Paradoxical psoriasis induced by IL-17 inhibitors: a case series of patients with axial spondyloarthritis and a systematic literature review.

Following the market authorization of interleukin (IL)-17 inhibitors, a growing number of cases of IL-17 inhibitor-induced paradoxical psoriasis (PsO) have been reported. Our objectives were to present two cases of IL-17 inhibitor-induced paradoxical PsO and to systematically review the literature for similar cases, summarizing and presenting the relevant data. A systematic literature review of previously presented cases of paradoxical PsO induced by IL-17 inhibitors was conducted. We presented two patients with axial spondyloarthritis (axSpA) and paradoxical PsO induced by secukinumab (SEC). One patient's psoriatic lesions responded well to adjuvant topical treatment, while the other patient required a combination of topical treatment and cyclosporine Α for successful treatment. SEC was continued in both cases. We also identified 35 patients with IL-17 inhibitor-induced paradoxical PsO in the literature review. The most frequent types of paradoxical PsO were palmoplantar pustular and plaque PsO, while the median latency period was 11 weeks. Approximately one-third of patients continued IL-17 inhibitor treatment with adjunctive therapy, primarily topical, which produced satisfactory results in most patients. Almost two-thirds of the patients discontinued the IL-17 inhibitor, with the majority of patients switching to another biological agent with a different mechanism of action or initiating other systemic antipsoriatic treatments, resulting in mainly satisfactory outcomes. Therefore, paradoxical PsO induced by IL-17 inhibitors appears to respond well in both patients who continue IL-17 inhibitors with adjunctive treatment and those who discontinue IL-17 inhibitors while switching to a different class of biological agent or initiating other systemic antipsoriatic treatments.

Real-world effectiveness of golimumab in adult patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis and an inadequate response to initial TNFi therapy in Greece: the GO-BEYOND prospective, observational study.

The impact of golimumab (GLM) on remission or low disease activity (LDA) was evaluated in patients with moderate-to-severe rheumatoid arthritis (RA), progressive psoriatic arthritis (PsA), or severe axial spondyloarthritis (axSpA), who failed previous treatment for their rheumatic disease with one initial tumor necrosis factor α inhibitor (TNFi). This is a multicenter, prospective, real-world observational 18-month study, conducted in Greece. The primary endpoint, assessed at 6 months, included the proportion of patients attaining LDA and/or remission (Disease Activity Score for 28 joints based on C-reactive protein [DAS28-CRP] ≤ 3.2), minimal disease activity (MDA; MDA criteria), and moderate disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] score 4-7), respectively. Other endpoints evaluated the persistence to GLM treatment and its impact on patients' work productivity (Work Productivity and Activity Impairment [WPAI] instrument) and quality of life (QoL; EuroQoL5 dimensions 3 levels [EQ-5D-3L] questionnaire). Descriptive statistics, the Wilcoxon signed-rank test, and Kaplan-Meier method were used for analyses. At 6 months, LDA was achieved by 46.4% of patients with RA, MDA by 57.1% of patients with PsA, and BASDAI 4-7 by 24.1% of patients with axSpA. For all study patients, persistence rates on GLM were high (85.1-93.7%) over 18 months; all WPAI domain scores and the EQ-5D-3L index score improved significantly (p < 0.001) from baseline to 18 months. GLM treatment was effective in patients with RA, PsA, or axSpA who had failed previous treatment with one TNFi and led to significant WPAI and QoL improvements. Persistence rates were high. Trial registration number and date of registration: As per the local regulations the study has been registered at the national registry for non-interventional studies https://www.dilon.sfee.gr/studiesp_d.php?meleti_id=MK8259-6995 .

Psoriatic onycho-pachydermo periostitis (POPP): a case report treated successfully with IL-17 blockade and a literature review on characteristics, pathogenesis, and treatment.

