Intramuscular neridronate in patients with rheumatoid arthritis using corticosteroids: evaluation of treatment adherence in a randomized, open-label comparison with other bisphosphonates.

BACKGROUND AND AIMS: Oral bisphosphonates have been used successfully in patients with rheumatoid arthritis (RA), but their use for the treatment of corticosteroid induced osteoporosis may be limited by poor compliance. Neridronate, an intramuscular and intravenous aminobisphosphonate approved for the treatment of osteogenesis imperfecta and Paget's disease, is also effective in postmenopausal osteoporosis. The aim of this study was to compare the adherence of intramuscular neridronate versus oral alendronate or risedronate in patients with RA with corticosteroid-induced osteopenia. METHODS: This randomised, open label, parallel-group, single centre study enrolled post-menopausal women (50-70 years), with RA and osteopenia (T-score >-2.5) who were receiving stable dose of methylprednisolone 5 mg or equivalent within the previous 3 months, and expected to continue therapy for at least 12 months. Patients were treated with intramuscular neridronate 25 mg administered once a month, or oral alendronate 70 mg or oral risedronate 35 mg both administered once-weekly, for 12 months. The main outcome measure was adherence to treatment over 1 year, assessed using the Morisky Medication Adherence Scale 4-item (MMAS-4; adherence defined as patients with MMAS-4 score ≥3). RESULTS: Of 87 women (mean age 61.5 ± 9.2 years) enrolled, 30 were randomized to neridronate, 27 to alendronate and 30 to risedronate therapy. Adherence rates after 12 months were significantly higher with neridronate than with alendronate or risedronate (76.7% vs 47.8% and 48.0%; p<0.05 for both versus neridronate). After 12 months, lumbar and femoral neck BMD and DAS28 were significantly improved in all groups compared with baseline (p<0.05) with no significant difference between the three treatment groups. CONCLUSION: Neridronate is associated with significantly improved adherence to therapy compared with alendronate and risedronate, and improves BMD and disease activity in postmenopausal women with RA and osteopenia. Intramuscular monthly neridronate represents a convenient treatment option for patients with RA using corticosteroids.

Radiofrequency Echographic Multi Spectrometry (REMS) for the diagnosis of osteoporosis in a European multicenter clinical context.

BACKGROUND: Radiofrequency Echographic Multi Spectrometry (REMS) is a non-ionizing technology for the densitometric assessment of osteoporosis. It has already been validated in Italian women with respect to the current clinical reference technology, Dual-energy X-ray Absorptiometry (DXA). PURPOSE: Aim of the current study was to assess the diagnostic accuracy of REMS technology with respect to DXA in a wider European clinical context. METHODS: A total of 4307 female Caucasian patients aged between 30 and 90 years underwent DXA and REMS scans at femoral neck and/or lumbar spine (the site depending on the medical prescription). The acquired data underwent a rigorous quality check in order to exclude the erroneous DXA and REMS reports. The diagnostic agreement between the two technologies was assessed, also stratifying for patients' age groups. The ability to recognise previously fractured patients was also investigated. RESULTS: Overall, 4245 lumbar spine scans and 4271 femoral neck scans were performed. The ability to discriminate patients with and without osteoporosis by femoral neck investigation resulted in sensitivity and specificity of 90.4% and 95.5%, respectively. For lumbar spine scans, a sensitivity of 90.9% and a specificity of 95.1% were obtained. The areas under the curve (AUCs) of the Receiver Operating Characteristic (ROC) curve evaluating the ability to discriminate groups of patients with previous osteoporotic fracture using DXA and REMS T-score values were 0.631 and 0.683 (p < 0.0001), respectively, for femoral neck scans, whereas 0.603 and 0.640 (p = 0.0002), respectively, for lumbar spine scans. CONCLUSION: The diagnostic effectiveness of REMS technology at reference anatomical sites for the assessment of osteoporosis has been confirmed in a large series of female patients, spanning from younger and pre-menopausal to elderly women up to 90 years, in a multicenter European clinical context.

