Background Few data are available on the incidence of osteoporosis (OP) in end-stage pulmonary diseases, particularly in lung transplant candidates. Yet, organ transplantation can be accompanied by low bone mineral density (BMD) owing to immunosuppressive therapy, particularly with oral glucocorticoids (GCs) use. Objectives Our primary aim was to evaluate the prevalence and therapeutic management of OP in lung transplant candidates. Our second objective was to determine the risk factors associated with OP, including the type of respiratory disorder. Methods We included 198 patients (103 women) out of 388 screened for lung transplantation at our institution between January 1998 and December 2020. BMD, measured by Dual-energy X-ray absorptiometry (DXA, Hologic (t-m)) at the lumbar spine (LS), total hip (TH), and femoral neck (FN), vertebral fracture assessment (VFA), as well as previous major osteoporotic fracture (MOF), were recorded. We systematically collected well-recognized OP risk factors, along with other factors suspected of affecting BMD such as inhaled (i) GCs use, pulmonary function tests, hypoxemia and type of pulmonary disorder. Results OP, as defined by BMD values (T-score ≤ -2.5) and/or fragility fracture (FF), MOF and/or vertebral fractures (VF), was observed in 118 patients (59.6%). Among these patients, 54 (45.8%) had only a T-score ≤ -2.5, while 36 (30.5%) had only an FF, with predominant vertebral fractures (77.8%). The median age (IQR) of the study population was 58 years (53.0-62.0), and 59 years in OP patients (54.2-62.0). Mean T-scores (±SD) were -1.62±1.52 at the LS, -1.43±1.05 at the TH and -1.98±1.14 at the FN. Mean T-scores (±SD) in OP patients were -2.15±1.31, -1.87±0.93 and -2.44±1.03, respectively. The mean (±SD) ten-year probability of major osteoporotic fracture assessed by the FRAX algorithms (FRAX score) was 11.6±11.2 %, and the mean FRAX adjusted to GCs dose (±SD) was 12.0±12.1 %. Nighty-eight patients (49.5%) achieved intervention threshold adjusted for age based on FRAX results and 110 patients (55.6%) when FRAX was adjusted to GCs dose. Seventy-eight OP patients (66.1%) achieved the FRAX intervention threshold, of whom 53 (67.9%) received calcium and/or vitamin D and 33 (42.3%) had received an add-on therapy, mostly a bisphosphonate (n=23, 69.7%) or denosumab (n=4, 12.1%). Eighty-four OP patients (71.2%) achieved the FRAX intervention threshold adjusted to GCs dose, of whom 59 (70.2%) received calcium and/or vitamin D and 37 (44.5%) had received an add-on therapy, mostly a bisphosphonate (n=25, 67.6%) or denosumab (n=5, 13.5%). Thirty-six OP patients (30.5%), 18 patients (33.3%) with only a T-score ≤ -2.5 and 12 patients with only an FF, did not receive any medication. In total, 153 patients had a chronic obstructive pulmonary disease (COPD, 77.3%), 33 an interstitial lung disease (ILD, 16.3%) and 12 (6.1%) suffered from another pulmonary disease. Among OP patients, 102 had a COPD (86.4%), 12 an ILD (10.2%) and 4 (3.4%) suffered from another pulmonary disease. Lower BMI, iGCs use, COPD, reduced FVC and severely impaired FEV1/FVC ratio were associated with OP. GCs treatment was associated with FF, regardless of the daily dosage. Conclusion Most of lung transplant candidates were suffering from OP and one third suffered from FF. Thus, performing DXA and VFA should be recommended in lung transplant candidates in order to start adequate osteoporosis treatment before lung transplantation. This is even more important in COPD patients, as this population displays an increased risk of OP compared to other end-stage diseases. OP diagnosis is important in those patients as their risk of fracture is likely to increase after transplantation. The large proportion of untreated (or insufficiently treated) patients stressed the need to develop specific strategies in this field. Finally, controlling some risk factors is crucial for the management and prevention of OP, for instance by, at least, tapering the dosage of both oral and inhaled GCs. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Edwin Curraj: None declared, François Carlier: None declared, Michel Dumonceaux: None declared, Patrick Evrard: None declared, Benoit Rondelet: None declared, Jean-Pierre Devogelaer: None declared, Yves Boutsen Speakers bureau: UCB, Grant/research support from: Viatris, Galapagos, Biogen, Amgen.

