Management of hand osteoarthritis: from an US evidence-based medicine guideline to a European patient-centric approach.

Hand osteoarthritis is the most common joint condition and is associated with significant morbidity. It is of paramount importance that patients are thoroughly assessed and examined when complaining of hand stiffness, pain, deformity or disability and that the patient's concerns and expectations are addressed by the healthcare professional. In 2019 the American College of Rheumatology and Arthritis Foundation (ACR/AF) produced guidelines which included recommendations for the treatment of hand osteoarthritis. An ESCEO expert working group (including patients) was convened and composed this paper with the aim to assess whether these guidelines were appropriate for the treatment of hand osteoarthritis therapy in Europe and whether they met with the ESCEO patient-centered approach. Indeed, patients are the key stakeholders in healthcare and eliciting the patient's preference is vital in the context of an individual consultation but also for informing research and policy-making. The patients involved in this working group emphasised the often-neglected area of aesthetic changes in hand osteoarthritis, importance of developing pharmacological therapies which can alleviate pain and disability and the need of the freedom to choose which approach (out of pharmacological, surgical or non-pharmacological) they wished to pursue. Following robust appraisal, it was recommended that the ACR/AF guidelines were suitable for a European context (as described within the body of the manuscript) and it was emphasised that patient preferences are key to the success of individual consultations, future research and future policy-making.

Positive Effect of Teriparatide on Areal Bone Mineral Density in Young Women with Anorexia Nervosa: A Pilot Study.

The present pilot study investigated the effect of Teriparatide 1-34 rh-PTH (TPT) in young women diagnosed with anorexia nervosa (AN), and markedly compromised Bone Mineral Density (BMD). Patients were included who had (i) very low BMD (defined as Z-Score < - 2.5 or T-Score < - 2.5 if available) in at least one of the assessed localizations (lumbar spine L1-L4, total hip, femoral neck) without any previous fragility fracture; or (ii) low bone mineral density (defined as Z-Score < - 1.5 or T-Score < - 1.5 if available) in at least one of the assessed localizations (lumbar spine L1-L4, total hip, femoral neck) and at least one previous fragility fracture. Ten patients with an age range of 21-33 were recruited and their bone outcome was assessed after 12, 18, and 24 months. After 24 months of TPT treatment, BMD improved by 13.5% in the spine, 5.0% in the femoral neck, and 4.0% in the hip. Radius cortical bone density (- 2.6%) and radius cortical thickness (- 6.4%) decreased significantly, while in tibia there was no significant decrease. Neither in radius nor in tibia a significant change in trabecular bone parameters occurred. During the treatment, the patients' body weight did not increase significantly. Patients did not experience severe adverse events; only mild side effects were observed. Although these results emerged from a single-arm prospective study, it seems that AN patients with a severely compromised bone situation can benefit from TPT. Larger studies are needed to ascertain the effect of this promising substance.

Assessment of Muscle Function and Physical Performance in Daily Clinical Practice : A position paper endorsed by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

It is well recognized that poor muscle function and poor physical performance are strong predictors of clinically relevant adverse events in older people. Given the large number of approaches to measure muscle function and physical performance, clinicians often struggle to choose a tool that is appropriate and validated for the population of older people they deal with. In this paper, an overview of different methods available and applicable in clinical settings is proposed. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were organized afterwards where the whole group could amend and discuss the recommendations further. Several characteristics should be considered when choosing a tool: (1) purpose of the assessment (intervention, screening, diagnosis); (2) patient characteristics (population, settings, functional ability, etc.); (3) psychometric properties of the tool (test-retest reliability, inter-rater reliability, responsiveness, floor and ceiling effects, etc.); (4) applicability of the tool in clinical settings (overall cost, time required for the examination, level of training, equipment, patient acceptance, etc.); (5) prognostic reliability for relevant clinical outcomes. Based on these criteria and the available evidence, the expert group advises the use of grip strength to measure muscle strength and the use of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice. The tools proposed are relevant for the assessment of muscle weakness and physical performance. Subjects with low values should receive additional diagnostic workups to achieve a full diagnosis of the underlying condition responsible (sarcopenia, frailty or other).

Energy requirement and food intake behaviour in young adult intact male cats with and without predisposition to overweight.

