. 2014 May-Jun;49(3):360-7. doi: 10.4085/1062-6050-49.2.23. Epub 2014 Feb 12.
7. Jarett Peikert, Kevin C Miller, Jay Albrecht, Jared Tucker, James Deal. Pre-exercise ingestion of pickle juice, hypertonic saline, or water and aerobic performance and thermoregulation. Controlled Clinical Trial. J Athl Train. 2014 Mar-Apr;49(2):204-9.doi: 10.4085/1062-6050-49.2.11. Epub 2014 Feb 25.
8. McKenney, M.A.; Miller, K.C.; Deal, J.E.; Garden-Robinson, J.A.; Rhee, Y.S. Plasma and Electrolyte Changes in Exercising Humans After Ingestion of Multiple Boluses of Pickle Juice. J. Athl. Train. 2015, 50, 141–146.
9. Stephanie E Hooper Marosek, Vijay Antharam, Katayoon Dowlatshahi. Quantitative Analysis of the Acetic Acid Content in Substances Used by Athletes for the Possible Prevention and Alleviation of Exercise-Associated Muscle Cramps. J Strength Cond Res. 2020 Jun;34(6):1539-1546. doi: 10.1519/JSC.0000000000003595.

lowing “strong” recommendations stand out in the summary and deserve special attention in this article:

• For more sustainable healthcare, we recommend the following: […]
• Promotion of environmentally friendly lifestyles: Education and counseling on plant-based nutrition, active mobility (such as walking and cycling), and sustainable everyday practices.
• Prioritizing resource-saving treatment options (where therapies are equivalent): recommending non-surgical measures such as exercise therapy, behavioral modification, and weight
  management before considering invasive procedures. [1]

In addition to promoting an active lifestyle with a focus on mobility (e.g., walking and cycling in everyday life, taking the stairs instead of the elevator), exercise therapy is an evidence-based treatment method of undisputed fundamental importance, which should now finally be taken into account in healthcare practice. But what exactly should this exercise therapy look like? To give this originally sports medicine-related and at the same time highly translational field more contour, it is worth taking a look at the recently published systematic review and meta-ana­lysis by Yan et al. [4]. The team of authors compared six training methods in terms of their effect on pain reduction, function, gait pattern, and quality of life. Among these, aerobic exercise (walking, running, cycling, swimming) performed best as a first-line treatment. In addition, strengthening, flexibility, and coordination exercises, as well as so-called mind-body exercises [5], were also examined and rated positively. The latter form of exercise, as part of mind-body medicine [6], which has already been considered in earlier studies on knee osteoarthritis [7, 8], can make a valuable contribution to the treatment of osteoarthritis symptoms, shifting the focus from the painful knee joint to the whole person. This is entirely in line with the holistic concept of whole-person health [9], which is also becoming increasingly important in the context of prehabilitation [10]. The affected person becomes an active part of the treatment team, which focuses on self-efficacy and teamwork and promotes adherence. Interventions from mind-body medicine can also be used when “traditional” therapeutic approaches such as aerobic exercise cannot be carried out due to physical condition or other obstacles.

Targeted Nutrition

In addition to exercise as therapy and behavioral adjustment in the sense of strengthening self-efficacy, the S3 guideline also explicitly mentions plant-based nutrition [1] as an important component of osteoarthritis treatment, thus emphasizing the concept of targeted nutrition [11]. Key aspects include sufficient protein intake with a targeted amino acid composition, the intake of collagen [12, 13] and fiber [14, 15], as well as supplementary systemic enzyme therapy [12, 13, 16, 17], multi-substance mixtures [18], and phytopharmaceu­ticals. Curcuma [19 – 24] in particular is playing an increasingly scientifically proven role in pain reduction and functional improvement in degenerative diseases such as osteoarthritis.

This knowledge deserves to be taken into account in daily care and tested in practice – not as a replacement, but as a supplement to established forms of therapy. We should seize the opportunity to further examine, apply, and criti­cally observe such approaches in order to expand the field of conservative and regenerative medicine with valuable biological options.

Mind-body medicine and shared medical appointments

Mind-body medicine is considered to be of additional importance in reducing inflammatory biomarkers [25] and in the individual management of psychosocial stress [26]. Self-management and patient education are individual and closely linked to lifestyle medicine. They require targeted training and continuing education strategies for both patients and therapists. These approaches must now be consistently integrated into real-world care – analogous to the already established sports and exercise therapy. Oncology provides an interes­ting, differentiated, and precise approach with the concept of exercise oncology [27], while the currently evolving field of prehabilitation [10] can serve as a framework. The “open window” that is emerging in relation to prehabilitation offers the opportunity to anchor these innovative approaches in the long term. Let’s take advantage of it and make the necessary changes in medical care a reality. As already emphasized in the article by Lison & Lison, there is virtually no alternative to all these developments [28].

The salutogenic potential is far from exhausted – rather, it paves the way for a new era of medical care, in line with the mind-body medicine concept coined by Professor Herbert Benson and Professor Jon Kabatt-Zinn [29] [6, 30].

The cost-efficient concept of shared medical appointments (SMA) [31, 32] also appears to be particularly forward-looking in this context. This model of joint medical consultations [29] enables the efficient, interdisciplinary, and team-oriented implementation of mind-body approaches as well as lifestyle medicine – with patients as active members of their therapeutic process.

