***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The effect on urine C-telopeptides of type II collagen ( uCTX-II ) of oral and transdermal estradiol treatment was compared using sample s from two r and omized , double-blind , placebo-controlled trials . A total of 171 healthy , Danish postmenopausal women , 45 - 65 years of age completed the 2-year study periods . The uCTX-II marker assessed cartilage degradation , and this response was compared with the effect on urine C-telopeptides of type I collagen ( uCTX-I ) , considered a specific marker of bone resorption . Doses in the oral estradiol treatment groups ( continuous combined therapy ) were 1 mg 17-beta-estradiol+1 mg drosperinone or 1 mg 17-beta-estradiol+2 mg drosperinone or 1 mg 17-beta-estradiol+3 mg drosperinone or placebo . Doses in the transdermal estradiol treatment groups ( continuous combined therapy ) were 45 microg 17-beta-estradiol+30 levonorgestrel or 45 microg 17-beta-estradiol+40 microg levonorgestrel or placebo . The effect of oral and transdermal estradiol therapy on cartilage degradation was reflected as a decrease of 19 - 30 % in uCTX-II ( P=0.02 and P=0.003 vs. placebo ) after 1 year of treatment . uCTX-I decreased 70 % ( P<0.0001 vs. placebo ) reflecting a pronounced effect on bone resorption that was consistent with a 2-year increase in spine and hip BMD of 7 - 8 % and 4 - 6 % , respectively . The results indicate that different regimens of postmenopausal HRT both have an effect on cartilage and bone thus protecting against osteoporosis and osteoarthritis ( OA ) . However , long-term clinical trials are needed to further investigate this issue BACKGROUND Glucosamine and chondroitin sulfate are used to treat osteoarthritis . The multicenter , double-blind , placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial ( GAIT ) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis . METHODS We r and omly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily , 1200 mg of chondroitin sulfate daily , both glucosamine and chondroitin sulfate , 200 mg of celecoxib daily , or placebo for 24 weeks . Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia . Assignment was stratified according to the severity of knee pain ( mild [ N=1229 ] vs. moderate to severe [ N=354 ] ) . The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24 . RESULTS The mean age of the patients was 59 years , and 64 percent were women . Overall , glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent . As compared with the rate of response to placebo ( 60.1 percent ) , the rate of response to glucosamine was 3.9 percentage points higher ( P=0.30 ) , the rate of response to chondroitin sulfate was 5.3 percentage points higher ( P=0.17 ) , and the rate of response to combined treatment was 6.5 percentage points higher ( P=0.09 ) . The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group ( P=0.008 ) . For patients with moderate-to-severe pain at baseline , the rate of response was significantly higher with combined therapy than with placebo ( 79.2 percent vs. 54.3 percent , P=0.002 ) . Adverse events were mild , infrequent , and evenly distributed among the groups . CONCLUSIONS Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee . Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain . ( Clinical Trials.gov number , NCT00032890 . ) BACKGROUND Paracetamol is a recommended symptomatic treatment of osteoarthritis ( OA ) , but in clinical trials sample sizes have been relatively small and variable daily doses of paracetamol have been used . OBJECTIVES To determine the therapeutic efficacy of paracetamol in OA of the knee and identify predictive factors of clinical response to treatment . METHODS A double blind , parallel group , placebo controlled trial of analgesic efficacy and safety of paracetamol versus placebo including 779 patients with OA of the knee . Patients were r and omly assigned to receive paracetamol 4 g/day ( n = 405 ) or placebo ( n = 374 ) for 6 weeks . Symptomatic OA of the knee was required at inclusion with global pain intensity of the knee during physical activities for the past 24 hours of > or=30 mm on a 100 mm visual analogue scale . The primary end point was a 30 % decrease of global pain intensity of the knee . Intention to treat analyses were performed . RESULTS The percentage of responders did not differ significantly between groups : 52.6 % and 51.9 % in paracetamol and placebo groups , respectively ( p = 0.840 ) . In a subgroup of patients with chronic mechanical knee pain without signs of inflammation ( n = 123 ) , the mean change in pain intensity from baseline was 25.2 mm v 15.2 mm , in the paracetamol ( n = 63 ) and placebo ( n = 60 ) groups , respectively-mean difference 10.0 mm ; 95 % CI 1.0 to 19.0 ; p = 0.0294 . No serious adverse events were attributable to treatment . CONCLUSION A statistically significant symptomatic effect of oral paracetamol 4 g/day over placebo was not found , suggesting that paracetamol use in symptomatic OA of the knee should be further explored . The tolerability and safety of paracetamol , at the recommended maximum dose of 4 g/day , was confirmed over 6 weeks In this prospect i ve r and omised study two treatments after non-traumatic medial meniscal tear diagnosed with radiological examination and magnetic resonance imaging were compared ; arthroscopic partial meniscectomy followed by supervised exercise or supervised exercise alone . The aim was to evaluate knee function and physical activity . Ninety patients ( mean age 56 years ) were evaluated using the  Knee Injury and Osteoarthritis Outcome Score , the Lysholm Knee Scoring Scale , the Tegner Activity Scale and a Visual Analogue Scale for knee pain prior to the intervention , after 8 weeks of exercise and after 6 months . According to the outcome scores arthroscopic partial medial meniscectomy combined with exercise did not lead to greater improvement than exercise alone . After the intervention both groups reported decreased knee pain , improved knee function and a high satisfaction ( P < 0.0001 ) . Forty-one per cent of the patients returned to their pre-injury activity level after 6 months . In conclusion , when evaluated with outcome scores , arthroscopic partial medial meniscectomy followed by supervised exercise was not superior to supervised exercise alone in terms of reduced knee pain , improved knee function and improved quality of life OBJECTIVE Osteoarthritis ( OA ) is the most common form of arthritis and the second most common cause of long-term disability among middle-aged and older adults in the United States .  Methylsulfonylmethane ( MSM ) is a popular dietary supplement used as a single agent and in combination with other nutrients , and purported to be beneficial for arthritis . However , there is paucity of evidence to support the use of MSM . METHODS A r and omized , double-blind , placebo-controlled trial was conducted . Fifty men and women , 40 - 76 years of age with knee OA pain were enrolled in an outpatient medical center . Intervention was MSM 3 g or placebo twice a day for 12 weeks ( 6g/day total ) . Outcomes included the Western Ontario and McMaster University Osteoarthritis Index visual analogue scale ( WOMAC ) , patient and physician global assessment s ( disease status , response to therapy ) , and SF-36 ( overall health-related quality of life ) . RESULTS Compared to placebo , MSM produced significant decreases in WOMAC pain and physical function impairment ( P<0.05 ) . No notable changes were found in WOMAC stiffness and aggregated total symptoms scores . MSM also produced improvement in performing activities of daily living when compared to placebo on the SF-36 evaluation ( P<0.05 ) . CONCLUSION MSM ( 3 g twice a day ) improved symptoms of pain and physical function during the short intervention without major adverse events . The benefits and safety of MSM in managing OA and long-term use can not be confirmed from this pilot trial , but its potential clinical application is examined . Underlying mechanisms of action and need for further investigation of MSM are discussed OBJECTIVE To investigate whether early changes in biochemical markers of bone ( NTX-I ) and cartilage ( CTX-II [ C-terminal crosslinking telopeptide of type II collagen ] ) degradation are associated with radiological progression in patients with knee osteoarthritis ( OA ) receiving risedronate .  