The Dutch multidisciplinary guideline osteoporosis and fracture prevention, taking a local guideline to the international arena.

BACKGROUND: In 2018, a grant was provided for an evidence-based guideline on osteoporosis and fracture prevention based on 10 clinically relevant questions. METHODS: A multidisciplinary working group was formed with delegates from Dutch scientific and professional societies, including representatives from the patient's organization and the Dutch Institute for Medical Knowledge. The purpose was to obtain a broad consensus among all participating societies to facilitate the implementation of the updated guideline. RESULTS: Novel recommendations in our guideline are as follows: - In patients with an indication for DXA of the lumbar spine and hips, there is also an indication for VFA. - Directly starting with anabolic drugs (teriparatide or romosozumab) in patients with a very high fracture risk; - Directly starting with zoledronic acid in patients 75 years and over with a hip fracture (independent of DXA); - Directly starting with parenteral drugs (denosumab, teriparatide, zoledronic acid) in glucocorticoid-induced osteoporosis with very high fracture risk; - A lifelong fracture risk management, including lifestyle, is indicated from the start of the first treatment. CONCLUSION: In our new multidisciplinary guideline osteoporosis and fracture prevention, we developed 5 "relatively new statements" that are all a crucial step forward in the optimization of diagnosis and treatment for fracture prevention. We also developed 5 flowcharts, and we suppose that this may be helpful for individual doctors and their patients in daily practice and may facilitate implementation.

Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review.

Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. BACKGROUND: Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. METHODS: Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). RESULTS: Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. CONCLUSION: Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved.

NT-proBNP and sRAGE levels in early rheumatoid arthritis.

OBJECTIVE: Several biomarkers of cardiovascular function are found to be increased in rheumatoid arthritis (RA), with some suggesting a relationship with disease activity and improvement with adequate anti-rheumatic treatment. Promising biomarkers include N-terminal pro-brain natriuretic peptide (NT-proBNP) and the soluble receptor form of advanced glycation end-products (sRAGE). The objective of this study was to investigate associations between NT-proBNP and sRAGE levels and markers of inflammation and disease activity in early RA patients and their changes during (effective) anti-rheumatic treatment. METHOD: Data from 342 consecutive early RA patients participating in the 'Parelsnoer' cohort were used. At baseline and after 6 months' disease activity, NT-proBNP and sRAGE levels were assessed. RESULTS: After 6 months, NT-proBNP decreased from 83 pmol/L (mean) at baseline to 69 pmol/L at follow-up (p < 0.001), while sRAGE increased from 997 pg/mL to 1125 pg/mL (p < 0.001). A larger decrease in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was associated with larger changes in NT-proBNP and sRAGE. For every point decrease in ESR, there was a 1.7-point decrease in NT-proBNP and a 2.2-point increase in sRAGE. For CRP, these values were 1.7 and 2.7, respectively (p < 0.001). CONCLUSION: Suppressing inflammation, independently of achieving remission, increases sRAGE levels and decreases NT-proBNP levels significantly. Whether this translates into a decrease in incident cardiovascular disease remains to be elucidated.

In RA patients without prevalent CVD, incident CVD is mainly associated with traditional risk factors: A 20-year follow-up in the CARRÉ cohort study.

OBJECTIVES: To extend our investigation of cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients to a follow up of more than 20 years, with a special focus on patients without prevalent CVD. METHODS: The CARRÉ study is an ongoing prospective cohort study on CV endpoints in RA patients. Results were compared to those of a reference cohort (n = 2484) enriched for type 2 diabetes mellitus (DM). Hazard ratios (HR) for RA and DM patients compared to non-RA/-DM controls were calculated with cox proportional hazard models, and adjusted for baseline SCORE1 (estimated 10-year CVD mortality risk based on CV risk factors). RESULTS: 238 RA patients, 117 DM patients and 1282 controls, without prevalent CVD at baseline were included. Analysis of events in these patients shows that after adjustment, no relevant 'RA-specific' risk remains (HR 1.16; 95%CI 0.88 - 1.53), whereas a 'DM-specific' risk is retained (1.73; 1.24 - 2.42). In contrast, adjusted analyses of all cases confirm the presence of an 'RA-specific' risk (1.50; 1.19 - 1.89). CONCLUSIONS: In RA patients without prevalent CVD the increased CVD risk is mainly attributable to increased presence of traditional risk factors. After adjustment for these factors, an increased risk attributable to RA only was thus preferentially seen in the patients with prevalent CVD at baseline. As RA treatment has improved, this data suggests that the 'RA-specific' effect of inflammation is preferentially seen in patients with prevalent CVD. We suggest that with modern (early) treatment of RA, most of the current increased CVD risk is mediated through traditional risk factors.

