Effects of Treatment With Risedronate and Alfacalcidol on Progression of Atherosclerosis in Postmenopausal Women With Type 2 Diabetes Mellitus Accompanied With Osteoporosis

IntroductionAccumulating evidence suggests that osteoporosis and cardiovascular disease have epidemiologic similarities. This study investigated the effects of treatment with risedronate and alfacalcidol on parameters of atherosclerosis in postmenopausal women with type 2 diabetes accompanied with osteoporosis.MethodsThirteen Japanese type 2 diabetes postmenopausal women with newly diagnosed osteoporosis (osteoporosis group) and 13 age- and weight-matched diabetic women with normal bone mineral density (control group) were enrolled in this 1-year prospective study. Risedronate (2.5 mg/d) and alfacalcidol (1 μg/d) were given to the osteoporosis group for a year. We measured parameters of atherosclerosis, such as ultrasonographically evaluated plaque score (PS) and abdominal aortic calcification score (AACS) calibrated by x-ray.ResultsPatients with osteoporosis had significantly higher PS and AACS than control [mean (range)—PS: 11.85 (0.00–27.50) versus 4.90 (0.00–10.90), P = 0.02 and AACS: 4.0 (0.0–14.0) versus 1.0 (0.0–7.0), P = 0.01]. After 1-year treatment, PS and AACS in the osteoporosis group were not statistically changed, whereas both parameters in the control group were significantly increased (P = 0.01 and P = 0.03, respectively). When percent changes in these parameters were compared between 2 groups, they were significantly different at any time points (at least P < 0.05).ConclusionsAtherosclerosis parameters in diabetic patients with osteoporosis were higher than those in patients without it. Combination therapy of risedronate with alfacalcidol might protect against progressive atherosclerosis.     

The significance of forearm bone mineral density evaluation in determining surgical indications in primary hyperparathyroidism

PurposeForearm osteoporosis is a well-known complication of primary hyperparathyroidism (PHPT). However, measuring forearm bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) at the distal radius is often neglected in clinical practice despite the fact that osteoporosis at any site is a criterion indicating surgery. We aimed to evaluate the importance and priority of forearm BMD and to determine its association with biochemical parameters.Material and methodsThree hundred fourteen patients (272 females, 42 males) with PHPT who had BMD measurements at 3 sites were recruited for this retrospective study. The effect on surgical indications of osteoporosis only in the forearm was evaluated. Group 1 (n = 151) with forearm osteoporosis and group 2 (n = 163) without were compared in terms of biochemical and clinical parameters.ResultsIn the overall study population, 165 of the 314 patients had osteoporosis in at least 1 site. Twenty seven percent (n = 86/314) had osteoporosis only in the forearm, while the other 2 sites (lumbar spine and femoral neck) were normal or osteopenic. Surgery was indicated based on osteoporosis only in the forearm in 10% of patients (n = 30/314). Corrected calcium and parathyroid hormone levels were significantly higher in group 1 than group 2 (p = 0.001 and p < 0.001, respectively) and were also negatively correlated with distal radius BMD, T-score and Z-score in the whole study group.ConclusionIncluding the distal radius in BMD measurement increased the number of patients diagnosed with osteoporosis and for whom surgery was indicated. Calcium and PTH were also more frequently elevated in patients with forearm osteoporosis. These results show that distal radius BMD is relevant to the management of PHPT.     

狄诺塞麦:治疗绝经期女性骨质疏松的新希望

狄诺塞麦是目前用于治疗绝经期骨质疏松的第一种单克隆抗体药物.它能与细胞核因子-κB受体活化因子配体(RANKL)结合,通过抑制破骨细胞的产生、功能和存活,减少骨吸收达到治疗作用.临床试验显示,在绝经后骨质疏松妇女中,狄诺塞麦增加骨密度(BMD)和降低骨折风险的作用优于安慰剂和阿仑膦酸,不良反应与安慰剂和阿仑膦酸相当.药...     