The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state of the art on the use of these biomarkers in different clinical or physiological situations like in postmenopausal women, osteoporosis in men, in elderly patients, in patients suffering from bone metastasis, in patients with chronic renal failure, in pregnant or lactating women, in intensive care patients, and in diabetics. We also gave our considerations on the analytical issues linked to the use of these biomarkers, on potential new emerging biomarkers, and on the use of bone turnover biomarkers in the follow-up of patients treated with new drugs for osteoporosis.

RADIOLOGIE ET IMAGERIE MEDICALE : Musculosquelettique - Neurologique - Maxillofaciale - 31-360-A-10

Objective: The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA).Design: Areas of potential attention were identified and the need for modifications, update or clarification was examined. Proposals were then developed based on literature reviews and through a consensus process.Results: It was agreed that the current guideline overall still reflects the current knowledge in OA, although two possible modifications were identified. The first relates to the number and timing of measurements required as primary endpoints during clinical trials of symptom-relieving drugs, either drugs with rapid onset of action or slow acting drugs. The suggested modifications are intended to take into consideration the time related clinical need and expected time response to these drugs - i.e., a more early effect for the first category in addition to the maintenance of effect, a more continuous benefit over the long-term for the latter - in the timing of assessments. Secondly, values above which a benefit over placebo should be considered clinically relevant were considered. Based on literature reviews, the most consensual values were determined for primary endpoints of both symptom-relieving drugs (i.e., pain intensity on a visual analogue scale (VAS)) and disease-modifying drugs (i.e., radiographic joint-space narrowing).Conclusions: This working document might be considered by the European regulatory authorities in a future update of the guideline for the registration of drugs in OA. (C) 2015 The Authors. Published by Elsevier Ltd and Osteoarthritis Research Society International.

Despite the proven predictive ability of bone mineral density, Fracture Risk Assessment Tool (FRAX®), bone turnover markers, and fracture for osteoporotic fracture, their use as targets for treatment of osteoporosis is limited.