In the recent article “Bashing Doctors Instead of Science,” published in Orthopedics and Trauma Surgery 2025 15(5), the authors, Dr. Burkhard Lembeck (President of the BVOU) and Janosch Kuno (BVOU Press Officer), emphasize “that patients rightly expect their healthcare providers to exhaust all conservative therapies before resorting to surgery, even if the evidence for them is weak. This applies in particular to chronic conditions such as osteoarthritis or tendon irritation, when standard therapies do not help.” Especially from this perspective, the article “Integrative Osteoarthritis Therapy” seems more relevant and important to us than ever. We look forward to further developments in this field.

 —————

“It is evident that over the past 30 years, medicine has recognized that the mysterious dynamic balance we call health encompasses both body and mind and can be strengthened through certain qualities of attention – qualities that can have a nourishing, regenerative, and healing effect. We all possess this ability – let’s put it to use.” Jon Kabat-Zinn from the book “Coming to Our Senses” (2005)

—————

Study Tip Tai Chi helps with knee pain and improves knee function in people with knee osteoarthritis. Zhu SJ, et al. Online Unsupervised Tai Chi Intervention for Knee Pain and Function in People With Knee Osteoarthritis: The RETREAT Randomized Clinical Trial. JAMA Intern Med. Published online October 27, 2025. doi:10.1001/jamainternmed.2025.5723

—————

Literature

[1] Deutsche Gesellschaft für Orthopädie und Unfallchirurgie e.V.: Prävention und Therapie der Gonarthrose Version 5.0, 15.07.2024: https://register.awmf.org/de/leitlinien/detail/187-050

[2] Stellungnahme des BVOU zur Kritik an IGeL-Leistungen. BVOU 2025 https://sportaerztezeitung.com/rubriken/therapie/20313/stellungnahme-des-bvou-zur-kritik-an-igel-leistungen/

[3] Hyaluron-Spritzen bei Kniearthrose. Nutzen und Risiko. NDR Visite 02.09.2025. https://sportaerztezeitung.com/rubriken/therapie/20498/hyaluron-spritzen-bei-kniearthrose/

[4] Yan L. et al. Comparative efficacy and safety of exercise modalities in knee osteoarthritis: systematic review and network meta-analysis. BMJ. 2025 Oct 15;391:e085242. doi: 10.1136/bmj-2025-085242. PMID: 41093618; PMCID: PMC12522397.

[5] Mind-body Exercises. sportärztezeitung online. https://sportaerztezeitung.com/rubriken/training/20038/mind-body-exercises/

[6] Erbeldinger, R. (2025). Mind-Body Medicine Completes Sports Medicine: Development of a Prophylaxis Model Through Sports Medicine. THE MIND Bulletin on Mind-Body Medicine Research, 7, 23-30. https://doi.org/10.61936/themind/202504306

[7] Kessler CS. et al. Effectiveness of an Ayurveda treatment approach in knee osteoarthritis – a randomized controlled trial. Osteoarthritis Cartilage. 2018 May;26(5):620-630. doi: 10.1016/j.joca.2018.01.022. Epub 2018 Feb 7. PMID: 29426006.

[8] Lim WB, Al-Dadah O. Conservative treatment of knee osteoarthritis: A review of the literature. World J Orthop. 2022 Mar 18;13(3):212-229. doi: 10.5312/wjo.v13.i3.212. PMID: 35317254; PMCID: PMC8935331.

[9] Whole Person Health: What It Is and Why It’s Important. National Center for Complementary and Integrative Health. https://www.nccih.nih.gov/health/whole-person-health-what-it-is-and-why-its-important

[10] Erbeldinger R, Roßberg M, Hub S, Henze A. Prähabilitation (Prähab). sportärztezeitung online. https://sportaerztezeitung.com/rubriken/therapie/20728/praehabilitation-praehab/

[11] Erbeldinger R. Targeted Nutrition – Nutritional Education. sportärztezeitung online. https://sportaerztezeitung.com/rubriken/ernaehrung/20110/targeted-nutrition/

[12] Wild-Bode C. Kollagen und Enzyme. sportärztezeitung 02/25. https://sportaerztezeitung.com/rubriken/therapie/19713/kollagen-und-enzyme/

[13] Niemeyer P, Herbort M, Post F. Nahrungsergänzung – Was kann ich bei Knorpelschaden oder Arthrose in Bezug auf Ernährung und Nahrungsergänzung tun? Podcast Listen2Science. 29.11.2024. https://sportaerztezeitung.com/rubriken/ernaehrung/18261/ernaehrungstherapie-und-nahrungsergaenzung/

[14] Pang A. et al. Short-chain fatty acids from gut microbiota restore Th17/Treg balance in rheumatoid arthritis: Mechanisms and therapeutic potential. Journal of Translational Autoimmunity, Volume 11, December 2025, 100316. https://doi.org/10.1016/j.jtauto.2025.100316

[15] Häger J. et al. The Role of Dietary Fiber in Rheumatoid Arthritis Patients: A Feasibility Study. Nutrients 2019, 11, 2392. https://doi.org/10.3390/nu11102392

[16] Henrotin Y. et al. Oral enzyme combination therapy reduces systemic inflammation, urinary CTXII and pain in knee osteoarthritis: a proof-of-mechanism, randomised, crossover, double-blind, placebo-controlled trial. RMD Open. 2025 Aug 12;11(3):e005433. doi: 10.1136/rmdopen-2025-005433. PMID: 40803821; PMCID: PMC12352264.

[17] Klein G. et al. Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs. Clin Exp Rheumatol. 2006 Jan-Feb;24(1):25-30. PMID: 16539815.

