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To assess the long-term effectiveness and safety of tocilizumab, abatacept, and tumor necrosis factor-α inhibitors (TNFi), in the Italian real-world setting of rheumatoid arthritis (RA). The records of adult RA patients from the Italian biologics' registry Gruppo Italiano Studio Early Arthritis (GISEA) were analyzed. Demographic and clinical data were obtained at entry. The disease remission rate (28-joint disease activity score calculated using the erythrocyte sedimentation rate [DAS28-ESR] ≤ 2.6) and frequency of adverse events (AEs) were evaluated at 2 years. From 1999 to 2014, 7539 patients were treated with biologics (61.3% in first- and 22.6% in second-line), 68% of cases received TNFi, 9.1% tocilizumab, and 8.6% abatacept. Treatment groups showed a similar DAS28 at entry. As first-line, tocilizumab induced a significantly higher remission rate than abatacept or TNFi at 6 (51 vs 23.3 and 26.2%, respectively; p < 0.0001) and 24 months (52.3 vs 33.3 and 34.4%, respectively; p < 0.01). A similar pattern was observed in later lines. The most common AEs reported were infections, reactions to biologics (more frequent among TNFi-treated patients), increased transaminase (more frequent among TCZ-treated patients), and cardiovascular events. In clinical practice, TCZ induced a rapid and long-lasting remission and in a higher percentage of patients compared to abatacept and TNFi, with a good safety profile. [ABSTRACT FROM AUTHOR]

Hypertension and related cardiovascular diseases are reported to be associated with osteoporosis. A nutritional pathway related to dairy intake has been postulated for both diseases. The aim of this study was to assess calcium intake from dairy sources as a possible pathogenic link between osteoporosis and hypertension. This was a cross-sectional observational study performed on 3,301 postmenopausal women referred for a densitometry screening. Osteoporosis was diagnosed by lumbar dual-energy X-ray absorptiometry and hypertension was defined by blood pressure data and/or the use of antihypertensive medication. Dairy food consumption was evaluated using a weekly food-frequency questionnaire. The odds of being affected by osteoporosis, hypertension, or both diseases were calculated for quartiles of dairy intake by logistic regression analyses. Women with hypertension were affected more frequently by osteoporosis (33.2 vs. 23.3 %; p = 0.000), and there was a higher prevalence of hypertension among women with osteoporosis (32.2 vs. 22.5 %; p = 0.000). The proportion of women with hypertension, osteoporosis, and both diseases significantly increased across decreasing quartiles of dairy intake. A dairy intake in the lowest quartile was a significant predictor of osteoporosis [OR (95 % CI): 1.43 (1.12, 1.82)] and hypertension [OR (95 % CI): 1.46 (1.15, 1.85)] when compared to the highest quartile. Similarly, a low dairy intake was associated with increased odds to have both the diseases [OR (95 % CI): 1.60 (1.10, 2.34)]. From these results we conclude that osteoporosis and hypertension are associated in postmenopausal women, and a low dairy intake may increase the risk of both diseases, acting as a possible pathogenic link. [ABSTRACT FROM AUTHOR]

In 87 patients with hereditary hemochromatosis, osteoporosis was detected in 25%, and osteopenia in 41%. Bone mineral density was independently associated with BMI, ALP levels, hypogonadism/menopause, and the amount of iron removed to reach depletion, but not with cirrhosis. Osteoporosis is influenced by iron overload in hemochromatosis. To analyze prevalence, clinical characteristics and genetic background associated with osteoporosis in a retrospective study in Italian patients with hereditary hemochromatosis (HHC). In 87 consecutive patients with HHC, bone mineral density was systematically evaluated by dual energy x-ray absorptiometry of the lumbar spine ( n = 87) and femoral neck ( n = 66). Osteoporosis was detected in 22 (25.3%), and osteopenia in 36 (41.4%) patients. Mean Z scores were −0.92 ± 1.42 at lumbar spine and −0.35 ± 1.41 at femoral neck. Lumbar spine T-score was independently associated with total ALP ( p = 0.002), hypogonadism/menopause ( p = 0.026), and iron overload ( p = 0.033 for ferritin and p = 0.017 for iron removed). We observed a borderline significance for BMI ( p = 0.069) and smoking status ( p = 0.086). Lumbar spine osteoporosis was independently associated with lower BMI (OR 0.73, 95% CI 0.54–0.94), total ALP (OR 1.17, 95% CI 1–1.39 per 10 unit increase) and the amount of iron removed (OR 1.53, 95% CI 1–2.5 per 5 g increase). HFE genotypes did not differ between patients with and without osteoporosis. Osteoporosis is observed in a quarter of unselected patients with HHC, independently of the genetic background, and is associated with ALP, hypogonadism, body weight, and severity of iron overload. [ABSTRACT FROM AUTHOR]