Purpose: In SEKOIA study, strontium ranelate 2g/day (SrRan) has shown structure-modifying activity associated with statistically significant symptomatic improvement compared to placebo in patients with knee osteoarthritis (OA). The purpose of this analysis was to determine the proportion of patients considered as symptomatic responders as per WOMAC pain sub-score or pain VAS improvement and OMERACT-OARSI-like responders, as well as the number of patients reaching MPCI (Minimal Perceptible Clinical Improvement) and MCII (Minimal Clinical Important Improvement). Methods: SEKOIA study was a double-blind, placebo-controlled, randomized, international 3-year study aiming to demonstrate the effects of strontium ranelate on the radiographic progression of knee osteoarthritis. It included men and women over 50 years old, with symptomatic primary knee OA (at least 40 on a 100 mm visual analog scale (VAS) on most days of the previous month, Kellgren and Lawrence [KL] grade 2 or 3, and joint space width [JSW] 2.5-5 mm). Symptoms were assessed every 6 months over 3 years using the WOMAC questionnaire and a 100 mm VAS. Proportions of patients with an improvement of at least 20% or 50% from baseline of their WOMAC pain sub-score or pain VAS, proportion of OMERACT-OARSI-like responders (calculated using improvement in pain and function but not patient's global assessment as it was not assessed in this study) and percentages of patients reaching MPCI or MCII published values, were compared between groups using a chi2 test. Results: The ITT population included 1371 (82%) patients presenting at baseline, mean ± SD, an age of 63±7 years, BMI of 30±5 kg/m2, VAS of 54±22 mm, and WOMAC of 132±62 mm. 61% were KL grade II and 69% were female. Over 3 years, a greater percentage of patients treated with SrRan 2g were considered as symptomatic responders compared to placebo:Tabled 1Placebo (N = 472) n (%)SrRan 2 g (N = 454) n (%)Difference relative to placebo [95% CI]p-valueWOMACResponders 20%297 (64.0)317 (72.0)8.0 [2.0 ; 14.1]0.010Responders 50%208 (44.8)223 (50.7)5.9 [-0.7 ; 12.4]0.078WOMAC Pain subscorePatients above MPCI threshold (9.7mm)255 (55)289 (65.5)10.6 [4.2 ; 16.9]0.001WOMAC Stiffness subscorePatients above MPCI threshold (10mm)247 (52.8)270 (60.1)7.4 [0.9 ; 13.8]0.025WOMAC Physical function subscorePatients above MPCI threshold (9.3mm)229 (49.1)257 (57.9)8.7 [2.3 ; 15.2]0.008Patients above MCII threshold (-9.1mm)231 (49.6)257 (57.9)8.3 [1.9 ; 14.8]0.012Knee pain by VASResponders 20%325 (69.7)336 (76.0)6.3 [0.5 ; 12.0]0.034Responders 50%249 (53.4)263 (59.5)6.1 [-0.4 ; 12.5]0.065Patients above MCII threshold (-19.9mm)277 (59.4)302 (67.7)8.3 [2.1; 14.5]0.010OMERACT-OARSI-like responders221 (47.0)244 (54.0)7.0 [0.5 ; 13.4]0.035MPCI responders were statistically significantly greater from M18 (pain and function WOMAC sub-scores, p = 0.003 and p = 0.013, respectively), and after 2 years for stiffness sub-score (p = 0.008), being close to statistical significance (p = 0.051) for physical function sub-score. When considering withdrawn patients as non-responders, results were similar. Open table in a new tab MPCI responders were statistically significantly greater from M18 (pain and function WOMAC sub-scores, p = 0.003 and p = 0.013, respectively), and after 2 years for stiffness sub-score (p = 0.008), being close to statistical significance (p = 0.051) for physical function sub-score. When considering withdrawn patients as non-responders, results were similar. Conclusions: Treatment with SrRan is associated with a greater number of patients with relevant improvement in symptoms. This can be evidenced from M18 considering MPCI responders.

This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. Zoledronic acid is significantly more effective than risedronate in increasing lumbar spine (LS) bone mineral density (BMD) in both prevention and treatment of glucocorticoid-induced osteoporosis.

This review summarizes the available evidence-based data that form the basis for therapeutic intervention and covers the current status of glucocorticoid-induced osteoporosis (GIOP) management, regulatory requirements, and risk-assessment options. Glucocorticoids are known to cause bone loss and fractures, yet many patients receiving or initiating glucocorticoid therapy are not appropriately evaluated and treated. An European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis workshop was convened to discuss GIOP management and to provide a report by a panel of experts. An expert panel reviewed the available studies that discussed approved therapeutic agents, focusing on randomized and controlled clinical trials reporting on bone mineral density and/or fracture risk of at least 48 weeks' duration. There is no evidence that GIOP and postmenopausal osteoporosis respond differently to treatments. The FRAX algorithm can be adjusted according to glucocorticoid dose. Available antiosteoporotic therapies such as bisphosphonates and teriparatide are efficacious in GIOP management. Several other agents approved for the treatment of postmenopausal osteoporosis may become available for GIOP. It is advised to stop antiosteoporotic treatment after glucocorticoid cessation, unless the patient remains at increased risk of fracture. Calcium and vitamin D supplementation as an osteoporosis-prevention measure is less effective than specific antiosteoporotic treatment. Fracture end-point studies and additional studies investigating specific subpopulations (pediatric, premenopausal, or elderly patients) would strengthen the evidence base and facilitate the development of intervention thresholds and treatment guidelines.