Do early life factors affect the development of knee osteoarthritis in later life: a narrative review

Osteoarthritis (OA) mainly affects older populations; however, it is possible that early life factors contribute to the development of OA in later life. The aim of this review is to describe the association between childhood or early adulthood risk factors and knee pain, structural imaging markers and development of knee OA in later life. A narrative overview of the literature synthesising the findings of literature retrieved from searches of computerised databases and manual searches was conducted. We found that only a few studies have explored the long-term effect of childhood or early adulthood risk factors on the markers of joint health that predispose people to OA or joint symptoms. High body mass index (BMI) and/or overweight status from childhood to adulthood were independently related to knee pain and OA in later life. The findings regarding the association between strenuous physical activity and knee structures in young adults are still conflicting. However, a favourable effect of moderate physical activity and fitness on knee structures is reported. Childhood physical activity and performance measures had independent beneficial effects on knee structures including knee cartilage in children and young adults. Anterior knee pain syndrome in adolescence could lead to the development of patellofemoral knee OA in the late 40s. Furthermore, weak evidence suggests that childhood malalignment, socioeconomic status and physical abuse are associated with OA in later life. The available evidence suggests that early life intervention may prevent OA in later life.     

经皮穴位电刺激联合下肢康复机器人在膝关节前交叉韧带损伤重建术后康复中的应用效果分析

摘要 目的：探讨经皮穴位电刺激联合下肢康复机器人在膝关节前交叉韧带损伤重建术后康复中的应用效果。方法：选取我院2019年1月到2022年12月收治的120例采取膝关节前交叉韧带损伤重建术的患者作为研究对象,分为观察组与对照组,每组60例。对照组采取常规术后康复治疗,观察组采取经皮穴位电刺激联合下肢康复机器人康复治疗,对比两组患者康复治疗效果,位置觉和运动觉,疼痛情况与肿胀情况,膝关节功能以及生活质量。结果：观察组治疗总有效率高于对照组（P＜0.05）;治疗前两组患者患肢肿胀值、视觉模拟量表（VAS）评分对比无差异（P＞0.05）,治疗后均降低,且观察组较对照组低（P＜0.05）;两组患者的治疗前膝关节75度、45度、15度位置觉,伸膝、屈膝运动觉对比无差异（P>0.05）,治疗后两组患者膝关节75度、45度、15度位置觉,伸膝、屈膝运动觉均下降,且观察组较对照组低（P＜0.05）;治疗前两组患者膝关节主观（IKDC）评分、膝关节功能（Lysholm）评分对比无差异（P＞0.05）,治疗后均降低,且观察组较对照组低（P＜0.05）;两组患者治疗前生活质量相关评分对比无差异（P＜0.05）,治疗后均升高,且观察组较对照组高（P＜0.05）。结论：经皮穴位电刺激联合下肢康复机器人在膝关节前交叉韧带损伤重建术后康复中应用效果显著,能够改善患者膝关节位置觉和运动觉,减轻远期疼痛情况与肿胀情况,提升膝关节功能,患者生活质量较好。     

Cannabinoid CB2 Receptors Regulate Central Sensitization and Pain Responses Associated with Osteoarthritis of the Knee Joint

Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies.Inhibitory cannabinoid 2 (CB₂) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB₂ receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB₂ receptor mRNA and protein expression in an OA pain model. The expression of CB₂ receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB₂ receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB₂ receptor mRNA and macroscopic knee chondropathy.These data provide new clinically relevant evidence that joint damage and spinal CB₂ receptor expression are correlated combined with converging pre-clinical evidence that activation of CB₂ receptors inhibits central sensitization and its contribution to the manifestation of chronic OA pain. These findings suggest that targeting CB₂ receptors may have therapeutic potential for treating OA pain.     

