Objective To evaluate fenebrutinib, an oral and highly selective noncovalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA). Methods Patients with RA and an inadequate response to methotrexate (MTX) (cohort 1; n = 480) were randomized to receive fenebrutinib (50 mg once daily, 150 mg once daily, or 200 mg twice daily), adalimumab (40 mg every other week), or placebo. Patients with RA and an inadequate response to tumor necrosis factor inhibitors (cohort 2; n = 98) received fenebrutinib (200 mg twice daily) or placebo. Both cohorts continued MTX therapy. Results In cohort 1, the percentages of patients in whom American College of Rheumatology 50% improvement criteria (ACR50) was achieved at week 12 were similar in the fenebrutinib 50 mg once daily and placebo groups, and were higher in the fenebrutinib 150 mg once daily group (28%) and 200 mg twice daily group (35%) than in the placebo group (15%) (P = 0.016 and P = 0.0003, respectively). Fenebrutinib 200 mg twice daily and adalimumab (36%) were comparable (P = 0.81). In cohort 2, ACR50 was achieved in more patients receiving fenebrutinib 200 mg twice daily (25%) than placebo (12%) (P = 0.072). The most common adverse events in the fenebrutinib groups included nausea, headache, anemia, and upper respiratory tract infections. Fenebrutinib had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Fenebrutinib and adalimumab caused overlapping as well as distinct changes in B cell and myeloid biomarkers. Conclusion Fenebrutinib demonstrates efficacy comparable to adalimumab in patients with an inadequate response to MTX, and safety consistent with existing immunomodulatory therapies for RA. These data support targeting both B and myeloid cells via this novel mechanism for potential efficacy in the treatment of RA.

Osteoporosis and hypertension are two frequent diseases among the aging population that share a similar etiopathology and often coexist. Moreover, treatment of hypertension affects bone mineral density and, therefore, can worsen osteoporosis. This narrative review considers the influence of the main etiologic factors that contribute to the development of hypertension and osteoporosis and examines the effect of the most often used antihypertensives on bones. A computerized literature search of relevant English publications regarding the etiology of hypertension and osteoporosis as well as the impact of antihypertensives on osteoporosis from 1996 to 2011 was completed in October 2011. The latest update in the search was performed from May to June 2012. The most relevant nongenetic factors in the etiology of osteoporosis and hypertension are low calcium intake, vitamin D and vitamin K deficiency, high consumption of sodium salt, and the effects of different forms of nitric oxide. Thiazide diuretics are the only antihypertensives that have a positive influence on bone mineral density. For other antihypertensive drugs, the data are conflicting, indicating that they may have a potentially negative or positive influence on bone mineral density and fracture risk reduction. Some studies did not find a correlation between the use of antihypertensives and bone mineral density. Due to the frequent coexistence of hypertension and osteoporosis, when selecting long-term antihypertensive therapy the potential effects of antihypertensive drugs on development, worsening, or improvement of osteoporosis should also be considered.

Pregnancy-associated spinal osteoporosis (PPSO) is a rare condition characterized by severe back pain occurring near the end of the first pregnancy or shortly afterward. The aim of this report is to present a 12-year follow-up of a patient with PPSO. Also, the outcomes of patient's two pregnancies and her infants after long-term treatment with bisphosphonates are assessed. A young woman was referred to our tertiary care hospital aged 30 years, due to intense pain in thoracic and lumbar region that started during the last month of her first pregnancy and got worse after delivery. Bone mineral density (BMD) measurement, clinical, and biochemical parameters were performed. Extremely low lumbar spine BMD, L2-L4: 0.627 g/cm(2), T-score -4.8, Z-score -4.3, 52% young adult indicated severe osteoporosis. Cyclical treatment with etidronate and then pamidronate was started, and a substantial increase in the BMD and the reduction in back pain intensity were observed. An increase in BMD of 44.8% over baseline was observed after 12 years of follow-up. Her two pregnancies were uneventful, and no neonatal adverse effects were observed. Control DXA scan in her girl child aged 6.8 years revealed low BMD at the lumbar spine. As PPSO seems to be an underdiagnosed severe disease, caution is recommended if back pain occurs in the last trimester or early post-partum period. Although pre-pregnancy use of bisphosponates does not pose a substantial fetal risk, their use in women of childbearing age might best be done only when strong clinical indications exist.

Low back pain and knee osteoarthritis are the most common causes of rheumatic troubles among all the nonspecific joint diseases. In the United States, low back pain (LBP) accounts for almost $ 20 billion in lost productivity annually (1), and more than $ 80 billion is spent each year in the management of the disorder (2). Currently, there is no currative treatment for both low back pain and knee osteoarthritis. Nonsteroid antiinflammatory drugs (NSAIDs) are widely used for symptomatic relief (3) due to their analgetic and anti-inflamatory effect..

