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Changes induced by chronic in vivo load alteration in the tibiofemoral joint of mature rabbits.

ABSTRACT: We investigated the relationship between the magnitude and duration of chronic compressive load alteration and the development and progression of degenerative changes in the rabbit tibiofemoral joint. Varus loading devices were attached to the hind limb of mature NZW rabbits. Altered compressive loads of 0%, 50%, and 80% body weight (BW) were applied to the tibiofemoral joint for 12 h per day for 12 and 24 weeks (n?=?4 animals/group). Compartment-specific assessment of the tibial plateau included histological assessments (articular cartilage, calcified cartilage, and subchondral bone thicknesses, degeneration score, and articular cartilage cellularity) and biomechanical measures (aggregate modulus, permeability, Poisson's ratio). Analyses of variance techniques were used to examine the relationship between each outcome measure with load magnitude and duration as independent variables in the model. Degenerative changes developed in the medial compartment with increased magnitude of compressive loading and included fibrillation, increased degeneration score, and reduced cellularity of the articular cartilage. Increased calcified cartilage thickness was observed in both the medial and lateral compartments following exposure to altered loading of 80% BW for 24 weeks. This work demonstrates that in vivo chronic compressive load alteration to the tibiofemoral joint can initiate progressive macroscopic and histological-based degenerative changes analogous to the early changes occurring in OA.

SUBMITTER: Roemhildt ML

PROVIDER: S-EPMC3387521 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Changes induced by chronic in vivo load alteration in the tibiofemoral joint of mature rabbits.

Roemhildt Maria L ML Beynnon Bruce D BD Gardner-Morse Mack M Badger Gary G Grant Calsey C

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20120217 9

We investigated the relationship between the magnitude and duration of chronic compressive load alteration and the development and progression of degenerative changes in the rabbit tibiofemoral joint. Varus loading devices were attached to the hind limb of mature NZW rabbits. Altered compressive loads of 0%, 50%, and 80% body weight (BW) were applied to the tibiofemoral joint for 12 h per day for 12 and 24 weeks (n = 4 animals/group). Compartment-specific assessment of the tibial plateau include ...[more]

PMID: 22344562

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Project description:BackgroundIt has been hypothesized that quadriceps muscle weakness is directly associated with the onset and progression of posttraumatic osteoarthritis after anterior cruciate ligament (ACL) injury and reconstruction (ACLR). This relationship, however, has not been studied with a prospective approach that includes the use of tibiofemoral joint space width difference (JSW-D) measurements to characterize the onset of posttraumatic osteoarthritis before the clinical manifestation of the disease.PurposeTo assess the relationship between thigh muscle strength and JSW-D at presurgery baseline and at 1- and 4-year follow-up after ACLR compared with healthy, noninjured participants of similar sex, age, body mass index, and activity level.Study designCohort study; Level of evidence, 3.MethodsA total of 39 unilateral ACL-injured patients and 32 healthy controls were followed prospectively. During each follow-up, JSW, isokinetic knee strength, single-legged hop, and clinical- and patient-oriented outcomes were assessed. At final follow-up, ACL-injured participants who had JSW-D values (considered as the injured minus normal knee) that were less than the 95% confidence interval of controls were considered to be in the ACLR-narrow group, while those with JSW-D values that fell within the confidence intervals were in the ACLR-normal group. Relationships were evaluated between ACLR groups and controls via multilevel regression, as well as Kruskal-Wallis tests for between-group comparisons at 4-year follow-up.ResultsAt 4-year follow-up, 30 participants (79%) were in the ACLR-normal group and 8 (21%) were in the ACLR-narrow group. At baseline, the extension, flexion, and extension/flexion ratio strength values for both ACLR groups were significantly lower than those of controls (P ≤ .05), while the ACLR-narrow group had significantly lower extension strength at 60 and 180 deg/s (P = .04 and .03, respectively), as well as extension/flexion ratio at 60 deg/s (P = .04) in comparison with the ACL-normal group. At 4-year follow-up, 60 deg/s extension strength deficits persisted in the ACLR-narrow group compared with controls and ACLR-normal participants (P = .01 and .04, respectively). Flexion strength at 180 and 300 deg/s was also significantly lower in the ACLR-narrow group compared with ACLR-normal (P = .02 and .04, respectively), as was single-legged hop distance (P = .04).ConclusionStrength deficits present within months after ACL injury and persist through 4 years after ACLR in participants with significantly narrowed JSW-D, compared with ACLR participants with normal JSW-D and controls. This study revealed a significant relationship between quadriceps strength loss that occurred soon after injury and JSW narrowing.

Project description:ObjectiveClinical evidence suggests that abnormal mechanical forces play a major role in the initiation and progression of osteoarthritis (OA). However, few studies have examined the mechanical environment that leads to disease. Thus, using a mouse tibial loading model, we quantified the cartilage contact stresses and examined the effects of altering tissue material properties on joint stresses during loading.DesignUsing a discrete element model (DEA) in conjunction with joint kinematics data from a murine knee joint compression model, the magnitude and distribution of contact stresses in the tibial cartilage during joint loading were quantified at levels ranging from 0 to 9 N in 1 N increments. In addition, a simplified finite element (FEA) contact model was developed to simulate the knee joint, and parametric analyses were conducted to investigate the effects of altering bone and cartilage material properties on joint stresses during compressive loading.ResultsAs loading increased, the peak contact pressures were sufficient to induce fibrillations on the cartilage surfaces. The computed areas of peak contact pressures correlated with experimentally defined areas of highest cartilage damage. Only alterations in cartilage properties and geometry caused large changes in cartilage contact pressures. However, changes in both bone and cartilage material properties resulted in significant changes in stresses induced in the bone during compressive loading.ConclusionsThe level of mechanical stress induced by compressive tibial loading directly correlated with areas of biological change observed in the mouse knee joint. These results, taken together with the parametric analyses, are the first to demonstrate both experimentally and computationally that the tibial loading model is a useful preclinical platform with which to predict and study the effects of modulating bone and/or cartilage properties on attenuating OA progression. Given the direct correlation between computational modeling and experimental results, the effects of tissue-modifying treatments may be predicted prior to in vivo experimentation, allowing for novel therapeutics to be developed.

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Changes induced by chronic in vivo load alteration in the tibiofemoral joint of mature rabbits.

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Changes induced by chronic in vivo load alteration in the tibiofemoral joint of mature rabbits.

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