Cost-effectiveness and cost-utility of add-on, low-dose prednisolone in patients with rheumatoid arthritis aged 65+: The pragmatic, multicenter, placebo-controlled GLORIA trial.

BACKGROUND: The GLORIA placebo-controlled trial found a favorable balance of benefit and harm for two years of prednisolone (5 mg/day) as add-on treatment for rheumatoid arthritis (RA) patients aged 65+. This study evaluated the cost-effectiveness of low-dose prednisolone in the treatment of RA. METHODS: The economic evaluation had a societal perspective with a time horizon of two years. Cost data were collected with questionnaires and from recorded events, and valued with standard Dutch unit prices of 2017. The primary effectiveness outcome was the disease activity score in 28 joints (DAS28). For cost-utility, quality-adjusted life years (QALYs) were estimated from the EuroQol-5 Dimension (EQ-5D) questionnaire. Bootstrapping assessed the uncertainty around the average differences in costs and health outcomes. RESULTS: In total, 444 of 451 randomized patients were included in the modified intention-to-treat analysis. Patients had median four active comorbidities at baseline. Mean total costs over two years were k€10.8 in the prednisolone group, k€0.5 (95% CI -4.0; 1.8) lower than in the placebo group. Total direct medical costs were k€0.5 (95% CI -4.0; 1.5) lower in the prednisolone group. The mean number of QALYs was similar in both groups (difference 0.02 [-0.03; 0.06] in favor of prednisolone). The DAS28 was 0.38 lower in the prednisolone group than in the placebo group (0.19; 0.56). CONCLUSION: With greater effectiveness (DAS28) at non-significantly lower costs, low-dose, add-on prednisolone is cost-effective for RA compared to placebo over two years. QALYs were equal in both groups, most likely due to the impact of multiple comorbidities.

Exercise intervention on cardiorespiratory fitness in rheumatoid arthritis patients with high cardiovascular disease risk: a single-arm pilot study.

OBJECTIVE: In patients with rheumatoid arthritis (RA) with cardiovascular disease risk, it is unknown whether exercises are safe, improve cardiorespiratory fitness and reduce disease-related symptoms and cardiovascular-disease (CVD) risk factors. We aimed to investigate in RA patients with CVD risk: (1) safety of medium to high-intensity aerobic exercises, (2) potential changes of cardiorespiratory fitness and (3) disease activity and CVD risk factors in response to the exercises. METHODS: Single-arm pilot-exercise intervention study including 26 consecutive patients (21 women) with > 4% 10-year risk of CVD mortality according to the Dutch Systematic Coronary Risk Evaluation. Aerobic exercises consisted of two supervised-sessions and five home-sessions per week for 12 weeks. Patients were required to exercise at intensities between 65 and 85% of their maximum heart rate. To assess safety, we recorded exercise related adverse events. Before and after the exercises, cardiorespiratory fitness was assessed with a graded maximal oxygen-uptake exercise test, while disease activity was evaluated via the Disease Activity Score-28 (DAS28) using the erythrocyte segmentation rate (ESR). Resting blood pressure, ESR and total cholesterol were assessed as CVD risk factors. RESULTS: Twenty out of 26 patients performed the 12-week exercises without any adverse events. According to patients, withdrawals were unrelated to the exercises. Exercises increased cardiorespiratory fitness (pre: 15.91 vs. post: 18.15 ml.kg-1 min-1, p = 0.003) and decreased DAS28 (pre: 2.86 vs. post: 2.47, p = 0.04). No changes were detected in CVD risk factors. CONCLUSION: A 12-week exercise intervention seems to be safe and improves cardiorespiratory fitness and disease activity in patients with RA with a high risk for cardiovascular diseases. Key Points 1. Rheumatoid arthritis patients with high cardiovascular disease risk were able to perform a maximum exercise test and a 12-week aerobic-based medium-to-high intensity exercise intervention. 2. The exercise intervention improved cardiorespiratory fitness and disease activity in rheumatoid arthritis patients with high cardiovascular disease risk. 3. Cardiorespiratory fitness levels were still low post-exercise intervention (i.e. 18.15 ml.kg-1min-1 compared to the 20.9 ml.kg-1min-1 baseline mean of the RA patients without CVD risk).

