Polarisation-sensitive optical coherence tomography measurement of retardance in fibrosis, a non-invasive biomarker in patients with systemic sclerosis.

Polarisation-sensitive optical coherence tomography (PS-OCT) offers a novel, non-invasive method of assessing skin fibrosis in the multisystem disease systemic sclerosis (SSc) by measuring collagen retardance. This study aimed to assess retardance as a biomarker in SSc. Thirty-one patients with SSc and 27 healthy controls (HC) underwent PS-OCT imaging. 'Skin score' was assessed by clinical palpation (0-3 scale). A subset of ten patients and ten age/sex-matched HC had a biopsy and longitudinal imaging. Histological assessment included quantification of epidermal thickness, collagen content (to assess fibrosis) and matrix metalloproteinase (MMP) activity (in situ zymography). PS-OCT images were assessed for epidermal thickness (structure) and fibrosis (retardance). Positive correlation was observed between epidermal thickness as measured by histology and structural PS-OCT (r = 0.79; p < 0.001). Retardance was: HC mean 0.21 (SD 0.21) radian/pixel; SSc skin score 0, 0.30 (0.19); skin score 1, 0.11 (0.16); skin score 2, 0.06 (0.12); skin score 3, 0.36 (0.35). Longitudinal retardance decreased at one-week across groups, increasing at one-month for HC/skin score 0-1; HC biopsy site retardance suggests scarring is akin to fibrosis. Relationships identified between retardance with both biopsy and skin score data indicate that retardance warrants further investigation as a suitable biomarker for SSc-related fibrosis.

Synovial volume vs synovial measurements from dynamic contrast enhanced MRI as measures of response in osteoarthritis.

OBJECTIVE: Synovium is increasingly a target of osteoarthritis (OA) treatment, yet its optimal measurement is unclear. Using dynamic contrast enhanced (DCE) MRI in knee OA patients before and after intraarticular steroid injection, we compared the responsiveness of static synovial volume measures to measures of dynamic changes in synovial enhancement, changes that are strongly related to synovial vascularity. METHODS: Ninety three patients underwent DCE-MRI before and 1-2 weeks after intra-articular injection of 80 mg methylprednisolone. Synovium was segmented and volume, relative enhancement rate (RER), maximum relative enhancement (REmax), late relative enhancement (RElate) and pharmacokinetic parameters (K(trans), ve) were calculated. KOOS (​knee injury and osteoarthritis outcome score) pain score was recorded before and after injection. Standardized change scores were calculated for each parameter. Linear regression and Pearson's correlations were used to investigate the relationship between change in MRI parameters and change in pain. RESULTS: The change in standardized score for the measures of synovial enhancement, RElate and REmax were -0.58 (95% CI -0.79 to -0.37) and -0.62 (95% CI -0.83 to -0.41) respectively, whereas the score for synovial volume was -0.30 (-0.52 to -0.09). Further, change in knee pain correlated more strongly with changes in enhancement (for both REmax and RElate, r = -0.27 (95% CI -0.45 to -0.07)) than with changes in synovial volume -0.15 (-0.35 to 0.05). CONCLUSION: This study suggests DCE-MRI derived measures of synovial enhancement may be more sensitive to the response to treatment and more strongly associated with changes in pain than synovial volume and may be better outcomes for assessment of structural effects of treatment in OA.

Sunlight exposure behaviour and vitamin D status in photosensitive patients: longitudinal comparative study with healthy individuals at U.K. latitude.

BACKGROUND: Low vitamin D status is prevalent in wintertime in populations at northerly latitudes. Photosensitive patients are advised to practise sun avoidance, but their sunlight exposure levels, photoprotective measures and resulting vitamin D status are unknown. OBJECTIVES: To examine seasonal vitamin D status in photosensitive patients relative to healthy individuals and to assess quantitatively behavioural and demographic contributors. METHODS: This was a longitudinal prospective cohort study (53·5°N) examining year-round 25-hydroxyvitamin D [25(OH)D] levels, sun-exposure behaviour and oral vitamin D intake in photosensitive patients diagnosed at a photoinvestigation unit (n = 53), compared with concurrently assessed healthy adults (n = 109). RESULTS: Photosensitive patients achieved seasonal 25(OH)D variation, but insufficient (< 20 ng mL(-1); 50 nmol L(-1)) and even deficient (< 10 ng mL(-1); 25 nmol L(-1)) levels occurred at the summer peak in 47% and 9% of patients, respectively, rising to 73% and 32% at the winter trough. Adjusting for demographic factors, the mean values were lower than for healthy volunteers by 18% [95% confidence interval (CI) 4-29] in summer (P = 0·02) and 25% (95% CI 7-39) in winter (P = 0·01). Behavioural factors explained 25(OH)D differences between cohorts. Patients demonstrated lower weekend ultraviolet B doses (P < 0·001), smaller skin surface area exposure (P = 0·004) and greater sunscreen use (P < 0·001), while average oral vitamin D intake was low in both groups (photosensitive: 2·94 µg per day). Supplementation and summer surface area exposure predicted summer peak and winter trough 25(OH)D levels. A 1 µg per day increment in supplementary vitamin D raised summer and winter 25(OH)D by 5% (95% CI 3-7) and 9% (95% CI 5-12), respectively (both P < 0·001). CONCLUSIONS: Photosensitive patients are, through their photoprotective measures, at high risk of year-round low vitamin D status. Guidance on oral measures should target this patient group and their physicians.