Psoriatic onycho-pachydermo periostitis (POPP) is characterized by psoriatic onychodystrophy, connective tissue thickening, and periostitis of the distal phalanges (DPs), producing a drumstick-like deformity. Our aim was to present the first case of POPP treated successfully with an IL-17 inhibitor, perform a literature review of its characteristics and treatment, and explore the possible pathogenesis. We conducted a systematic review of previously presented POPP cases. We present a patient with methotrexate (MTX)-resistant treatment POPP, who had significant resolution of symptoms and inflammatory lesions on post-treatment MRI with secukinumab 150 mg. We also identified 31 cases of POPP (27 males; mean age 44.9 years) in the literature review. There was great toe involvement in 24 cases, and distal interphalangeal (DIP) involvement in 14 cases, with frequent radiographically evident damage. Seventeen of 31 patients received systematic treatment other than biologics, mostly MTX, with no satisfactory results. Anti-TNF agents were used successfully in 5 cases, mostly after disease modifying anti-rheumatic drug (DMARD) failure. Imaging studies in nail psoriasis and DIP psoriatic arthritis have shown an anatomical link among the nail, the DP bone, and the DIP joint entheses, suggesting that POPP may be a subtype of nail disease with excessive involvement of DP tissues (nail, soft tissue, enthesis, and bone). IL-17 inhibition could be an alternative therapeutic option in DMARD-resistant cases of POPP. Conventional treatment achieves modest success, but anti-TNF agents appear to be much more effective. Based on imaging studies, POPP may be a particular subtype of nail disease.

Long-term effect of TNF inhibitors on radiographic progression in ankylosing spondylitis is associated with time-averaged CRP levels.

OBJECTIVE: To investigate whether the impact of long-term treatment (>3 years) with TNF inhibitors (TNFi) on radiographic progression in AS is associated with the level of acute phase reactants during therapy. METHODS: One hundred and one consecutive AS patients under TNFi [65 men; age: 41.6±11 years (mean±SD), with symptom duration: 17±10 years] were included in this retrospective study. Lateral X-rays of cervical and lumbar spine, obtained before TNFi initiation, were compared to those obtained after a period of 7±2.5 (range: 3-15) years. The levels of CRP and ESR were evaluated every 6 months. The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) assessed the radiographic damage. New syndesmophyte formation or ΔmSASSS-score/year≥1 unit/year was defined as radiographic progression. RESULTS: Forty-seven patients (46.5%) showed radiographic progression. ΔmSASS-score/year was positively correlated with both, baseline CRP (r=0.35, P<0.001) and ESR (r=0.3, P<0.01), as well as with time-averaged CRP (r=0.3, P<0.01). Furthermore, ΔmSASS-score/year was significantly higher (P<0.0001) in patients with syndesmophytes at baseline [0.9 (0.4-1.8), median (IQR)] compared to those without [0 (0-0.4)]. In the multivariate logistic regression analysis, independent risk factors for spinal radiographic progression during TNFi treatment were the presence of syndesmophytes at baseline (OR: 14.7, 95%CI:4.9-44) and the time-averaged CRP>5mg/L (OR:7.6, 95%CI: 2.5-23). No gender differences were observed. CONCLUSION: In AS patients with long standing disease, radiographic progression during TNFi treatment is significantly associated with higher levels of time-averaged CRP.

Vascular acrosyndromes in young adult population. Definition of clinical symptoms and connections to joint hypermobility.

OBJECTIVES: Clinical recognition of vascular acrosyndromes is often challenging. The term Raynaud's phenomenon (RP) is commonly overused to describe any form of cold-related disorder. This study aims to formally evaluate peripheral vascular symptoms affecting the population, aged ≤ 40 years, and identify any correlations to joint hypermobility (JH). PATIENTS AND METHODS: Fifty patients (31 males, 19 females) with vasomotor symptoms enrolled in this five-year prospective observational study. Clinical examination by a rheumatologist and a vascular surgeon was performed along with cardiology, echocardiographic and Doppler evaluation. Patients underwent blood cell count, biochemistry, thyroid and selectively immunologic testing. Twenty-four (48%) of them performed nailfold capillaroscopy. The SPSS for Windows, v.17.0, Chicago, USA, was used for the statistical analyses. RESULTS: Twenty-eight patients (56%) presented with erythromelalgia (EM), 6 (12%) with acrocyanosis (AC) and 9 (18%) as a combination of the above disorder. RP diagnosed in five (10%) while two patients (4%) presented as a mix of EM-RP. There was no correlation with abnormal laboratory tests. Increased incidence of JH was found in EM and AC patients. Among those who were tested with nailfold capillaroscopy, 75% had abnormalities ranged from mild to autoimmune-like diseases. CONCLUSIONS: Erythromelalgia is the commonest functional vasculopathy in young population followed by acrocyanosis and a combination of these conditions. Joint hypermobility is markedly increased, indicating that dysautonomy may be considered the causative factor following a trigger event. Overall, RP was observed in 14% of patients. Clinical recognition of these disorders avoids unnecessary investigation. Key Points • Vascular acrosyndromes in young adults are commonly functional disorders resembling vascular algodystrophy induced by thermic stress. • Dysautonomy of joint hypermobility is the co-factor influencing the appearance of the vascular disorders. • Raynaud's phenomenon accounts to approximately 14% of vascular acrosyndromes presented in the young adult population.

