Characteristics Associated with Acute-Phase Response following First Zoledronic Acid Infusion in Brazilian Population with Osteoporosis

We aimed to evaluate characteristics associated with acute-phase response (APR) following first zoledronic acid infusion in a Brazilian cohort. This retrospective cohort study enrolled all adults with osteoporosis who underwent a first zoledronic acid infusion at our centre between June 2015 and June 2019. Clinical demographics (age, sex, diabetes, smoking, body mass index, and previous oral bisphosphonate use) and laboratory data (calcium, parathyroid hormone, renal function, and serum 25-hydroxyvitamin D and carboxy-terminal crosslinked telopeptide of type 1 collagen [CTX], both before and after infusion) were compared between patients with and without APR. We evaluated association magnitude between the presence of APR and clinical variables through logistic regression. This study enrolled 400 patients (women, 80%). APR was observed in 24.5% (n = 98) of patients. The mean symptom duration in days was 3.5 ± 2.8. Patients with APR were younger (67 ± 12 vs. 71 ± 11 years; p = 0.001 ), used oral bisphosphonates less frequently (34% × 50%; p = 0.005 ), and had greater baseline CTX (0.535 ng/mL [0.375, 0.697] × 0.430 [0.249, 0.681]; p = 0.03 ) and ΔCTX (−69 [−76; −50] × −54 [−72; −23]; p = 0.002 ) than those without APR. The other variables were similar between the groups. Only ΔCTX was associated (OR, 0.62; 95% CI 0.41–0.98) with APR after accounting for age and bisphosphonate use. APR occurred in 24.5% of the cohort. Younger age and absence of prior oral bisphosphonate use were associated with APR following first zoledronic acid infusion. APR was associated with ΔCTX (but no other variables) after adjusting for these factors.

Interstitial Lung Disease in a Woman with Rheumatoid Arthritis Treated with Denosumab: A Case Report

The present report describes the case of an 84-year-old female Japanese patient with rheumatoid arthritis (RA) who experienced exacerbation of interstitial lung disease (ILD) after denosumab (Dmab) treatment. The onset of RA occurred in 2008, and the patient had been treated with intravenous or subcutaneous injection of tocilizumab (TCZ) since 2009. In July 2013, she experienced a lumbar vertebral fracture and began treatment with 60-mg Dmab injection every 6 months in January 2014. The patient had a history of mild ILD and was evaluated for ILD by chest computed tomography (CT) imaging prior to the start of Dmab use. The vertebral fracture did not recur after the initiation of Dmab treatment, and her osteoporosis was successfully treated. However, she expressed a concern of exacerbations of cough and respiratory discomfort that had occurred since September 2019. The chest CT image in November 2015 showed minor ILD progression, whereas the image in September 2019 showed severe exacerbation of ILD. To treat this exacerbation, 10 mg of methylprednisolone (mPSL) and 2.5 mg of tacrolimus (TAC) were administered, and Dmab was discontinued. The patient was subsequently switched to oral bisphosphonate. The patient’s respiratory discomfort and the finding of interstitial lung lesion in CT imaging improved after Dmab discontinuation. This case showed that exacerbation of ILD may occur after Dmab treatment, and physicians should consider the risks of Dmab-related ILD in patients with RA complicated by ILD.

POS0167 SECONDARY PREVENTION OF VERTEBRAL FRACTURES IN REAL PRACTICE

Background:Vertebral fractures increases the risk of new fractures and deaths. There are different antiresorptive medications to prevent a secondary fracture, as bisphosphonates, teriparatide or denosumab, but little is known about the effects of secondary fracture appearance in real life.Objectives:To evaluate the appearance of new vertebral fractures depending on the treatment used for secondary prevention.Methods:We conducted a prospective descriptive study of patients with a first diagnosis of vertebral fracture from 2010 to 2017 and assessed the subsequent finding of new fractures. We selected patients with at least 3 years of secondary prevention with antiresorptive drugs or with sequential treatment (anabolic followed by, at least, 1 year with antiresorptive drugs), and excluded those who experienced new fractures within the first 6 months of treatment.Results:A total of 400 patients were selected from an initial base of 1018 patients. The average age of onset of the first fracture was 69.7 years, 84% of female patients and 16% of female patients. 38.5% suffered dorsal fractures, 33.75% lumbar fractures and 27.75% dorsolumbar fractures. We classified the secondary prevention strategies according to the different therapeutic options, as we can see in Table 1.We analysed the association between the appearance of new vertebral fracture corrected by sex with the age of the initial fracture its location. No association was found.We also performed a multivariate Bayesian model of logistic regression, in order to analyze the association between the appearance of new vertebral fracture and factors as the age of the initial fracture, its sex and the pharmacologic option used as secondary prevention. No statistically significant differences were observed between the different antiresorptive treatments and their efficacy as a secondary prevention of vertebral fractures. However, there was a tendency for a smaller occurrence of new fractures in patients undergoing sequential treatment. On the other hand, similar results were observed between denosumab and oral bisphosphonates, observing somewhat worse data with zoledronate (figure 1), probably due to patients under zoledronate treatment showed high osteoporotic risk and worse prognosis.Pharmacologic optionPatients (%)New fractures (%)Denosumab192 (48%)10 (5.21%)Teriparatide (up to 2 years) + Denosumab (at least 1 year)86 (21.5%)0 (0%)Oral bisphosphonate (alendronate, risedronate or ibandronate)58 (14.5%)3 (5.17%)Zoledronate33 (8.25%)4 (12.12%)Teriparatide (up to 2 years) + oral bisphosphonate (at least 1 year)28 (7%)2 (7.14%)Teriparatide (up to 2 years) + Zoledronate (at least 1 year)3 (0,75%)0 (0%).Conclusion:No differences between the different secondary prevention options in terms of the appearance of new fractures were observed.Disclosure of Interests:None declared

