Dataset Information

Obesity and load-induced posttraumatic osteoarthritis in the absence of fracture or surgical trauma.

ABSTRACT: Osteoarthritis is increasingly viewed as a heterogeneous disease with multiple phenotypic subgroups. Obesity enhances joint degeneration in mouse models of posttraumatic osteoarthritis (PTOA). Most models of PTOA involve damage to surrounding tissues caused by surgery/fracture; it is unclear if obesity enhances cartilage degeneration in the absence of surgery/fracture. We used a nonsurgical animal model of load-induced PTOA to determine the effect of obesity on cartilage degeneration 2 weeks after loading. Cartilage degeneration was caused by a single bout of cyclic tibial loading at either a high or moderate load magnitude in adult male mice with severe obesity (C57Bl6/J + high-fat diet), mild obesity (toll-like receptor 5 deficient mouse [TLR5KO]), or normal adiposity (C57Bl6/J mice + normal diet and TLR5KO mice in which obesity was prevented by manipulation of the gut microbiome). Two weeks after loading, cartilage degeneration occurred in limbs loaded at a high magnitude, as determined by OARSI scores (P < .001). However, the severity of cartilage damage did not differ among groups. Osteophyte width and synovitis of loaded limbs did not differ among groups. Furthermore, obesity did not enhance cartilage damage in limbs evaluated 6 weeks after loading. Constituents of the gut microbiota differed among groups. Our findings suggest that, in the absence of surgery/fracture, obesity may not influence cartilage loss after a single mechanical insult, suggesting that either damage to surrounding tissues or repeated mechanical insult is necessary for obesity to influence cartilage degeneration. These findings further illustrate heterogeneity in PTOA phenotypes and complex interactions between mechanical/metabolic factors in cartilage loss.

SUBMITTER: Luna M

PROVIDER: S-EPMC7855296 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Obesity and load-induced posttraumatic osteoarthritis in the absence of fracture or surgical trauma.

Luna Marysol M Guss Jason D JD Vasquez-Bolanos Laura S LS Alepuz Adrian J AJ Dornevil Sophie S Strong Jasmin J Alabi Denise D Shi Qiaojuan Q Pannellini Tania T Otero Miguel M Brito Ilana L IL van der Meulen Marjolein C H MCH Goldring Steven R SR Hernandez Christopher J CJ

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20200717 5

Osteoarthritis is increasingly viewed as a heterogeneous disease with multiple phenotypic subgroups. Obesity enhances joint degeneration in mouse models of posttraumatic osteoarthritis (PTOA). Most models of PTOA involve damage to surrounding tissues caused by surgery/fracture; it is unclear if obesity enhances cartilage degeneration in the absence of surgery/fracture. We used a nonsurgical animal model of load-induced PTOA to determine the effect of obesity on cartilage degeneration 2 weeks aft ...[more]

PMID: 32658313

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Project description:Posttraumatic osteoarthritis (PTOA) is associated with abnormal and increased subchondral bone remodeling. Inhibiting altered remodeling immediately following joint damage can slow PTOA progression. Clinically, however, inhibiting remodeling when significant joint damage is already present has minimal effects in slowing further disease progression. We sought to determine the treatment window following PTOA initiation in which inhibiting remodeling can attenuate progression of joint damage. We hypothesized that the most effective treatment would be to inhibit remodeling immediately after PTOA initiation. We used an animal model in which a single bout of mechanical loading was applied to the left tibia of 26-week-old male C57Bl/6 mice at a peak load of 9 N to initiate load-induced PTOA development. Following loading, we inhibited bone remodeling using daily alendronate (ALN) treatment administered either immediately or with 1 or 2 weeks' delay up to 3 or 6 weeks post-loading. A vehicle (VEH) treatment group controlled for daily injections. Cartilage and subchondral bone morphology and osteophyte development were analyzed and compared among treatment groups. Inhibiting remodeling using ALN immediately after load-induced PTOA initiation reduced cartilage degeneration, slowed osteophyte formation, and preserved subchondral bone volume compared to VEH treatment. Delaying the inhibition of bone remodeling at 1 or 2 weeks similarly attenuated cartilage degeneration at 6 weeks, but did not slow the development of osteoarthritis (OA)-related changes in the subchondral bone, including osteophyte formation and subchondral bone erosions. Immediate inhibition of subchondral bone remodeling was most effective in slowing PTOA progression across the entire joint, indicating that abnormal bone remodeling within the first week following PTOA initiation played a critical role in subsequent cartilage damage, subchondral bone changes, and overall joint degeneration. These results highlight the potential of anti-resorptive drugs as preemptive therapies for limiting PTOA development after joint injury, rather than as disease-modifying therapies after joint damage is established. © 2021 American Society for Bone and Mineral Research (ASBMR).

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.

Project description:PurposePosttraumatic arthritis (PTA) may develop years after acetabular fracture, hindering joint function and causing significant chronic musculoskeletal pain. Given the delayed onset of PTA, few studies have assessed outcomes of delayed total hip arthroplasty (THA) in acetabular fracture patients. This study systematically reviewed the literature for outcomes of THA in patients with PTA and prior acetabular fracture.MethodsPubmed, EMBASE, SCOPUS, and Cochrane library were searched for articles containing the keywords "acetabular", "fracture", "arthroplasty", and "post traumatic arthritis" published between 1995 and August 2017. Studies with less than 10 patients, less than 2 years of follow-up, conference abstracts, and non-English language articles were excluded. Data on patient demographics, surgical characteristics, and outcomes of delayed THA, including implant survival, complications, need for revision, and functional scores, was collected from eligible studies.ResultsWith 1830 studies were screened and data from 10 studies with 448 patients were included in this review. The median patient age on date of THA was 51.5 years, ranging from 19 to 90 years. The median time from fracture to THA was 37 months, with a range of 27-74 months. Mean follow-up times ranged from 4 to 20 years. The mean Harris hip scores (HHS) improved from 41.5 pre-operatively, to 87.6 post-operatively. The most prevalent postoperative complications were heterotopic ossification (28%-63%), implant loosening (1%-24%), and infection (0%-16%). The minimum 5-year survival of implants ranged from 70% to 100%. Revision rates ranged from 2% to 32%.ConclusionDespite the difficulties associated with performing THA in patients with PTA from previous acetabular fracture (including soft tissue scarring, existing hardware, and acetabular bone loss) and the relatively high complication rates, THA in patients with PTA following prior acetabular fracture leads to significant improvement in pain and function at 10-year follow-up. Further high quality randomized controlled studies are needed to confirm the outcomes after delayed THA in these patients.

Dataset Information

Obesity and load-induced posttraumatic osteoarthritis in the absence of fracture or surgical trauma.

Publications

Obesity and load-induced posttraumatic osteoarthritis in the absence of fracture or surgical trauma.

Similar Datasets

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