Bone mineral density in patients with systemic sclerosis and its association with hand involvement

Aim of the workThe aim of the present study is to assess bone mineral density (BMD) in systemic sclerosis (SSc) patients and to determine associated factors.Patients and methodsSixty-five female SSc patients (mean age 39.5 ± 13.5 years, disease duration 7.3 ± 5.9 years), and forty age- and sex- matched controls were included. Forty-seven patients had limited SSc and 18 had diffuse type. Patients were subjected to clinical and functional assessment. BMD was quantified at the distal radius, femoral neck and lumbar spine (L2–4) by dual energy X-ray absorptiometry.ResultsSSc patients had a higher frequency of osteoporosis at the distal radius and osteopenia at the lumbar spine (p = 0.001 and 0.002, respectively), but the BMD at the femoral neck was not significantly different from the control group. Patients with osteoporosis at the distal radius had a significantly higher frequency of hand deformities (p < 0.05) and higher functional scores reflecting more disability than patients without (p = 0.01), while patients with osteoporosis at the lumbar spine were significantly older (p < 0.001) and had a longer disease duration than those without (p = 0.001). No associations were found between menopausal status, SSc subtype, skin score, internal organ affection and osteoporosis at the three skeletal sites.ConclusionPatients with SSc have lower bone mineral density than controls at the distal radius and lumbar spine. Osteoporosis at the distal radius is associated with the presence of hand deformity and functional disability, while osteoporosis at the lumbar spine is associated with older age and longer disease duration.     

Impact of coexisting overactive bladder in Medicare patients with osteoporosis

BackgroundOsteoporosis and overactive bladder (OAB) are prevalent conditions in older adults and are independent risk factors for falls and fractures. A paucity of evidence exists examining the impact of coexisting OAB in patients with osteoporosis.ObjectiveTo examine the impact of OAB on healthcare resource utilization (HRU), clinical outcomes, and healthcare costs among older adult patients with osteoporosis.MethodsThis retrospective analysis compared patients with osteoporosis with and without OAB. Patients with an osteoporosis diagnosis, enrolled in a Medicare Advantage plan, and aged 65–89 inclusive were eligible. Incident OAB among patients with prevalent osteoporosis was identified. A comparison group of patients with osteoporosis but no evidence of OAB was propensity score matched on baseline characteristics. Fall and/or fracture outcomes, HRU and healthcare costs were evaluated during 12 months of follow-up. Bivariate comparisons of outcomes were conducted. Ordinary least squared regression was used to examine the relationship between OAB and total healthcare costs.ResultsAfter matching, 5,526 patients in each group were included. Patients with osteoporosis and OAB demonstrated greater all-cause HRU across all encounter types compared to patients without OAB (all P values < 0.001). Patients with osteoporosis and OAB had a greater frequency of any fall/fracture (17.7% vs. 14.9%, P < 0.001). Patients with osteoporosis and OAB had 35% greater all-cause total healthcare costs than patients without OAB (P < 0.001).ConclusionsPatients with OAB and osteoporosis had significantly greater all-cause HRU and costs. Falls and fractures were significantly more common in patients with osteoporosis and OAB compared to patients with osteoporosis without OAB.     

Denosumab for the treatment of adult multisystem Langerhans cell histiocytosis

PurposeAn etiological treatment is currently lacking for Langerhans Cell Histiocytosis (LCH). Receptor activator of nuclear factor κB ligand (RANKL) appears to play a central role in the lesional immunological process inducing compensatory osteoprotegerin (OPG) activation. In a preliminary study we aimed to evaluate for the first time the use of denosumab, a RANKL inhibitor, as a targeted treatment strategy in LCH in order to support and enhance endogenous OPG action in order to control or alter the lesional immunological process.ProceduresTwo adult female patients with painful osteolytic bone lesions and concomitant pulmonary involvement received bimonthly denosumab 120 mg in a total of 4 doses.ResultsBoth patients reported an immediate pain relief within the first two weeks following the 1st dose of denosumab. One month following the last dose an almost full remission of the initial osteolytic and lung lesions was observed, although an apparent new bone lesion was detected in one patient that was treated with a single intralesional steroid injection. No adverse events were recorded throughout the treatment period. Both patients have no active disease 6 months following the last denosumab dose.ConclusionsDenosumab could be considered an effective treatment option in adults with multisystem LCH also exerting a significant analgesic effect in bone lesions, warranting further investigation.     