Obesity is a common problem in cats. In the experimental cat family of the institute of animal nutrition besides a "normal" lean phenotype, cats with predisposition to an overweight phenotype are present. To investigate energy requirements and food intake behaviour of intact male cats of different phenotypes, six "normal" lean cats (GL) and six cats disposed to overweight (GO) were used. At the beginning of the experiment, all cats had an ideal body condition score of 5. To reach this the GO cats had to pass a weight-loss program. Energy requirements of the cats were determined using respiration chambers, whereas the amount and frequency of food intake was measured with a feeding station recording the data automatically. Energy requirement at weight constancy of the GO cats was even on fat-free mass (FFM) significantly (P = 0.02) lower (162.6 kJ/kg FFM/d) than that of the "normal" lean cats (246 kJ/kg FFM/d). The GO cats also showed a higher food intake 34.5 ± 1.5 g dry matter/kg body weight(0.67) compared to the GL cats (24.0 ± 2.1 g dry matter/kg body weight(0.67))(P = 0.001). In conclusion quantifiable differences in food intake and behaviour in cats predisposed to overweight compared to "normal" lean cats were found.

[Epidemiology and treatment of osteoporosis in men]. / Epidemiologie und Behandlung der Osteoporosebei Männern.

Osteoporosis is a disease characterized by an increased fragility of bone due to micro and macro structural changes of bone tissue and as a consequence a higher risk of fractures. Both women and men can be concerned by the problem, but in men a secondary origin is generally found with less fractures than in women, but with more morbidity. Both the diagnosis and the therapy are relatively similar in men as compared to women with postmenopausal osteoporosis. This paper is aimed at critically discussing the various differences in osteoporosis between men and women starting with some epidemiological considerations and ending with the therapeutical aspects.

Bone mineral density in young women on methadone substitution.

Little is known about bone mineral density (BMD) in patients with heroin addiction and subsequent methadone substitution. The goal of this study was to compare bone mass density of young HIV-negative women on long-term methadone treatment to a local group of young healthy women. Eleven women (aged 20-29) with previous heroin dependence and current methadone substitution (20-140 mg, median 60, daily) for 1.5-9 (median 3) years were compared to 30 healthy women (aged 20-28). Participants were examined with dual-energy X-ray absorptiometry of the lumbar spine (L2-L4), of the total proximal hip area, and of the femoral neck. Patients and controls had neither current nor lifetime underweight condition, had comparable ages at menarche, and did not differ significantly in current body mass index (21.9 ± 4.0, respectively, 20.5 ± 1.5 kg/m(2)) in spite of a largely unhealthy lifestyle (cigarette, alcohol, and cocaine consumption in patients). Patients' total-hip parameters were marginally lower than those of controls (BMD P = 0.054, T score P = 0.049), whereas the femoral neck and lumbar spine parameters did not differ significantly between the two groups. Long-term methadone substitution in HIV-negative women seems to slightly affect bone mass density.

Physical activity interventions to improve daily walking activity in cancer survivors.

BACKGROUND: Cancer patients may benefit from physical exercise programs. It is unclear, however, how sustained levels of physical activity are best achieved in this population. A systematic review was performed to summarize the current evidence of the effect of physical activity interventions on daily walking activity enhancement in cancer survivors, and to review the literature for its methodological quality. METHODS: A search in Medline, PEDro and the Cochrane databases was performed for English literature citations (randomized controlled trials; 'RCTs'). In a first step, one reviewer abstracted data from the included studies on patients, physical activity interventions and outcomes. Two independent reviewers reviewed the methodological quality of these studies. Data were pooled using random-effects calculations. RESULTS: Our search identified 201 citations. Five RCTs that reported changes in daily step activity over time were identified, and were reviewed for methodological quality and substantive results. The median score across studies for methodological quality based on the PEDro criteria was 8. These 5 RCTs evaluated 660 participants with a mean age of 53.6 (SD 4.2) years. The mean change in daily step activity for patients with a physical exercise intervention was 526 daily steps (SD 537), with a range from -92 to 1299 daily steps. The data of three studies reporting the effect of combined physical activity and counseling on daily walking activity in breast cancer survivors were pooled, however; the I(2) was 79%, indicating statistical heterogeneity between the three trials. CONCLUSION: The 5 RCTs reviewed were of good methodological quality. Together they suggest that combined physical activity and counseling improves daily step activity in (breast) cancer survivors. Studies that define a step goal appear to be more effective in improving daily walking activity than studies that do not do so. However, the current results should be interpreted with caution because of the observed clinical and statistical heterogeneity. Future studies are warranted to evaluate the effects of goal targeted physical activity, with or without counseling, on daily walking in various cancer populations.