The Effect of Anti-rheumatic Drugs on the Skeleton.

The therapeutic armamentarium for rheumatoid arthritis has increased substantially over the last 20 years. Historically antirheumatic treatment was started late in the disease course and frequently included prolonged high-dose glucocorticoid treatment which was associated with accelerated generalised bone loss and increased vertebral and non-vertebral fracture risk. Newer biologic and targeted synthetic treatments and a combination of conventional synthetic DMARDs prevent accelerated systemic bone loss and may even allow repair of cortical bone erosions. Emerging data also gives new insight on the impact of long-term conventional synthetic DMARDs on bone health and fracture risk and highlights the need for ongoing studies for better understanding of "established therapeutics". An interesting new antirheumatic treatment effect is the potential of erosion repair with the use of biologic DMARDs and janus kinase inhibitors. Although several newer anti-rheumatic drugs seem to have favorable effects on bone mineral density in RA patients, these effects are modest and do not seem to influence the fracture risk thus far. We summarize recent developments and findings of the impact of anti-rheumatic treatments on localized and systemic bone integrity and health.

How does hip osteoarthritis differ from knee osteoarthritis?

Hip and knee osteoarthritis (OA) are leading causes of global disability. Most research to date has focused on the knee, with results often extrapolated to the hip, and this extends to treatment recommendations in clinical guidelines. Extrapolating results from research on knee OA may limit our understanding of disease characteristics specific to hip OA, thereby constraining development and implementation of effective treatments. This review highlights differences between hip and knee OA with respect to prevalence, prognosis, epigenetics, pathophysiology, anatomical and biomechanical factors, clinical presentation, pain and non-surgical treatment recommendations and management.

Patient perspective on remission in rheumatoid arthritis: Validation of patient reported outcome instruments to measure absence of disease activity.

OBJECTIVE: Patients have identified pain, fatigue and independence as the most important domains that need to be improved to define remission in rheumatoid arthritis (RA). This study identified and validated instruments for these domains and evaluated their added value to the ACR/EULAR Boolean remission definition. METHODS: Patients with a 28-joint Disease Activity Score (DAS28) ≤3.2 or in self-perceived remission (declaring their disease activity 'as good as gone') from the Netherlands, Portugal, Australia, and Canada, were assessed at 0, 3 and 6 months for patient-reported outcomes and the WHO-ILAR RA core set. Instrument validity was evaluated cross-sectionally, longitudinally and for the ability to predict future good outcome in terms of physical functioning. Logistic regression quantified the added value to Boolean remission. RESULTS: Of 246 patients, 152 were also assessed at 3, and 142 at 6 months. Most instruments demonstrated construct validity and discriminative capacity. Pain and fatigue were best captured by a simple numerical rating scale (NRS). Measurement of independence proved more complex, but a newly developed independence NRS was preferred. NRS for pain, fatigue and independence, in addition to or instead of patient global assessment did not add enough information to justify modification of the current Boolean definition of remission in RA. CONCLUSION: Key elements of the patient perspective on remission in RA can be captured by NRS pain, fatigue, and independence. Although this study did not find conclusive evidence to improve the current definition of remission in RA, the information from these instruments adds value to the physician's assessment of remission and further bridges the gap between physician and patient.