Nociceptor activation and pain

This paper reviews advances in our knowledge on the physiological properties of human nociceptors and their capacity to signal pain. Conventional microneurography was used in combination with intraneural microstimulation in subjects who estimated the magnitude of pain from nociceptor stimulation. The experimental evidence favours the notion that C polymodal nociceptors can provide a peripheral neuronal basis for determination of heat pain threshold and also an essential peripheral code for suprathreshold magnitude judgments of heat pain. Furthermore, sensitized C polymodal nociceptors can contribute to hyperalgesia after a mild heat injury to hairy skin. Temporal summation is documented for dull, delayed C fibre pain, which is different in quality and less accurately projected than the fast, sharp pain from high-threshold A delta nociceptors. A segmental organization is shown for projected and referred pain from deep structures. Examples are given of central inhibition of pain by a prostaglandin synthetase inhibitor, and by physical manoeuvres such as vibration and cooling. Recent reports on microneurographic findings after nerve injury indicate that the technique may be useful for future studies on pathophysiological pain mechanisms.     

Mechanical contributors to sex differences in idiopathic knee osteoarthritis

The occurrence of knee osteoarthritis (OA) increases with age and is more common in women compared with men, especially after the age of 50 years. Recent work suggests that contact stress in the knee cartilage is a significant predictor of the risk for developing knee OA. Significant gaps in knowledge remain, however, as to how changes in musculoskeletal traits disturb the normal mechanical environment of the knee and contribute to sex differences in the initiation and progression of idiopathic knee OA. To illustrate this knowledge deficit, we summarize what is known about the influence of limb alignment, muscle function, and obesity on sex differences in knee OA. Observational data suggest that limb alignment can predict the development of radiographic signs of knee OA, potentially due to increased stresses and strains within the joint. However, these data do not indicate how limb alignment could contribute to sex differences in either the development or worsening of knee OA. Similarly, the strength of the knee extensor muscles is compromised in women who develop radiographic and symptomatic signs of knee OA, but the extent to which the decline in muscle function precedes the development of the disease is uncertain. Even less is known about how changes in muscle function might contribute to the worsening of knee OA. Conversely, obesity is a stronger predictor of developing knee OA symptoms in women than in men. The influence of obesity on developing knee OA symptoms is not associated with deviation in limb alignment, but BMI predicts the worsening of the symptoms only in individuals with neutral and valgus (knock-kneed) knees. It is more likely, however, that obesity modulates OA through a combination of systemic effects, particularly an increase in inflammatory cytokines, and mechanical factors within the joint. The absence of strong associations of these surrogate measures of the mechanical environment in the knee joint with sex differences in the development and progression of knee OA suggests that a more multifactorial and integrative approach in the study of this disease is needed. We identify gaps in knowledge related to mechanical influences on the sex differences in knee OA.     

Analysis of muscle activation patterns during transitions into and out of high knee flexion postures

Increased risk of medial tibiofemoral osteoarthritis (OA) is linked to occupations that require frequent transitions into and out of postures which require high knee flexion (>90°). Muscle forces are major contributors to joint loading, and an association between compressive forces due to muscle activations and the degeneration of joint cartilage has been suggested. The purpose of this study was to evaluate muscle activation patterns of muscles crossing the knee during transitions into and out of full-flexion kneeling and squatting, sitting in a low chair, and gait. Both net and co-activation were greater when transitioning out of high flexion postures, with maximum activation occurring at knee angles greater than 100°. Compared to gait, co-activation levels during high flexion transitions were up to approximately 3 times greater. Co-activation was significantly greater in the lateral muscle group compared to the medial group during transitions into and out of high flexion postures. These results suggest that compression due to activation of the medial musculature of the knee may not be the link between high knee flexion postures and increased medial knee OA observed in occupational settings. Further research on a larger subject group and workers with varying degrees of knee OA is necessary.     