[18] Post F. Hafer und Herzgesundheit. sportärztezeitung 02/25. https://sportaerztezeitung.com/rubriken/ernaehrung/19698/hafer-und-herzgesundheit/

[19] Zeng L. et al. Efficacy and Safety of Curcumin and Curcuma longa Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial. Front Immunol. 2022 Jul 22;13:891822. doi: 10.3389/fimmu.2022.891822. PMID: 35935936; PMCID: PMC9353077.

[20] Montagnino J. et al. Optimizing orthobiologic therapies with exercise, diet, and supplements. PM R. 2025 Apr;17(4):452-462. doi: 10.1002/pmrj.13320. Epub 2025 Jan 24. PMID: 39853939.

[21] Brockmüller A, Shakibaei M. Epigenetische Wirksamkeit von Curcumin. sportärztezeitung 04/23. https://sportaerztezeitung.com/rubriken/ernaehrung/15026/epigenetische-wirksamkeit-von-curcumin/

[22] Kuptniratsaikul V. et al. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study. Clin Interv Aging. 2014 Mar 20;9:451-8. doi: 10.2147/CIA.S58535. PMID: 24672232; PMCID: PMC3964021.

[23] Peng Y. et al. Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures. Drug Des Devel Ther. 2021 Nov 2;15:4503-4525. doi: 10.2147/DDDT.S327378. PMID: 34754179; PMCID: PMC8572027.

[24] Bittel M. et al. Kurkuma- und Curcuminoid-Behandlung bei Gonarthrose. Zeitschrift für Phytotherapie 2022; 43(06): 243-249 doi: 10.1055/a-1924-9460

[25] Mehta D. et al. Turning Down the Heat: Mind-Body Strategies Against Inflammaging. Journal of Integrative and Complementary MedicineVol. 31, No. 10. Published Online: 14 October 2025. https://doi.org/10.1177/2768360525138371

[26] Denninger JW. et al. Psychological assessments, allostatic load and gene expression analyses in a randomized controlled trial comparing meditation, yoga, and stress education. Front Psychol. 2025 Sep 12;16:1653242. doi: 10.3389/fpsyg.2025.1653242. PMID: 41020112; PMCID: PMC12463968.

[27] Voland, A. et al. Update onkologische Sport- und Bewegungstherapie. Fokus Onkol 28, 40–47 (2025). https://doi.org/10.1007/s15015-025-4316-9

[28] Lison A, Lison D. Teilhaben. Sportmedizin und Rehabilitation. sportärztezeitung 04/25

[29] Michalsen A. Ordnungstherapie, Stressreduktion und Mind-Body-Medizin – Begleittherapien bei chronischen Nierenerkrankungen. Dialyse aktuell 2015; 19(5): 264-269. DOI: 10.1055/s-0035-1556951

[30] Dossett ML, Fricchione GL, Benson H. A New Era for Mind-Body Medicine. N Engl J Med. 2020 Apr 9;382(15):1390-1391. doi: 10.1056/NEJMp1917461. PMID: 32268025; PMCID: PMC7486127.

[31] Erbeldinger R. Group Medical Visits. sportärztezeitung online. https://sportaerztezeitung.com/rubriken/therapie/20203/group-medical-visits/

[32] Branch A. How to use shared medical appointments in under-resourced communities. September 4, 2025. https://lifestylemedicine.org/how-to-use-shared-medical-appointments-in-under-resourced-communities/

Chronic pain after surgical procedures affects up to 30 – 50 % of patients who have undergone surgery and represents a significant challenge, including in follow-up care [1]. Scar tissue after lumbar spine surgery in particular can contribute to persistent pain due to increased tissue stiffness, reduced mobility, and nerve irritation [2]. The visible skin scar is only the “tip of the iceberg,” as fibrotic changes can continue deep into the tissue layers and affect nerve structures [3]. The aim of this study was to investigate the influence of microneedling on objective tissue parameters and subjective pain reports.

Study design and patient population

A prospective, descriptive observation was conducted. Thirty-one patients aged > 18 and < 80 years were included. All patients had chronic painful scarring for at least six months following surgery on the lumbar spine. Patients < 18 and > 80 years of age, with psychosomatic illnesses and secondary diseases that would have made it difficult to causally attribute the pain symptoms, were excluded. 

• Gender: 71 % female
• Median age: 57 years
• Average BMI: 28.7 kg/m²
• Observation period: 12 days (T1–T2) 

Intervention

Treatment was performed using micro­needling (Dermaroller®, Medical Device MC910 1.0 mm) in the area of the postoperative scar tissue with a force of approximately 2 newtons and a rolling speed of 10 cm per second.

Ten repetitions were performed in each direction on the scar tissue, as well as 0.5 mm to the right and left of the scar tissue along the scar. This application was repeated a total of three times per patient during the twelve days of inpatient stay.  

Measurement methods & statistics

Tissue stiffness: Of the five device-specific measurement parameters of the Myoton Pro, we selected the parameters Dynamic / Stiffness and Tone / Frequency in this study, as both parameters are best suited for indirectly determining tissue stiffness. The measurements were taken on the left, center, and right sides of the scar at fixed tissue markers. Indirect tissue stiffness was measured before the first treatment and one day after the last treatment.  Pain intensity: A numerical rating scale (NRS 0 – 10) was used before the first and after the last intervention. The evaluation was descriptive. 

Changes between T1 and T2 were represented by median values, and the NRS change was statistically tested.