Cardiorespiratory fitness and physical activity in people who have rheumatoid arthritis at an increased risk of cardiovascular disease: a cross-sectional study.

Lower cardiorespiratory fitness (CRF) and physical activity (PA) associate with higher cardiovascular disease (CVD) risk, but the relationship between CRF and PA in people who have rheumatoid arthritis (RA) at an increased CVD risk (CVD-RA) is not known. The objectives of this study were to determine the levels of CRF and PA in people who have CVD-RA and to investigate the association of CRF with PA in people who have CVD-RA. A total of 24 consecutive patients (19 women) with CVD-RA (> 4% for 10-year risk of fatal CVD development as calculated using the Systematic Coronary Risk Evaluation)-were included in the study. CRF was assessed with a graded maximal exercise test determining maximal oxygen uptake (VO2max). PA was assessed with an accelerometer to determine the amount of step count, sedentary, light and moderate-to-vigorous physical activity (MVPA) minutes per day. Mean age of patients was 65.3 ± 8.3 years. CRF mean values were 16.3 ± 1.2 ml·kg-1 min-1, mean step count per day was 6033 ± 2256, and the mean MVPA time was 16.7 min per day. Significant positive associations were found for CRF with step count (B = 0.001, P = 0.01) and MVPA time (B = 0.15, P = 0.02); a negative association was found for CRF with sedentary time (B = - 0.02, P = 0.03). CRF is low and is associated with step count, sedentary time and MVPA time in people who have RA at an increased CVD risk.

Accuracy of an algorithm to identify rheumatoid arthritis in the Longitudinal Ageing Study Amsterdam population: a validation study.

Objective: In view of global ageing and the scarcity of knowledge about disease determinants in older individuals with rheumatoid arthritis (RA), an algorithm with optimal diagnostic accuracy was developed to identify RA patients in the Longitudinal Ageing Study Amsterdam (LASA).Method: Four case ascertainment algorithms were constructed and assessed for validity in LASA, an ongoing cohort study (≥ 55 years) representing the general older population of the Netherlands. Data sources used to identify the diagnosis RA were: self-reported morbidity, specialist diagnosis, and medication. A validation subsample of LASA participants was taken to verify RA diagnosis by a standard procedure using a checklist.Results: Data from 272/300 (91%) participants were verified. Four algorithms were developed: 'treatment', 'diagnosis', 'treatment or diagnosis', and 'treatment and diagnosis'. The algorithm 'treatment and diagnosis' showed the best measurement properties: specificity 100%, positive predictive value 100%, and area under the receiver operating characteristics curve 0.72. Applying this algorithm in the LASA sample (mean age 71 years) revealed a prevalence of RA of 1.0% (19/1908 participants).Conclusion: An algorithm for RA identification in the LASA population was developed, with high diagnostic accuracy. It provides an accurate tool to identify older adults with RA in LASA and, after validation, may be applicable in other large population-based studies.

Vertebral fracture: epidemiology, impact and use of DXA vertebral fracture assessment in fracture liaison services.