Gait and neuromuscular pattern changes are associated with differences in knee osteoarthritis severity levels

Knee osteoarthritis (OA) is a multifactoral, progressive disease process of the musculoskeletal system. Mechanical factors have been implicated in the progression of knee OA, but the role of altered joint mechanics and neuromuscular control strategies in progressive mechanisms of the disease have not been fully explored. Previous biomechanical studies of knee OA have characterized changes in joint kinematics and kinetics with the disease, but it has been difficult to determine if these biomechanical changes are involved in the development of disease, are in response to degenerative changes in the joint, or are compensatory mechanisms in response to these degenerative changes or other related factors as joint pain. The goal of this study was to explore the association between biomechanical changes and knee OA severity in an effort to understand the changing role of biomechanical factors in the progression of knee OA. A three-group cross-sectional model was used that included asymptomatic subjects, subjects clinically diagnosed with moderate knee OA and severe knee OA subjects just prior to total joint replacement surgery. Principal component analysis and discriminant analysis were used to determine the combinations of electromyography, kinematic and kinetic waveform pattern changes at the knee, hip and ankle joints during gait that optimally separated the three levels of severity. Different biomechanical mechanisms were important in discriminating between severity levels. Changes in knee and hip kinetic patterns and rectus femoris activation were important in separating the asymptomatic and moderate OA gait patterns. In contrast, changes in knee kinematics, hip and ankle kinetics and medial gastrocnemius activity were important in discriminating between the moderate and severe OA gait patterns.     

Spatial summation of perceived pressure,sharpness and mechanically evoked cutaneous pain

Psychophysically, spatial summation can be demonstrated as a decrease in threshold accompanying an increased field of stimulation. The present study examined to what extent different mechanically evoked percepts (pressure, sharpness, and pain) show spatial summation. Various probes were used to apply prescribed forces to the dorsal surface of the digits of 19 healthy subjects. The threshold for three perceptual qualities showed differing degrees of spatial summation: sharpness showed no statistically significant spatial summation; pain demonstrated some significant summation (46% on average); pressure showed the greatest degree of spatial summation (76% on average). The lack of significant spatial summation for sharpness threshold is consistent with the theory that perceived sharpness can be evoked by near threshold activity of a single nociceptor. The modest amount of spatial summation for pain implies that distinctly suprathreshold activation of nociceptors is required for mechanically evoked pain perception, and such input summates centrally, but not completely. The greater spatial summation observed for pressure vs. pain thresholds implies a greater degree of central summation for slowly adapting mechanoreceptors vs. nociceptors.     

Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis

Introduction

We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism.

Methods

Using Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis (hyaluronic acid: sHA).

Results

sCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA.

Conclusions

These results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA.     

Obesity profiles with knee osteoarthritis: correlation with pain, disability, disease progression

Objectives: To identify the prevalence of overweight among community‐dwelling adults diagnosed as having knee osteoarthritis (OA) and the relationship between the weight status of these individuals, selected disease‐related outcomes, and disease progression. Research Methods and Procedures: The BMIs of 82 women and 18 men with unilateral or bilateral knee OA were examined on a single occasion along with data on physical comorbidities, pain, and function and subjected to correlation analyses. BMIs from two additional samples, one that included 16 women with and without knee OA and one that included 24 women and 6 men with knee joint OA that required surgery for the subsequent onset of hip OA, were also assessed. Results: At least 80% of all present cohorts were overweight or obese. Those with higher BMIs reported more pain than those with lower BMIs (p < 0.05) and pain was related to perceived physical exertion (p < 0.05). Body mass indices were not significantly correlated with generic gait measures, but an inverse trend toward the time spent in the gait cycle (r = ?0.63; p = 0.097) that may impact the disease process was identified. Those with comorbidities had the same body mass, on average, as those with no comorbidities, and those with bilateral disease were heavier than those with unilateral disease. Discussion: A high body mass is present in most adults with knee OA. Moreover, being overweight may affect knee joint impact rates and pain incrementally. Having high body weights may heighten the risk for bilateral knee joint, as well as hip joint, OA.     

