Osteoarthritis as a disease of mechanics
TL;DR: It is contended that the mechanically induced joint injury leads to variable inflammatory responses but that the role of this inflammation in worsening structural damage in an already osteoarthritic joint has not yet been proven.
About: This article is published in Osteoarthritis and Cartilage.The article was published on 2013-01-01 and is currently open access. It has received 463 citations till now. The article focuses on the topics: Osteoarthritis.
Citations
More filters
TL;DR: It is shown that knee OA long existed at low frequencies, but since the mid-20th century, the disease has doubled in prevalence, contradict the view that the recent surge in knee osteoarthritis occurred simply because people live longer and are more commonly obese.
Abstract: Knee osteoarthritis (OA) is believed to be highly prevalent today because of recent increases in life expectancy and body mass index (BMI), but this assumption has not been tested using long-term historical or evolutionary data. We analyzed long-term trends in knee OA prevalence in the United States using cadaver-derived skeletons of people aged ≥50 y whose BMI at death was documented and who lived during the early industrial era (1800s to early 1900s; n = 1,581) and the modern postindustrial era (late 1900s to early 2000s; n = 819). Knee OA among individuals estimated to be ≥50 y old was also assessed in archeologically derived skeletons of prehistoric hunter-gatherers and early farmers (6000-300 B.P.; n = 176). OA was diagnosed based on the presence of eburnation (polish from bone-on-bone contact). Overall, knee OA prevalence was found to be 16% among the postindustrial sample but only 6% and 8% among the early industrial and prehistoric samples, respectively. After controlling for age, BMI, and other variables, knee OA prevalence was 2.1-fold higher (95% confidence interval, 1.5-3.1) in the postindustrial sample than in the early industrial sample. Our results indicate that increases in longevity and BMI are insufficient to explain the approximate doubling of knee OA prevalence that has occurred in the United States since the mid-20th century. Knee OA is thus more preventable than is commonly assumed, but prevention will require research on additional independent risk factors that either arose or have become amplified in the postindustrial era.
567 citations
Cites background from "Osteoarthritis as a disease of mech..."
...Substantial evidence indicates that knee OA is proximately caused by the breakdown of joint tissues from mechanical loading (4) and inflammation (5), but the deeper underlying causes of knee OA’s high prevalence remain unclear and poorly tested, hindering efforts to prevent and treat the disease....
[...]
...Given evidence that nearly all knee OA is associated with loading-induced damage to joint tissues (4), either because the loads are abnormal or the tissues are structurally weak, one especially important source of environmental change that warrants greater attention is whether and how joint loading has altered....
[...]
TL;DR: A vigorous inflammatory response occurs very early after joint injury but is then sustained at a lower level at the later phases, which should provide hope for the future of disease modification tin PTOA.
296 citations
TL;DR: In a proposed model of RA as a site-specific manifestation of a systemic autoimmune disorder, early cartilage damage in the context of immune activation leads to a specific cellular response within articular joints that could explain not only the organ specificity of RA, but also the chronic nature and perpetuation of the disease.
Abstract: Cartilage damage is a key feature of degenerative joint disorders-primarily osteoarthritis (OA)-and chronic inflammatory joint diseases, such as rheumatoid arthritis (RA). Substantial progress has been made towards understanding the mechanisms that lead to degradation of the cartilage matrix in either condition, which ultimately results in the progressive remodelling of affected joints. The available data have shown that the molecular steps in cartilage matrix breakdown overlap in OA and RA. However, they have also, to a great extent, changed our view of the roles of cartilage in the pathogenesis of these disorders. In OA, cartilage loss occurs as part of a complex programme that resembles aspects of embryonic bone formation through endochondral ossification. In RA, early cartilage damage is a key trigger of cellular reactions in the synovium. In a proposed model of RA as a site-specific manifestation of a systemic autoimmune disorder, early cartilage damage in the context of immune activation leads to a specific cellular response within articular joints that could explain not only the organ specificity of RA, but also the chronic nature and perpetuation of the disease.
224 citations
TL;DR: To evaluate the efficacy and safety of intraarticular sprifermin (recombinant human fibroblast growth factor 18) in the treatment of symptomatic knee osteoarthritis (OA).
