This narrative review explores the therapeutic potential of repurposing medications originally developed or approved for osteoporosis to treat non-osteoporotic conditions. Given their pharmacologic profiles and safety data, these agents offer promising therapeutic alternatives in both rare and common diseases with unmet clinical needs. Evidence from preclinical models, observational data, and randomised trials supports the repositioning of several osteoporosis drugs. Cyclic etidronate has shown efficacy in halting arterial calcification progression in pseudoxanthoma elasticum. Pamidronate has demonstrated symptom improvement in adult chronic nonbacterial osteitis. Neridronate is approved only in Italy for complex regional pain syndrome type I. Denosumab has shown therapeutic effects in Langerhans cell histiocytosis and has structural benefits in erosive hand osteoarthritis and rheumatoid arthritis. Parathyroid hormone analogues (rhPTH [1-84] and teriparatide) improve calcium-phosphate homeostasis in chronic and genetic hypoparathyroidism. Calcilytics, though originally discontinued for osteoporosis, show emerging promise in autosomal dominant hypoparathyroidism. In contrast, zoledronic acid has not demonstrated consistent clinical benefit in knee osteoarthritis. Strontium ranelate, despite showing structure-modifying effects in osteoarthritis, is no longer marketed due to safety concerns. Alendronate and denosumab in fibrous dysplasia yielded mixed results, with concerns about rebound effects after denosumab withdrawal. Repurposing osteoporosis medications represents a cost-effective, timely strategy to expand treatment options across diverse clinical indications. While promising outcomes have been demonstrated-particularly in rare diseases-rigorous, indication-specific clinical trials are essential to confirm efficacy, safety, and long-term outcomes. The accumulated pharmacologic and clinical experience with these agents offers a strong foundation for their continued exploration beyond osteoporosis.

Juvenile idiopathic arthritis (JIA) is characterised by arthritis onset before the age of 16, persisting for at least 6weeks without a known cause. Symptoms include joint swelling, inflammatory pain (worse at night and in the morning), or also back, heel, or buttock pain. Timely diagnosis and referral to a paediatric rheumatologist are crucial to reduce errors, invasive procedures, and long-term complications. Around 5000 children under 16 are affected by JIA in France. The current international classification recognises 7 subgroups: the systemic form, oligoarthritis, polyarthritis without rheumatoid factor, polyarthritis with rheumatoid factor (juvenile rheumatoid arthritis), enthesitis associated with JIA (juvenile spondyloarthropathy), JIA associated with psoriasis and undifferentiated JIA. A new classification divides JIA into 5 groups: the systemic form, early-onset oligo- and polyarthritis with anti-nuclear antibodies (associated with a risk of chronic anterior uveitis), polyarthritis with rheumatoid factor, juvenile spondyloarthropathy and non-groupable forms. JIA management involves a multidisciplinary team led by a paediatric rheumatologist, using targeted therapies (biologics, small molecules) and numerous health professionals (physiotherapist, occupational therapist, etc.), improving overall outcomes. Physicians (paediatricians or general practitioners) play a vital role in overall management, ensuring treatment compliance, monitoring effectiveness, and managing infection risks. This includes updating vaccination schedules and addressing febrile episodes. We present recent international recommendations including the "treat-to-target" approach, consisting in setting precise objectives at the beginning and during the evolution, which involves regularly assessing the patient's situation to adapt treatments, control inflammation and disease complications, limit the toxicity of treatments. This strategy aims to achieve, ideally in a few months an inactive disease or complete remission. Regarding systemic JIA (or pediatric Still's disease), we pay attention to particularly severe clinical forms in very young children, which may be life-threatening by major activation of the immune system (macrophage activation syndrome) or secondary pulmonary involvement. For non-systemic forms, i.e. oligoarthritis, polyarthritis, enthesitis related JIA (or juvenile spondylarthropathies) and JIA associated with psoriasis, we specify the state of current knowledge and uncertainties regarding prognosis and therapeutic choices.

Our study aimed to estimate the incidence and risk factors of cancer among rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ) and followed for five years in the French registry (REGATE). The REGATE registry is a French prospective cohort study investigating the safety of TCZ in RA (registration no: 910346). Data were collected using an e-CRF between 2011 and 2016 and with a questionnaire specifically distributed to participating centers that reported malignancies in REGATE. We mainly focused on solid cancers, hematological malignancies, and non-melanoma skin cancers (NMSC). To identify potential risk factors associated with cancer, we performed a univariate analysis and a multivariate analysis using Cox proportional hazards models. Our study included 1496 patients with RA who were treated with TCZ for a mean duration of 32.0 (±22.0) months and followed for an average of 47 (±15.2) months, resulting in a total exposure of 3990.9 patient-years (PY). Of these patients, 63 (4.2%) were diagnosed with a total of 75 cancers during the follow-up period (35 solid neoplasms, 11 hematological malignancies, 3 melanomas, and 26 NMSC). The overall incidence of cancer excluding NMSC was 7.5/1000 PY (exposure time). Our multivariate analysis revealed that high age (HR=1.05 [1.02-1.08]), current smoker (HR=2.65 [1.27-5.53]) and male 2.38 [1,18-4,80]) were independent risk factors for solid cancers. Age and active smoking were associated with higher risk of hematological malignancies. We found no additional risk factors of cancer for RA patients under TCZ, beyond those already known in the general population.