Reductions in systolic blood pressure with liraglutide in patients with type 2 diabetes: Insights from a patient-level pooled analysis of six randomized clinical trials

AimsTo quantify the effect of liraglutide on systolic blood pressure (SBP) and pulse in patients with type 2 diabetes (T2D), and assess the influence of covariates on observed SBP reductions.MethodsA patient-level pooled analysis of six phase 3, randomized trials was conducted.ResultsThe analysis included 2792 randomized patients. In the intention-to-treat population (n = 2783), mean [± SE] SBP reductions from baseline with liraglutide 1.2 mg (2.7 [0.8] mmHg) and 1.8 mg (2.9 [0.7] mmHg) once daily were significantly greater than with placebo (0.5 [0.9] mmHg; P = 0.0029 and P = 0.0004, respectively) after 26 weeks, and were evident after 2 weeks. Liraglutide was also associated with significantly greater SBP reductions than glimepiride and, at a dose of 1.8 mg, insulin glargine and rosiglitazone. SBP reductions with liraglutide weakly correlated with weight loss (Pearson’s correlation coefficient: 0.08–0.12; P ≤ 0.0148). No dependence of these reductions on concomitant antihypertensive medications was detected (P = 0.1304). Liraglutide 1.2 and 1.8 mg were associated with mean increases in pulse of 3 beats per minute (bpm), versus a 1 bpm increase with placebo (P < 0.0001 for each dose versus placebo).ConclusionsLiraglutide reduces SBP in patients with T2D, including those receiving concomitant antihypertensive medication.     

Efficacy and Safety of Oral Conivaptan,a Vasopressin-Receptor Antagonist,Evaluated in a Randomized,Controlled Trial in Patients With Euvolemic or Hypervolemic Hyponatremia

BackgroundIn most cases of hyponatremia, arginine vasopressin secretion is inappropriately high. This placebo-controlled, randomized, double-blind multicenter study evaluated the efficacy and safety of oral conivaptan, a V_1A/V₂-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia.MethodsEighty-three patients with serum [Na⁺] less than 130 mEq/L were stratified by volume status and randomly assigned to placebo or conivaptan 40 or 80 mg/d for 5 days.ResultsConivaptan increased the baseline-adjusted area under the serum [Na⁺]-time curve significantly more than placebo (P = 0.0001). Patients given either dose of conivaptan demonstrated a serum [Na⁺] of 4 mEq/L or greater above baseline significantly faster than those given placebo (P < 0.001) and maintained that increase for a greater total time (P = 0.0001). The least squares mean change in serum [Na⁺] from baseline to end of treatment was also significantly greater with conivaptan 40 and 80 mg/d (6.8 and 8.8 mEq/L, respectively) (P = 0.0001) than that with placebo (1.2 mEq/L). The percentage of patients who obtained an increase from baseline in serum [Na⁺] of 6 mEq/L or greater or normal serum [Na⁺] was significantly higher among patients given conivaptan 40 and 80 mg/d (67% and 88%, respectively) than among those given placebo (20%; P < 0.001). Conivaptan was well tolerated; the most frequent adverse events were urinary tract infection, anemia, pyrexia, cardiac failure, hypotension, and hypokalemia.ConclusionOral conivaptan was effective in increasing serum [Na⁺] in patients with euvolemic or hypervolemic hyponatremia and had a favorable safety profile.     