Results

Dynamic/Stiffness (Fig. 2)

The measurements showed the following median changes between T1 and T2:

• Left: – 8.3  N/m
• Center: – 9.7  N/m
• Right: + 3.0  N/m

Tone / Frequency (Fig. 3)

Area LWS/erector spinae – left/right and scar area in T1 and T2 (descriptive)

Pain intensity (Fig. 4)

The median NRS was 5 points in T2, which was significantly lower than in T1 with 7 points (Wilcoxon test for paired differences, p <  0.001). The NRS thus showed a significant reduction in pain intensity between T1 and T2.

Discussion & limitations

The results of this study suggest that microneedling can reduce scar-associated tissue stiffness. The observed reduction in pain is consistent with previous stu­dies, which showed an improvement in scar-related parameters in up to 74 % of patients after microneedling [4, 5].

Whether altered tissue stiffness and improved pain symptoms can also positively influence tissue mobility and thus movement economy should be the subject of further studies. The limited number of cases and the absence of a control group limit the significance of the fin­dings. In addition, this is a very limited observation in the context of standard inpatient therapies. 

Conclusion for practice

Microneedling is a minimally invasive, easily integrated treatment option for chronic scar pain after lumbar spine surgery. The method leads to objective improvements in tissue stiffness and a significant reduction in pain intensity. Objective changes in tissue stiffness and a significant reduction in pain support its use in a comprehensive approach to scar-related pain. Microneedling can be an effective addition to a multimodal therapeutic approach for painful scar tissue. Randomized, controlled studies with functional endpoints are needed to confirm its full clinical relevance.

Literature

1. Brown BC et al. The hidden cost of skin scars: quality of life after skin scarring. J Plast Reconstr Aesthet Surg. 2008;61:1049–1058.
2. Tos P et al. Painful scar neuropathy: principles of diagnosis and treatment. Plast Aesthet Res. 2015;2:156–164.
3. Choinière M et al. Pain and paresthesia related to scar tissue. Pain. 1991.
4. Svenning M, Drejøe JB. Microneedling in mature burn scars. JMCRR. 2019;2:277–281.
5. Abd-Elsayed A et al. Diagnosis, treatment, and management of painful scar. J Pain Res. 2022;15:1–12.

Conflict of interest: There is no conflict of interest.

Reframing OA as a chronic wound with a stalled healing immune response explains the failures of these prior cytokine studies. The osteoarthritic joint remains locked in a low-grade state of inflammation, with the release of degradative enzymes such as matrix metalloproteinases (MMPs). This non-healing wound leads to collagen breakdown, hyaluronic acid fragmentation, and persistent inflammation through a feed-forward cycle. To effectively treat chronic conditions like OA a paradigm shift from fighting inflammation to resolving it through immune stimulation is necessary. If successful healing depends on actively resolving inflammation, could orthobiologic therapies be the tools capable of triggering this process? 

In Healing Joints and Nerves, this emer­ging paradigm shift in the treatment of OA and other chronic pain conditions is brought to life and made accessible to a broader audience.

Platelet-rich plasma

Therapeutic immune stimulation can be harnessed through orthobiologic therapies such as platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs). PRP contains platelets, their growth factors, and variable concentrations of leukocytes. When the platelet dose is sufficient, this combination of factors is capable of reactivating a stalled healing cascade and reducing the pain associated with OA (Figure 1). At its core, PRP isn’t an anti-inflammatory treatment. It uses acute inflammation to act as an immune stimulant. The criti­cal role of immune activation is further supported by recent studies demonstrating that PRP is likely to be effective only when the platelet and leukocyte doses are robust (Bansal, Leon et al. 2021, Berrigan, Bailowitz et al. 2025). Variability and lack of processing stand­ards continue to be problematic for PRP use in clinical practice.

Mesenchymal “stem cells”

Likewise, MSCs also work through immune modulation. MSCs, originally isolated from bone marrow in the 1980s by Dr. Arnold Caplan, demonstrate the ability to differentiate into chondrocytes in cell culture. Early laboratory experiments generated great enthusiasm for the potential of cartilage regrowth, based on these in vitro studies. However, the role of MSCs in vivo differs significantly from their activity in a lab culture dish. Once injected, MSC viability lasts from 24 hours to several weeks, depen­ding on the injection route and the rate of macrophage phagocytosis (de Witte, Luk et al. 2018, Satué, Schüler et al. 2019). Contrary to Dr. Caplan’s initial hypothesis, the pain relief from MSC injections doesn’t come from cartilage regrowth. Instead, pain relief results from MSCs’ secreted factors (Chen, Park et al. 2015, de Witte, Luk et al. 2018) and from macrophage activation (Guo, Imai et al. 2017).

Dr. Caplan increasingly understood the immune-based mechanisms of MSCs, and he eventually authored the 2017 editorial, “Mesenchymal Stem Cells: Time to Change the Name!” (Caplan 2017). He argued we should call these cells “medicinal signaling cells” to better reflect their biological functions. Despite his pleading, MSCs are still commonly referred to as “stem cells” in the lay press and medical publications. Although MSCs have shown analgesic benefits in several clinical studies, a recent multi-center, randomized clinical trial has called into question their potential advantages over traditional treatments such as corticosteroid injection (Mautner, Gottschalk et al. 2023).