平衡性训练对膝关节内侧副韧带损伤患者膝关节功能恢复的效果研究

目的:研究平衡性训练对膝关节内侧副韧带(MCL)损伤患者膝关节功能恢复的效果。方法:选取2014年8月至2016年8月北京体育大学运动员膝关节MCL损伤患者112例为研究对象,根据随机数字表法将其分为对照组(n=56)与观察组(n=56)。对照组予以常规康复训练干预,观察组则在对照组的基础上加用平衡性训练干预,两组患者干预时间均为4周,分别比较两组干预前和干预4周后膝关节功能变化情况、疼痛程度、膝关节平衡能力以及生活质量的变化。结果:干预后两组患者Lysholm评分均较干预前升高,且观察组明显高于对照组,差异有统计学意义(P0.05)。干预后两组患者视觉模拟(VAS)评分均明显低于干预前,且观察组明显低于对照组,差异均有统计学意义(均P0.05)。干预后,两组患者总体稳定指数(OSI)、前后方向的稳定指数(APSI)、左右方向的稳定指数(MLSI)水平均低于干预前,且观察组患者OSI、APSI、MLSI水平均低于对照组,差异均有统计学意义(均P0.05)。观察组患者满意度较对照组明显升高,差异有统计学意义(P0.05)。结论:为膝关节MCL损伤患者实施平衡性训练能较好地改善其膝关节功能,并缓解疼痛,同时可帮助其提高膝关节的平衡能力,增加了满意度,适于推广。     

Prognostic factors for progression of clinical osteoarthritis of the knee: a systematic review of observational studies

IntroductionWe performed a systematic review of prognostic factors for the progression of symptomatic knee osteoarthritis (OA), defined as increase in pain, decline in physical function or total joint replacement.MethodWe searched for available observational studies up to January 2015 in Medline and Embase according to a specified search strategy. Studies that fulfilled our initial inclusion criteria were assessed for methodological quality. Data were extracted and the results were pooled, or if necessary summarized according to a best evidence synthesis.ResultsOf 1,392 articles identified, 30 met the inclusion criteria and 38 determinants were investigated. Pooling was not possible due to large heterogeneity between studies. The best evidence synthesis showed strong evidence that age, ethnicity, body mass index, co-morbidity count, magnetic resonance imaging (MRI)-detected infrapatellar synovitis, joint effusion and baseline OA severity (both radiographic and clinical) are associated with clinical knee OA progression. There was moderate evidence showing that education level, vitality, pain-coping subscale resting, MRI-detected medial femorotibial cartilage loss and general bone marrow lesions are associated with clinical knee OA progression. However, evidence for the majority of determinants was limited (including knee range of motion or markers) or conflicting (including age, gender and joint line tenderness).ConclusionStrong evidence was found for multiple prognostic factors for progression of clinical knee OA. A large variety in definitions of clinical knee OA (progression) remains, which makes it impossible to summarize the evidence through meta-analyses. More research on prognostic factors for knee OA is needed using symptom progression as an outcome measure. Remarkably, only few studies have been performed using pain progression as an outcome measure. The pathophysiology of radiographic factors and their relation with symptoms should be further explored.     

Soy protein may alleviate osteoarthritis symptoms

Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.     

Local ASIC3 modulates pain and disease progression in a rat model of osteoarthritis

Background

Recent data have suggested a relationship between acute arthritic pain and acid sensing ion channel 3 (ASIC3) on primary afferent fibers innervating joints. The purpose of this study was to clarify the role of ASIC3 in a rat model of osteoarthritis (OA) which is considered a degenerative rather than an inflammatory disease.

Methods

We induced OA via intra-articular mono-iodoacetate (MIA) injection, and evaluated pain-related behaviors including weight bearing measured with an incapacitance tester and paw withdrawal threshold in a von Frey hair test, histology of affected knee joint, and immunohistochemistry of knee joint afferents. We also assessed the effect of ASIC3 selective peptide blocker (APETx2) on pain behavior, disease progression, and ASIC3 expression in knee joint afferents.

Results

OA rats showed not only weight-bearing pain but also mechanical hyperalgesia outside the knee joint (secondary hyperalgesia). ASIC3 expression in knee joint afferents was significantly upregulated approximately twofold at Day 14. Continuous intra-articular injections of APETx2 inhibited weight distribution asymmetry and secondary hyperalgesia by attenuating ASIC3 upregulation in knee joint afferents. Histology of ipsilateral knee joint showed APETx2 worked chondroprotectively if administered in the early, but not late phase.