A randomised controlled trial of high dose vitamin D in recent-onset type 2 diabetes

AimsVitamin D insufficiency has been associated with impaired pancreatic beta-cell function. We aimed to determine if high dose oral vitamin D3 (D) improves beta-cell function and glycaemia in type 2 diabetes.MethodsFifty adults with type 2 diabetes diagnosed less than 12 months, with normal baseline serum 25-OH D (25D), were randomised to 6000 IU D (n = 26) or placebo (n = 24) daily for 6 months. Beta-cell function was measured by glucagon-stimulated serum C-peptide (delta C-peptide [DCP], nmol/l). Secondary outcome measures were fasting plasma glucose (FPG), post-prandial blood glucose (PPG), HbA1c and insulin resistance (HOMA-IR).ResultsIn the D group, median serum 25D (nmol/l) increased from 59 to 150 (3 months) and 128 (6 months) and median serum 1,25D (pmol/l) from 135 to 200 and 190. After 3 months, change in DCP from baseline in D (+0.04) and placebo (−0.08) was not different (P = 0.112). However, change in FPG (mmol/l) was significantly lower in D (−0.40) compared to placebo (+0.1) (P = 0.007), as was the change in PPG in D (−0.30) compared to placebo (+0.8) (P = 0.005). Change in HbA1c (%) between D (−0.20) and placebo (−0.10) was not different (P = 0.459). At 6 months, changes from baseline in DCP, FPG, PPG and HbA1c were not different between groups.ConclusionOral D3 supplementation in type 2 diabetes was associated with transient improvement in glycaemia, but without a measurable change in beta-cell function this effect is unlikely to be biologically significant. High dose D3 therefore appears to offer little or no therapeutic benefit in type 2 diabetes.     

Acute effect of sildenafil on myocardial ischemic territories in patients with stable coronary artery disease

ObjectivesTo test the safety of sildenafil in patients with stable coronary artery disease (CAD).MethodsSixty-one patients with stable CAD, documented by coronary angiography were included in this phase I study. Patients were randomized to either single dose sildenafil or matched placebo. Speckle tracking echocardiography was done at baseline and 60 min after sildenafil/placebo intake to calculate peak systolic strain (PSS) of the most severely affected myocardial segments and the global longitudinal PSS.ResultsThe baseline mean segmental PSS in the sildenafil group changed by 52%, −3 ± 1% at baseline versus −7 ± 2% after sildenafil intake, P = 0.01. However, no significant changes were reported in the placebo group, −7 ± 3% at baseline versus −7.25 ± 3%, P = 0.1. The baseline mean global longitudinal PSS in the sildenafil group changed by 9% (−15 ± 4% at baseline versus −18 ± 3% after sildenafil, P = 0.03). In placebo patients, the change was only 3% from baseline (−14.8 ± 2% at baseline compared to −15 ± 2% after placebo intake, P = 0.1). Sildenafil was well tolerated without clinical or hemodynamic deterioration after its intake.ConclusionSildenafil intake is safe in patients with stable CAD, it induced marginal improvements in the peak systolic strain of different myocardial ischemic territories.     

Prevalence and risk factors of osteopenia/osteoporosis in Turkish HIV/AIDS patients

BackgroundRecent studies showed a high frequency of low bone mineral density (BMD) in HIV-infected patients and no reports have been issued in Turkey. Our aim was to evaluate BMD and risk factors for osteopenia/osteoporosis in HIV-infected patients that attended an outpatient clinic in Istanbul, Turkey.MethodIn order to determine the prevalence of BMD, 126 HIV-infected patients had been studied with dual energy X-ray absorptiometry (DEXA). The association between BMD and age, gender, body mass index (BMI), habits, 25(OH)vitamin D, HIV RNA, CD4 lymphocyte nadir, using and duration of highly active antiretroviral treatment (HAART) were investigated by using multivariate analysis.ResultsMedian age was 40.1 years (range, 20–70); 84% were male; 35.7% patients had AIDS, 63.5% were treated with HAART. Osteopenia and osteoporosis were diagnosed in 53.9% and 23.8%, respectively. Mean plasma HIV RNA was 5.2 (SD 1.0) log₁₀ copies/mL and CD4 lymphocyte nadir was 313.8 (SD 226.2)/mm³. Factors associated with bone loss were high viral load (p = 0.034), using (p = 0.033) and duration of HAART (p = 0.008). No correlation had been seen between sex and osteopenia/osteoporosis (p = 0.794). However, males showed higher rates of osteoporosis than females (p = 0.042).ConclusionsOur results show a very high prevalence of bone mass reduction in Turkish HIV-infected patients. This study supports the importance of both HIV and antiretroviral therapy in low BMD.     