Autologous Conditioned Serum (ACS)

Immune-based methods to resolve inflammation are also a core element of the orthobiologic therapy, autologous conditioned serum (ACS). ACS represents the physiological whole-blood secretome, encompassing the full spectrum of mediators released by all blood cells during an incubation phase- a process that mirrors the crucial phase of natural tissue healing. This generates a biologically potent composition inclu­ding growth factors, cytokines, lipid mediators, neutrophil-derived factors and exosomes which leads to effective tissue regeneration and pain resolution. Therapy concepts including this parti­cular ACS are invented by a German biotech company called Orthogen. The extended benefits are shown in over 45 clinical studies of ACS (Baltzer, Moser et al. 2009, Baltzer, Ostapczuk et al. 2013, Damjanov, Barac et al. 2018, Hang N 2025) including indications for OA, spinal and nerve tissue diseases and other pathologies. Because benefits of Orthogen-ACS appeared to extend beyond the duration of growth factors and anti-inflammatory cytokines such as IL-1, Dr. Buchheit and research teams pursued additional mechanistic studies. Using laboratory models of neuropathy and chronic pain, the scientific teams demonstrated that ACS resolved inflammation, provided lasting pain relief, and even improved nerve function (Buchheit, Huh et al. 2023). The mediator profile of ACS is well characterized and recent analyses have demonstrated a marked increase in exosomes. When tested for function, the exosome contribution to ACS was significant, supporting long-term pain relief and tissue homeostasis through targeted intercellular signaling. 

The unique and highly activated secretome profile including the diverse combination of factors in ACS has the ability to reduce the catabolic effects of corticosteroids (CS). Concerns about the potential negative impact of repeated CS injections have increased in recent years (McAlindon, LaValley et al. 2017). However, the side effects of CS appear to be markedly reduced with the addition of ACS. Combined treatment appears to enhance pain relief and reduce the risk of tissue injury associated with corticosteroids (Damjanov, Barac et al. 2018). By addressing acute pain instantly while simultaneously stimulating the body’s natural regenerative processes, it offers both short-term relief and long-term healing that can promote lasting effects. 

There is a clear paradigm shift in tre­ating OA and other chronic pain conditions. OA isn’t simply “wear and tear,” nor is it primarily an inflammatory condition like autoimmune diseases. Instead, OA is a chronic wound that requires treatment through immune stimulation and activation of the healing process. Regenerative therapies such as PRP, MSCs, and ACS do not work by “fighting” inflammation. They stimulate innate, immune-based repair mechanisms through various pathways. PRP delivers growth factors. MSCs promote macrophage ­activation. ACS functions through high concentrations of growth factors, lipid mediators, inflammation-­resolving cytokines, and exosomes. Collectively, these mechanisms restore joint balance, encourage tissue repair, and relieve pain.

Relevant Recent Publications:

Buchheit T, Huh Y, Maixner W, Cheng J,
Ji RR. Neuroimmune modulation of pain and regenerative pain medicine. J Clin Invest. 2020;130(5):2164-76. PubMed PMID: 32250346

Buchheit T, Hunt C, Eldrige J, Eshraghi Y, Souza D. Product characteristics should be reported in all biological therapy publications. Reg Anesth Pain Med. 2022. PubMed PMID: 35318261

Buchheit T, Huh Y, Breglio A, Bang S, Xu J, Matsuoka Y, et al. Intrathecal administration of conditioned serum from different species resolves Chemotherapy-Induced neuropathic pain in mice via secretory exosomes. Brain Behav Immun. 2023. PMID: 37150265

Buchheit T, Hunt C, Eldrige J, Eshraghi Y, Souza D. Autologous Conditioned Plasma is not Platelet-Rich Plasma. Reg Anesth Pain Med. 2026. PMID: 41672585

Buchheit, T: Healing Joints and Nerves: Immune Stimulation and the New Science of Regenerative Therapies. Bull Publishing Company. 2026

References

Aitken, D., L. L. Laslett, F. Pan, I. K. Haugen, P. Otahal, N. Bellamy, P. Bird and G. Jones (2018). „A randomised double-blind placebo-controlled crossover trial of HUMira (adalimumab) for erosive hand OsteoaRthritis – the HUMOR trial.“ Osteoarthritis Cartilage 26(7): 880–887.

Baltzer, A. W. A., C. Moser, S. A. Jansen and R. Krauspe (2009). „Autologous conditioned serum (Orthokine) is an effective treatment for knee osteoarthritis.“ Osteoarthritis and Cartilage 17(2): 152–160–160.

Baltzer, A. W. A., M. S. Ostapczuk, D. Stosch, F. Seidel and M. Granrath (2013). „A New Treatment for Hip Osteoarthritis: Clinical Evidence for the Efficacy of Autologous Conditioned Serum.“ Orthopedic Reviews 5(2): e13.

Bansal, H., J. Leon, J. L. Pont, D. A. Wilson, A. Bansal, D. Agarwal and I. Preoteasa (2021). „Platelet-rich plasma (PRP) in osteoarthritis (OA) knee: Correct dose critical for long term clinical efficacy.“ Sci Rep 11(1): 3971.

Berrigan, W. A., Z. Bailowitz, A. Park, A. Reddy, R. Liu and D. Lansdown (2025). „A Greater Platelet Dose May Yield Better Clinical Outcomes for Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Systematic Review.“ Arthroscopy 41(3): 809–817.e802.

Buchheit, T., Y. Huh, A. Breglio, S. Bang, J. Xu, Y. Matsuoka, R. Guo, A. Bortsov, J. Reinecke, P. Wehling, T. Jun Huang and R. R. Ji (2023). „Intrathecal administration of conditioned serum from different species resolves Chemotherapy-Induced neuropathic pain in mice via secretory exosomes.“ Brain Behav Immun 111: 298–311.

Caplan, A. I. (2017). „Mesenchymal Stem Cells: Time to Change the Name!“ STEM CELLS Translational Medicine 6(6): 1445–1451–1451.