Vertebral fractures are independent risk factors for vertebral and nonvertebral fractures. Since vertebral fractures are often missed, the relatively new introduction of vertebral fracture assessment (VFA) for imaging of the lateral spine during DXA-measurement of the spine and hips may contribute to detect vertebral fractures. We advocate performing a VFA in all patients with a recent fracture visiting a fracture liaison service (FLS). Fracture liaison services (FLS) are important service models for delivering secondary fracture prevention for older adults presenting with a fragility fracture. While commonly age, clinical risk factors (including fracture site and number of prior fracture) and BMD play a crucial role in determining fracture risk and indications for treatment with antiosteoporosis medications, prevalent vertebral fractures usually remain undetected. However, vertebral fractures are important independent risk factors for future vertebral and nonvertebral fractures. A development of the DXA technology, vertebral fracture assessment (VFA), allows for assessment of the lateral spine during the regular DXA bone mineral density measurement of the lumbar spine and hips. Recent approaches to the stratification of antiosteoporosis medication type according to baseline fracture risk, and differences by age in the indication for treatment by prior fracture mean that additional information from VFA may influence initiation and type of treatment. Furthermore, knowledge of baseline vertebral fractures allows reliable definition of incident vertebral fracture events during treatment, which may modify the approach to therapy. In this manuscript, we will discuss the epidemiology and clinical significance of vertebral fractures, the different methods of detecting vertebral fractures, and the rationale for, and implications of, use of VFA routinely in FLS. • Vertebral fracture assessment is a tool available on modern DXA instruments and has proven ability to detect vertebral fractures, the majority of which occur without a fall and without the signs and symptoms of an acute fracture. • Most osteoporosis guidelines internationally suggest that treatment with antiosteoporosis medications should be considered for older individuals (e.g., 65 years +) with a recent low trauma fracture without the need for DXA. • Younger individuals postfracture may be risk-assessed on the basis of FRAX® probability including DXA and associated treatment thresholds. • Future fracture risk is markedly influenced by both site, number, severity, and recency of prior fracture; awareness of baseline vertebral fractures facilitates definition of true incident vertebral fracture events occurring during antiosteoporosis treatment. • Detection of previously clinically silent vertebral fractures, defining site of prior fracture, might alter treatment decisions in younger or older FLS patients, consistent with recent IOF-ESCEO guidance on baseline-risk-stratified therapy, and provides a reliable baseline from which to define new, potentially therapy-altering, vertebral fracture events.

Long-term effects on bone mineral density after four years of treatment with two intensive combination strategies, including initially high-dose prednisolone, in early rheumatoid arthritis patients: the COBRA-light trial.

In this study, no difference in bone loss was observed between patients with early RA initially treated with COmbinatietherapie Bij Reumatoide Artritis (COBRA) (including initially 60 mg/day prednisolone) and patients treated with COBRA-light (including initially 30 mg/day prednisolone) during 4-year observation. PURPOSE: To assess changes in bone mineral density (BMD) after 4 years in early rheumatoid arthritis (RA) patients initially treated with COBRA-light or COBRA therapy. METHODS: In a 1 year, open-label, randomised, non-inferiority trial, patients were assigned to COBRA-light (methotrexate 25 mg/week plus initially prednisolone 30 mg/day) or COBRA (methotrexate 7.5 mg/week, sulfasalazine 2 g/day plus initially prednisolone 60 mg/day) therapy. After 1 year, antirheumatic treatment was at the discretion of treating rheumatologists. BMD was measured at baseline and after 1, 2 and 4 years at hips and lumbar spine with dual-energy X-ray absorptiometry. BMD changes between treatment strategies on average over time were compared with GEE analysis. RESULTS: Data from 155 out of 162 patients could be analysed: 68% were female with a mean age of 52 (SD 13) years. Both COBRA-light and COBRA therapy showed declines in BMD at the total hip of -3.3% and -1.7%, respectively (p = 0.12), and the femoral neck, -3.7% and -3.0%, respectively (p = 0.95). At the lumbar spine, both treatment groups showed minor decline in BMD over 4 years: -0.5% and -1.0%, respectively (p = 0.10). CONCLUSION: In a treat-to-target design in early RA, over 4 years, no differences between groups were found in change in BMD at total hip, femoral neck and the lumbar spine. At the hip, bone loss was around 3% in both groups, while mild bone loss was observed at lumbar spine, both in patients starting prednisolone 60 and 30 mg/day. These data suggest that the well-known negative effects of prednisolone can be modulated by modern treatment of RA.

Determinants of pain and activity limitations in foot osteoarthritis: An exploratory cross-sectional study in the Amsterdam-foot cohort.