The aim of this study was to investigate factors related to osteoporosis in postmenopausal women in Belgrade. A case-control study was conducted during 2006-2007. The study group consisted of 100 newly diagnosed osteoporosis patients and 100 age-matched controls (± 2 years). The inclusion criteria for the case group were newly diagnosed osteoporosis confirmed by dual-energy X-ray absorptiometry of the lumbar spine and being menopausal (at least 2 years of amenorrhea). The inclusion criteria for the control group were postmenopausal women with confirmed normal bone mineral density of the lumbar spine by dual-energy X-ray absorptiometry. All study participants were interviewed using a structured questionnaire. Univariate and multivariate logistic regression analyses were used. The following factors were significantly independently related to osteoporosis: low body weight (P < 0.001), thin constitution in childhood (P = 0.002), history of previous fracture (P = 0.033), menopause at age <47 years (P < 0.001), family history of fracture (P = 0.005), and less frequent consumption of cheese (P = 0.027) and fish (P = 0.020). The majority of factors identified may be modifiable and could be influenced to prevent postmenopausal osteoporosis.

Objective: To investigate the association of high baseline serum levels of metalloproteinases-3 (MMP-3) with structural damage to hand and feet joints, assessed by ultrasonography (US), in patients with early, treatment-naïve rheumatoid arthritis (RA), without initial X-ray-visible erosions, during 24 months follow-up. Methods: Sixty-three early RA (European League Against Rheumatism/American College of Rheumatology 2010), disease-modifying anti-rheumatic drugs/glucocorticoid naïve patients (mean age 53.4 ± 14.1) with symptom duration ≤12 months, had baseline serum levels of MMP-3 tested. OMERACT US group definition was used to detect the presence, as well as longitudinal diameter of erosions by US at study entry and after 24 months, at the level of wrists, metacarpophalangeal (MCP2/MCP5) joints of both hands, and fifth metatarsophalangeal joints. Results: Complete data were collected from 52 out of 63 patients. High baseline serum levels of MMP-3 (MMP-3-positive) were found in 46/63 patients. 122 bone erosions in total (1.9 bone erosions/patients) were detected by US at baseline visit and 213 erosions (4.3/patients) after 24 months. MMP-3 positive patients had significantly higher total number of erosions than MMP-3-negative (p = 0.039) and higher increase in size of bone erosions in the feet but not in the hand joints after follow-up (OR 4.82 [1.23–18.9], p = 0.024; OR 1.17 [0.320–4.26], p = 0.816 respectively). Conclusion: After 2 years of follow-up, US assessment showed a higher number of new bone erosions in MMP-3-positive compared to MMP-3-negative patients with early RA and no visible initial radiographic changes. High baseline levels of MMP-3 predict significantly higher structural damage progression at the level of feet, but not at the level of hand joints.

Background/Aim. Osteoporosis mainly affects women in the early years following menopause. The aim of this study was to determine the level of knowledge about osteoporosis and osteoporosis related risk factors in postmenopausal women in Serbia. Methods. The study included postmenopausal women regardless if suffering from osteoporosis or not. Assessment of knowledge was carried out by using the Osteoporosis Knowledge Assessment Tool -Shorter Version (OKAT-S) questionnaire that was validated for Serbian population. Answers to the 9 questions were coded as 1 -true, or 0 -false or "do not know". Also, the following risk factors data for osteoporosis were collected: age, the onset and duration of menopause, body mass index (BMI), data on fractures, the incidence of falls, smoking, lifestyle (active, sedentary), regular sunbathing, calcium and vitamin D supplementation, intake of milk and dairy products. Results. A total of 132 postmenopausal women responded to the questionnaire with the response rate of 90.41%. Their knowledge varied from Vujasinović Stupar N, et al. Vojnosanit Pregl 2017; 74(5): 445-449.

Objective: The aim of this paper is to reportthe first case of drug-induced eosinophilic myocarditis (EM) in a patient with hereditary periodic fever syndrome (PFS). Case: A 28-year-old man with hyper-IgD syndrome, one of the PFS, developed a sulfasalazine-induced systemic hypersensitivity reaction complicated by EM. Thirteen days after sulfasalazine introduction, which had been given for arthritis, the patient developed fever, facial/neck edema, rash and cardiogenic shock, and died within 8 h. The autopsy revealed hemophagocytosis, while acute heart failure caused by necrotizing EM was established as the cause of death. Conclusion: This was a case of drug-induced EM in a patient with PFS that had an atypical presentation, rapid evolution and poor outcome.