Abstract: Objective. We evaluated in a proof-of-concept double-blind placebo-controlled randomized trial the efficacy and safety of intra-articular sprifermin (recombinant human fibroblast growth factor 18) in patients with symptomatic knee OA. Methods. Sprifermin was evaluated as intra-articular injection at 10, 30, and 100μg. Primary efficacy endpoint was change in central medial femorotibial compartment (cMFTC) cartilage thickness at 6 and 12 months using quantitative MRI (qMRI). Primary safety endpoints were nature, incidence and severity of local and systemic treatment-emergent adverse events, acute inflammatory reactions and laboratory assessments. Secondary endpoints included changes in total and compartment femorotibial cartilage thickness and volume by qMRI, joint space width (JSW) from radiographs, and Western Ontario McMaster Universities (WOMAC) pain. Results. 192 patients were randomized and evaluated for safety, 180 completed the trial, 168 evaluated for primary efficacy endpoint. We found no statistically significant dose-response in change in cMFTC cartilage thickness. Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral femorotibial cartilage thickness and volume, and in JSW narrowing in the lateral femorotibial compartment. All groups improved in WOMAC pain, with statistically significant less improvement at 12 months in patients receiving 100μg sprifermin than placebo. There was no significant difference in SAEs, TEAEs, AIRs between sprifermin and placebo groups. Conclusion. There was no statistically significant relationship between treatment group and reduction in cMFTC cartilage thickness. However, pre-specified structural secondary endpoints showed statistically significant dose-dependent reductions following sprifermin treatment. Sprifermin was not associated with any local or systemic safety concerns. Clinicaltrials.gov identification: NCT01033994. © 2014 American College of Rheumatology. (Less)
218 citations
TL;DR: In this article, the authors focus on the pathophysiological aspects of osteoarthritis development and progression, review the current concepts and discuss the future of personalized medicine for OA.
210 citations
References
More filters
TL;DR: It seems likely that narrowing of the joint space will predispose to early degenerative changes, but a connection between these appearances and later osteoarthritis is not yet established and is too indefinite to justify clinical deductions.
Abstract: Changes in the knee joint after meniscectomy include ridge formation, narrowing of the joint space, and flattening of the femoral condyle. Investigations suggest that these changes are due to loss of the weight-bearing function of the meniscus. Meniscectomy is not wholly innocuous; it interferes, at least temporarily, with the mechanics of the joint. It seems likely that narrowing of the joint space will predispose to early degenerative changes, but a connection between these appearances and later osteoarthritis is not yet established and is too indefinite to justify clinical deductions.
1,808 citations
"Osteoarthritis as a disease of mech..." refers background in this paper
...The hypothesis that I will entertain is that OA is caused by increased forces across a local area of a joint either from (1) abnormal anatomy (congenital or acquired) leading to increased focal stress with the overall load across the joint being normal; or...
[...]
TL;DR: This is the first demonstration that in primary knee OA varus alignment increases risk of medial OA progression, that valgus alignment increased risk of lateral OA progress, that burden of malalignment predicts decline in physical function, and that these effects can be detected after as little as 18 months of observation.
Abstract: ContextKnee osteoarthritis (OA) is a leading cause of disability in older persons.
Few risk factors for disease progression or functional decline have been identified.
Hip-knee-ankle alignment influences load distribution at the knee; varus and
valgus alignment increase medial and lateral load, respectively.ObjectiveTo test the hypotheses that (1) varus alignment increases risk of medial
knee OA progression during the subsequent 18 months, (2) valgus alignment
increases risk of subsequent lateral knee OA progression, (3) greater severity
of malalignment is associated with greater subsequent loss of joint space,
and (4) greater burden of malalignment is associated with greater subsequent
decline in physical function.Design and SettingProspective longitudinal cohort study conducted March 1997 to March
2000 at an academic medical center in Chicago, Ill.ParticipantsA total of 237 persons recruited from the community with primary knee
OA, defined by presence of definite tibiofemoral osteophytes and at least
some difficulty with knee-requiring activity; 230 (97%) completed the study.Main Outcome MeasuresProgression of OA, defined as a 1-grade increase in severity of joint
space narrowing on semiflexed, fluoroscopically confirmed knee radiographs;
change in narrowest joint space width; and change in physical function between
baseline and 18 months, compared by knee alignment at baseline.ResultsVarus alignment at baseline was associated with a 4-fold increase in
the odds of medial progression, adjusting for age, sex, and body mass index
(adjusted odds ratio [OR], 4.09; 95% confidence interval [CI], 2.20-7.62).
