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Osteoarthritis in HIV May Be Accelerated - new study
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"Is treated HIV infection associated with knee cartilage degeneration and structural changes? A longitudinal study using data from the osteoarthritis initiative"
Our study showed a more heterogeneous and disordered cartilage matrix composition in PLWH on ART, suggesting that treated HIV infection may accelerate the degeneration of the knee cartilage matrix.
Osteoarthritis (also known as OA) is a common joint disease that most often affects middle-age to elderly people. It is commonly referred to as "wear and tear" of the joints, but we now know that OA is a disease of the entire joint, involving the cartilage, joint lining, ligaments, and bone.
Osteoarthritis is a common form of arthritis that often affects the knee. In the first stage, symptoms are mild, but by the fourth, a person may need surgery.
Osteoarthritis (OA) of the knee affects the bones, the cartilage, and the synovium in the knee joint.
Cartilage is a slippery tissue that provides a smooth surface for joint motion and acts as a cushion between the bones.
Synovium is soft, and it lines the joints. It produces fluid, called synovial fluid, for lubrication, and it supplies nutrients and oxygen to the cartilage.
As these functions break down, they no longer protect the bones of the knee joint, and bone damage occurs.
Staying active, maintaining a healthy weight and some treatments might slow progression of the disease and help improve pain and joint function...If you have joint pain or stiffness that doesn't go away, make an appointment with your doctor. Osteoarthritis occurs when the cartilage that cushions the ends of bones in your joints gradually deteriorates. Cartilage is a firm, slippery tissue that enables nearly frictionless joint motion. Eventually, if the cartilage wears down completely, bone will rub on bone.
Osteoarthritis has often been referred to as a "wear and tear" disease. But besides the breakdown of cartilage, osteoarthritis affects the entire joint. It causes changes in the bone and deterioration of the connective tissues that hold the joint together and attach muscle to bone. It also causes inflammation of the joint lining.
The risk of osteoarthritis increases with age. Women are more likely to develop osteoarthritis, though it isn't clear why. If your job or a sport you play places repetitive stress on a joint, that joint might eventually develop osteoarthritis. Carrying extra body weight contributes to osteoarthritis in several ways, and the more you weigh, the greater your risk. Increased weight adds stress to weight-bearing joints, such as your hips and knees. Also, fat tissue produces proteins that can cause harmful inflammation in and around your joints. Certain metabolic diseases can increase risk. These include diabetes and a condition in which your body has too much iron (hemochromatosis). Osteoarthritis is a degenerative disease that worsens over time, often resulting in chronic pain. Joint pain and stiffness can become severe enough to make daily tasks difficult.
Depression and sleep disturbances can result from the pain and disability of osteoarthritis. https://www.mayoclinic.org/diseases-conditions/osteoarthritis/symptoms-causes/syc-20351925
OA of the knee can cause pain and stiffness. The symptoms worsen over time. https://www.medicalnewstoday.com/kc/stages-osteoarthritis-knee-310579
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A recent cross-sectional study [16] suggested that tibial cartilage volume of HIV-infected patients was reduced and associated with increased central fat accumulation, which may potentially influence the subsequent development of knee OA. However, there is limited knowledge about the association of HIV/ART with knee OA. In particular, little is known how HIV and ART affect the composition of knee cartilage and how they affect the severity and progression of knee OA..... the purpose of our study was to evaluate knee joint health in individuals with HIV treated with ART using quantitative and structural MRI-based parameters and compare these with matched controls using a longitudinal study design........Osteoarthritis (OA) is one of the most common rheumatological disorders, which affects 240 million people globally and 27 million people in the USA [6, 7]. Although aging remains the most important risk factor for OA, MetS, which is a combination of hypertension, dyslipidemia, diabetes (or insulin resistance) and abdominal obesity, may also play an essential role in the occurrence and development of OA [8]. MetS also affects up to half of HIV-infected patients receiving ART [9]. While studies have reported an increased prevalence and severity of radiographic hand osteoarthritis in patients with HIV-1 infection, in particular associated with MetS, the exact pathophysiology of OA in PLWH is not well understood [10, 11]. Studies have reported more heterogeneous cartilage T2 relaxation times in diabetics, indicating increased articular cartilage degeneration [12, 13]. The detrimental impact of dyslipidemia, obesity and MetS-associated chronic low-grade inflammation on cartilage metabolism have also been demonstrated [8, 14, 15]. .......the direct or indirect consequences of immunodeficiency, chronic inflammatory status and cumulative toxic effects of ART, aging patients with HIV infection are reported to have increased risk for "non-AIDS" comorbidities such as cardiovascular diseases, neurocognitive diseases, liver and kidney diseases, metabolic syndrome (MetS), cancers and rheumatic diseases [1, 2, 3, 4]. With the increasing life expectancy of PLWH, the impact of these "non-AIDS" comorbidities are gaining clinical significance [5].