Chen, G., C. K. Park, R. G. Xie and R. R. Ji (2015). „Intrathecal bone marrow stromal cells inhibit neuropathic pain via TGF-beta secretion.“ J Clin Invest 125(8): 3226–3240.

Damjanov, N., B. Barac, J. Colic, V. Stevanovic, A. Zekovic and G. Tulic (2018). „The efficacy and safety of autologous conditioned serum (ACS) injections compared with betamethasone and placebo injections in the treatment of chronic shoulder joint pain due to supraspinatus tendinopathy: a prospective, randomized, double-blind, controlled study.“ Med Ultrason 20(3): 335–341.

de Witte, S. F. H., F. Luk, J. M. Sierra Parraga, M. Gargesha, A. Merino, S. S. Korevaar, A. S. Shankar, L. O’Flynn, S. J. Elliman, D. Roy, M. G. H. Betjes, P. N. Newsome, C. C. Baan and M. J. Hoogduijn (2018). „Immunomodulation By Therapeutic Mesenchymal Stromal Cells (MSC) Is Triggered Through Phagocytosis of MSC By Monocytic Cells.“ Stem Cells 36(4): 602–615.

Guo, W., S. Imai, J. L. Yang, S. Zou, M. Watanabe, Y. X. Chu, Z. Mohammad, H. Xu, K. D. Moudgil, F. Wei, R. Dubner and K. Ren (2017). „In vivo immune interactions of multipotent stromal cells underlie their long-lasting pain-relieving effect.“ Sci Rep 7(1): 10107.

Hang N, H. G., Wehling J, Reinecke J, Hang M (2025). „Orthogen Autologous Conditioned Serum: An Update of the currently published Clinical Studies.“ Medical research Archives 13.

Kloppenburg, M., R. Ramonda, K. Bobacz, W. Y. Kwok, D. Elewaut, T. W. J. Huizinga, F. P. B. Kroon, L. Punzi, J. S. Smolen, B. Vander Cruyssen, R. Wolterbeek, G. Verbruggen and R. Wittoek (2018). „Etanercept in patients with inflammatory hand osteoarthritis (EHOA): a multicentre, randomised, double-blind, placebo-controlled trial.“ Ann Rheum Dis 77(12): 1757–1764.

Mautner, K., M. Gottschalk, S. D. Boden, A. Akard, W. C. Bae, L. Black, B. Boggess, P. Chatterjee, C. B. Chung, K. A. Easley, G. Gibson, J. Hackel, K. Jensen, L. Kippner, C. Kurtenbach, J. Kurtzberg, R. A. Mason, B. Noonan, K. Roy, V. Valentine, C. Yeago and H. Drissi (2023). „Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial.“ Nat Med 29(12): 3120–3126.

McAlindon, T. E., M. P. LaValley, W. F. Harvey, L. L. Price, J. B. Driban, M. Zhang and R. J. Ward (2017). „Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial.“ JAMA : the journal of the American Medical Association 317(19): 1967–1975.

Satué, M., C. Schüler, N. Ginner and R. G. Erben (2019). „Intra-articularly injected mesenchymal stem cells promote cartilage regeneration, but do not permanently engraft in distant organs.“ Sci Rep 9(1): 10153.

Parallel to steroid injections, hyaluronic acid injections have become established as a form of cartilage protection therapy due to their viscous supplementation effect. In recent years, the combined use of steroids and hyaluronic acid has become increasingly popular. The aim is to combine the rapid effect of steroids with the structural protective effect of hyaluronic acid. 

The dilemma in practice: quick relief – long-term damage?

The strong anti-inflammatory effect of cortisone is undisputed and often leads to rapid clinical improvement in osteoarthritis, but this short-term solution has a downside. Research has shown that corticosteroids trigger the programmed cell death of cartilage cells [1] and that repeated injections therefore carry the risk of cartilage damage and accelerated osteoarthritis progression [2]. This circumstance presents practitioners and patients with the challenge that symptomatic relief could mask progressive structural damage to the joint.

Hyaluronic acid: More than just a lubricant

This is where hyaluronic acid (HA) comes into play, whose effect goes far beyond that of a pure “lubricant” for viscosupplementation. HA is a biologically active molecule with multiple functions in the joint:

• Mechanical protection: HA improves the viscoelastic properties of the synovial fluid, thereby providing mechanical protection for the joint surfaces.
•  

  Anti-inflammatory: HA modulates the inflammatory response, among other things by interacting with CD44 receptors on the cartilage cells, which inhibits the release of inflammatory mediators.

• Chondroprotection: HA directly protects the cartilage cells from the cell-damaging effects of steroids.

Preclinical and clinical evidence: What does the science say?

Combination therapy is a promising approach, whose synergistic effects have already been proven in several studies. A randomized, double-blind, placebo-c­ontrolled multicenter study from 2018 involving 368 patients showed that the combined administration of cortisone and hyaluronic acid led to significantly faster and more pronounced pain relief than the respective single therapies [3]. While the cortisone effect dominated in the first few weeks, the hyaluronic acid component provided lasting improvement for up to 26 weeks. The well-tole­rated combination thus appears not only to enable effective short-term symptom control, but also to cushion the potentially adverse effects of cortisone on cartilage through the protective effect of hyaluronic acid, offering longer-term benefits. These clinical results are supported by several preclinical studies. In an in vitro model, bovine osteochondral tissue cultures were treated with inflammatory mediators (interleukin-1β and interleukin-17) to simulate an osteo­arthritis-like environment [4].