Conclusions

Local ASIC3 immunoreactive nerve is strongly associated with weight-bearing pain and secondary hyperalgesia in MIA-induced OA model. APETx2 inhibited ASIC3 upregulation in knee joint afferents regardless of the time-point of administration. Furthermore, early administration of APETx2 prevented cartilage damage. APETx2 is a novel, promising drug for OA by relieving pain and inhibiting disease progression.     

Neuromuscular alterations during walking in persons with moderate knee osteoarthritis.

This paper compared the neuromuscular responses during walking between those with early-stage knee osteoarthritis (OA) to asymptomatic controls. The rationale for studying those with mild to moderate knee OA was to determine the alterations in response to dynamic loading that might be expected before severe pain, joint space narrowing and joint surface changes occur. We used pattern recognition techniques to explore both amplitude and shape changes of the surface electromyograms recorded from seven muscles crossing the knee joint of 40 subjects with knee OA and 38 asymptomatic controls during a walking task. The principal patterns for each muscle grouping explained over 83% of the variance in the waveforms. This result supported the notion that the main neuromuscular patterns were similar between asymptomatic controls and those with OA, reflecting the specific roles of the major muscles during walking. ANOVA revealed significant (p<0.05) differences in the principal pattern scores reflecting both amplitude and shape alterations in the OA group and among muscles. These differences captured subtle changes in the neuromuscular responses of the subjects with OA throughout different phases of the gait cycle and most likely reflected changes in the mechanical environment (joint loading, instability) and pain. The subjects with OA attempted to increase activity of the lateral sites and reduce activity in the medial sites, having minimal but prolonged activity during late stance. Therefore, alterations in neuromuscular responses were found even in this high functioning group with moderate knee OA.     

Pain and its relationship with muscle strength and proprioception in knee OA: results of an 8-week home exercise pilot study

Muscle strength and proprioception deficits have been recognized in knee OA. Pain is the symptomatic hallmark of knee OA. Indirect evidence suggests that muscle strength and proprioception deficits may be interrelated and that pain may have a confounding influence on the measurement of these factors in knee OA. However, these relationships have never been clearly evaluated. Therefore, the purpose of this investigation was to investigate relationships between pain, muscle strength, and proprioception in subjects with knee OA before and after an 8-week home exercise program. This study evaluated thirty-eight subjects with knee OA. Subjects were taught standard quadriceps strengthening exercises that were to be performed daily at home. Pain, muscle strength, and proprioceptive function were measured at baseline and after 8 weeks of therapy. Significant improvements in pain (42%, p<0.001) and quadriceps muscle strength (30%, p<0.001) were noted. Significant indirect associations were observed between pain and both muscle strength (rho=-0.39, p=0.01) and proprioceptive acuity (rho=-0.35, p=0.03) at baseline. Changes in pain were directly associated with changes in muscle strength (rho=0.45, p=0.005) and proprioceptive acuity (rho=0.41, p=0.01) with exercise. The association of pain with both muscle strength and proprioception should prompt future studies to consider and adjust for the influence of pain on neuromuscular factors in knee OA.     

Experimentally reduced hip abductor function during walking: Implications for knee joint loads