CONCLUSIONS:
Our study showed a more heterogeneous and disordered cartilage matrix composition in PLWH on ART, suggesting that treated HIV infection may accelerate the degeneration of the knee cartilage matrix. In addition, compared with the HIV negative group, PLWH had significantly more severe knee joint effusion over 8 years. Moreover, at baseline PLWH had significantly more signal abnormalities of the IPFP and the SPFP [fat pads], consistent with more severe joint effusion and knee synovitis. Our results suggest that treated HIV infection is associated with compositional changes of the cartilage matrix and increased knee joint inflammation, but findings appear not to have a significant impact on structural knee degeneration. - (30% female, mean baseline age 52.1 ± 6.2 years, mean baseline BMI 27.6 ± 3.7 kg/m2)
Cartilage damage is the hallmark of knee OA, and cartilage matrix degeneration is an essential event that determines the irreversible progression of knee OA [29]. To date, only one study reported that total body fat and android fat were inversely associated with knee tibia cartilage volume in PLWH [16]. In our study, PLWH showed a more heterogeneous and disordered cartilage matrix composition in the longitudinal analysis of cartilage GLCM texture parameters. Interestingly, we did not find any significant differences in WORMS cartilage scores, indicating that findings in HIV infection may predominantly affect the knee cartilage matrix. However due to small sample size we may not have had enough power to detect significant differences. The exact mechanism of cartilage degeneration in PLWH remains to be elucidated. In the setting of HIV-related joint disease there are at least two aspects worth considering: First, the HIV-associated sarcopenia may reduce the strength of muscle around the knee joint and affect the normal knee joint biomechanics [30], which may promote cartilage degeneration. The fatty infiltration in the muscles surrounding the knee joint may also be involved in the alteration of muscle strength [4, 31]. Secondly, multiple metabolic abnormalities associated with HIV, medications, and chronic inflammation have been reported to have deleterious effects on cartilage metabolism, including hypertension, hyperglycemia, lipodystrophy among others [2, 4, 8, 13, 14, 15]. For example, subchondral ischemia resulting from hypertension may compromise the nutrient exchange of cartilage, and hyperglycemia may induce cartilage matrix stiffness, subchondral bone destruction and chondrocyte dysfunction [14]. To date, little is known about whether HIV/ART can directly affect chondrocytes and the cartilage matrix. However, considering that HIV was reported to be able to infect chondrocytes [32], the more direct association between HIV/ART and cartilage matrix needs to be further explored.
Synovial inflammation can exacerbate cartilage degeneration by secreting more catabolic and pro-inflammatory mediators [33]. In turn, cartilage breakdown products also promote the inflammation of synovium [33, 34]. There is evidence that synovitis can be present at all stages of knee OA and is associated with cartilage destruction, knee pain and the progression of knee OA [21, 33, 34]......As a local adipose tissue, abnormal IPFP and SPFP can secrete proinflammatory cytokines and adipokines, and thus may aggravate the local synovial inflammation [22, 35].
Since HIV viral proteins have previously been reported to enhance osteoclast activity and inhibit osteoblast activity and certain ART combinations are known to detrimentally affect bone structure [38, 39, 40], our findings of lower subchondral cyst scores in PLWH seem counter-intuitive. However, given the complex effects of HIV and ART on bone resorption and bone formation, additional mechanisms may be involved reducing the development of subchondral cysts.