A discrete-choice experiment to assess patients' preferences for osteoarthritis treatment: An ESCEO working group.

OBJECTIVE: To evaluate the preferences of patients with osteoarthritis for treatment. METHODS: A discrete-choice experiment was conducted among adult OA patients who were presented with 12 choice sets of two treatment options and asked in each to select the treatment they would prefer. Based on literature reviews, expert consultation, patient survey and expert meeting, treatment options were characterized by seven attributes: improvement in pain, improvement in walking, ability to manage domestic activities, ability to manage social activities, improvement in overall energy and well-being, risk of moderate/severe side effects and impact on disease progression. Random parameters logit model was used to estimate patients' preferences and a latent class model was conducted to explore preferences classes. RESULTS: 253 OA patients from seven European countries were included (74% women; mean age 71.3 years). For all seven treatment attributes, significant differences were observed between levels. Given the range of levels of each attribute, the most important treatment attribute in this group was impact on disease progression (29.5%) followed by walking improvement (17.1%) and pain improvement (16.3%). The latent class model identified two preference classes. In the first class (probability of 56%), patients valued impact of disease progression the most (39%). In the second class, walking improvement and improvement in overall energy and well-being were the most important (23%). CONCLUSION: This study suggests that all seven treatment attributes were important for OA patients. Overall, given the range of levels, the most important outcomes were impact on disease progression and improvement in pain and walking.

Compromising postural balance in the elderly.

BACKGROUND: Additional tasks that are assumed to disturb standing postural control can be divided in added motor or added cognitive tasks. It is unknown which type of task causes the most disturbances of postural control in elderly. OBJECTIVE: The aim of this study was to determine whether the dual tasking disturbance of postural control in elderly is caused by vocal articulation or by limited attentional resources. METHODS: 39 elderly (81 +/- 7 years) were tested on a force plate in a two-legged standing position. Seven balance variables were assessed: maximum displacement and standard deviation amplitude in the medial-lateral (ML, SDML) and anterior-posterior (AP, SDAP) direction, average speed of displacement (V) and the area of the 95th percentile ellipse (AoE) and sway path (PL) per given time. The following task combinations were tested: no secondary task, repeating a number aloud (articulation), counting backwards aloud (articulation and attention), and counting backwards silently (attention). All tasks were tested with and without vision. RESULTS: A factorial ANOVA revealed main effects of additional tasks in PL, ML, SDML, AP, AoE and V. Bonferroni post-hoc analysis in a vision situation showed significant difference between no task and counting backwards aloud task in balance variables ML (p = 0.006), SDML (p = 0.002), AP (p = 0.020) and V (p = 0.003), respectively. All no-vision situations showed no significant difference between the different tasks. CONCLUSION: The findings suggest that the combined articulation and attention-demanding secondary task stressed the attentional system of elderly to such an extent that it compromised the performance of the primary task (quiet standing). The counting backwards aloud task may be used as dual task for clinical balance assessment in at-risk populations. This task was best able to disturb postural control.

Reliability of ambulatory walking activity in patients with hematologic malignancies.