Use of a non-specific immunomodulation therapy as a therapeutic vasculogenesis strategy in no-option critical limb ischemia patients

Background/aimsInflammatory mediators contribute to the impairment of vasculogenesis by reducing endothelial progenitor cells (EPCs) mobilization in atherosclerotic vasculopathy.We tested the hypothesis that administration of an oxygen/ozone mixture (IMT) might counteract this pathophysiological mechanism and enhance limb tissue perfusion in patients with critical limb ischemia (CLI).MethodsRandomized patients with rest pain or ischemic ulcers and transcutaneous oxygen tension (TcPO₂) <40 mmHg and/or toe pressure <50 mmHg received placebo (n = 74) or a non-specific immunomodulation therapy (IMT) (n = 77), autologous blood exposed to oxygen/ozone gas mixture by intragluteal injection, on day 1, 2, 7, and once a week thereafter for at least 22 weeks. Patients were evaluated for changes in TcPO₂, levels of circulating EPCs (CD34/KDR-positive cells) and inflammation (tumor necrosis factor-α—TNF-α).ResultsTcPO₂ and CD34/CD133-positive cells increased at 22 weeks in IMT group (P < 0.01) whereas no changes were observed in placebo group. TNF-α levels decreased at 6 months in IMT group (P < 0.001) whereas no changes were observed in placebo group. There was a strong positive correlation between CD34/KDR-positive cells and TcPO₂ (r = 0.56, P < 0.01). Moreover, there was an inverse correlation between CD34/KDR-positive cells and TNF-α (r = ?0.51, P < 0.01).ConclusionsIntramuscular injection of IMT may improve wound healing and limb salvage in patients with CLI.     

Hyoscine N-butylbromide for adenoma detection during colonoscopy: A randomized,double-blind,placebo-controlled study

BackgroundHyoscine N-butylbromide (HBB), commonly used during colonoscopy to facilitate cecal intubation, has been proposed to increase the adenoma detection rate (ADR).AimsTo evaluate whether HBB administration increases the adenoma detection rate and influences patients’ tolerance.MethodsConsecutive colonoscopy outpatients were randomized after cecal intubation to receive either 20 mg HBB or placebo i.v. The number, size, histology and location of polyps were recorded. The air retained in the abdomen was either indirectly estimated by ΔAC (difference in the abdominal circumference measured before and after colonoscopy) or directly evaluated by patients’ perception (visual analogic scale, range 0–100).Results402 patients (44% male; mean age 57.7 ± 12.5 years) received either HBB or placebo. No differences in ADR (31.7% vs. 28%, p = 0.48), advanced-ADR (7.4% vs. 10.5%, p = 0.35) were observed between HBB and placebo group, respectively. A significantly lower detection rate of flat/depressed lesions was observed in the HBB group (0.5% vs. 5.5%, p = 0.003). The ΔAC and the bloating perception were comparable between the two groups (p = 0.22 and p = 0.48, respectively).ConclusionsHBB administered before colonoscope withdrawal does not increase adenoma detection rate and seems to hamper the visualization of flat/depressed lesions. This finding raises concerns on the indiscriminate use of HBB during colonoscopy.     