Studies have described the MRI features of OA-associated Hoffa-synovitis, which presents with distinguishable non-diffuse, heterogeneous alteration in signal intensity, often involving characteristically discrete portions of the IPFP and/or surrounding structures [17, 20, 21, 22]. In our study, two out of ten HIV-infected subjects presented a diffuse and homogeneous increased signal intensity throughout the whole IPFP, which was different from the imaging features of OA-associated Hoffa-synovitis and was not observed in the 20 HIV negative subjects.
This special Hoffa-synovitis has been confirmed to be a non-specific inflammation, primarily composed of synovial proliferation and chronic nonspecific perivascular inflammatory cell infiltration [18]. The histological changes of SPFP signal alteration in HIV positive individuals remains unclear. However, in previous knee OA studies have been reported that SPFP signal changes may be similar to that observed in the IPFP which is characterized by inflammation, swelling, hypertrophy and fibrosis [23, 24]. Moreover, we found more severe effusion-synovitis at all timepoints in PLWH compared to controls. This difference likely results from the chronic inflammatory status promoting the release of proinflammatory mediators and could explain why HIV-infected subjects had more severe Hoffa-synovitis and SPFP synovitis at baseline.
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Is treated HIV infection associated with knee cartilage degeneration and structural changes? A longitudinal study using data from the osteoarthritis initiative
BMC Musculoskeletal Disorders 2019
Yao Liu1,2, Sarah C. Foreman1, Gabby B. Joseph1, Jan Neumann1, Phyllis C. Tien3,4, Xiaoming Li2, Nancy E. Lane5,
Michael C. Nevitt6, Charles E. McCulloch6 and Thomas M. Link1*
Background
Metabolic disorders presenting in HIV-infected patients on antiretroviral therapy (ART) may increase the risk of osteoarthritis. However, structural changes of the knee in HIV infected subjects are understudied. The aim of this study is to investigate knee cartilage degeneration and knee structural changes over 8 years in subjects with and without HIV infection determined based on the use of ART.
Subjects with HIV infection were identified based on the use of typical HIV ART combinations at baseline as recorded in the baseline medication inventory, a database of prescription medications taken by participants in the past 30 days (Additional file 2). Inclusion criteria required subjects in the HIV cohort to be on ART regime for at least one year and for control subjects to not take any type of antiretroviral medications during the follow-up period. HIV subjects were frequency matched with control subjects 1:2 for age, sex, race, baseline body mass index (BMI) and Kellgren-Lawrence (K&L) grades. Categories for the matching were defined by combination of: sex (male or female), K&L grade (0, 1, 2, 3, 4), age (5 year intervals), BMI (2.5 kg/m2 intervals) and race (White or Caucasian, Black or African American). Individuals with a history of rheumatoid arthritis were excluded.
Methods
We studied 10 participants from the Osteoarthritis Initiative who received ART at baseline and 20 controls without ART, frequency matched for age, sex, race, baseline body mass index (BMI) and Kellgren & Lawrence grade. Knee abnormalities were assessed using the whole-organ magnetic resonance imaging score (WORMS) and cartilage T2 including laminar and texture analyses were analyzed using a multislice-multiecho spin-echo sequence.
Signal abnormalities of the infrapatellar fat pad (IPFP) and suprapatellar fat pad (SPFP) were assessed separately using a semi-quantitative scoring system. Linear regression models were used in the cross-sectional analysis to compare the differences between ART/HIV subjects and controls in T2 (regular and laminar T2 values, texture parameters) and morphologic parameters (subscores of WORMS, scores for signal alterations of IPFP and SPFP). Mixed effects models were used in the longitudinal analysis to compare the rate of change in T2 and morphological parameters between groups over 8 years.