Treatment with anti-resorptive agents over 13 months was associated with for three to fivefold lower bone mineral density changes and 1.5-fold increased risk of incidence fracture in vitamin D insufficient as compared to vitamin D repleted postmenopausal osteoporotic women. Several drugs were registered for the treatment of osteoporosis on the basis of clinical trials in which vitamin D repletion was a pre-requisite inclusion criteria and vitamin D supplements were used as adjunctive therapy. However, in routine clinical practice these supplements are not consistently recommended. We studied 1515 women with postmenopausal osteoporosis under treatment with anti-resorbing agents (alendronate, risedronate, raloxifene) for 13.1 months with an adherence > 75%. The patients were classified as vitamin D deficient ( N = 514) or vitamin D repleted ( N = 1001) according to risk factors ( N = 1062) or the level of 25(OH) vitamin D [25(OH)D] above or below 50 nmol/l ( N = 453). Vitamin D deficient and vitamin D repleted subjects differed significantly for annualized spine and hip bone mineral density (BMD) changes adjusted for all available confounding factors (type of treatment, age, global calcium intake, baseline BMD values). One hundred fifty one patients suffered from a new incident clinical fracture. The adjusted odds ratio for incident fractures in vitamin D deficient as compared to vitamin D repleted women was 1.77 (1.20 – 2.59, 95% CI; p = 0.004). Optimal vitamin D repletion seems to be necessary to maximize the response to anti-resorbers in terms of both BMD changes and anti-fracture efficacy. [ABSTRACT FROM AUTHOR]

None of the available osteoporosis therapies completely abolish the risk of fracture. Among 862 patients on treatment with antiresorptive agents (alendronate, risedronate, and raloxifene) for >1 year a fragility fracture was observed in 9.5%/year. This incidence is considerably higher than that observed in randomized clinical trials. Available osteoporosis therapies reduced in randomized controlled trials (RCTs) the risk of fracture by 30–50%. The proportion of patients suffering from new fractures while on active treatment (“inadequate clinical treatment response” or ICR) can be derived from the data of the RCTs, where confounding factors are usually controlled by the exclusion criteria. In the retrospective part of the ICARO study we observed a 8.9% annual incidence of ICR. Here we report the results of the longitudinal part of the study. The study includes 862 women with severe postmenopausal osteoporosis. Ninety-two of these patients (10.7%) were defined as having ICR (9.5%/year) during therapy with antiresorptive drugs (alendronate, risedronate, and raloxifene) for at least 1 year. The ICR patients were comparable to patients who did not sustain clinical fractures with regard to body mass index, follow-up duration, number of prevalent vertebral fractures, type of osteoporosis treatment, proportion of patients taking calcium and vitamin D supplements, and compliance with treatment. Those with ICR were significantly older ( p = 0.032) and more frequently had multiple vertebral deformities ( p = 0.013). The incidence of ICR during treatment with antiresorptive agents among patients with severe postmenopausal osteoporosis in a routine setting is considerably higher than that observed in randomized clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Poor adherence to prescribed treatments is widespread in clinical practice and this can lead to potentially life-threatening events. This problem is apparently very common for osteoporosis treatment but the causes of discontinuation and low compliance are complex and poorly defined. Methods: Global adherence to osteoporosis treatment was specifically addressed in a nation-wide survey carried out in 9851 postmenopausal women referred to 141 Italian centres for osteoporosis management for a follow-up assessment, at least one year after having been prescribed a treatment with one of the following drugs: calcium±vitamin D supplements alone (CaVitD), hormone replacement therapy (HRT), raloxifene 60 mg (RLX), intramuscular clodronate 100 mg/7-14 days (CLOD), risedronate 5 mg/day (RIS) and alendronate 10mg/daily (ALN10) or 70 mg once weekly (ALN OW). Results: Overall 19.1% of the patients discontinued the prescribed drug before attending the bone mass reevaluations, more than half of them within the first 6 months. The discontinuation rate was significantly different between the treatments. The medications most frequently interrupted within one year were CLOD (28.7%; p < 0.01 versus any other treatment), while by far the least interrupted was ALN-OW (6.9%; p < 0.001 versus any other treatment). The most frequent reasons for discontinuation were drug related side effects, insufficient motivation to treatment and fear of side effects. The prevalence of the reasons for discontinuation were different among treatments: safety concerns were very common for HRT, lack of motivation was the most common cause for CaVitD and CLOD, and drug related side effects for RIS, ALN and RLX. Persistence to treatment was significantly higher in patients with previous vertebral fractures, densitometric osteoporosis, on corticosteroid or anti-inflammatory treatments. A significantly increased risk of treatment interruption was found among patients on benzodiazepine or gastroprotective agents and in patients in whom a bone measurement was not readily available. The highest compliance to recommended dosing was observed with ALN OW and HRT (p < 0.001 versus any other) and the lowest for CaVitD (p < 0.01 versus any other). Poor treatment compliance (< 50% drug taken) was significantly related to benzodiazepine and gastroprotective use, while a significantly better compliance was associated with recognized risk factors for osteoporosis: early menopause, low bone mass values values, previous vertebral fractures. The poorest adherence was observed when treatments were prescribed by General practitioners (GPs), and orthopaedic surgeons (p < 0.01 versus global mean). Conclusions: The results of this large survey of Italian osteoporotic women indicates that the most important determinant of both persistence and compliance to treatment is the type of drug prescribed with a definite advantage of ALN-OW. Treatment compliance is particularly poor for CaVitD and this emphasizes the need for new ways to supplement at least vitamin D. The main reasons for discontinuation are side effects and lack of motivation while the best treatment adherence was observed in patients with severe and well documented osteoporosis. [ABSTRACT FROM AUTHOR]