Efficacy and safety of sitagliptin added to ongoing metformin and pioglitazone combination therapy in a randomized,placebo-controlled, 26-week trial in patients with type 2 diabetes

AimsTo assess efficacy and safety of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in combination therapy with metformin (≥ 1500 mg/day) and pioglitazone (≥ 30 mg/day) in patients with type 2 diabetes (T2DM) with inadequate glycemic control (hemoglobin A_1c [HbA_1c] ≥ 7.5% and ≤ 11%).MethodsThis placebo-controlled, double-blind study included 313 patients, mean baseline HbA_1c = 8.7%, who were randomized to receive sitagliptin 100 mg/day or placebo for 26 weeks.ResultsThe addition of sitagliptin led to significant (P < .001) mean changes from baseline relative to placebo in HbA_1c (? 0.7%), fasting plasma glucose (? 1.0 mmol/L), and 2-h post-meal glucose (? 2.2 mmol/L). In patients with baseline HbA_1c ≥ 9.0%, mean changes from baseline in HbA_1c were ? 1.6% and ? 0.8% for the sitagliptin and placebo groups, respectively (between-group difference ?0.8%; P < .001). The incidences of reported adverse events were generally similar between the treatment groups. Incidences of symptomatic hypoglycemia were 7/157 [4.5%] and 6/156 [3.8%] in the sitagliptin and placebo groups, respectively (P = .786). Two patients, both in the placebo group, experienced an episode of hypoglycemia that required non-medical assistance.ConclusionsIn this 26-week study, addition of sitagliptin to combination therapy with metformin and pioglitazone improved glycemic control and was generally well tolerated.     

Angiotensin II receptor antagonism with telmisartan increases number of endothelial progenitor cells in normotensive patients with coronary artery disease: A randomized,double-blind,placebo-controlled study

IntroductionCirculating endothelial progenitor cells (EPCs) provide an endogenous repair mechanism of the dysfunctional endothelium and therefore can play a crucial role in the pathophysiology of coronary artery disease (CAD). Angiotensin II receptor antagonism has been shown to be able to increase EPCs in hypertension but its effect in patients with CAD is unknown. Aim of this study was to evaluate whether telmisartan, an angiotensin II receptor antagonist, can modify the number of subpopulations of EPCs and may in turn affect the endothelial function of normotensive patients with CAD.MethodsIn a prospective double-blind parallel group study, 40 normotensive patients with CAD were randomly treated with telmisartan (80 mg) or placebo for 4 weeks at time of coronary angiography. Measurements of EPCs and assessment of flow-mediated dilatation (FMD) of the brachial artery was performed before and after therapy.ResultsAbsolute number of EPCs was similar at baseline in the telmisartan and placebo groups. After 4 weeks treatment, CD34+/KDR+/CD45? cells increased significantly in the telmisartan group (from 0.010 ± 0.003 to 0.014 ± 0.004%, P = 0.0001) but not in the placebo group (from 0.009 ± 0.004 to 0.009 ± 0.005%, NS). Similarly, CD133+/KDR+/CD45? cells raised significantly with telmisartan (from 0.003 ± 0.002 to 0.006 ± 0.002%, P = 0.0001) but not with placebo (from 0.004 ± 0.003 to 0.003 ± 0.002%, NS). Also, CD14+/CD45+ cells increased significantly with telmisartan (from 0.005 ± 0.002 to 0.008 ± 0.002%, P = 0.0001) and were unchanged with placebo (0.006 ± 0.002 vs. 0.005 ± 0.003%, NS). FMD improved significantly in patients who received telmisartan (10.4 ± 3.9%, P = 0.0015 vs. baseline) but did not change in the placebo group (5.9 ± 2.8%; P = 0.32 vs. baseline; telmisartan vs. placebo, P = 0.002). A significant positive correlation was found in the telmisartan group between the improvement in FMD and the increase in CD34+/KDR+/CD45? cells and CD133+/KDR+/CD45? cells (r = 0.55, P < 0.01, and r = 0.49, P < 0.05, respectively).ConclusionAngiotensin II receptor antagonism with telmisartan increases the number of regenerative EPCs and improves endothelial function in normotensive patients with CAD. These novel effects are interrelated and can explain, at least in part, why telmisartan has beneficial cardiovascular effects independent of its blood pressure lowering action.     