Radiofrequency echographic multi spectrometry for the prediction of incident fragility fractures: A 5-year follow-up study.

PURPOSE: To investigate the effectiveness of the T-score values provided by Radiofrequency Echographic Multi Spectrometry (REMS) in the identification of patients at risk for incident osteoporotic fractures. METHODS: A population of Caucasian women (30-90 years), enrolled from 2013 to 2016, underwent dual X-ray absorptiometry (DXA) and REMS scans at axial sites. The incidence of fragility fractures was assessed during a follow-up period up to 5 years. Afterwards, patients with and without incident fractures were stratified in two age-matched groups with a 1: 2 proportion (Group F' and Group NF', respectively). The performance of REMS T-score in discriminating between the two groups was quantitatively assessed and compared with DXA. RESULTS: 1516 patients were enrolled and 1370 completed the follow-up (mean ± SD: 3.7 ± 0.8 years; range: 1.9-5.0 years). Fracture incidence was 14.0%. Age-matched groups included 175 fractured patients and 350 non-fractured ones, respectively (median age 70.2 [interquartile range: 61.0-73.3] and 67.3 [65.4-69.8] years, p-value ns). The groups resulted also balanced for height, weight and BMI (p-values ns). As expected, the differences in REMS T-score (for vertebral site, -2.9 [-3.6 to -1.9] in Group F', -2.2 [-2.9 to -1.2] in Group NF') and DXA T-score (-2.8 [-3.3 to -1.9] in Group F', -2.2 [-2.9 to -1.4] in Group NF') were statistically significant (p-value <0.001). Analogous results were obtained for femoral neck. Considering the T-score cut-off of -2.5, REMS identified Group F' patients with a sensitivity of 65.1% and specificity of 57.7% of (OR = 2.6, 95%CI: 1.77-3.76, p < 0.001), whereas DXA showed a sensitivity of 57.1% and a specificity of 56.3% (OR = 1.7, 95%CI: 1.20-2.51, p-value = 0.0032). For femoral neck, REMS sensitivity and specificity were 40.2% and 79.9%, respectively, with an OR of 2.81 (95%CI: 1.80-4.39, p < 0.001). DXA, instead, showed a sensitivity and specificity of 42.3% and 79.3%, respectively, with an OR of 2.68 (95%CI: 1.71-4.21, p < 0.001). CONCLUSIONS: REMS T-score resulted an effective predictor for the risk of incident fragility fractures in a population-based sample of female subjects, representing a promising parameter to enhance osteoporosis diagnosis in the clinical routine.

Major osteoporotic fragility fractures: Risk factor updates and societal impact.

Osteoporosis is a silent disease without any evidence of disease until a fracture occurs. Approximately 200 million people in the world are affected by osteoporosis and 8.9 million fractures occur each year worldwide. Fractures of the hip are a major public health burden, by means of both social cost and health condition of the elderly because these fractures are one of the main causes of morbidity, impairment, decreased quality of life and mortality in women and men. The aim of this review is to analyze the most important factors related to the enormous impact of osteoporotic fractures on population. Among the most common risk factors, low body mass index; history of fragility fracture, environmental risk, early menopause, smoking, lack of vitamin D, endocrine disorders (for example insulin-dependent diabetes mellitus), use of glucocorticoids, excessive alcohol intake, immobility and others represented the main clinical risk factors associated with augmented risk of fragility fracture. The increasing trend of osteoporosis is accompanied by an underutilization of the available preventive strategies and only a small number of patients at high fracture risk are recognized and successively referred for therapy. This report provides analytic evidences to assess the best practices in osteoporosis management and indications for the adoption of a correct healthcare strategy to significantly reduce the osteoporosis burden. Early diagnosis is the key to resize the impact of osteoporosis on healthcare system. In this context, attention must be focused on the identification of high fracture risk among osteoporotic patients. It is necessary to increase national awareness campaigns across countries in order to reduce the osteoporotic fractures incidence.