OBJECTIVES: To determine the relative and absolute reliability of the assessment of ambulatory walking activity during 2 consecutive weeks in patients with hematologic malignancies recovering at home from their medical treatment and to compare the physical activity level of hematologic cancer patients after high-dose chemotherapy with healthy subjects. DESIGN: Test-retest study of 2 consecutive 7-day recordings using the microprocessor-based step accelerometer 3 (SAM3). SETTING: Home and community. PARTICIPANTS: Patients (n=23) with hematologic malignancies recovering from high-dose chemotherapy and healthy controls (n=30). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The intraclass correlation coefficient (ICC(3,1)) and its 95% confidence interval (CI), SE of measurement procedure and its 95% CI, the smallest detectable difference (SDD), the coefficient of variation (CV), and t tests for the variables total steps and peak activity. RESULTS: The day-to-day and week-to-week CVs for walking activity and peak activity were 35.17% and 13.17% and 18.61% and 6.90%, respectively. For relative reliability, the ICCs for 2 consecutive 7-day recordings including the 95% CI for total steps and peak activity were 0.90 (95% CI, 0.75-0.98) and 0.85 (95% CI, 0.66-0.94), respectively. The absolute reliability for total steps and peak activity including the SE of measurement procedure and the 95% CI were 564 (95% CI, +/-1106) and 2.42 steps (95% CI, +/-4.74), respectively, for 2 consecutive 7-day recordings. The week-to-week SDD was 1564 for total steps and 6.70 for peak activity. The 7-day mean for total step activity was 5355 for the patients with hematologic malignancies and 6364 for healthy subjects (P<0.05). CONCLUSIONS: The results of this study indicate that there is good relative reliability for the assessment of 2 consecutive 7-day recordings of ambulatory walking activity, and it showed that the SDD derived from this sample may be useful in detecting changes in daily walking activity in hematologic cancer patients who are recovering from intensive medical treatment. The study also documented compromised levels of ambulatory walking activity among hematologic cancer patients recovering from high-dose chemotherapy as compared with healthy controls.

Hand-held dynamometry in patients with haematological malignancies: measurement error in the clinical assessment of knee extension strength.

BACKGROUND: Hand-held dynamometry is a portable and inexpensive method to quantify muscle strength. To determine if muscle strength has changed, an examiner must know what part of the difference between a patient's pre-treatment and post-treatment measurements is attributable to real change, and what part is due to measurement error. This study aimed to determine the relative and absolute reliability of intra and inter-observer strength measurements with a hand-held dynamometer (HHD). METHODS: Two observers performed maximum voluntary peak torque measurements (MVPT) for isometric knee extension in 24 patients with haematological malignancies. For each patient, the measurements were carried out on the same day. The main outcome measures were the intraclass correlation coefficient (ICC +/- 95%CI), the standard error of measurement (SEM), the smallest detectable difference (SDD), the relative values as % of the grand mean of the SEM and SDD, and the limits of agreement for the intra- and inter-observer '3 repetition average' and the 'highest value of 3 MVPT' knee extension strength measures. RESULTS: The intra-observer ICCs were 0.94 for the average of 3 MVPT (95%CI: 0.86-0.97) and 0.86 for the highest value of 3 MVPT (95%CI: 0.71-0.94). The ICCs for the inter-observer measurements were 0.89 for the average of 3 MVPT (95%CI: 0.75-0.95) and 0.77 for the highest value of 3 MVPT (95%CI: 0.54-0.90). The SEMs for the intra-observer measurements were 6.22 Nm (3.98% of the grand mean (GM) and 9.83 Nm (5.88% of GM). For the inter-observer measurements, the SEMs were 9.65 Nm (6.65% of GM) and 11.41 Nm (6.73% of GM). The SDDs for the generated parameters varied from 17.23 Nm (11.04% of GM) to 27.26 Nm (17.09% of GM) for intra-observer measurements, and 26.76 Nm (16.77% of GM) to 31.62 Nm (18.66% of GM) for inter-observer measurements, with similar results for the limits of agreement. CONCLUSION: The results indicate that there is acceptable relative reliability for evaluating knee strength with a HHD, while the measurement error observed was modest. The HHD may be useful in detecting changes in knee extension strength at the individual patient level.

Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say?

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recommended and prescribed to treat pain in osteoarthritis. While measured to have a moderate effect on pain in osteoarthritis, NSAIDs have been associated with wide-ranging adverse events affecting the gastrointestinal, cardiovascular, and renal systems. Gastrointestinal toxicity is found with all NSAIDs, which may be of particular concern when treating older patients with osteoarthritis, and gastric adverse events may be reduced by taking a concomitant gastroprotective agent, although intestinal adverse events are not ameliorated. Cardiovascular toxicity is associated with all NSAIDs to some extent and the degree of risk appears to be pharmacotherapy specific. An increased risk of acute myocardial infarction and heart failure is observed with all NSAIDs, while an elevated risk of hemorrhagic stroke appears to be restricted to the use of diclofenac and meloxicam. All NSAIDs have the potential to induce acute kidney injury, and patients with osteoarthritis with co-morbid conditions including hypertension, heart failure, and diabetes mellitus are at increased risk. Osteoarthritis is associated with excess mortality, which may be explained by reduced levels of physical activity owing to lower limb pain, presence of comorbid conditions, and the adverse effects of anti-osteoarthritis medications especially NSAIDs. This narrative review of recent literature identifies data on the safety of non-selective NSAIDs to better understand the risk:benefit of using NSAIDs to manage pain in osteoarthritis.