The combined use of hyaluronic acid and glucocorticoids showed a significantly stronger inhibition of cartilage-­degrading enzymes such as matrix metalloproteinases and proinflammatory cytokines compared to single doses. At the same time, the vitality of the cartilage cells was better preserved and there was a reduction in structural cartilage degradation.

A similar study investigated the effects of combination therapy on arthritic human cartilage cells in a 2D cell culture [5]. Here, too, a significantly stronger chondroprotective effect was demonstrated, including reduced expression of cartilage-degrading genes and preser­vation of collagen type II synthesis and cell vitality. Another study also examined the effects of co-administration of hyaluronic acid with steroids and various local anesthetics in a human cell culture [6]. As can be seen in Figure 2, hyaluronic acid enhanced the positive effects of glucocorticoids while significantly reducing their cell-damaging effects, especially in combination with individual local anesthetics.

Conclusion

In summary, both clinical and preclinical studies suggest that the combination of hyaluronic acid with glucocorticoids represents a promising addition to conservative osteoarthritis therapy due to synergistic effects. The simultaneous use of both substances not only enables effective short-term symptom control, but also offers longer-term benefits by protecting the cartilage structure and cushioning the potentially adverse effects of steroids. For daily practice, this means that combined administration is a worthwhile, potentially safer, and more effective alternative to cortisone injections alone.

Literature

1. Nakazawa F, Matsuno H, Yudoh K, Watanabe Y, Katayama R, Kimura T. Corticosteroid treatment induces chondrocyte apoptosis in an experimental arthritis model and in chondrocyte cultures. Clin Exp Rheumatol. 2002;20:773–81.
2. McAlindon TE, LaValley MP, Harvey WF, Price LL, Driban JB, Zhang M, et al. Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis a randomized clinical trial. JAMA – J Am Med Assoc. 2017;
3. Hangody L, Szody R, Lukasik P, Zgadzaj W, Lénárt E, Dokoupilova E, et al. Intraarticular Injection of a Cross-Linked Sodium Hyaluronate Combined with Triamcinolone Hexacetonide (Cingal) to Provide Symptomatic Relief of Osteoarthritis of the Knee: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Trial. Cartilage. 2018;9:276–83.
4. Bauer C, Moser LB, Kern D, Jeyakumar V, Nehrer S. The Combination of Glucocorticoids and Hyaluronic Acid Enhances Efficacy in IL-1β/IL-17-Treated Bovine Osteochondral Grafts Compared with Individual Application. Int J Mol Sci. 2023;24.
5. Bauer C, Moser LB, Jeyakumar V, Niculescu-Morzsa E, Kern D, Nehrer S. Increased Chondroprotective Effect of Combining Hyaluronic Acid with a Glucocorticoid Compared to Separate Administration on Cytokine-Treated Osteoarthritic Chondrocytes in a 2D Culture. Biomedicines [Internet]. 2022;10. Available from: https://www.mdpi.com/2227-9059/10/7/1733
6. Moser LB, Bauer C, Jeyakumar V, Niculescu‐morzsa EP, Nehrer S. Hyaluronic acid as a carrier supports the effects of glucocorticoids and diminishes the cytotoxic effects of local anesthetics in human articular chondrocytes in vitro. Int J Mol Sci. 2021;22.

Conservative therapy and its mechanisms of action can be understood in the context of prehabilitation as a kind of “open window” to rehabilitation. It can provide an initial impetus to activate the body’s own adaptation and regene­ration processes while simultaneously strengthening the patient’s self-management. This perspective applies to both conservative and physical therapies as well as to interventional or surgical procedures.

Orthobiological therapies and patient-related influencing factors

Orthobiological therapies such as Platelet-­Rich Plasma (PRP) / ACP, Blood Clot Secretome (BCS), ACS (IL-1RA), or cell-based procedures are increasingly being used to treat musculoskeletal disorders. At the same time, clinical studies show considerable variability in treatment outcomes in some cases (Filardo et al. 2023; Andia & Maffulli 2024).

An important reason for this could be that these therapies use autologous biological products. The quality of the injected material therefore potentially depends not only on technical manufacturing processes but also on the patient’s biological condition. A recent review by Montagnino et al. discusses that lifestyle factors such as exercise, diet, and certain supplements could influence platelet count and function as well as the quality of cell-based products (Montagnino et al., 2025). 

However, the authors explicitly emphasize that these correlations currently appear primarily biologically plausible, while robust clinical evidence remains limited and further translational research is still needed.

Biopsychosocial Expansion of Prehabilitation

Against this backdrop, an expansion of the prehabilitation approach that takes psychological and social aspects into account alongside biological factors appears sensible. Such a biopsychosocial understanding of prehabilitation also aligns with newer concepts of so-called metabolic optimization prior to orthobiological therapies. In their review, Fernandes and Rodeo describe how systemic factors such as metabolic health, chronic inflammatory processes, sleep quality, or lifestyle behaviors can influence the organism’s regenerative environment (Fernandes & Rodeo 2026).

These systemic factors can influence both the quality of autologous biological products and the regenerative capacity of the target tissue. At the same time, the authors emphasize that many of these strategies are currently based primarily on preclinical or indirect evidence (Fernandes & Rodeo 2026).

Mind-Body Medicine as a Potential Co-Therapy

In this context, the field of mind-body medicine is also discussed. Programs such as Mindfulness-Based Stress Reduction (MBSR), developed by Jon Kabat-­Zinn, or the Relaxation Response described by Herbert Benson are among the best-studied structured mind-body interventions.