Increased osteoclastogenesis in patients with vertebral fractures following discontinuation of denosumab treatment.

OBJECTIVE: To test the hypothesis that rebound of bone remodeling is responsible for clinical vertebral fractures reported in a few patients with osteoporosis after cessation of denosumab treatment. DESIGN: In this case-control study we compared clinical and biochemical characteristics of postmenopausal women with clinical vertebral fractures 8-16 months after the last injection of denosumab (Dmab/Fx+, n = 5) with those of treatment-naïve women with such fractures (Fx+, n = 5). In addition, 5 women who discontinued denosumab treatment but did not sustain vertebral fractures 18-20 months after the last injection were studied (Dmab/Fx-, n = 5). METHODS: We measured serum microRNAs, gene expression of mRNAs of factors regulating formation and activity of osteoclasts and biochemical markers of bone and mineral metabolism. In Dmab/Fx+ and Fx+ women, blood was taken 4-8 weeks after the fracture. RESULTS: Compared to Fx+ women, Dmab/Fx+ women had higher serum P1NP and CTx levels, and significantly lower serum miR-503 and miR-222-2 that downregulate osteoclastogenesis and osteoclast activity, and higher RANK (13-fold) and CTSK (2.6-fold) mRNA. The respective values of Dmab/Fx- women were in the same direction as those of Dmab/Fx+ women but of a lesser magnitude. CONCLUSIONS: Bone fragility in women with clinical vertebral fractures after stopping denosumab therapy is pathophysiologically different from that of treatment-naïve women with osteoporosis and clinical vertebral fractures and it is associated with upregulation of markers of osteoclast formation and activity. The small number of women with this rare event studied is a limitation.

Serum levels of Dkk-1, sclerostin and VEGF in patients with ankylosing spondylitis and their association with smoking, and clinical, inflammatory and radiographic parameters.

OBJECTIVE: To evaluate serum Dickkopf-1 (Dkk-1), sclerostin and vascular endothelial growth factor (VEGF) levels in patients with ankylosing spondylitis (AS) compared to healthy controls as well as their association with smoking, and clinical, inflammatory and radiographic parameters. METHODS: Serum samples for total Dkk-1, sclerostin and VEGF were obtained from 57 tumour necrosis factor (TNF) inhibitor naïve patients with AS and 34 sex-, age- and body mass index (BMI)-matched controls. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), modified Stroke AS Spine Score (mSASSS) and smoking status were assessed for each patient. RESULTS: There was no significant difference in serum bone metabolism markers between AS patients and controls. Dkk-1 levels were significantly (P<0.05) higher in AS patients with elevated ESR and CRP and no syndesmophytes, and were significantly (P<0.001) correlated with sclerostin levels (r=0.592). VEGF levels were significantly (P<0.05) higher in AS patients with current and ever smoking, elevated ESR and CRP, and high BASDAI and BASFI, and were significantly (P<0.05) correlated with ESR (r=0.284), CRP (r=0.285), BASDAI (r=0.349) and BASFI (r=0.275). In multivariate regression analyses, high Dkk-1 levels were significantly (P≤0.001) associated with elevated ESR and CRP, no syndesmophytes and high sclerostin levels, and high VEGF levels significantly (P<0.05) with ever smoking, and elevated ESR and CRP. CONCLUSION: In AS, serum Dkk-1 concentrations appear to be related not only to syndesmophyte formation but also to systemic inflammation. Furthermore, high VEGF levels may be associated with smoking exposure.

Circulating sclerostin and Dickkopf-1 levels in patients with nonalcoholic fatty liver disease.