Recommendations for the Reporting of Harms in Manuscripts on Clinical Trials Assessing Osteoarthritis Drugs: A Consensus Statement from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

BACKGROUND: There is strong evidence of under-reporting of harms in manuscripts on randomized controlled trials (RCTs) compared with the volume of raw data retrieved from these trials. Many guidelines have been developed to tackle this, but they have failed to address some important issues that would allow for standardization and transparency. As a consequence, harms reporting in manuscripts remains suboptimal. OBJECTIVE: The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) aimed to deliver accurate recommendations for better reporting of harms in clinical trials manuscripts on anti-osteoarthritis (OA) drugs. These could help to better inform clinicians on harms recorded in RCTs and further help researchers conducting meta-analyses. METHODS: Using the outcomes of several systematic reviews on the safety of anti-OA drugs, we summarized the ways in which harms have been reported in OA RCT manuscripts to date. Next, we drafted some recommendations and initiated a modified Delphi process that involved a panel of clinicians and clinical researchers to build an expert consensus on recommendations from the ESCEO for the reporting of harms in future manuscripts on RCTs assessing anti-OA drugs. RESULTS: These recommendations emphasize that all treatment-emergent adverse events (AEs) should always be taken into account for harms reporting, with no frequency threshold, and describe how specific AEs should be reported; they also provide a list of the most relevant organ systems to be considered according to each class of drug for reporting of harms within the results section of a manuscript. Irrespective of the drug, the ESCEO recommends that total, severe and serious AEs and withdrawals due to AEs should always be reported; guidance on the reporting of specific events pertaining to each category is provided. The ESCEO also recommends the reporting of information on drug effect on biological parameters, with specific guidance. CONCLUSIONS: These recommendations may contribute to improve transparency in the field of safety of anti-OA medications. Pharmaceutical companies developing drugs for OA, and researchers conducting clinical trials, are encouraged to comply with them when reporting harms-related results in manuscripts on RCTs. The ESCEO also encourages journals to refer to the ESCEO recommendations in their instructions to authors for the publication of manuscripts on trials of anti-OA medications.

Safety of Opioids in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

OBJECTIVE: We aimed to assess the safety of opioids in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. METHODS: A comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with opioids in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal (GI) disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, renal and urinary disorders, respiratory, thoracic and mediastinal disorders, as well as overall severe and serious AEs and drug-related AEs. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once). RESULTS: Database searches identified 2189 records, from which, after exclusions, 17 papers were included in the meta-analysis. More disorders of the lower GI tract (constipation, fecaloma) were reported with both immediate-release (IR) and extended-release (ER) formulations of opioids versus placebo: IR opioids (relative risk [RR] 5.20, 95% confidence interval [CI] 3.42-7.89); ER opioids (RR 4.22, 95% CI 3.44-5.17). The risk of upper GI AEs increased fourfold with ER opioids compared with placebo (RR 4.03, 95% CI 0.87-18.62), and the risk of nausea, vomiting or loss of appetite increased four- to fivefold with both formulations: IR opioids (RR 3.39, 95% CI 2.22-5.18); ER opioids (RR 4.03, 95% CI 3.37-4.83). An increased risk of dermatologic AEs (rash and pruritis; IR opioids: RR 3.60, 95% CI 1.74-7.43; ER opioids: RR 7.87, 95% CI 5.20-11.89) and central nervous system disorders (dizziness, headache, fatigue, somnolence, insomnia; IR opioids: RR 2.76, 95% CI 1.90-4.02; ER opioids: RR 2.76, 95% CI 2.19-3.47) was found with all opioid formulations versus placebo. CONCLUSIONS: Our results confirm that there are considerable safety and tolerability issues surrounding the use of opioids in OA, and support the recommendation of international and national guidelines to use opioids in OA after other analgesic options, and for short time periods.