Objectives: Osteoarthritis (OA) of the foot-ankle complex is understudied. Understanding determinants of pain and activity limitations is necessary to improve management of foot OA. The aim of the present study was to investigate demographic, foot-specific and comorbidity-related factors associated with pain and activity limitations in patients with foot OA. Methods: This exploratory cross-sectional study included 75 patients with OA of the foot and/or ankle joints. Demographic and clinical data were collected with questionnaires and by clinical examination. The outcome variables of pain and activity limitations were measured using the Foot Function Index (FFI). Potential determinants were categorized into demographic factors (e.g., age, sex), foot-specific factors (e.g., plantar pressure and gait parameters), and comorbidity-related factors (e.g., type and amount of comorbid diseases). Multivariable regression analyses with backward selection (p-out≥0.05) were performed in two steps, leading to a final model. Results: Of all potential determinants, nine factors were selected in the first step. Five of these factors were retained in the second step (final model): female sex, pain located in the hindfoot, higher body mass index (BMI), neurological comorbidity, and Hospital Anxiety and Depression Scale (HADS) score were positively associated with the FFI score. The explained variance (R 2 ) for the final model was 0.580 (adjusted R 2  â€‹= â€‹0.549). Conclusion: Female sex, pain located in the hindfoot, higher BMI, neurological comorbidity and greater psychological distress were independently associated with a higher level of foot-related pain and activity limitations. By addressing these factors in the management of foot OA, pain and activity limitations may be reduced.

Is a treat-to-target strategy in osteoporosis applicable in clinical practice? Consensus among a panel of European experts.

A panel of European experts was convened to establish consensus on a treat-to-target strategy in osteoporosis. Panellists agreed that the ultimate goals of treating osteoporosis are recovering pre-fracture functional level and reducing subsequent fracture risk; there was consensus that total hip bone mineral density is currently the most appropriate treatment target in clinical practice. INTRODUCTION: A modified Delphi approach was convened to establish consensus among European experts on best practice management for patients with fragility fractures and whether a treat-to-target (T2T) strategy is applicable in osteoporosis. METHODS: A panel of 12 clinical experts (from eight European countries) voted on 13 final statements relating to a T2T strategy for osteoporosis across three rounds of blinded, remotely conducted electronic surveys (Likert scale: 'strongly disagree', 'disagree', 'unable to answer', 'agree', 'strongly agree'). When panellists disagreed, they were asked how the statement could be adjusted to allow for a positive response, which was used to refine the statement for the following round. Consensus was defined as ≥ 75% agreement with a statement. Panellists were selected by UCB Pharma, which provided financial and logistical support. RESULTS: Consensus was reached for 13/13 statements. Panellists agreed that the most important goals for fragility fracture patients are recovery of pre-fracture functional level and reduction of subsequent fracture risk. There was also consensus that a T2T strategy is applicable to osteoporosis and that bone mineral density (BMD) is currently the most clinically appropriate target. With regard to the definition of a specific BMD treatment target and timeframes applicable to T2T in osteoporosis, no clear consensus was reached; panellists emphasised that these would need to be individually determined. CONCLUSIONS: According to a panel of European experts, the main goals of fracture management are to recover pre-fracture functional level and reduce fracture risk. Total hip BMD seems to be the most clinically appropriate treatment target within a T2T strategy.

A patient-level key performance indicator set to measure the effectiveness of fracture liaison services and guide quality improvement: a position paper of the IOF Capture the Fracture Working Group, National Osteoporosis Foundation and Fragility Fracture Network.