There is increasing evidence for bone-liver interplay. The main aim of this study was to determine serum sclerostin and Dickkopf (DKK)-1 levels in patients with nonalcoholic fatty liver disease (NAFLD) and their association with the disease severity. Patients with biopsy-proven NAFLD, 13 with nonalcoholic simple steatosis (SS) and 14 with steatohepatitis (NASH), and 20 gender-, age-, body mass index- and waist circumference-matched controls were enrolled. Serum sclerostin, DKK-1, bone turnover markers, vitamin D, insulin and standard biochemical and hematologic parameters were measured; lumbar spinal dual-energy X-ray absorptiometry was performed. We observed that there was a progressive decline in serum sclerostin levels from the controls (76.1 ± 6.8) to SS (53.5 ± 6.4) and NASH (46.0 ± 8.1 pmol/l) patients (p = 0.009); in adjusted pairwise comparisons, sclerostin was significantly higher in the controls than in NASH patients (p = 0.012). Although serum DKK-1 did not differ between groups (p = 0.135), there was a trend toward U-shaped distribution (controls 35.8 ± 2.8; SS 27.3 ± 2.9; NASH 36.8 ± 4.4 pmol/l). Higher DKK-1 levels were independently associated with NASH. Regarding specific histological lesions, DKK-1 levels were marginally lower in NAFLD patients with lower (≤33 %) than higher (>33 %) steatosis grade (27.7 ± 3.1 and 38.8 ± 4.7 pmol/l, respectively; p = 0.049). No other significant difference was observed within histological lesions. In conclusion, serum sclerostin levels were lower in NASH patients than in controls. DKK-1 levels were independently associated with NASH in NAFLD patients. The potential importance of these findings indicates a possible bone-liver interaction and warrants further investigation.

The effect of smoking on clinical and radiographic variables, and acute phase reactants in patients with ankylosing spondylitis.

To investigate the association between smoking and clinical, inflammatory and radiographic parameters in patients with ankylosing spondylitis (AS). One hundred and six tumour necrosis factor inhibitor naïve patients with AS were included in the study. The erythrocyte sedimentation rate, C-reactive protein, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI) and modified Stroke AS Spine Score (mSASSS) were assessed cross-sectionally for each patient. Smoking history was obtained, and smoking pack years were calculated. Current smokers had significantly higher BASDAI (p < 0.001) and a trend for higher BASFI (p = 0.059). Ever smokers had significantly higher BASFI (p = 0.035) and a trend for higher mSASSS (p = 0.063) compared to never smokers. Pack years (smoking intensity) were positively correlated with duration of inflammatory back pain (r = 0.628, p < 0.001), BASFI (r = 0.443, p < 0.001) and mSASSS (r = 0.683, p < 0.001). Multivariate regression analyses showed that current smoking was independently associated with a higher BASDAI score [regression coefficient (B) = 14.75, p < 0.001] and increasing pack years were independently associated with higher mSASSS (B = 0.26, p = 0.005). In patients with AS, current smoking was strongly and independently associated with higher disease activity, and cumulative smoking exposure with more radiographic spinal damage. In AS smokers, smoking cessation should be strongly recommended.

Denosumab in treatment-naïve and pre-treated with zoledronic acid postmenopausal women with low bone mass: Effect on bone mineral density and bone turnover markers.

PURPOSE: To compare denosumab-induced changes in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD), bone markers and free soluble receptor activator of nuclear factor kappaB ligand (sRANKL) between treatment naïve postmenopausal women with low bone mass (naïve group) and those who were previously treated with a single zoledronic acid infusion (post-Zol group). PROCEDURES: Procollagen type 1N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTx) and sRANKL levels were measured in serum samples obtained at baseline and 3, 6 and 12months after denosumab initiation. LS and FN BMD were measured at baseline and 12months. RESULTS: LS and FN BMD increased significantly in both naïve and post-Zol group (p<0.001 and p=0.025 vs. p<0.001 and p=0.017, respectively). Despite the higher P1NP and CTx levels in naïve patients at baseline (both p<0.001), denosumab caused comparable decreases in both groups at month 3, which returned to post-Zol group baseline levels at month 6 and 12 in all patients. Similarly, sRANKL levels decreased significantly at month 3 in both groups and returned to baseline levels at months 6 and 12. CONCLUSIONS: In patients previously treated with zoledronic acid, sequential denosumab treatment is effective in terms of BMD increases and bone turnover suppression. Despite the lower baseline levels in patients pre-treated with zoledronic acid, bone markers are similarly decreased in both groups following denosumab administration and maintain their reversibility. Denosumab reversibly suppresses endogenous free sRANKL levels in both naïve and zoledronic acid pre-treated patients.

Management of glucocorticoid-induced osteoporosis: clinical data in relation to disease demographics, bone mineral density and fracture risk.