Hip and knee functions are intimately connected and reduced hip abductor function might play a role in development of knee osteoarthritis (OA) by increasing the external knee adduction moment during walking. The purpose of this study was to test the hypothesis that reduced function of the gluteus medius (GM) muscle would lead to increased external knee adduction moment during level walking in healthy subjects. Reduced GM muscle function was induced experimentally, by means of intramuscular injections of hypertonic saline that produced an intense short-term muscle pain and reduced muscle function. Isotonic saline injections were used as non-painful control. Fifteen healthy subjects performed walking trials at their self-selected walking speed before and immediately after injections, and again after 20 min of rest, to ensure pain recovery. Standard gait analyses were used to calculate three-dimensional trunk and lower extremity joint kinematics and kinetics. Surface electromyography (EMG) of the glutei, quadriceps, and hamstring muscles were also measured. The peak GM EMG activity had temporal concurrence with peaks in frontal plane moments at both hip and knee joints. The EMG activity in the GM muscle was significantly reduced by pain (?39.6%). All other muscles were unaffected. Peaks in the frontal plane hip and knee joint moments were significantly reduced during pain (?6.4% and ?4.2%, respectively). Lateral trunk lean angles and midstance hip joint adduction and knee joint extension angles were reduced by ?1°. Thus, the gait changes were primarily caused by reduced GM function. Walking with impaired GM muscle function due to pain significantly reduced the external knee adduction moment. This study challenge the notion that reduced GM function due to pain would lead to increased loads at the knee joint during level walking.     

An in vivo investigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis

Introduction  

Subchondral bone cysts (SBC) have been identified in patients with knee osteoarthritis (OA) as a cause of greater pain, loss of cartilage and increased chance of joint replacement surgery. Few studies monitor SBC longitudinally, and clinical research using three-dimensional imaging techniques, such as magnetic resonance imaging (MRI), is limited to retrospective analyses as SBC are identified within an OA patient cohort. The purpose of this study was to use dual-modality, preclinical imaging to monitor the initiation and progression of SBC occurring within an established rodent model of knee OA.     

A musculoskeletal finite element model of rat knee joint for evaluating cartilage biomechanics during gait

Abnormal loading of the knee due to injuries or obesity is thought to contribute to the development of osteoarthritis (OA). Small animal models have been used for studying OA progression mechanisms. However, numerical models to study cartilage responses under dynamic loading in preclinical animal models have not been developed. Here we present a musculoskeletal finite element model of a rat knee joint to evaluate cartilage biomechanical responses during a gait cycle. The rat knee joint geometries were obtained from a 3-D MRI dataset and the boundary conditions regarding loading in the joint were extracted from a musculoskeletal model of the rat hindlimb. The fibril-reinforced poroelastic (FRPE) properties of the rat cartilage were derived from data of mechanical indentation tests. Our numerical results showed the relevance of simulating anatomical and locomotion characteristics in the rat knee joint for estimating tissue responses such as contact pressures, stresses, strains, and fluid pressures. We found that the contact pressure and maximum principal strain were virtually constant in the medial compartment whereas they showed the highest values at the beginning of the gait cycle in the lateral compartment. Furthermore, we found that the maximum principal stress increased during the stance phase of gait, with the greatest values at midstance. We anticipate that our approach serves as a first step towards investigating the effects of gait abnormalities on the adaptation and degeneration of rat knee joint tissues and could be used to evaluate biomechanically-driven mechanisms of the progression of OA as a consequence of joint injury or obesity.     

Comparison of hamstring neuromechanical properties between healthy males and females and the influence of musculotendinous stiffness

The hamstrings limit anterior cruciate ligament (ACL) loading, and neuromuscular control of these muscles is crucial for dynamic knee joint stability. Sex differences in electromechanical delay (EMD) and rate of force production (RFP) have been reported previously, and attributed to differences in musculotendinous stiffness (MTS). These characteristics define the neuromechanical response to joint perturbation, and sex differences in these characteristics may contribute to the greater female ACL injury risk. However, it is unclear if these differences exist in the hamstrings, and the relationship between MTS and neuromechanical function has not been assessed directly. Hamstring MTS, EMD, the time required to produce 50% peak force (Time50%), and RFP were assessed in 20 males and 20 females with no history of ACL injury. EMD did not differ significantly across sex (p = 0.788). However, MTS (p < 0.001) and RFP (p = 0.003) were greater in males, Time50% (p = 0.013) was shorter in males, and Time50% was negatively correlated with MTS (r = −0.332, p = 0.039). These results suggest that neuromechanical hamstring function in females may limit dynamic knee joint stability, potentially contributing to the greater female ACL injury risk. However, future research is necessary to determine the direct influences of MTS and neuromechanical function on dynamic knee joint stability and ACL injury risk.