Short term effects of sildenafil citrate therapy in secondary pulmonary hypertension

ObjectivesTo study the short term effects of sildenafil citrate therapy in patients with secondary pulmonary hypertension.MethodsForty patients with known symptomatic secondary pulmonary hypertension due to valvular heart disease, chronic thromboembolic disease, chronic obstructive pulmonary disease, interstitial pulmonary fibrosis, and idiopathic dilated cardiomyopathy were included in this phase II study. Patients were allocated in a randomized, placebo controlled design to either sildenafil or placebo for 6 weeks. Baseline and 6 week follow up included assessment of hemodynamic parameters, functional class using the NYHA classification, echocardiographic measurements of pulmonary artery systolic pressure and left ventricular ejection fraction.ResultsThe mean NYHA class at 6 weeks was 2.05 ± 0.4 in the sildenafil group versus 2.6 ± 0.6 in the placebo group, p = 0.02. The mean systolic pulmonary artery pressure significantly decreased in the sildenafil group at 6 weeks (43 ± 4 mmHg), compared to placebo patients (53 ± 7 mmHg), p = 0.02. Ejection fraction was higher in the sildenafil group, 59 ± 12% versus 54 ± 14% in the placebo group, but did not reach statistically significant difference. Sildenafil was well tolerated with minimal side effects.ConclusionOur data suggest that sildenafil therapy may provide benefits to selected patients with pulmonary hypertension secondary to cardiac or pulmonary diseases.     

Intravenous Iron Replacement Improves Exercise Tolerance in COPD: A Single-Blind Randomized Trial

IntroductionIron deficiency affects exercise capacity because of the critical role iron plays in the optimal functioning of skeletal muscle metabolism. We hypothesized that intravenous iron may improve exercise tolerance, quality of life (QoL), and daily physical activity (DPA) in patients with chronic obstructive pulmonary disease (COPD).MethodsThis was a placebo-controlled, single-blind, parallel-group, randomized clinical trial. Iron deficiency was defined as a ferritin level < 100 ng/mL or a ferritin level between 100 and 299 ng/mL with a transferrin saturation < 20%, with or without mild anaemia. Patients were randomized at a 2:1 ratio to receive intravenous ferric carboxymaltose or placebo. The primary objective was to investigate whether intravenous iron replacement improved endurance time from baseline by at least 33%. The secondary objectives were to evaluate impact on QoL using the COPD Assessment Test (CAT) and on DPA by accelerometry.ResultsWe included 66 patients, 44 (66.7%) in the intervention group and 22 (33.3%) in the placebo group. Among patients receiving ferric carboxymaltose, 23 (52.3%) achieved the primary endpoint compared to 4 (18.2%) in the placebo group [p = 0.009; relative risk 3.12, (95% CI, 1.19–8.12)]. CAT score decreased ?3 (?6.0–1.3) points from baseline in the intervention group (p = 0.007), in contrast to placebo group [?1 (?4.0–2.3) points, p = 0.236] with no differences in DPA and adverse events in both groups.ConclusionsIron replacement improved exercise capacity and QoL in stable COPD patients with iron deficiency. The treatment was well tolerated.Clinical Trial registrationEudraCT 2016-001238-89.     

Serum leptin and osteoporosis in postmenopausal women with primary knee osteoarthritis

Aim of the workThe purpose of this study was to evaluate the relationship of serum leptin level and osteoporosis in postmenopausal women with knee osteoarthritis (KOA).Patients and methodsThe study included 40 postmenopausal women with primary KOA and 37 age-matched postmenopausal healthy controls. Plain X-ray knees were performed and assessed using the Kellgren–Lawrence (KL) grading scale. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry (DXA) in lumbar spine, hip and forearm regions. As a bone turn-over marker serum osteocalcin was measured. Serum leptin level was assessed in patients and control.ResultsThe mean age of the KOA patients was 58.05 ± 5.7 years. Osteoporosis was detected among 15% of the KOA patients and 35.1% of the control. The BMD was significantly increased at the spine and wrist in the patients than in the control (p = 0.011 and p = 0.015 respectively). The serum osteocalcin was comparable between patients (19.74 ± 8.05 ng/ml) and control (21.2 ± 8.36 ng/ml) (p = 0.5). Serum leptin was significantly higher in the patient (58.7 ± 27.17 ng/ml) compared to the control (48.75 ± 13.19 ng/ml) (p = 0.048), and significantly correlated with the degree of KOA (p = 0.017). No significant correlation was found between serum osteocalcin level or the BMD and the degree of KOA. There was a significant negative correlation between serum osteocalcin level and forearm BMD in KOA patients (r = −0.33, p = 0.038).ConclusionsAlthough postmenopausal women with KOA had significantly higher BMD, both diseases can coexist. It seemed that osteoarthritis does not prevent the occurrence of osteoporosis. Our study suggested a promising role of leptin as a biomarker of KOA.     