An Advanced Quantitative Echosound Methodology for Femoral Neck Densitometry.

The aim of this paper was to investigate the clinical feasibility and the accuracy in femoral neck densitometry of the Osteoporosis Score (O.S.), an ultrasound (US) parameter for osteoporosis diagnosis that has been recently introduced for lumbar spine applications. A total of 377 female patients (aged 61-70 y) underwent both a femoral dual X-ray absorptiometry (DXA) and an echographic scan of the proximal femur. Recruited patients were sub-divided into a reference database used for ultrasound spectral model construction and a study population for repeatability assessments and accuracy evaluations. Echographic images and radiofrequency signals were analyzed through a fully automatic algorithm that performed a series of combined spectral and statistical analyses, providing as a final output the O.S. value of the femoral neck. Assuming DXA as a gold standard reference, the accuracy of O.S.-based diagnoses resulted 94.7%, with k = 0.898 (p < 0.0001). Significant correlations were also found between O.S.-estimated bone mineral density and corresponding DXA values, with r(2) up to 0.79 and root mean square error = 5.9-7.4%. The reported accuracy levels, combined with the proven ease of use and very good measurement repeatability, provide the adopted method with a potential for clinical routine application in osteoporosis diagnosis.

A novel ultrasound methodology for estimating spine mineral density.

We investigated the possible clinical feasibility and accuracy of an innovative ultrasound (US) method for diagnosis of osteoporosis of the spine. A total of 342 female patients (aged 51-60 y) underwent spinal dual X-ray absorptiometry and abdominal echographic scanning of the lumbar spine. Recruited patients were subdivided into a reference database used for US spectral model construction and a study population for repeatability and accuracy evaluation. US images and radiofrequency signals were analyzed via a new fully automatic algorithm that performed a series of spectral and statistical analyses, providing a novel diagnostic parameter called the osteoporosis score (O.S.). If dual X-ray absorptiometry is assumed to be the gold standard reference, the accuracy of O.S.-based diagnoses was 91.1%, with k = 0.859 (p < 0.0001). Significant correlations were also found between O.S.-estimated bone mineral densities and corresponding dual X-ray absorptiometry values, with r(2) values up to 0.73 and a root mean square error of 6.3%-9.3%. The results obtained suggest that the proposed method has the potential for future routine application in US-based diagnosis of osteoporosis.

Screening and early diagnosis of osteoporosis through X-ray and ultrasound based techniques.

Effective prevention and management of osteoporosis would require suitable methods for population screenings and early diagnosis. Current clinically-available diagnostic methods are mainly based on the use of either X-rays or ultrasound (US). All X-ray based methods provide a measure of bone mineral density (BMD), but it has been demonstrated that other structural aspects of the bone are important in determining fracture risk, such as mechanical features and elastic properties, which cannot be assessed using densitometric techniques. Among the most commonly used techniques, dual X-ray absorptiometry (DXA) is considered the current "gold standard" for osteoporosis diagnosis and fracture risk prediction. Unfortunately, as other X-ray based techniques, DXA has specific limitations (e.g., use of ionizing radiation, large size of the equipment, high costs, limited availability) that hinder its application for population screenings and primary care diagnosis. This has resulted in an increasing interest in developing reliable pre-screening tools for osteoporosis such as quantitative ultrasound (QUS) scanners, which do not involve ionizing radiation exposure and represent a cheaper solution exploiting portable and widely available devices. Furthermore, the usefulness of QUS techniques in fracture risk prediction has been proven and, with the last developments, they are also becoming a more and more reliable approach for assessing bone quality. However, the US assessment of osteoporosis is currently used only as a pre-screening tool, requiring a subsequent diagnosis confirmation by means of a DXA evaluation. Here we illustrate the state of art in the early diagnosis of this "silent disease" and show up recent advances for its prevention and improved management through early diagnosis.

Ibandronate and cementless total hip arthroplasty: densitometric measurement of periprosthetic bone mass and new therapeutic approach to the prevention of aseptic loosening.

