Elizabeth Marjanovic

A randomised trial of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions

Objective Braces used to treat (PF) osteoarthritis (OA) may reduce contact stress across the PF joint. We hypothesised that in PF OA, braces would decrease knee pain and shrink PF bone marrow lesions (BMLs). Methods Eligible subjects had painful PF OA. Subjects were randomly allocated to brace or no brace for 6 weeks. Knee MRIs were acquired at baseline and 6 weeks. We measured BMLs on post-contrast fat suppressed sagittal and proton density weighted axial images. The primary symptom outcome was change in pain at 6 weeks during a preselected painful activity, and the primary structural outcome was BML volume change in the PF joint. Analyses used multiple linear regression. Results We randomised 126 subjects aged 40–70 years (mean age 55.5  years; 72 females (57.1%)). Mean nominated visual analogue scale (0–10 cm) pain score at baseline was 6.5 cm. 94 knees (75%) had PF BMLs at baseline. Subjects wore the brace for a mean of 7.4 h/day. 6 subjects withdrew during the trial. After accounting for baseline values, the brace group had lower knee pain than the control group at 6 weeks (difference between groups −1.3 cm, 95% CI −2.0 to −0.7; p<0.001) and reduced PF BML volume (difference −490.6 mm3, 95% CI −929.5 to −51.7; p=0.03) but not tibiofemoral volume (difference −53.9 mm3, 95% CI −625.9 to 518.2; p=0.85). Conclusions A PF brace reduces BML volume in the targeted compartment of the knee, and relieves knee pain. Trial registration number UK. ISRCTN50380458.

The use of visual assessment of dental radiographs for identifying women at risk of having osteoporosis: the OSTEODENT project

OBJECTIVE The objective of this study was to investigate the diagnostic accuracy of visual assessment of the trabecular pattern in intraoral periapical radiographs to identify female subjects at risk of having osteoporosis. STUDY DESIGN Six hundred female subjects underwent intraoral periapical radiography of the maxillary and mandibular premolar region. Five observers assessed the trabecular pattern as dense, heterogeneous, or sparse, with the aid of reference images. All patients received a central dual energy x-ray absorptiometry (DXA) examination of the hip and lumbar spine. RESULTS With sparse trabecular pattern as indicative of osteoporosis, mean specificity was high (91.6 for the upper jaw and 90.8 for the lower jaw) while the sensitivity was low (28.2 for the upper and lower jaw). The mean intraobserver agreement was comparable for radiographs of the upper and lower jaw (median kappa(w) 0.53 and 0.57, respectively). CONCLUSION Visual assessment of the trabecular pattern in intraoral periapical radiographs of premolar regions is a potential method to identify women at risk of having osteoporosis.

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

Summary 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.

Osteoporosis detection using intraoral densitometry

OBJECTIVES To determine the diagnostic accuracy of mandibular and maxillary bone density in detecting osteoporosis using receiver operating characteristic (ROC) analysis. METHODS 671 women between 45 years and 70 years of age underwent dual energy X-ray absorptiometry (DXA) of the hip and lumbar spine. This was the gold standard for diagnosing osteoporosis. Intraoral radiography of the upper and lower right premolar region was performed, using an aluminium wedge as a densitometric reference. Jaw bone density was determined using dedicated software. Observer differences and ROC curves were analysed. RESULTS For detecting osteoporosis using jaw bone density, the area under the ROC curve (A(z)) was 0.705. For separate analysis of mandibular and maxillary films, sensitivity varied from 33.9% to 38.7% and specificity from 83.5% to 85.3% when using a threshold of 4.3 mm Al equivalent. CONCLUSIONS Density of the premolar region reaches a fair diagnostic accuracy, which might improve when including additional factors in the analysis and refining the densitometric tool.

Synovial tissue volume: a treatment target in knee osteoarthritis (OA).