Valgus alignment at baseline was associated with a nearly 5-fold increase
in the odds of lateral progression (adjusted OR, 4.89; 95% CI, 2.13-11.20).
Severity of varus correlated with greater medial joint space loss during the
subsequent 18 months (R = 0.52; 95% CI, 0.40-0.62
in dominant knees), and severity of valgus correlated with greater subsequent
lateral joint space loss (R = 0.35; 95% CI, 0.21-0.47
in dominant knees). Having alignment of more than 5° (in either direction)
in both knees at baseline was associated with significantly greater functional
deterioration during the 18 months than having alignment of 5° or less
in both knees, after adjusting for age, sex, body mass index, and pain.ConclusionThis is, to our knowledge, the first demonstration that in primary knee
OA varus alignment increases risk of medial OA progression, that valgus alignment
increases risk of lateral OA progression, that burden of malalignment predicts
decline in physical function, and that these effects can be detected after
as little as 18 months of observation.
1,388 citations
TL;DR: The results suggest that the baseline adduction moment of the knee, which reflects the dynamic load on the medial compartment, can predict radiographic OA progression at the six year follow up in patients with medial compartment knee OA.
Abstract: Objective: To test the hypothesis that dynamic load at baseline can predict radiographic disease progression in patients with medial compartment knee osteoarthritis (OA).
Methods: During 1991–93 baseline data were collected by assessment of pain, radiography, and gait analysis in 106 patients referred to hospital with medial compartment knee OA. At the six year follow up, 74 patients were again examined to assess radiographic changes. Radiographic disease progression was defined as more than one grade narrowing of minimum joint space of the medial compartment.
Results: In the 32 patients showing disease progression, pain was more severe and adduction moment was higher at baseline than in those without disease progression (n=42). Joint space narrowing of the medial compartment during the six year period correlated significantly with the adduction moment at entry. Adduction moment correlated significantly with mechanical axis (varus alignment) and negatively with joint space width and pain score. Logistic regression analysis showed that the risk of progression of knee OA increased 6.46 times with a 1% increase in adduction moment.
Conclusions: The results suggest that the baseline adduction moment of the knee, which reflects the dynamic load on the medial compartment, can predict radiographic OA progression at the six year follow up in patients with medial compartment knee OA.
1,292 citations
TL;DR: A systematic review of cohort and case-control studies evaluating the association of demographic, comorbid, and other patient-determined factors with onset of knee OA found there are identifiable factors which can be targeted for prevention of disabling knee pain.
1,166 citations
TL;DR: The geometric prosthesis was the best condylar prosthesis for osteoarthritis with moderate to severe deformity, but gave the worst results in knees with rheumatoid arthritis.
Abstract: Twenty-nine knees with unicondylar, sixty-four with duocondylar, fifty with Guepar, and fifty with geometric prostheses were studied. The follow-up ranged from two to three and one-half years. The unicondylar prosthesis was used in the mildest cases and gave the least complications, but the quality of results was not superior to that achieved with the other prostheses. The duocondylar model was best suited for knees with rheumatoid arthritis and mild deformity. The geometric prosthesis was the best condylar prosthesis for osteoarthritis with moderate to severe deformity, but gave the worst results in knees with rheumatoid arthritis. The Guepar prosthesis was used in the worst knees and gave the best results, but it had the highest infection rate and was the most difficult to salvage. A radiolucency was observed in about 60 per cent of the condylar replacements around the tibial component and in 45 per cent of the Geupar replacements around the femoral component. The significance of this cannot yet be determined but it suggest that the fixation may not be ideal. In all types, residual pain was most frequently attributed to the patellar compartment. Patellectomy was not a solution.
875 citations