An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

OBJECTIVES: The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) sought to revisit the 2014 algorithm recommendations for knee osteoarthritis (OA), in light of recent efficacy and safety evidence, in order to develop an updated stepwise algorithm that provides practical guidance for the prescribing physician that is applicable in Europe and internationally. METHODS: Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process, a summary of evidence document for each intervention in OA was provided to all members of an ESCEO working group, who were required to evaluate and vote on the strength of recommendation for each intervention. Based on the evidence collected, and on the strength of recommendations afforded by consensus of the working group, the final algorithm was constructed. RESULTS: An algorithm for management of knee OA comprising a stepwise approach and incorporating consensus on 15 treatment recommendations was prepared by the ESCEO working group. Both "strong" and "weak" recommendations were afforded to different interventions. The algorithm highlights the continued importance of non-pharmacological interventions throughout the management of OA. Benefits and limitations of different pharmacological treatments are explored in this article, with particular emphasis on safety issues highlighted by recent literature analyses. CONCLUSIONS: The updated ESCEO stepwise algorithm, developed by consensus from clinical experts in OA and informed by available evidence for the benefits and harms of various treatments, provides practical, current guidance that will enable clinicians to deliver patient-centric care in OA practice.

Type 2 diabetes mellitus and osteoarthritis.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) are common diseases that frequently co-exist, along with overweight/obesity. While the mechanical impact of excess body weight on joints may explain lower limb OA, we sought to explore whether T2DM is linked to OA outside of excess weight and whether T2DM may play a role in OA pathophysiology. The consequence of T2DM on OA outcomes is a question of research interest. METHODS: We conducted a critical review of the literature to explore the association between T2DM and OA, whether any association is site-specific for OA, and whether the presence of T2DM impacts on OA outcomes. We also reviewed the literature to assess the safety of anti-OA treatments in patients with T2DM. RESULTS: T2DM has a pathogenic effect on OA through 2 major pathways involving oxidative stress and low-grade chronic inflammation resulting from chronic hyperglycemia and insulin resistance. T2DM is a risk factor for OA progression and has a negative impact on arthroplasty outcomes. Evidence is mounting for safety concerns with some of the most frequently prescribed anti-OA medications, including paracetamol, non-steroidal anti-inflammatory drugs, and corticosteroid injections, while other anti-OA medications may be safely prescribed in OA patients with T2DM, such as glucosamine and intra-articular hyaluronic acid. CONCLUSIONS: Future research is needed to better understand whether diabetes control and prevention can modulate OA occurrence and progression. The selection of therapy to treat OA symptoms in patients with T2DM may require careful consideration of the evidence based to avoid untoward safety issues.

DLX3 c.561_562delCT mutation causes attenuated phenotype of tricho-dento-osseous syndrome.

The distal-less homeobox gene DLX3 is expressed in a variety of tissues including placenta, skin, hair, teeth, and bone. Mutation of DLX3 (c.571_574delGGGG) causes the tricho-dento-osseous syndrome (TDO), characterized by abnormal hair, teeth, and bone. Evaluation of a kindred segregating the DLX3 c.561_562delCT mutation revealed distinct changes in the hair, teeth, and bones as has been observed with the DLX3 c.571_574delGGGG mutation. Previously, the DLX3 c.561_562delCT mutation was associated with autosomal dominant amelogenesis imperfecta with taurodontism. The present study shows that the DLX3 c.560_561delCT mutation causes an attenuated TDO phenotype with less severe hair, tooth, and bone manifestations compared with individuals having the DLX3 c.571_574delGGGG mutation. Careful phenotyping of individuals with allelic DLX3 mutations reveals marked differences in phenotypic severity indicating that the carboxy-terminus of the DLX3 protein is critical in determining its function during development in these different tissues.

The reliability of postural balance measures in single and dual tasking in elderly fallers and non-fallers.