INTRODUCTION: Glucocorticoid-induced osteoporosis (GIOP) is the most common type of secondary osteoporosis. Patient selection and the treatment choice remain to be controversial. None of the proposed management guidelines are widely accepted. We evaluate the available clinical data, the efficacy of current medication and we propose an overall algorithm for managing GIOP. AREAS COVERED: This article provides a critical review of in vivo and clinical evidence regarding GIOP and developing evidence-based algorithm of treatment. Data base used includes MEDLINE® (1950 to May 2014). EXPERT OPINION: Patient-specific treatment is the gold standard of care. Glucocorticoid (GC)-treated patients must comply with a healthy lifestyle and receive 1000 mg of calcium and at least 800 mg of Vitamin D daily. Bisphosphonate (BP) therapy is the current standard of care for prevention and treatment of GIOP. Most of bisphosphonates demonstrated benefit in lumbar bone mineral density (BMD) and some in hip BMD. Alendronate, risedronate and zoledronate showed vertebral anti-fracture efficacy in postmenopausal women and men. Scarce data however when compared head to head with BP efficacy. In post-menopausal women, early antiresorptive BP treatment appears to be efficient and safe. In premenopausal women and patients at high risk of fracture receiving long-term GC therapy however, teriparitide may be advised alternatively.

Circulating periostin levels in patients with AS: association with clinical and radiographic variables, inflammatory markers and molecules involved in bone formation.

OBJECTIVE: The aim of this study was to evaluate serum periostin levels in patients with AS in comparison with healthy controls as well as their association with clinical, inflammatory and radiographic parameters and molecules involved in bone formation. METHODS: Serum samples for periostin, total Dickkopf-1 (Dkk-1), sclerostin, VEGF and inflammatory markers were obtained from 65 TNF inhibitor-naive patients with AS. The BASDAI, BASFI, modified Stoke AS Spine Score and BASRI for the spine (BASRI-s) were assessed for each patient. Serum periostin levels were also measured in 36 sex-, age- and BMI-matched controls. RESULTS: Serum periostin levels were significantly lower in AS patients compared with controls [234.4 pg/ml (s.e.m. 7.5) vs 291.4 (s.e.m. 8.3), respectively; P < 0.001]. Periostin levels were higher in AS patients with elevated CRP (P = 0.005), high BASDAI (P = 0.014) and low BASRI-s (P = 0.033) and were correlated with BMI (r = -0.304, P = 0.014), ESR (r = 0.395, P = 0.001), CRP (r = 0.413, P = 0.001), BASRI-s (r = -0.242, P = 0.047) and sclerostin (r = -0.280, P = 0.024). In multiple regression analysis, periostin levels were an independent variable of CRP (ß = 0.160, P = 0.009) and sclerostin levels (ß = -0.311, P = 0.012). CONCLUSION: Our data suggest that periostin levels are low in patients with AS. Among AS patients, periostin levels are higher in those with higher disease activity, higher systemic inflammation and less extensive radiographic damage. Periostin is independently associated with CRP and sclerostin levels.

Pachymeningitis in granulomatosis with polyangiitis: a case report and a review of the literature.

Central nervous involvement, mainly with symptoms of cranial neuropathies, occurs in 2-8% of patients with granulomatosis with polyangiitis (GPA). Meningeal involvement, with persistent and severe headache as main manifestation and abnormal thickening and enhancement of the dural mater on postcontrast magnetic resonance imaging, is extremely rare. We present a case of pachymeningitis due to limited GPA, providing simultaneously a literature review.

Efficacy of Anti-TNF Agents as Adjunctive Therapy for Knee Synovitis Refractory to Disease-Modifying Antirheumatic Drugs in Patients with Peripheral Spondyloarthritis.

Our aim was to evaluate the effectiveness of tumour necrosis factor (TNF) inhibitors as add-on therapy for knee synovitis that did not respond to disease-modifying antirheumatic drugs (DMARDs) and other standard treatments in patients with peripheral spondyloarthritis (SpA). We retrospectively studied 27 SpA patients, in whom an anti-TNF agent was added for active peripheral arthritis with knee synovitis refractory to DMARDs and treatment with low-dose oral corticosteroids and/or nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular (IA) corticosteroids. As response of knee synovitis, were considered the absence of swelling, tenderness, and decreased range of movement in the clinical examination, after 4 months of anti-TNF therapy. In twenty-four (88.9%) of the patients there was response of knee synovitis. No statistical differences in gender (P = 0.53), age (P = 0.88), disease subtype (P = 0.22), and pattern of arthritis (P = 0.20) between knee synovitis responders and nonresponders were found. Fourteen patients managed to stop DMARD therapy and six, all of whom were initially on DMARDs combination, to decrease the number of DMARDs to one, maintaining simultaneously the response of knee synovitis. Our results imply a beneficial effect of adjunctive anti-TNF therapy on knee synovitis not responding to DMARDs and other standard treatments in patients with peripheral SpA.