The International Osteoporosis Foundation (IOF) Capture the Fracture® Campaign with the Fragility Fracture Network (FFN) and National Osteoporosis Foundation (NOF) has developed eleven patient-level key performance indicators (KPIs) for fracture liaison services (FLSs) to guide quality improvement. INTRODUCTION: Fracture Liaison Services (FLSs) are recommended worldwide to reduce fracture risk after a sentinel fracture. Given not every FLS is automatically effective, the IOF Capture the Fracture working group has developed and implemented the Best Practice Framework to assess the organisational components of an FLS. We have now developed a complimentary KPI set that extends this assessment of performance to the patient level. METHODS: The Capture the Fracture working group in collaboration with the Fragility Fracture Network Secondary Fragility Fracture Special Interest Group and National Osteoporosis Foundation adapted existing metrics from the UK-based Fracture Liaison Service Database Audit to develop a patient-level KPI set for FLSs. RESULTS: Eleven KPIs were selected. The proportion of patients: with non-spinal fractures; with spine fractures (detected clinically and radiologically); assessed for fracture risk within 12 weeks of sentinel fracture; having DXA assessment within 12 weeks of sentinel fracture; having falls risk assessment; recommended anti-osteoporosis medication; commenced of strength and balance exercise intervention within 16 weeks of sentinel fracture; monitored within 16 weeks of sentinel fracture; started anti-osteoporosis medication within 16 weeks of sentinel fracture; prescribed anti-osteoporosis medication 52 weeks after sentinel fracture. The final KPI measures data completeness for each of the other KPIs. For these indicators, levels of achievement were set at the < 50%, 50-80% and > 80% levels except for treatment recommendation where a level of 50% was used. CONCLUSION: This KPI set compliments the existing Best Practice Framework to support FLSs to examine their own performance using patient-level data. By using this KPI set for local quality improvement cycles, FLSs will be able to efficiently realise the full potential of secondary fracture prevention and improved clinical outcomes for their local populations.

Alternative and complementary therapies in osteoarthritis and cartilage repair.

Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of 'alternative' therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects.

The Clinical Relevance of Hyperkyphosis: A Narrative Review.

The kyphosis angle of the thoracic spine tends to increase with aging. Hyperkyphosis is a kyphosis angle, exceeding the normal range. This narrative literature review aims to provide an overview of the current literature concerning kyphosis measurement methods, the etiology and adverse health effects of hyperkyphosis. As of yet, a well-defined threshold for hyperkyphosis is lacking. To attain more generalizability and to be able to compare study results in older adults, we propose to define age-related hyperkyphosis as a Cobb angle of 50° or more in standing position. Hyperkyphosis may be a potentially modifiable risk factor for adverse health outcomes, like fall risk and fractures. Additionally, hyperkyphosis may indicate the presence of osteoporosis, which is treatable. Prospective and intervention studies, using a Cobb angle of 50° as a clear and uniform definition of hyperkyphosis, are warranted to investigate the clinical relevance of hyperkyphosis.

Course and predictors of upper leg muscle strength over 48 months in subjects with knee osteoarthritis: Data from the osteoarthritis initiative.

Objectives: Weakness of upper leg muscles has a negative impact on future disease and functional status in subjects with knee osteoarthritis (OA). The aims of the present study were to (i) describe the course of muscle strength over 48 months and (ii) identify baseline predictors for a decline in upper leg muscle strength over time in subjects with knee OA. Methods: Data were obtained from the Osteoarthritis Initiative (OAI) database, a multicenter, observational study of knee OA. Upper leg muscle strength (in N/kg) was measured at baseline, 24 and 48 months. Potential baseline predictors included demographics, OA-specific and health and lifestyle related factors. Linear mixed model analyses were performed. Results: A total of 1390 subjects with knee osteoarthritis were included. A statistically significant decline of muscle strength was found between baseline and 24 months (B = -0.186, 95%CI [-0.358,-0.014], p = 0.03), but not between other time points (24-48 months p = 0.89, and baseline and 48 months p = 0.058). Predictors of a decline in muscle strength over time included demographic predictors (older age, being female, higher body mass index (BMI)), one lifestyle predictor (lower dietary protein intake) and one OA-specific predictor (radiographic severity). Conclusions: Muscle strength declined over time in subjects with knee OA. The identified predictors may help clinicians to select and treat subjects with knee OA at risk of a decline in muscle strength.