Studies of the mechanisms of periprosthetic bone loss have led to the development of pharmacologic strategies intended to enhance bone mass recovery after surgery and consequently prevent aseptic loosening and prolong the implant survival. Bisphosphonates, potent anti-resorptive drugs widely used in the treatment of osteoporosis and other disorders of bone metabolism, were shown to be particularly effective in reducing periprosthetic bone resorption in the first year after hip and knee arthroplasty, both cemented and cementless. Based on these results, we investigated the inhibitory effects of ibandronate on periprosthetic bone loss in a 2-year study of postmenopausal women that underwent cementless total hip arthroplasty. In the first 6 months both groups (A, treated with ibandronate 3 mg i.v. within five days after surgery and then with oral ibandronate 150 mg/month, plus calcium and vitamin D supplementation; and B, treated with calcium and vitamin D supplementation only) experienced bone loss, though to a lesser extent in group A. After 12 months, group A showed a remarkable BMD recovery, that was statistically significant versus baseline values (about +1, 74% of global BMD) and most evident in region R1 (+3, 81%) and R2 (+4, 12%); in group B, on the contrary, BMD values were unchanged compared with those at 6 months post-surgery. Quality of life scores also showed a greater improvement in group A, both at 6 and 12 months after surgery, likely because of the pain-reducing effects of ibandronate treatment.

Clinical utility of clodronate in the prevention and management of osteoporosis in patients intolerant of oral bisphosphonates.

Bisphosphonates have a long history in the treatment of osteoporosis and bone-related disease. This review focuses on the use of a specific nonaminobisphosphonate, clodronate, which appears to be much better tolerated than other bisphosphonates and free of high-risk contraindications. Specifically, this paper reviews its use in the prevention of osteoporosis in postmenopausal women, taking into account its tolerability profile and recent safety issues arising regarding the use of bisphosphonates.

Ibandronate and periprosthetic bone mass: new therapeutic approach in periprosthetic loosening prevention.

A prosthetic implant modifies the physiological transmission of loads to the bone, initiating a remodeling process.Studies of the mechanisms responsible for periprosthetic bone loss contributed to the definition of new pharmacological strategies that may prevent aseptic implant loosening. Bisphosphonates are a class of drugs useful to this purpose, and have been shown to be effective in reducing periprosthetic resorption during the first year after the implant. We aimed to assess the inhibitory effect on periprosthetic osteolysis of ibandronate, a highly potent aminobisphosphonate, administered orally and IV with an extended interval between doses and optimal treatment adherence. In view of the fact that periprosthetic remodeling takes place during the first 6-12 months after surgery and is ultimately responsible for prosthesis longevity, we may conclude that the administration of high dosage ibandronate postsurgery by IV bolus and subsequently as cyclic oral treatment reduced cortical osteopenia in the metaphyseal region, and in the calcar region of the proximal femur. This therapy might therefore be used as preventive measure against postsurgical osteopenia and probably also against aseptic loosening.

Tolerance to etoricoxib in 37 patients with urticaria and angioedema induced by nonsteroidal anti-inflammatory drugs.

BACKGROUND: The use of cyclooxygenase-2 inhibitors, a new class of analgesic drugs, is suggested in patients with hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVE: To evaluate tolerance to etoricoxib, a new cyclooxygenase-2 inhibitor, in NSAID-sensitive patients with urticaria-type adverse reactions. PATIENTS: Thirty-seven patients with adverse reactions to NSAIDs. METHODS: Single-blind, placebo-controlled oral challenge with increasing doses of etoricoxib. RESULTS: Thirty-four patients tolerated etoricoxib treatment without adverse reactions, but a generalized urticarial rash developed in 3 patients (8%). CONCLUSIONS: Etoricoxib, like other cyclooxygenase-2 inhibitors, is a well-tolerated drug in most NSAID-sensitive patients. However, according to our experience, a previous challenge test in a safe environment may be necessary before prescribing the drug to such patients.