The effect on the gastrointestinal tract of various forms of alendronate in comorbid patients taking NSAIDs

Introduction. The use of bisphosphonates is associated with some risk of side effects. Gastrointestinal tract complications are particularly important in clinical practice, as they constitute the main reason for refusing bisphosphonate therapy.Objective: To evaluate the effect of various forms of alendronate on the gastrointestinal tract in comorbid patients taking NSAIDs.Materials and methods. The study included 88 women aged 58–65 years (mean age 61.5 ± 3.5 years) with polyosteoarthrosis combined with postmenopausal osteoporosis, who received NSAIDs at medium therapeutic doses to manage a pain syndrome for a long time (3–5 years). The patients were divided into two groups: a group of patients receiving alendronate in the form of a buffered solution (n = 45), and a group of patients receiving alendronate in the form of non-dissolving tablets (n = 43). The first group used Binosto (adendronic acid) 70 mg as effervescent tablets once a week. The results were assessed before initiation of treatment and 6 months after treatment with bisphosphonates. Symptoms were evaluated using the GerdQ questionnaire. Esophageal mucosal injury and gastroduodenal ulceration were assessed by upper gastrointestinal endoscopy.Results and discussion. After 6-month treatment, comparison of the two groups showed that the percentage of patients with a total GerdQ score of ≥ 8 points was significantly higher in the group of patients taking alendronate in the form of non-dissolving tablets (p = 0.04). The endoscopic findings showed that the number of patients with grade A reflux esophagitis in group 1 increased by 3.3%. The number of grade A reflux esophagitis cases in group 2 increased by 2.2%, those of grade B, C and D cases by 2.4%. The number of gastroduodenal ulcer cases also increased by 2.2% and 4.7% in groups 1 and 2, respectively. The number of gastroduodenal erosions increased by 3.5% in group 1 and 7% in group 2.Сonclusion. Symptoms were less severe in patients receiving alendronate in the form of a solution, which points to the importance of choosing the optimal oral bisphosphonate for each patient.

A Clinical and Histological Study about the Socket Preservation in a Patient under Oral Bisphosphonates Treatment: A Case Report

The aim of the present study is to assess the clinical and histological healing of a post-extractive alveolus following the procedure for socket preservation, in a patient receiving oral bisphosphonates for more than 6 years. After the extraction, enzymatically-deantigenated horse bone granules and an equine pericardium membrane were used to preserve the tooth socket. The patient was placed on a monthly follow-up in order to monitor the healing process. A 3 mm trephine bur was used to drill the bone for implant site preparation and to collect the bone sample. No signs and symptoms related to osteonecrosis of the jaws were reported. Histological data showed that, after 5 months, the mean percentages of trabecular bone, bone marrow and residual bone graft were respectively 45.74 ± 0.09%, 48.09 ± 0.08%, and 6.16 ± 0.01%. The residual graft material appeared to be osteointegrated and none of the particles appeared to be encapsulated. The present case report supports the guidelines that assume that patients undergoing oral bisphosphonate therapy can be eligible for surgical therapy. More clinical studies with larger sample sizes are needed to support this clinical evidence.

Severe Oral Mucosal Ulceration Associated with Oral Bisphosphonate Use: The Importance of Imparting Proper Instructions on Medication Administration and Intake

Oral bisphosphonates are approved for the treatment of bone loss associated with several conditions including postmenopausal osteoporosis. Although generally well tolerated, adverse effects such as gastroesophageal reflux and oesophageal and peptic ulceration may occur. Oral mucositis and ulceration are lesser-known side effects. Proper counselling and rigorous adherence to the administration instructions are crucial. We describe a case of bisphosphonate-induced severe oral mucosal ulceration in an elderly woman that was caused by incorrect instructions and/or incorrect understanding of instructions for oral alendronate intake.