We assessed the clinical usefulness of quantitative ultrasound (QUS) in defining the prevalence rates of osteoporosis and osteopenia and their association with fractures of the forearm, vertebrae, and hip. The ESOPO study was conducted in 2001 and assessed a random sample of 11,011 women and 4,981 men, in 83 centers spread all over Italy. A large array of risk factors was investigated, and self-reported history of fractures was collected in a questionnaire. After the patient had undergone interview and a brief physical examination, QUS of the heel was performed, using the Achilles apparatus (GE-Lunar, Madison, USA). The prevalence rate of osteoporosis in women 40–79 years old was approximately 18.5%, while the rate of osteopenia was about 44.7%; in men 60–79 years of age the rates were 10% and 36%, respectively. A strong association with fractures was found for osteoporosis and osteopenia in both men and women, independently of all traditional risk factors, including age. These results confirm the suitability of US measurements as a tool for detecting individuals at risk of fractures. [ABSTRACT FROM AUTHOR]

In order to evaluate the usefulness of calcaneal quantitative ultrasound (QUS) in the assessment of male osteoporosis, a cross-sectional, population-based study was performed. A cohort of 4,832 men, randomly selected, community-dwelling, aged 60–80 years and representative of the general older male Italian population was recruited. QUS measurements were assessed in 83 centers distributed all over Italy and equipped with an Achilles device (GE-Lunar, Madison, Wisconsin, USA). All participants were administered a questionnaire covering lifestyle variables and medical history. Low-energy fractures that had occurred since age 50 were recorded. Overall, 43 subjects reported a previous hip fracture and 455 subjects reported other non-spinal fractures. Univariate analysis showed that fractured subjects were older, with a lower level of outdoor physical activity and a more frequent history of prolonged bedridden periods in comparison with unfractured subjects. Men reporting non-spinal fractures showed a higher prevalence of smoking, while no difference was found among groups in anthropometric measures and calcium intake. QUS measurements showed that all QUS parameters were significantly lower in both fracture groups ( p <0.001). Multiple logistic regression analysis demonstrated that each SD reduction in QUS measures was associated with an approximate doubling of the risk for hip fracture, independent of age and other clinical variables (broadband ultrasound attenuation [BUA]: odds ratio [OR]=2.24; 95% confidence interval [CI] 1.61–3.08; stiffness index: OR=2.19; CI 1.56–3.11; speed of sound [SOS]: OR=1.71; CI 1.18–3.24) and with an increase of the risk of other non-spinal fractures (BUA: 1.38; CI 1.22–1.59; stiffness index: OR=1.27; CI 1.17–1.38; SOS: OR=1.14; CI 0.96–1.40). It can be concluded that calcaneal QUS measurement is associated with the risk for hip fracture and any non-spinal fractures among a community-dwelling cohort of elderly men. The strength of the association between QUS measurement and fracture is similar to that observed in elderly women. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify the determinants of bone mass as measured by quantitative ultrasound (QUS) in premenopausal women. The study population is part of the "Epidemiological Study On the Prevalence of Osteoporosis" (ESOPO) on risk of the general population of Italy. We report the data on 2727 premenopausal women aged 40-50 years who are still regularly menstruating. Bone stiffness (called simplicity stiffness), which is derived from the values of broadband ultrasound attenuation (BUA) and speed of sound (SoS), was measured by a heel QUS device (Achilles Apparatus, Lunar, Co. USA). The most commonly recognized determinants of bone mass were modelled with stiffness by multiple regression analysis or analysis of variance (ANOVA). Bone stiffness was negatively related to age and number of cigarettes and positively to body weight, body weight at 25 years, height and estimated daily calcium intake. By multiple regression analysis, independent, positive, predictors of bone stiffness were age, weight at 25 years and daily calcium intake. Bone stiffness adjusted for age and body weight at 25 years was positively associated with outdoor activity score and negatively with number of pregnancies, chronic use of any drug, smoking and subjective health status. Bone stiffness was also somewhat (p < 0.015) negatively related to history of prolonged bedrest and thyroxin use. In conclusion, our results indicate that risk factors usually associated in other studies with DXA-BMD in elderly women are also associated with calcaneal bone stiffness, as measured by QUS in premenopausal women. These findings should help to identify premenopausal women at risk and to design an early strategy for osteoporosis prevention based on eliminating modifiable risks. [ABSTRACT FROM AUTHOR]