Tooth loss and osteoporosis: to assess the association between osteoporosis status and tooth number.

BACKGROUND: Osteopenia and osteoporosis are conditions characterised by a reduction in bone mineral density. There is contradictory evidence whether osteoporotic patients have greater tooth loss than non-osteoporotic patients. OBJECTIVE: To investigate the association between tooth number and osteoporotic status, taking into account the effect of other confounding variables such as age, smoking status, alcohol consumption and the use of hormone replacement therapy. SETTING: Three hundred and fifty-nine patients were recruited from the Manchester region between March 2008 and June 2010. SUBJECTS AND METHODS: Data were collected on osteoporotic status, smoking status, alcohol consumption, age and the use of hormone replacement therapy. Dental panoramic tomographs were taken for each patient and the teeth present were charted and counted. Data were analysed using SPSS software (version 19). RESULTS: Complete data was available for 333 patients. Twenty-seven percent of individuals (90) were classified as osteoporotic. There was a significant relationship between molar tooth number and osteoporotic status (p = 0.017, 95% CI -1.339 to -0.137). CONCLUSION: Clinicians should inform osteoporotic patients they may be at greater risk of tooth loss and instigate more intensive preventive regimens for these individuals.

Do patients with osteoporosis have an increased prevalence of periodontal disease? A cross-sectional study.

UNLABELLED: The study examined if women with osteoporosis were at increased risk of periodontal disease. Three hundred eighty females aged 45-65 years with recent dual-energy X-ray absorptiometry (DXA) scans of the spine and proximal femur agreed to a dental examination. No association was established between the presence of severe periodontal disease and osteoporosis. INTRODUCTION: The purpose of this study is to determine whether patients with osteoporosis have an increased severity and extent of periodontal disease, taking full account of confounding factors. METHODS: Volunteer dentate women (45-65 years), who had undergone recent DXA of the femur and lumbar spine, received a clinical examination of their periodontal tissues by a single trained operator who was blind to the subject's osteoporosis status. Clinical examinations were performed within 6 months of the DXA. Basic Periodontal Examination score, gingival bleeding score, periodontal pocket depth, recession and calculus were the periodontal outcome measures. Potential confounding factors were recorded. Logistic regression was performed for the dichotomous outcome measure of severe periodontal disease (present or absent) with osteoporotic status, adjusting for confounding factors. RESULTS: There were 380 dentate participants for whom DXA data were available. Of these, 98 had osteoporosis. When compared with osteoporotic subjects, those with normal bone mineral density were significantly younger (p = 0.01), had a higher body mass index (p = 0.03) and had more teeth (p = 0.01). The prevalence of severe periodontal disease in the sample was 39 %. The unadjusted odds ratio for the association between osteoporosis and severe periodontal disease was 1.21 (0.76 to 1.93). The adjusted odds ratio analysis including other covariates (age, smoking, hormone replacement therapy, alcohol) was 0.99 (0.61 to 1.61). CONCLUSION: No association was established between the presence of severe periodontal disease and osteoporosis.

Bone marrow lesions in knee osteoarthritis change in 6-12 weeks.

OBJECTIVES: Knee osteoarthritis (OA) is thought to be a slowly evolving disease with glacial changes in cartilage morphology necessitating trials of potential treatments lasting 1-2 years with evidence that over 6 months change in cartilage is not detectable. In contrast to cartilage, bone has the capacity to adapt rapidly, such as after fracture. We tested whether bone marrow lesions (BMLs) change in volume in 6 and 12 weeks, suggesting they may provide evidence of short term fluctuations of joint damage. METHODS: In 62 patients with patellofemoral knee OA (mean age 55.7 years, 59.7% women, mean BMI 31.0), we obtained baseline, 6 and 12 week knee MRIs with contrast enhancement. Of those with BMLs at baseline, we assessed BML volume on the axial proton density fat saturated (FS) images and postcontrast sagittal T1 weighted FS images. We manually segmented BML volumes, testing repeatability of BML volumes in knees remeasured. Using the standard deviation of the difference between repeated measurements to calculate Bland-Altman Limits of Agreement, we determined how much BML volume change represented a change greater than due to chance. RESULTS: Fifty-two patients had BMLs at baseline. Test-retest reliability for BML volume was high (ICC 0.89, 95% CI 0.80-0.97). All knees showed at least some change in BML volume by 6 and 12 weeks. On the axial view at 6 weeks, 20/49 (40.8%) knees showed BML volume changes greater than the limits of agreement with similar results at 12 weeks. BML changes were evenly divided among knees with enlarging and shrinking BMLs. 63.3% of the knees had more than 50% change in BML volume at either 6 or 12 weeks on the axial view and 48.7% on the sagittal view. CONCLUSIONS: Knee BML volumes change in several weeks in many persons with knee OA. To the extent that they could be regarded as treatment targets, trials testing BML effects could avoid the usual prolonged structure modification trials.