DESIGN Two thous and four hundred and eighty three patients with medial compartment knee OA were r and omized in two 24-month studies in North America ( NA ) and European Union ( EU ) . Studies evaluated risedronate 5 mg/day , 35 mg/week ( EU ) , 50 mg/week ( NA ) , and 15 mg/day ( NA and EU ) , compared to placebo in reducing signs and symptoms and in slowing radiographic progression . One thous and eight hundred and eighty five patients from the pooled EU and NA studies with available NTX-I/CTX-II at both baseline and 6 months and radiographs at baseline and at 24 months were analyzed . RESULTS Risedronate produced a dose-dependent reduction of NTX-I and CTX-II observed at 6 months which continued up to 24 months . Patients who had CTX-II levels returned to low levels ( < 150 ng/mmol creatinine ) at 6 months had a lower risk of radiographic progression at 24 months than patients whose CTX-II levels were increased both at baseline and 6 months [ odds-ratio ( 95 % confidence interval ) : 0.57 ( 0.39 - 0.85 ) after adjustment for demographics and joint space width ] . The lowest risk of progression was observed in patients who had low CTX-II levels both at baseline and at 6 months [ odds-ratio 0.36 ( 0.21 - 0.63 ) ] . No significant association between NTX-I levels and radiological progression was observed . CONCLUSION CTX-II decreased with risedronate in patients with knee OA and levels reached after 6 months were associated with radiological progression at 24 months . Monitoring a marker of cartilage degradation 6 months after initiating treatment may be instructive in identifying patients with low progression Objectives .To estimate cost and outcomes of the Arthritis Foundation aquatic exercise classes from the societal perspective . Design .R and omized trial of 20-week aquatic classes .  Cost per quality -adjusted life year ( QALY ) gained was estimated using trial data . Sample size was based on 80 % power to reject the null hypothesis that the cost/QALY gained would not exceed $ 50,000 . Subjects and Methods . Recruited 249 adults from Washington State aged 55 to 75 with a doctor-confirmed diagnosis of osteoarthritis to participate in aquatic classes .  The Quality of Well-Being Scale ( QWB ) and Current Health Desirability Rating ( CHDR ) were used for economic evaluation , supplemented by the arthritis-specific Health Assessment Question naire ( HAQ ) , Center for Epidemiologic Studies -Depression Scale ( CES-D ) , and Perceived Quality of Life Scale ( PQOL ) collected at baseline and postclass . Outcome results applied to life expectancy tables were used to estimate QALYs . Use of health care facilities was assessed from diaries/ question naires and Medicare reimbursement rates used to estimate costs . Nonparametric bootstrap sampling of costs/QALY ratios established the 95 % CI around the estimates . Results .Aquatic exercisers reported equal ( QWB ) or better ( CHDR , HAQ , PQOL ) health-related quality of life compared with controls . Outcomes improved with regular class attendance . Costs/QALY gained discounted at 3 % were $ 205,186 using the QWB and $ 32,643 using the CHRD . Conclusion .Aquatic exercise exceeded $ 50,000 per QALY gained using the community-weighted outcome but fell below this arbitrary budget constraint when using the participant-weighted measure . Confidence intervals around these ratios suggested wide variability of cost effectiveness of aquatic exercise BACKGROUND Treatment of osteoarthritis is usually limited 
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Among non-pharmacological therapies , ES for pain relief was unchanged for self-management , education , exercise and acupuncture .
Among pharmacological therapies , the cumulative evidence for the benefits and harms of oral and topical non-steroidal anti-inflammatory drugs , diacerhein and intra-articular ( IA ) corticosteroid was not greatly changed .
ES for pain relief from IA hyaluronic acid , glucosamine sulphate , chondroitin sulphate and avocado soybean unsponifiables also diminished and there was greater heterogeneity of outcomes and more evidence of publication bias .
Among surgical treatments further negative RCTs of lavage/debridement were published and the pooled results demonstrated that benefits from this modality of therapy were no greater than those obtained from placebo .
CONCLUSION Publication of a large amount of new research evidence has result ed in changes in the calculated risk-benefit ratio for some treatments for OA .