BACKGROUND: The purpose of this study was to determine the reliability of a forceplate postural balance protocol in a group of elderly fallers and non-fallers. The measurements were tested in single and dual-task conditions, with and without vision. METHODS: 37 elderly (mean age 73 +/- 6 years) community-dwellers were included in this study. All were tested in a single (two-legged stance) and in a dual-task (two-legged stance while counting backwards aloud in steps of 7's) condition, with and without vision. A forceplate was used for registering postural variables: the maximal and the root-mean-square amplitude in medio-lateral (Max-ML, RMS-ML) and antero-posterior (Max-AP, RMS-AP) direction, mean velocity (MV), and the area of the 95% confidence ellipse (AoE). Reliability of the test protocol was expressed with intraclass correlation coefficients (ICC), with 95% limits of agreement (LoA), and with the smallest detectable difference (SDD). RESULTS: The ICCs for inter-rater reliability and test-retest reliability of the balance variables were r = 0.70-0.89. For the variables Max-AP and RMS-AP the ICCs were r = 0.52-0.74. The SDD values were for variable Max-ML and Max-AP between 0.37 cm and 0.83 cm, for MV between 0.48 cm/s and 1.2 cm/s and for AoE between 1.48 cm2 and 3.75 cm2. The LoA analysis by Bland-Altman plots showed no systematic differences between test-retest measurements. CONCLUSION: The study showed good reliability results for group assessment and no systematic errors of the measurement protocol in measuring postural balance in the elderly in a single-task and dual-task condition.

Guidelines for the conduct of pharmacological clinical trials in hand osteoarthritis: Consensus of a Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

OBJECTIVES: To gather expert opinion on the conduct of clinical trials that will facilitate regulatory review and approval of appropriate efficacious pharmacological treatments for hand osteoarthritis (OA), an area of high unmet clinical need. METHODS: The European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) organized a working group under the auspices of the International Osteoporosis Foundation (IOF) and the World Health Organization (WHO). RESULTS: This consensus guideline is intended to provide a reference tool for practice, and should allow for better standardization of the conduct of clinical trials in hand OA. Hand OA is a heterogeneous disease affecting different, and often multiple, joints of the thumb and fingers. It was recognized that the various phenotypes and limitations of diagnostic criteria may make the results of hand OA trials difficult to interpret. Nonetheless, practical recommendations for the conduct of clinical trials of both symptom and structure modifying drugs are outlined in this consensus statement, including guidance on study design, execution, and analysis. CONCLUSIONS: While the working group acknowledges that the methodology for performing clinical trials in hand OA will evolve as knowledge of the disease increases, it is hoped that this guidance will support the development of new pharmacological treatments targeting hand OA.

Does weight gain induce cortical and trabecular bone regain in anorexia nervosa? A two-year prospective study.

This prospective study examines bone density and structure over a two-year time period in women with anorexia nervosa (AN) under weight gain treatment. Twenty-four women with AN were examined at baseline and at two annual follow-up examinations. In 9 AN patients BMI increased whereas in 15 it remained unchanged or decreased. Dual energy X-ray absorptiometry (DXA) was performed on the lumbar spine, the femoral neck and the whole hip and three-dimensional peripheral quantitative computer tomography (3D-pQCT) was performed on the ultradistal radius. ANOVAs for repeated measures were used to examine change over time in BMI and bone parameters. At baseline, patients with increased BMI had significantly higher bone density of femoral neck and total hip, and higher levels in all 3D-pQCT parameters of the ultradistal radius, compared to the group with unchanged or decreased BMI. The two groups did not differ at baseline in bone density of the spine. ANOVAs showed that bone density of the total hip increased significantly and that overall bone density (D100), the density of the trabecular area (D.Trab.) and the cortical thickness (C.Th.) in the ultradistal radius decreased significantly. Group x time interactions showed that changes over time were different in the two groups with regard to spine density and in the parameters D100, D.Trab. and C.Th. of the ultradistal radius. In the group with increased BMI the spine density dropped at the first follow-up whereas at the second follow-up it rose again to baseline. Patients with unchanged or decreased BMI showed a small but steady increase in spine density. The group changes of D100, D.Trab. and C.Th. of the ultradistal radius all followed the same pattern. Bone mineral density at all locations measured with both technologies (DXA and 3D-pQCT) did not vary according to BMI changes. The course of bone density and structure at different locations was different, and, despite weight increase, bone regain appeared to need different time periods.