: The purpose of this study was to assess whether dietary changes aimed at reducing serum cholesterol can increase the risk of osteoporosis (OP) and fracture. The study group consisted of 311 postmenopausal women with high serum cholesterol levels and following a diet low in dairy products (calcium intake estimated at less than 300 mg/day) for 27.3 ± 29.1 months. This sample was compared with a case–control group of 622 healthy postmenopausal women paired for age and age at menopause and with a calcium intake estimated at more than 1 g/day. Bone mineral density was measured at the lumbar spine by dual-energy X-ray absorptiometry. Prevalence of OP was significantly higher in women with a low dairy calcium intake (42.1% vs 22.3%; p<0.0001), as was the number of Colles” fractures occurring after menopause (4.5% vs 1.6%; p = 0.008). Multiple logistic regression analyses demonstrated that a diet low in dairy calcium was a risk factor for OP (OR = 2.52, 95% CI 1.84–3.45) and Colles” fracture (OR = 2.72, 95% CI 1.18–6.26). In the low dairy calcium group, diet duration significantly influenced the risk of OP (OR = 1.13, 95% CI 1.01–1.25 for 1 year of diet). No differences in further risk factors for coronary heart disease were found between the groups, but the proportion of women physically active was lower in the women with high serum cholesterol levels. A diet that severely limits calcium intake from dairy products in an attempt to correct raised serum cholesterol levels is a risk factor for postmenopausal OP and Colles” fracture. Dietary intervention methods to lower serum cholesterol in postmenopausal women should maintain an adequate calcium intake by providing calcium from low-fat dairy products or calcium supplements. [ABSTRACT FROM AUTHOR]

To evaluate whether the prevalence of osteoporosis and related risk factors might be influenced by the level of education, as has been demonstrated for many other chronic diseases, 6160 postmenopausal women at their first densitometric referral were interviewed about reproductive variables, past and current use of estrogens, prevalence of chronic diseases, and lifestyle factors such as calcium intake, physical activity, smoking and overweight. This sample was stratified by years of formal education. Densitometric evaluation was performed by dual-energy X-ray absorptiometry. Age at menarche, past exposure to oral contraceptives, use of hormone replacement therapy, prevalence of chronic diseases, physical activity, overweight and smoking showed significant trends according to the years of education. The prevalence of osteoporosis showed an inverse relationship with level of education, ranging from 18.3% for the most educated to 27.8% for the least educated women. Multiple logistic regression analysis demonstrated a predictive role toward osteoporosis by age, age at menarche and menopause, hormone replacement therapy, calcium intake, physical activity and body mass index. Using the lowest educational level as reference category, increases in educational status were associated with a significantly reduced risk for osteoporosis (OR = 0.76, 95% CI 0.65–0.90 for 6–8 years of schooling; OR = 0.68, 95% CI 0.57–0.82 for 9 years or more). This study shows differences in the prevalence of osteoporosis among educational classes and the protective role played by increases in formal education. If these results are confirmed in other population studies, public health intervention programs will have to consider the socioeconomic and cultural background of the population strata that run a greater risk of osteoporosis. [ABSTRACT FROM AUTHOR]

