Carrie A. Karvonen-Gutierrez

The evolving role of obesity in knee osteoarthritis

Purpose of reviewThe frequency of knee osteoarthritis continues to accelerate, likely because of the increasing proliferation of obesity, particularly in men and women 40–60 years of age at the leading edge of the ‘baby boom’ demographic expansion. The increasing pervasiveness of obesity and the growing appreciation of obesitys accompanying metabolic/inflammatory activities suggest rethinking the knee osteoarthritis paradigm. Recent findingsWhereas once knee osteoarthritis was considered a ‘wear-and-tear’ condition, it is now recognized that knee osteoarthritis exists in the highly metabolic and inflammatory environments of adiposity. Cytokines associated with adipose tissue, including leptin, adiponectin, and resistin, may influence osteoarthritis though direct joint degradation or control of local inflammatory processes. Further, pound-for-pound, not all obesity is equivalent for the development of knee osteoarthritis; development appears to be strongly related to the co-existence of disordered glucose and lipid metabolism. Additionally, obesity loads may be detected by mechanoreceptors on chondrocyte surfaces triggering intracellular signaling cascades of cytokines, growth factors, and metalloproteinases. SummaryThis review summarizes recent literature about obesity, knee osteoarthritis and joint pain. Consideration of adipocytokines, metabolic factors, and mechanical loading-metabolic factor interactions will help to broaden the thinking about targets for both prevention and intervention for knee osteoarthritis.

Knee osteoarthritis in obese women with cardiometabolic clustering

OBJECTIVEnTo assess the role of obesity and metabolic dysfunctionality with knee osteoarthritis (OA), knee joint pain, and physical functioning performance, adjusted for joint space width (JSW) asymmetry.nnnMETHODSnKnee OA was defined as a Kellgren/Lawrence score > or =2 on weight-bearing radiographs. Obesity was defined as a body mass index > or =30 kg/m2. Cardiometabolic clustering classification was based on having > or =2 of the following factors: low levels of high-density lipoprotein cholesterol; elevated levels of low-density lipoprotein cholesterol, triglycerides, blood pressure, C-reactive protein, waist:hip ratio, or glucose; or diabetes mellitus. The difference between lateral and medial knee JSW was used to determine joint space asymmetry.nnnRESULTSnIn a sample of women (n = 482, mean age 47 years), prevalences of knee OA and persistent knee pain were 11% and 30%, respectively. The knee OA prevalence in nonobese women without cardiometabolic clustering was 4.7%, compared with 12.8% in obese women without cardiometabolic clustering and 23.2% in obese women with cardiometabolic clustering. Nonobese women without cardiometabolic clustering were less likely to perceive themselves as limited compared with women in all other obesity/cardiometabolic groups (P < 0.05). Similar associations were seen with knee pain and physical functioning measures. The inclusion of a joint space asymmetry measure was associated with knee OA but not with knee pain or physical functioning.nnnCONCLUSIONnKnee OA was twice as frequent in obese women with cardiometabolic clustering compared with those without, even when considering age and joint asymmetry. Obesity/cardiometabolic clustering was also associated with persistent knee pain and impaired physical functioning.

Quality of Life Scores Predict Survival Among Patients With Head and Neck Cancer

PURPOSEnThe purpose of this study was to examine whether quality of life (QOL) scores predict survival among patients with head and neck cancer, controlling for demographic, health behavior, and clinical variables.nnnPATIENTS AND METHODSnA self-administered questionnaire was given to 495 patients being treated for head and neck cancer while they were waiting to be seen for a clinic appointment. Data collected from the survey included demographics, health behaviors, and QOL as measured by Short Form-36 (SF-36) physical and mental component scores and the Head and Neck QOL scores. Clinical measures were collected by chart abstraction. Kaplan-Meier plots and univariate and multivariate Cox proportional hazards models were used to determine the association between QOL scores and survival time.nnnRESULTSnAfter controlling for age, time since diagnosis, marital status, education, tumor site and stage, comorbidities, and smoking, the SF-36 physical component score and three of the four Head and Neck QOL scales (pain, eating, and speech domains) were associated with survival. Controlling for the same variables, the SF-36 mental component score and the emotional domain of the Head and Neck QOL were not associated with survival.nnnCONCLUSIONnQOL instruments may be valuable screening tools to identify patients who are at high risk for poor survival. Those with low QOL scores could be followed more closely, with the potential to identify recurrence earlier and perform salvage treatments, thereby possibly improving survival for this group of patients.