Clinical trial: Preliminary efficacy and safety study of a new Budesonide-MMX® 9 mg extended-release tablets in patients with active left-sided ulcerative colitis

BackgroundUlcerative colitis (UC) is a chronic inflammatory disease with relapses. Many patients need systemic corticosteroids to induce clinical remission.AimEfficacy and safety of Budesonide-MMX^® 9 mg tablets, a new oral, extended-release formulation, were evaluated in patients suffering from active, left-sided UC with colitis activity index (CAI) < 14.Methods36 patients were treated once daily for 4 weeks with Budesonide-MMX^® 9 mg tablets or placebo. In an additional 4-week period, all patients received Budesonide-MMX^®. CAI, endoscopic index and histology were assessed after 4 and 8 weeks. Primary end-point was remission, and/or CAI reduction by 50% after 4 weeks. Morning cortisol was assayed after 4 and 8 weeks, and a short ACTH-test was performed at week 8.Results32 patients were analysed. After 4 weeks, 47.1% of the patients in the Budesonide-MMX^® 9 mg tablets group achieved the primary end-point vs. 33.3% of patients on placebo. In addition, 47.1% of budesonide patients and another 33.3% of placebo recipients improved without remission by 4 weeks. The CAI reduction was significant with Budesonide (p < 0.0001) tablets and not with placebo (p = 0.1). Neither morning cortisol nor pituitary–adrenal axis was more frequently suppressed with Budesonide tablets than with placebo.ConclusionsBudesonide-MMX^® 9 mg tablets induced a fast and significant clinical improvement of active left-sided UC without suppression of adrenocortical functions and without important toxicity EudraCT number 2004-000896-33.     

The relationship between plasma homocysteine levels and bone mineral density in post-menopausal women

BackgroundWhether or not mild hyperhomocysteinemia and low serum levels of folates or vitamin B12 are risk factors for osteoporosis in the elderly is controversial.Aims and methodsTo investigate whether or not plasma levels of total homocysteine (tHcy) and serum levels of folates and vitamin B12 are associated with bone mineral density (BMD), we carried out a cross-sectional study on 446 post-menopausal women (mean age: 65.1 ± 9.4 years), consecutively seen at the Siena Unit (Tuscany region, Central Italy) for BMD evaluation over a two-year period. BMD of the total femur, femoral neck and lumbar spine was detected by dual-energy X-ray absorptiometry.ResultsThe age-adjusted geometric mean of plasma tHcy levels (µmol/L) was 9.96 ± 1.29 in women with normal BMD, 11.06 ± 1.32 in those with osteopenia and 11.88 ± 1.35 in those with osteoporosis (p < 0.0001). On multiple linear regression analysis, adjusting for age, body mass index, folates, vitamin B12, creatinine clearance, smoking habit and alcohol intake, tHcy was negatively related to BMD of the total femur [β estimate for log-homocysteine: ? 0.050 (95% CI: ? 0.100 to ? 0.001, p = 0.048; R² = 0.02)], but not of femoral neck or lumbar spine. There was no significant association between BMD and serum levels of folates and vitamin B12.ConclusionstHcy is negatively associated with BMD of the total femur. The contribution of tHcy to explain the variance of BMD is small (2% of the total variance) but clinically relevant, considering the high prevalence of osteoporosis among post-menopausal women and the possibility to lower tHcy by vitamin supplementation.