Prediction of osteoporosis with dental radiographs and age.

OBJECTIVES: In this study age and the trabecular pattern present on dental radiographs were used to predict the presence of osteoporosis. The objective was to evaluate the contribution of the trabecular pattern to the prediction. METHODS: In this project, 671 women between 45 and 71 years of age were recruited. Medical history was obtained and dental radiographs were made. Bone mineral density (BMD) was measured at three sites to assess the presence of osteoporosis according to the World Health Organization criteria. The radiographs were subjected to image analysis methods yielding measurements of the trabecular pattern. Thereafter, discriminant analysis was used to predict the presence of osteoporosis by means of the trabecular pattern and age. Sensitivity and specificity of age and the trabecular pattern were compared. Also, it was checked whether the inclusion of the trabecular pattern improved the sensitivity and specificity that were obtained when only age was used as the predictor. RESULTS: The sensitivity and specificity of the trabecular pattern present on dental radiographs were almost equal to those of age. However, combining age with the trabecular pattern increased the sensitivity from 0.71 to 0.75 and the specificity from 0.72 to 0.78; the latter increase was statistically significant. CONCLUSIONS: The trabecular pattern predicts the presence of osteoporosis just as well as age does. When combining the trabecular pattern with age, the sensitivity and specificity increased. Only the latter increase was statistically significant.

The impact of accurate positioning on measurements made by peripheral QCT in the distal radius.

SUMMARY: Data from pQCT sections at the forearm were examined to assess the impact of positioning on measurements. Two thousand five hundred fifty one scans were analysed. The results showed 25% of scans were not performed in the same anatomical location at follow-up when one section was scanned. These results have implications for accurate follow-up BMD measurements. INTRODUCTION: pQCT of the distal radius is routinely performed using a single section of 2 mm thickness. Accurate positioning is essential to maximise long-term repeatability. We perform two adjacent sections which, permits us to select sections at baseline and follow-up that are in the most similar anatomical site for calculating longitudinal change. This study aimed to assess baseline and follow-up pQCT forearm data to examine variability and determine whether performing two sections, as opposed to one section, improved accuracy when monitoring long-term change in BMD. METHODS: Two adjacent 1.2 mm pQCT radial sections were performed at: baseline n = 2,551 (1,896F:655M) and follow-up n = 335F. RESULTS: Baseline: difference between adjacent 1.2 mm forearm sections: total BMD 19.3 mg/cm(3) (females) and 16.7 mg/cm(3) (males); trabecular BMD 3.1 mg/cm(3) (females) and 2.35 mg/cm(3) (males); CSA 16.2 mm(2) (females) and 17.7 mm(2) (males) (all significant). FOLLOW-UP: percentage of scans at baseline and follow-up performed in the same anatomical location: one section performed-75%, two sections performed-95%. CONCLUSION: When performing a single section at the distal radius it is difficult to perform scans in the same anatomical location at visits. Performing two or more sections can overcome this problem in some individuals and provide more accurate BMD measurements.

Selecting regions of interest on intraoral radiographs for the prediction of bone mineral density.

OBJECTIVES: A previous study showed that the trabecular pattern on dental radiographs correlates with femoral and spinal bone mineral density (BMD). The objective of this study was to determine if the correlation is affected by the size and location of the region of interest (ROI). METHODS: In a European research project on osteoporosis, BMD was measured at the left hip and the lumbar spine of 525 women. From all subjects, intraoral radiographs were made of the premolar region in the upper and lower jaws. Two ROIs were indicated manually on each scanned image. The smallest region involved only trabecular bone and the largest also included parts of the neighbouring teeth. The ROIs were subjected to automatic image analysis, yielding 26 measurements per ROI. Stepwise linear regression was used to predict femoral and spinal BMD. RESULTS: Inner and outer regions predicted BMD equally well. The radiographs of lower and upper jaw also predicted BMD equally well. Combining inner and outer regions did not improve the prediction of femoral and spinal BMD, but combining lower and upper jaws did. CONCLUSIONS: This study shows that it is possible to include parts of neighbouring teeth in the ROI used to assess the trabecular pattern and predict BMD. This simplifies the process of selecting the ROIs because no efforts have to be made to exclude neighbouring teeth. Combining ROIs of lower and upper jaws significantly improves the prediction of BMD.