• These programs aim to reduce stress responses
• improve autonomic regulatory processes
• and potentially influence immunological and neuroendocrine parameters.

A review on mind-body medicine in pain therapy describes that an eight-week MBSR program can lead to clinically relevant pain reductions in a significant proportion of participants (Paul 2023).

These findings primarily pertain to pain and stress modulation. The direct impact of such interventions on ortho­biological therapies such as PRP has not yet been sufficiently investigated.

Diet and Potential Effects on PRP

In addition to psychosocial factors, the role of diet is increasingly being discussed. A recent clinical study by Platzer et al. examined the relationship between different dietary patterns and the composition of PRP. In this study, vegan, vegetarian, and omnivorous diets were compared. The results show that certain molecular components of PRP – par­ti­cularly the pro-inflammatory cytokine interleukin-6 (IL-6 – may differ between dietary groups, while cell counts in the PRP remained largely comparable (Platzer et al. 2026). These data suggest that dietary habits may influence the molecular properties of PRP, although no direct clinical re­commendations can currently be derived from this. Similar considerations are also found in other studies, which suggest that dietary and lifestyle factors could influence systemic inflammatory activity and thus potentially regenerative processes (Andia & Maffulli 2024; McLarnon et al. 2024).

Curcumin and Other Phytonutrients

Curcumin is frequently discussed in the context of inflammatory musculoske­letal disorders and has demonstrated anti-inflammatory and signal-modulating properties in experimental studies (Nguyen et al. 2025). 

Furthermore, pharmacological and experimental studies show that curcumin may have platelet-modulating or antiplatelet effects by influencing various platelet activation signaling pathways (Liu et al. 2022).

In the context of PRP, this means:

An influence of curcumin on platelet-­dependent processes appears biologically plausible; however, its specific significance for PRP collection or the clinical efficacy of PRP therapies has not yet been sufficiently investigated. Similar considerations apply to other polyphenols such as resveratrol, quercetin, or anthocyanins, which may also exhibit platelet-modulating properties. 

The potential influence of such substances is therefore likely to depend significantly on dosage, formulation, and timing of administration, as well as on the individual metabolic context.

Nutrition, Metabolic Health, and Regeneration

Recent studies on metabolic optimi­zation prior to orthobiological therapies indicate that systemic factors such as

• obesity
• insulin resistance
• chronic inflammatory processes
• physical inactivity
• sleep disorders

can influence tissue regenerative capa­city and possibly also the efficacy of orthobiological therapies (Fernandes & Rodeo 2026). Diets with an anti-inflammatory profile – such as the Mediter­ranean or plant-based diets – are therefore discussed as potentially favorable conditions.

Here, too, most data are mechanistic or indirect, and clinical studies on the direct improvement of PRP outcomes are currently lacking (Montagnino et al. 2025; Fernandes & Rodeo 2026).

Conclusion

In summary, it can be stated that:

The preparation of patients prior to medical interventions can be viewed from a biopsychosocial perspective. Lifestyle factors such as exercise, diet, metabolic health, and stress regulation can influence the organism’s biological environment and thus potentially also modulate regenerative therapies. However, the current state of the literature shows that many of these relationships are so far primarily biologically plausible and cannot yet be considered esta­blished clinical recommendations.

Prehabilitation can therefore be understood as a potential “open window” in which patients can actively contribute to optimizing their baseline condition. In this sense, it can serve as a bridge between therapy, rehabilitation, and prevention – provided that the measures are implemented within the framework of a medically sound indication and patient-centered education.

Literature

1. Andia I, Maffulli N. Platelet-rich plasma for musculoskeletal conditions. Int Orthop. 2024.
2. Fernandes G, Rodeo SA. Metabolic Optimization Before Orthobiologic Therapies. Sports Health. 2026.
3. Filardo G et al. Platelet-rich plasma in musculoskeletal medicine: variability and clinical outcomes. Knee Surg Sports Traumatol Arthrosc. 2023.
4. Liu Z et al. Anti-platelet and antithrombotic effects of curcumin. Biomed Pharmacother. 2022.
5. McLarnon J et al. Patient factors influencing PRP therapy outcomes. Orthop J Sports Med. 2024.
6. Montagnino J et al. Optimizing orthobiologic therapies with exercise, diet, and supplements. PM&R. 2025.
7. Paul A. Mind-body-Medizin in der Schmerztherapie. Schmerz. 2023.
8. Platzer H et al. Dietary Patterns Are Associated with Blood Cell Profiles and the Molecular Composition of Platelet-Rich Plasma. Nutrients. 2026.

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Editor’s Note

Supplement: PRP, protein, and soluble fiber

In the context of PRP injections, a targeted, personalized nutritional therapy appears biologically plausible and clinically beneficial. In addition, we would like to emphasize that an adequate supply of proteins, essential amino acids, and soluble dietary fiber in particular forms the structural and metabolic basis of regenerative processes. This is not considered problematic before, during, or after PRP interventions—nor before surgical procedures or physical therapies (see: Outcomes of Cancer Surgery and Malnutrition in Internal Medicine

Especially in the prehabilitation phase, this form of targeted nutrition, including cholesterol-lowering dietary strategies, can support the biological prerequisites for tissue adaptation and the healing response. It is suitable for any medical intervention when applied as targeted nutrition.

See also: CHOLESTERINSENKENDE WIRKUNG VON HAFER UND METABOLISCHES SYNDROM

and  BALLASTSTOFFE REDUZIEREN RISIKO FÜR HERZ-KREISLAUFERKRANKUNGEN, PANKREASKREBS UND DIVERTIKULOSE

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