Central skeletal sarcoidosis: a case report with sustained remission only on methotrexate, and a literature review on the imaging approach, treatment, and assessment of disease activity.

We report a case of multifocal involvement of the central skeleton in a patient with long-term stage I pulmonary sarcoidosis who experienced sustained clinical remission of musculoskeletal symptoms while on methotrexate (MTX) alone. Concomitant normalization of laboratory tests [inflammatory markers and angiotensin-converting enzyme (ACE) levels] was observed, and improvements were seen in follow-up magnetic resonance imaging (MRI) of the lumbar spine and bone scintigraphy. To date, there are no specific tools for the assessment of skeletal disease activity in sarcoidosis. Our case suggests that inflammatory markers and ACE levels, when initially elevated, bone scintigraphy, and-in the case of vertebral involvement-MRI could serve as such tools. A literature review on the imaging approach, treatment, and disease activity monitoring of skeletal sarcoidosis is also provided.

Leflunomide addition in patients with articular manifestations of psoriatic arthritis resistant to methotrexate.

In contrast to rheumatoid arthritis, in psoriatic arthritis (PsA), the efficacy of disease-modifying antirheumatic drugs (DMARDs) combination has not been documented. We conducted a retrospective study to evaluate the effectiveness of leflunomide (LEF) addition in 11 PsA patients with articular manifestations that failed to respond to methotrexate (MTX) monotherapy [disease activity score in 28 joints (DAS28) > 3.2)]. Eight of them, all with moderate disease activity (DAS28 < 5.1) at baseline, tolerated the combination. A statistically significant improvement of the mean DAS28, based on erythrocyte sedimentation rate (ESR), and its variables, and C-reactive protein (CRP) at 12-16 weeks after LEF addition was observed. Mean change of DAS28 in patients with polyarticular disease did not differ compared with those with oligoarticular. Based on the European League Against Rheumatism (EULAR) response criteria, none of our patients achieved a good response, seven had a moderate response, and one was a non-responder. The two patients with the lower DAS28 at baseline attained low disease activity (LDA, DAS28 ≤ 3.2), while none reached remission (DAS28 ≤ 2.6). Achievement of clinical remission or at least LDA has been recently proposed as the goal of treatment in PsA. Our results imply that LEF addition may serve as an alternative therapeutic modality for patients with moderately active PsA and, as lower as possible, residual disease activity after the initial therapy with MTX alone.

The role of cytokines and adipocytokines in zoledronate-induced acute phase reaction in postmenopausal women with low bone mass.

OBJECTIVE: Patients treated with intravenous zoledronate frequently experience an acute phase reaction (APR) characterized by flu-like symptoms and increased levels of inflammatory cytokines. We aimed to define the role of various cytokines/adipocytokines in zoledronate-induced APR and develop a prognostic model for its prediction. PATIENTS AND MEASUREMENTS: Fifty-one postmenopausal women with low bone mass were subjected to zoledronate intravenous infusion. Patients were divided into those who experienced APR (APR+) and those who did not (APR-). APR was clinically defined by body temperature and the visual analogue pain scale for musculoskeletal symptoms. White blood cell count, leucocytic subpopulations, C-reactive protein, interleukin-6, tumour necrosis factor-alpha, visfatin, resistin and leptin were measured before and 48 h following the infusion. The quantitative insulin sensitivity check index (QUICKI) and homoeostasis model of assessment - insulin resistance (HOMA-IR) were calculated to assess insulin sensitivity and resistance, respectively. RESULTS: (APR+) patients were younger and had lower baseline visfatin and higher baseline lymphocytes and phosphate compared with APR- patients. QUICKI decreased and HOMA-IR increased in APR+ patients while remained unchanged in APR- patients. In binary logistic regression analysis, a model containing previous bisphosphonate treatment, age, body mass index, lymphocytes and visfatin, which predicted zoledronate-induced APR with 82·1% sensitivity and 73·9% specificity, was selected. In this model, lymphocytes (P = 0·010) and visfatin (P = 0·029) at baseline could independently predict APR. CONCLUSIONS: Zoledronate-induced APR is associated with serum increases of pro-inflammatory cytokines and an increase of insulin resistance. Patients with higher lymphocytes and lower visfatin levels at baseline are at higher risk for APR.