Isometric Quadriceps Strength in Women with Mild, Moderate, and Severe Knee Osteoarthritis

Palmieri-Smith RM, Thomas AC, Karvonen-Gutierrez C, Sowers MF: Isometric quadriceps strength in women with mild, moderate, and severe knee osteoarthritis. Objective:Quadriceps weakness is a common clinical sign in persons with moderate-to-severe osteoarthritis and results in physical disability; however, minimal data exist to establish whether quadriceps weakness is present in early stages of the disease. Therefore, our purpose was to determine whether quadriceps weakness was present in persons with early radiographic and cartilaginous evidence of osteoarthritis. Further, we sought to determine whether quadriceps strength decreases as osteoarthritis severity increases. Design:Three hundred forty-eight women completed radiologic and magnetic resonance imaging evaluation, in addition to strength testing. Anterior-posterior radiographs were graded for tibiofemoral osteoarthritis severity using the Kellgren-Lawrence scale. Scans from magnetic resonance imaging were used to assess medial tibiofemoral and patellar cartilage based on a modification of the Noyes scale. The peak knee extension torque recorded was used to represent strength. Results:Quadriceps strength (Nm/kg) was 22% greater in women without radiographic osteoarthritis than in women with osteoarthritis (P < 0.05). Quadriceps strength was also greater in women with Noyes medial tibial and femoral cartilage scores of 0 when compared in women with Noyes grades 2 and 3–5 (P ≤ 0.05). Conclusions:Women with early evidence of osteoarthritis had less quadriceps strength than women without osteoarthritis as defined by imaging.

Associations of Anatomical Measures from MRI with Radiographically Defined Knee Osteoarthritis Score, Pain, and Physical Functioning

BACKGROUNDnThe prevalence of knee osteoarthritis is traditionally based on radiographic findings, but magnetic resonance imaging is now being used to provide better visualization of bone, cartilage, and soft tissues as well as the patellar compartment. The goal of this study was to estimate the prevalences of knee features defined on magnetic resonance imaging in a population and to relate these abnormalities to knee osteoarthritis severity scores based on radiographic findings, physical functioning, and reported knee pain in middle-aged women.nnnMETHODSnMagnetic resonance images of the knee were evaluated for the location and severity of cartilage defects, bone marrow lesions, osteophytes, subchondral cysts, meniscal and/or ligamentous tears, effusion, and synovitis among 363 middle-aged women (724 knees) from the Michigan Study of Womens Health Across the Nation. These findings were related to Kellgren-Lawrence osteoarthritis severity scores from radiographs, self-reported knee pain, self-reported knee injury, perception of physical functioning, and physical performance measures to assess mobility. Radiographs, physical performance assessment, and interviews were undertaken at the 1996 study baseline and again (with the addition of magnetic resonance imaging assessment) at the follow-up visit during 2007 to 2008.nnnRESULTSnThe prevalence of moderate-to-severe knee osteoarthritis changed from 3.7% at the baseline assessment to 26.7% at the follow-up visit eleven years later. Full-thickness cartilage defects of the medial, lateral, and patellofemoral compartments were present in 14.5% (105 knees), 4.6% (thirty-three knees), and 26.2% (190 knees), respectively. Synovitis was identified in 24.7% (179) of the knees, and joint effusions were observed in 70% (507 knees); 21.7% (157) of the knees had complex or macerated meniscal tears. Large osteophytes, marked synovitis, macerated meniscal tears, and full-thickness tibial cartilage defects were associated with increased odds of knee pain and with 30% to 40% slower walking and stair-climbing times.nnnCONCLUSIONSnMiddle-aged women have a high prevalence of moderate-to-severe knee osteoarthritis corroborated by strong associations with cartilage defects, complex and macerated meniscal tears, osteophytes and synovitis, knee pain, and lower mobility levels.