Sjögren's disease is the autoimmune disease with the highest risk of lymphoma development. There is no consensus on the optimal way to manage Sjögren's disease complicated by lymphoma. We aimed to describe characteristics, therapeutic strategies, and outcomes of non-Hodgkin lymphoma associated with Sjögren's disease, and their effect on lymphoma and Sjögren's disease prognoses. We did a multicentre, retrospective, observational study including patients with Sjögren's disease according to the 2016 American College of Rheumatology-European League Against Rheumatism criteria who did not fulfil diagnostic criteria for other connective tissue diseases. We included patients with a lymphoma diagnosis made before Jan 1, 2020, from two expert centres in Paris (France); from the French, multicentre, prospective Assessment of Systemic Signs and Evolution of Sjögren's Syndrome cohort; and via practitioners registered with the Club Rhumatismes et Inflammation. Using inverse probability of treatment weighting, the effect of lymphoma treatment was compared in relation to three endpoints: lymphoma progression-free survival, new Sjögren's disease systemic activity, and overall survival. Exploratory analyses also aimed to identify factors associated with lymphoma relapse, new Sjögren's disease systemic activity, and overall survival. People with lived experience were not involved in this research. 106 patients with Sjögren's disease who developed lymphoma were included in the study. The most frequent histological subtype was mucosa-associated lymphoid tissue lymphoma (68 [64%] of 106 patients), followed by other marginal zone subtypes (14 [13%] of 106 patients) and diffuse large B-cell lymphoma (14 [13%] of 106 patients). Among the 82 patients with marginal zone lymphoma (72 [88%] women and ten (12%) men; mean age at lymphoma diagnosis 57·5 years [SD 14·8]), multivariable analysis showed that pulmonary localisation was associated with mortality (hazard ratio [HR] 7·92 [95% CI 1·70-37·0]). A watch and wait approach was proposed in 19 (23%) of 82 patients with marginal zone lymphoma, 13 (16%) had first-line localised treatment (surgery or radiotherapy), and 50 (61%) had first-line systemic treatment. After a median follow-up of 7 years, 26 patients (32%) had lymphoma relapse, nine (11%) died, and 27 (33%) had new Sjögren's disease systemic activity. After inverse probability of treatment weighting, patients with systemic treatment at lymphoma diagnosis had a reduced risk of new Sjögren's disease activity (HR 0·43 [95% CI 0·21-0·90]). When comparing patients treated with a combination of chemotherapy and anti-CD20 therapy (n=32) with patients treated with monotherapy (n=18) as a first-line therapy for lymphoma, lymphoma-progression-free survival was improved in patients treated with combination therapy (HR 0·36 [95% CI 0·14-0·94]). The were no differences in new Sjögren's disease systemic activity or overall survival according to combination therapy or monotherapy. A systemic treatment strategy for Sjögren's disease-associated lymphoma, rather than localised treatment or a watch and wait strategy, reduces the risk of new Sjögren's disease systemic activity and combination therapy is associated with decreased risk of lymphoma relapse. None.

Single nucleotide polymorphisms in non-HLA genes are involved in the development of rheumatoid arthritis (RA). SNPS in genes: PADI4 (rs2240340), STAT4 (rs7574865), CD40 (rs4810485), PTPN22 (rs2476601), and TRAF1 (rs3761847) have been described as risk factors for the development of autoimmune diseases, including RA. This study aimed to assess the prevalence of polymorphisms of these genes in the Polish population of patients with rheumatoid arthritis as compared to healthy controls. 324 subjects were included in the study: 153 healthy subjects and 181 patients from the Department of Rheumatology, Medical University of Lodz who fulfilled the criteria of rheumatoid arthritis diagnosis. Genotypes were determined by Taqman SNP Genotyping Assay. rs2476601 (G/A, OR = 2.16, CI = 1.27-3.66; A/A, OR = 10.35, CI = 1.27-84.21), rs2240340 (C/T, OR = 4.35, CI = 2.55-7.42; T/T, OR = 2.80, CI = 1.43-4.10) and rs7574865 (G/T, OR = 1.97, CI = 1.21-3.21; T/T, OR = 3.33, CI = 1.01-11.02) were associated with RA in the Polish population. Rs4810485 was also associated with RA, however after Bonferroni's correction was statistically insignificant. We also found an association between minor alleles of rs2476601, rs2240340, and rs7574865 and RA (OR = 2.32, CI = 1.47-3.66; OR = 2.335, CI = 1.64-3.31; OR = 1.88, CI = 1.27-2.79, respectively). Multilocus analysis revealed an association between CGGGT and rare (below 0.02 frequency) haplotypes (OR = 12.28, CI = 2.65-56.91; OR = 3.23, CI = 1.63-6.39). In the Polish population, polymorphisms of the PADI4, PTPN22, and STAT4 genes have been detected, which are also known risk factors for RA in various other populations.