Background Synovitis occurring frequently in osteoarthritis (OA) may be a targeted outcome. There are no data examining whether synovitis changes following intra-articular intervention. Methods Persons aged 40 years and older with painful knee OA participated in an open label trial of intra-articular steroid therapy. At all time points they completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. They had a contrast-enhanced (CE) MRI immediately prior to an intra-articular steroid injection with a repeat scan within 20 days. Response status was assessed using the Osteoarthritis Research Society International (OARSI) response criteria. OARSI responders were followed until their pain relapsed either within 20% of baseline or 6 months, shortly after which a third MRI was performed. Synovial tissue volume (STV) was measured on postcontrast knee images. We looked at changes in the STV and in pain, and their association. Results 120 subjects with preinjection and postinjection CE MRI were followed. Their mean age was 62.3 years (SD=10.3) and 62 (52%) were women. The median time between injection and follow-up scan was 8 days (IQR 7–14 days). 85/120 (71%) were OARSI responders. Pain decreased (mean change in KOOS=+23.9; 95% CI 20.1 to 27.8, p<0.001) following steroid injection, as did mean STV (mean change=−1071 mm3; 95% CI −1839 mm3 to −303 mm3, p=0.01). Of the 80 who returned for a third MRI, pain relapsed in 57, and in the 48 of those with MRI data, STV increased between follow-up and final visit (+1220 mm3; 95% CI 25 mm3 to 2414 mm3, p=0.05). 23 were persistent responders at 6 months and, in these, STV did not increase (mean change=−202 mm3; 95% CI −2008 mm3 to 1604 mm3, p=0.83). Controlling for variation over time, there was a significant association between synovitis volume and KOOS pain (b coefficient—change in KOOS pain score per 1000 mm3 change in STV=−1.13; 95% CI −1.87 to −0.39, p=0.003), although STV accounted for only a small proportion of the variance in change in pain. Conclusions Synovial tissue volume in knee OA shrinks following steroid therapy, and rebounds in those whose pain relapses. It can be considered a treatment target in symptomatic knee OA. Trial registration number ISRCTN07329370.

The role of the dental surgeon in detecting osteoporosis: the OSTEODENT study

Objective To determine if thinning (<3 mm width) of the lower cortical border of the mandible on dental panoramic radiographs, as well as other clinical risk factors, may provide a useful diagnostic test for osteoporosis in young postmenopausal women.Design Six hundred and fifty-two subjects (age range 45-70 years) were involved in this multi-centre, cross-sectional study.Setting Patients were recruited from centres in Leuven (Belgium), Athens (Greece), Manchester (UK), and Malmo (Sweden).Subjects and methods The subjects age, body weight, whether the patient took hormone replacement therapy or had a history of low trauma fracture were used to form a clinical osteoporosis risk assessment (the OSteoporosis Index of RISk or OSIRIS index). Each patient also received a dental panoramic radiographic examination.Results One hundred and forty subjects had osteoporosis involving at least one of the measurement sites (lumbar spine, femoral neck or total hip). Those with osteoporosis tended to have a low OSIRIS score and a thinned cortical mandibular border. The area under the ROC curve for using both cortical width and OSIRIS to predict osteoporosis was 0.90 (95% CI = 0.87 to 0.92). There was a significant improvement in the diagnostic ability of the combined OSIRIS and cortical width test over both tests applied separately (p <0.001). The cost effectiveness of the cortical width and OSIRIS model was improved by using a high specificity threshold rather than high sensitivity. However, this analysis ignores the costs associated with missed cases of osteoporosis.Conclusion Dentists have a role to play in the detection and referral of patients at high risk of osteoporosis.

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.

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.

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

Summary 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 (Ktrans, 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 Pearsons 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.

Sun Exposure Behavior, Seasonal Vitamin D Deficiency, and Relationship to Bone Health in Adolescents

CONTEXT Vitamin D is essential for bone health in adolescence, when there is rapid bone mineral content accrual. Because cutaneous sun exposure provides vitamin D, there is no recommended oral intake for UK adolescents. OBJECTIVE Our objective was to assess seasonal vitamin D status and its contributors in white Caucasian adolescents and examine bone health in those found deficient. DESIGN Prospective cohort study was undertaken. SETTING Six schools in Greater Manchester, UK, were included. PARTICIPANTS Participants were 131 adolescents between 12 and 15 years of age. INTERVENTION(S) Seasonal assessment of circulating 25-hydroxyvitamin D (25OHD), personal sun exposure, and dietary vitamin D. Adolescents deficient (25OHD <10 ng/ml/25 nmol/liter) in at least one season underwent dual-energy X-ray absorptiometry (lumbar spine, femoral neck), with bone mineral apparent density correction for size, and peripheral quantitative computed tomography (distal radius) for volumetric bone mineral density (BMD). MAIN OUTCOME MEASURE Serum 25OHD and BMD measurements. RESULTS Mean 25OHD was highest in September: 24.1 (SD, 6.9) ng/ml and lowest in January: 15.5 (5.9) ng/ml. Over the year, 16% were deficient in ≥ one season and 79% insufficient (25OHD <20 ng/ml/50 nmol/liter) including 28% in September. Dietary vitamin D was low year-round, whereas personal sun exposure was seasonal and predominantly across the school week. Holidays accounted for 17% variation in peak 25OHD (P < .001). Nineteen adolescents underwent bone assessment, which showed low femoral neck bone mineral apparent density vs matched reference data (P = .0002), three with Z less than or equal to -2.0 distal radius trabecular volumetric BMD. CONCLUSIONS Sun exposure levels failed to provide adequate vitamin D, with approximately one-quarter of adolescents insufficient even at summer peak. Seasonal vitamin D deficiency was prevalent and those affected had low BMD. Recommendations on vitamin D acquisition are indicated in this age-group.