Change in adipocytokines and ghrelin with menopause.

OBJECTIVESnTo determine if ghrelin and adipocytokine (leptin, adiponectin, resistin) levels vary with menopause stage or with estradiol (E2), testosterone (T), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) concentrations measured in three stages of the menopause transition.nnnMETHODSnA study of adipocytokines and menopause was nested in a population-based, longitudinal study of Caucasian women [Michigan Bone Health and Metabolism Study (MBHMS)]. Annual serum and urine samples, available from the MBHMS repository, were selected to correspond to the pre-, peri-, and postmenopause stages of the menopause transition. Participants included forty women, stratified into obese versus non-obese groups based upon their baseline body mass index, who had specimens corresponding to the three menopause stages.nnnRESULTSnMean resistin levels were approximately two times higher during premenopause compared to peri- or postmenopause. There were significantly lower adiponectin and higher ghrelin levels in the perimenopause stage, compared to either the pre- or postmenopause stage. Increases in FSH concentrations were significantly and positively associated with higher leptin in non-obese women (P<0.01) but not in obese women (P<0.23). Increases in FSH concentrations were also significantly (P<0.005) and positively associated with higher adiponectin concentrations but were negatively associated with ghrelin concentrations (P<0.005). Associations remained following adjustment for waist circumference, waist circumference change, chronological age, and time between measures.nnnCONCLUSIONSnMenopause stages and underlying FSH changes are associated with notable changes in levels of the metabolically active adipocytokines and ghrelin and these changes may be related to selected health outcomes observed in women at mid-life.

A Clinical Trial of Neuromuscular Electrical Stimulation in Improving Quadriceps Muscle Strength and Activation Among Women With Mild and Moderate Osteoarthritis

Background Neuromuscular electrical stimulation (NMES) has demonstrated efficacy in improving quadriceps muscle strength (force-generating capacity) and activation following knee replacement and ligamentous reconstruction. Yet, data are lacking to establish the efficacy of NMES in people with evidence of early radiographic osteoarthritis. Objective The purpose of this study was to determine whether NMES is capable of improving quadriceps muscle strength and activation in women with mild and moderate knee osteoarthritis. Design This study was a randomized controlled trial. Methods Thirty women with radiographic evidence of mild or moderate knee osteoarthritis were randomly assigned to receive either no treatment (standard of care) or NMES treatments 3 times per week for 4 weeks. The effects of NMES on quadriceps muscle strength and activation were evaluated upon study enrollment, as well as at 5 and 16 weeks after study enrollment, which represent 1 and 12 weeks after cessation of NMES among the treated participants. The Western Ontario and McMaster Universities Osteoarthritis Index and a 40-foot (12.19-m) walk test were used at each testing session. Results Improvements in quadriceps muscle strength or activation were not realized for the women in the intervention group. Quadriceps muscle strength and activation were similar across testing sessions for both groups. Limitations Women were enrolled based on radiographic evidence of osteoarthritis, not symptomatic osteoarthritis, which could have contributed to our null finding. A type II statistical error may have been committed despite an a priori power calculation. The assessor and the patients were not blinded to group assignment, which may have introduced bias into the study. Conclusions Four weeks of NMES delivered to women with mild and moderate osteoarthritis and mild strength deficits was insufficient to induce gains in quadriceps muscle strength or activation. Future research is needed to examine the dose-response relationship for NMES in people with early radiographic evidence of osteoarthritis.

Longitudinal changes of serum COMP and urinary CTX-II predict X-ray defined knee osteoarthritis severity and stiffness in women