Results
At baseline, individuals on ART had significantly greater size of IPFP signal abnormalities (P = 0.008), higher signal intensities of SPFP (P = 0.015), higher effusion scores (P = 0.009), and lower subchondral cysts sum scores (P = 0.003) compared to the controls. No significant differences were found between the groups in T2-based cartilage parameters and WORMS scores for cartilage, meniscus, bone marrow edema patterns and ligaments (P > 0.05). Longitudinally, the HIV cohort had significantly higher global knee T2 entropy values (P = 0.047), more severe effusion (P = 0.001) but less severe subchondral cysts (P = 0.002) on average over 8 years.
The interaction between time and the HIV group was significant for the texture parameters global knee contrast and variance (Table 3). On average over all timepoints, global knee entropy values were significantly higher in the HIV group compared to the control group (P = 0.047, Fig. 1a). Global T2 values (P = 0.809, Fig. 1b), global T2 values of bone layer (P = 0.669) and articular layer (P = 0.180) were slightly higher on average over all timepoints in the HIV group but not significantly (p > 0.05).
Conclusions
Knees of individuals with HIV on ART had a more heterogeneous cartilage matrix, more severe synovitis and abnormalities of the IPFP and SPFP, which may increase the risk of incident knee osteoarthritis.
Since the introduction and constant optimization of antiretroviral therapy (ART), the life expectancy of people living with HIV (PLWH) has increased significantly over the past decades and is now similar to or approaching that of an HIV-negative person [1]. However, the direct or indirect consequences of immunodeficiency, chronic inflammatory status and cumulative toxic effects of ART, aging patients with HIV infection are reported to have increased risk for "non-AIDS" comorbidities such as cardiovascular diseases, neurocognitive diseases, liver and kidney diseases, metabolic syndrome (MetS), cancers and rheumatic diseases [1, 2, 3, 4]. With the increasing life expectancy of PLWH, the impact of these "non-AIDS" comorbidities are gaining clinical significance [5].
Osteoarthritis (OA) is one of the most common rheumatological disorders, which affects 240 million people globally and 27 million people in the USA [6, 7]. Although aging remains the most important risk factor for OA, MetS, which is a combination of hypertension, dyslipidemia, diabetes (or insulin resistance) and abdominal obesity, may also play an essential role in the occurrence and development of OA [8]. MetS also affects up to half of HIV-infected patients receiving ART [9]. While studies have reported an increased prevalence and severity of radiographic hand osteoarthritis in patients with HIV-1 infection, in particular associated with MetS, the exact pathophysiology of OA in PLWH is not well understood [10, 11]. Studies have reported more heterogeneous cartilage T2 relaxation times in diabetics, indicating increased articular cartilage degeneration [12, 13]. The detrimental impact of dyslipidemia, obesity and MetS-associated chronic low-grade inflammation on cartilage metabolism have also been demonstrated [8, 14, 15].
A recent cross-sectional study [16] suggested that tibial cartilage volume of HIV-infected patients was reduced and associated with increased central fat accumulation, which may potentially influence the subsequent development of knee OA. However, there is limited knowledge about the association of HIV/ART with knee OA. In particular, little is known how HIV and ART affect the composition of knee cartilage and how they affect the severity and progression of knee OA.
Torshizy et al. [17] and Petscavage et al. [18] described MR imaging signal alterations of the infrapatellar fat pad (IPFP) and the suprapatellar fat pad (SPFP) in PLWH with non-specific knee pain, that was characterized by global homogeneous increase in signal throughout IPFP or SPFP on fluid sensitive sequences. The IPFP, also known as Hoffa's fat pad, not only plays a role in absorbing mechanical force generated by joint movement but affects the occurrence and development of knee OA by producing and releasing important inflammatory mediators [19]. Several studies [20, 21, 22, 23, 24] have reported that signal intensity alterations of the IPFP and the SPFP are important imaging biomarkers for knee OA. In the setting of HIV, however, it is not known whether and how signal alteration within the IPFP and SPFP change over time and whether it increases the risk of OA in HIV-infected patients.
Thus, the purpose of our study was to evaluate knee joint health in individuals with HIV treated with ART using quantitative and structural MRI-based parameters and compare these with matched controls using a longitudinal study design.
![0516192](../images/051719/051619-9/0516192.gif)
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