Three new cases of transient osteoporosis of the hip are reported. Diagnosis was achieved by plain radiographs, bone scintiscan, magnetic resonance imaging and X-ray absorptiometry of proximal femurs. The densitometry showed at the Ward's triangle a mean reduction of bone mineral density in the affected side of 36%. All subjects were treated with i.v. clodronate for ten consecutive days with a complete recovery of femoral density within 4 months. X-ray absorptiometry allows a quantification of the demineralization process and can be useful in the long term evaluation of this entity. [ABSTRACT FROM AUTHOR]

To evaluate whether metatarsal fracture in postmenopausal women can be related to osteoporosis, a sample of 113 postmenopausal women with metatarsal fracture due to minor trauma were recruited. Demographic and clinical data were compared with a control group of 339 healthy age-matched women and with a sample of 224 women with wrist fracture. In all women, bone mineral density (BMD) was measured at the lumbar spine by dual-energy X-ray absorptiometry. The average age of the metatarsal fracture group was slightly lower than that of the wrist fracture group (56.9 vs 58.4 years). Women with metatarsal and wrist fracture had a significantly higher age at menarche, lower age at menopause and lower body mass index when compared with controls. In both fracture groups BMD was significantly lower compared with controls. In stepwise logistic regression models, factors associated with metatarsal fracture risk were age at menopause (odds ratio [OR] 0.86; 95% confidence interval [CI] 0.81–0.92) and BMD (OR per — 1 SD 2.44; CI 1.92–3.11). Factors associated with wrist fracture risk included age at menopause (OR 0.89; CI 0.84–0.93) and BMD (OR per — 1 SD 2.65; CI 2.17–3.24). The similarities existing in risk factors and their estimates between a well-recognized osteoporotic fracture such as wrist fracture and metatarsal fracture, support the hypothesis that the latter can be included among osteoporotic fractures. [ABSTRACT FROM AUTHOR]

The purpose of this study was to measure pyridinium crosslinks in serum by high performance liquid chromatography (HPLC) and to correlate levels with urinary excretion in patients with different osteometabolic conditions. Blood and spot urine samples were collected between 9 and 11 A.M. in 92 early postmenopausal, untreated women (age 52.3 ± 2.6 years, months since menopause 20.4 ± 9.6), 17 patients with active Paget's disease (10 males, aged 65.1 ± 12.6) and 24 healthy premenopausal women (aged 28.4 ± 4.2). Urinary excretion of the total fraction (free + peptide bound) of pyridinolines (Pyr, Dpyr) was measured by HPLC. Before HPLC analysis, serum samples were submitted to a clean-up procedure by ultrafiltration. In 42 postmenopausal women, bone loss was calculated from two bone mass measurements (L2–L4, DXA), performed at study entry and after 12 months. Statistical analysis was performed by Student's t test for independent samples and linear regression analysis. In pagetic patients' serum levels of Pyr and Dpyr were more than threefold increased over the mean observed in healthy controls and were closely correlated with total alkaline phosphatase levels (Pyr: r = 0.73; Dpyr: r = 0.72, P < 0.0005). Compared with controls, postmenopausal women had significantly increased levels of both urinary and serum Pyr and Dpyr ( P < 0.003). In pagetic patients and postmenopausal women, crosslinks serum levels were correlated with their urinary excretion with r values ranging from 0.46 to 0.84. In postmenopausal women, only serum Dpyr correlated with the rate of bone loss (r =−0.36, P= 0.02). The data suggest that serum levels of pyridinium cross-links are correlated with urinary excretion in patients with different osteometabolic conditions. The determination of serum levels prevents limitations related to urinary specimen collection and may be a more practical method for routine application, avoiding corrections for urinary creatinine which could be misleading. [ABSTRACT FROM AUTHOR]

The plasma and synovial fluid concentrations of synthetic salmon calcitonin in 10 patients with knee joint effusions have been compared after a single i.v. dose of 200 I. U. calcitonin. Plasma and synovial fluid concentrations of calcitonin were measured using a specific RIA before and 30 and 60 min after administration. Calcitonin was not detectable at zero time in plasma or in synovial fluid. Plasma calcitonin concentrations 60 min after administration were significantly lower than at 30 min, while the synovial fluid concentration remained relatively constant. The results show that synthetic salmon calcitonin penetrates into the articular cavity after a single i.v. dose of 200 I. U. and that a steady concentration persists there over 60 min. [ABSTRACT FROM AUTHOR]