OBJECTIVEnTo ascertain the predictive role of longitudinally acquired biochemical measures of cartilage turnover in relation to X-ray defined knee osteoarthritis (OAK), knee pain and functioning.nnnMETHODSnThis is a feasibility study based on 72 enrollees of the Michigan site of Study of Womens Health Across the Nation (SWAN), a longitudinal, population-based cohort study with 11 annual visits to characterize health at the mid-life. At visits in 1996, 1998 and 2007, radiographs were evaluated for the presence of OAK [>or=2 on the Kellgren and Lawrence (K-L) scale]. Knee pain and stiffness were assessed by interview. Functioning was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Cartilage oligomeric matrix protein (COMP) and Type II collagen telopeptides (CTX-II) were assayed in serum and urine samples collected on alternate years from 1997 to 2006. We related trajectories of the cartilage biochemical markers from these five time points to OAK severity (no OAK, K-L score<2; mild OAK, K-L score=2; moderate/severe OAK, K-L score=3 or 4), pain, stiffness, or functioning, using longitudinal non-linear mixed modeling.nnnRESULTSnThe 2007 prevalence of X-ray defined OAK was 50% in these 72 women. Upward trajectories of COMP (P=0.02) and CTX-II (P=0.006) were associated with increased OAK severity and body size. COMP trajectories were associated with pain and stiffness, but not functioning. CTX-II trajectories were associated with stiffness scores, but not knee pain or functioning scores.nnnCONCLUSIONnMultiple, biennial measures of COMP or CTX-II taken over a 10-year period were predictive of subsequent OAK and knee stiffness.

Testosterone, sex hormone-binding globulin and free androgen index among adult women: chronological and ovarian aging

BACKGROUNDnIn this study, levels and rates of change in total testosterone (T), sex hormone-binding globulin (SHBG) and free androgen index (FAI) were related to chronological age and to the final menstrual period (FMP) as an indicator of ovarian aging.nnnMETHODSnData were annually acquired over a 15-year period in 629 women of the Michigan Bone Health and Metabolism Study cohort. Data were censored for hormone therapy use. Endogenous androgen patterns over time were described with stochastic processes and bootstrapping.nnnRESULTSnWith ovarian aging, T levels rose from a mean of 18 ng/dl commencing 10 years prior to the FMP to 27 ng/dl at the FMP. Over the 20-year period encompassing the FMP, modeled mean SHBG levels changed from 58 to 34 nM and the FAI ratio increased from 1.6 to 2.9 in a non-linear manner. With chronological aging, total T levels increased (P < 0.0001) from 43 to 50 years, but not thereafter. SHBG declined steadily with age with a modestly greater rate of change between 49 and 54 years. The FAI increased from 1.3 to 2.5 from 34 to 58 years.nnnCONCLUSIONSnT increased from approximately age 40 until the FMP whereas SHBG had rate of change patterns reflecting both chronological and ovarian aging components. These data provide new insight into the endogenous androgen patterns at mid-life.

Sex dimorphism in the association of cardiometabolic characteristics and osteophytes-defined radiographic knee osteoarthritis among obese and non-obese adults: NHANES III

OBJECTIVEnTo examine the relationship of knee osteoarthritis (OA) with cardiovascular and metabolic risk factors by obesity status and gender.nnnMETHODSnData from 1,066 National Health and Nutrition Examination Survey III participants (≥60 years of age) was used to examine relationships of osteophytes-defined radiographic knee OA and cardiovascular and metabolic measures. Analyses were considered among obese [body mass index (BMI)≥30 kg/m(2)] and non-obese (BMI<30 kg/m(2)) men and women.nnnRESULTSnThe prevalence of osteophytes-defined radiographic knee OA was 34%. Leptin levels and homeostatic model assessment-insulin resistance (HOMA-IR), a proxy measure of insulin resistance, were significantly associated with knee OA; those with knee OA had 35% higher HOMA-IR values and 52% higher leptin levels compared to those without knee OA. The magnitude of the association between HOMA-IR and knee OA was strongest among men, regardless of obesity status; odds ratios (ORs) for HOMA-IR were 34% greater among non-obese men (OR=1.18) vs obese women (OR=0.88). Among obese women, a 5-μg/L higher leptin was associated with nearly 30% higher odds of having knee OA (OR=1.28). Among men, ORs for the association of leptin and knee OA were in the opposite direction.nnnCONCLUSIONSnCardiometabolic dysfunction is related to osteophytes-defined radiographic knee OA prevalence and persists within subgroups defined by obesity status and gender. A sex dimorphism in the direction and magnitude of cardiometabolic risk factors with respect to knee OA was described including HOMA-IR being associated with OA prevalence among men while leptin levels were most important among women.