Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin-like growth factor I (IGF-I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing, but the effect of local IGF-I administration on tendon collagen synthesis in human has not been studied. The purpose of this study was to study whether local injections of IGF-I would have a stimulating effect on tendon collagen synthesis. Twelve healthy nonsmoking men [age 62 ± 1 years (mean ± SEM), BMI 27 ± 1] participated. Two injections of either human recombinant IGF-I (0.1 mL Increlex©) or saline (control) into each patellar tendon were performed 24-h apart, respectively. Tendon collagen fractional synthesis rate (FSR) was measured by stable isotope technique in the hours after the second injection. Simultaneously, interstitial peritendinous (IGF-I) and [procollagen type I N-terminal propeptide (PINP)], as a marker for type I collagen synthesis, were determined by microdialysis technique. Tendon collagen FSR and PINP were significantly higher in the IGF-I leg compared with the control leg (P

This thesis examines two main hypotheses: 1. Obese knee osteoarthritis (KOA) patients can achieve symptomatic improvements following diet intervention regardless of their level of structural damage and overall joint malfunctioning: 2. Rapid weight-loss in obese patients with KOA will lead to improvements in KOA related pathology that can be assessed and evaluated by MRI. Data for the studies were obtained from obese KOA patients who were recruited for a 16 week diet intervention trial, the CAROT-trial (ClinicalTrials.gov identification no.: NCT00655941). Inclusion criteria were age ≥ 50 years, BMI ≥ 30 kg/square metro plus symptomatic and verified KOA. Patients underwent a 16 weeks dietary programme with formula products and counselling. Baseline and week 16 assessments included clinical examinations, MRI and CR of the most symptomatic knee, muscle strength tests, gait analyses, blood samples and collection of patient-reported outcomes with a variety of generic and specific health status questionnaires. MRI scans were graded by the BLOKS and CR was analysed by measuring the mJSW and grading the knee as described by KL. 388 possible subjects were pre-screened, 192 were enrolled. Following the 16 weeks diet intervention 175 patients remained in the study. 187 (97%) MRI scans were completed at baseline, 172 (98 %) MRI scans obtained at week 16 and this left the study with 169 (97%) patients with complete MRI datasets at week 16. No statistical significant differences were detected between baseline characteristics of all the initially included patients (n = 192) and the 169 patients included in the per protocol analyses performed in study III (p 10%) and those who did not. Furthermore, changes in clinical symptoms and BML scores were not associated. The limitations of this thesis were that the MRI analyses were based on single determinations of MRI variables and that the studies did not assess between scan reliability. The MRI protocol for this study did not include all the recommended sequences for BLOKS. Analysing BMLs with the use of only coronal STIR and T1w sequences is considered adequate for a reasonable assessment of the tibial and femoral bones. However, we recognize the limitations this strategy withholds in terms of correctly assessing BMLs located at the margins of our slices when only having a single plane view included in our MRI protocol. Due to an inadequate coverage we did not analyse BMLs in patella, and this confined the thesis to only study changes in the tibial and femoral bones. BLOKS contains separate scores for effusion and synovitis and we have assessed all MRI scans according to this discrimination well knowing that this procedure is biased and that a recent paper has proposed the combination of the two scores. MRI technology allows for an excellent discrimination and delineation of synovitis and synovial effusion by performing MRI with I.V. gadolinium and post-contrast T1 FS images, but due to extensive requirements and longer scans times for such examinations we proceeded with our, in this matter, suboptimal MRI protocol. The optimal assessment of KOA would be achieved by performing three radiographic views, posteroanterior, lateral and skyline, but for this study we chose a radiographic protocol only including the first two mentioned as this procedure was somewhat similar to the routine examination for KOA applied on a daily basis at our Department of Radiology. The results of this thesis support existing guidelines suggesting that diet intervention in obese KOA patients is beneficial for symptomatic improvements. The new information from the thesis is that improvement in clinical symptoms is possible for the majority of patients, independent of their pre-study level of structural damage and measures of joint malfunctioning. The present results also demonstrated that a rapid weight-loss had no association to changes in BML scores and established that changes observed in symptoms and BML scores, following a 16 weeks diet intervention, were not related.

Muscle sound gives a local picture of muscles involved in a particular movement and is independent of electrical signals between nerve and muscle. Sound recording (acoustic myography) is a well-known noninvasive technique that has suffered from not being easily applicable, as well as not being able to register at sufficient sampling speed. With modern amplifiers and digital sound recording this has changed, and such assessment during movement outside a laboratory setting may be possible. Our aim was to develop a setup for muscle-sound assessment, which could be reliably applied in any local setting. A group of healthy subjects were assessed during standing, stair climbing, walking, and running. Piezoelectric microphones were applied to the skin using contact gel. A digital sound recorder enabled sampling speeds of around 96,000 Hz. Surface electromyography was measured in parallel as a comparison. The recorded signals were assessed and described in terms of signal frequency (Hz) and peak-to-peak amplitude (mV) using Chart software. Bioimpedance of the involved muscles was measured. Sound recording was shown to be an easy noninvasive method for assessment of muscle function during movement with the possibility of being applied in most clinical, sports, and home settings. Muscle sound gives a representation of the work of each muscle group during a complex movement, illustrated here by a step test, which revealed both concentric and eccentric activity. The method in the presented new setup has great potential for assessment of function in patients with musculoskeletal complaints in out-of-clinic settings, as well as in sports.

Objectives: To investigate the responsiveness to treatment and the reliability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rheumatoid arthritis (RA) knee joints. Methods: DCE-MRI was performed in 12 clinically active RA knee joints before and 1, 7, 30, and 180 days after intra-articular injection with 80 mg methylprednisolone. Using semi-automated image processing software, DCE-MRI parameters, including the initial rate of enhancement (IRE) and maximal enhancement (ME), were generated for three regions of interest (ROIs): 'Whole slice', 'Quick ROI', and 'Precise ROI'. The smallest detectable difference (SDD), the smallest detectable change (SDC), and intra- and inter-reader intraclass correlation coefficients (ICCs) were used to assess the reliability of DCE-MRI. Responsiveness to treatment was assessed by the standardized response mean (SRM). Results: In all patients clinical remission of the knee was achieved at day 7. All DCE-MRI parameters decreased from day 0 to day 7. Using the Quick and Precise ROI methods, respectively, IRE decreased by 63% and 69%, ME decreased by 11% and 11%, N decreased by 55% and 57%, and IRE × N decreased by 84% and 85%. The intra- and inter-reader ICCs were very high (0.96-1.00). The decrease in DCE-MRI parameters was larger than the SDC for all patients. SRM was large for all parameters, ranging from -1.04 to -2.40. When the Whole slice ROI method was used, no parameters were responsive to treatment. Conclusions: DCE-MRI analysed using semi-automatic software is a reliable and responsive tool for assessing treatment in RA knees joints. Rough manual delineation of the joint to omit enhancement artefacts is necessary.