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Introduction: The aim of this study was to estimate the prevalence and determinants of vitamin D deficiency in patients with rheumatoid arthritis (RA) as compared to healthy controls and to analyze the association between 25-hydroxyvitamin D (25(OH)D) with disease activity and disability., Methods: The study includes 1,191 consecutive RA patients (85% women) and 1,019 controls, not on vitamin D supplements, from 22 Italian rheumatology centres. Together with parameters of disease activity, functional impairment, and mean sun exposure time, all patients had serum 25(OH)D measured in a centralized laboratory., Results: A total of 55% of RA patients were not taking vitamin D supplements; the proportion of these with vitamin D deficiency (25(OH)D level <20 ng/ml) was 52%. This proportion was similar to that observed in control subjects (58.7%). One third of supplemented patients were still vitamin D deficient. In non-supplemented RA patients 25(OH)D levels were negatively correlated with the Health Assessment Questionnaire Disability Index, Disease Activity Score (DAS28), and Mobility Activities of daily living score. Significantly lower 25(OH)D values were found in patients not in disease remission or responding poorly to treatment, and with the highest Steinbrocker functional state. Body mass index (BMI) and sun exposure time were good predictors of 25(OH)D values (P < 0.001). The association between disease activity or functional scores and 25(OH)D levels remained statistically significant even after adjusting 25(OH)D levels for both BMI and sun exposure time., Conclusions: In RA patients vitamin D deficiency is quite common, but similar to that found in control subjects; disease activity and disability scores are inversely related to 25(OH)D levels.

Summary: 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., Introduction: To analyze prevalence, clinical characteristics and genetic background associated with osteoporosis in a retrospective study in Italian patients with hereditary hemochromatosis (HHC)., Methods: 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)., Results: 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., Conclusions: 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.

Unlabelled: 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., Introduction: 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., Methods: 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)., Results: 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)., Conclusions: 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.

Effective drug therapies are available for a wide range of chronic medical conditions but adherence to medications is currently low with poor health outcomes. Evidences support that drug nonadherence is a universal problem more than a disease- and drug-specific problem. Although several methods have been proposed for the assessment of adherence, accurate measurement continues to be difficult and most studies produced inconsistent results on determinants of nonadherence. Osteoporosis is a chronic, asymptomatic illness before fracture, and poor adherence with antiresorptive medications is a significant problem in preventing its adverse consequences. Currently approved therapies for osteoporosis are effective and lower fracture risk, but about 50% of patients discontinues treatment within 12 months of initiation. Poor adherence has been associated with increased fracture risk and increased resource use and hospitalization. Causes of nonadherence to osteoporosis therapies are unknown. Some variables predictive of nonadherence have been found (older age, comorbidity, previous fractures, bone mineral density assessment, number of medications, institutionalisation) but explain only a small proportion of the variability of adherence. Patients may fail to remain on their medication for reasons that include inconvenience or complexity of dosing, high cost, side effects and lack of appreciation of the benefits of therapy. Potential solutions of poor adherence of osteoporosis may include a close monitoring of persistence and compliance, an improved relationship between physician and patient, and newer medications with extended dosing intervals.

Unlabelled: 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., Introduction: 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., Methods: 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., Results: 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)., Conclusions: 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.

Corticosteroids remain a key component in the management of many disorders. Bone loss resulting from long-term administration of these drugs is common and osteoporosis induced by corticosteroids is the most frequent cause of secondary osteoporosis in nearly 50% of individuals on chronic corticosteroid therapy suffering from an osteoporotic fracture at some point. This article reviews the epidemiology and pathogenesis of glucocorticoid-induced osteoporosis.

Objective: The aim of this study was to retrospectively examine the pattern of utilization in clinical practice and the costs of therapy of infliximab in the treatment of refractory rheumatoid arthritis (RA)., Methods: Ninety-five RA patients (22 newly treated and 73 maintenance patients) who received at least one infliximab infusion during a selected observation period of one year were studied. After induction phase, infliximab was given at initial dose of 3 mg/kg every 8 weeks. Based on clinical efficacy measured by Disease Activity Score 28 (DAS 28) index, dose adjustments were performed by increasing pro kg dose and/or reducing infusion interval. Overall one-year's treatment costs were also examined., Results: Sixteen (17%) out of 95 patients discontinued treatment before the end of the study owing to lack of efficacy (15) or adverse events (1). Thirteen (59%) out of 22 newly treated patients experienced treatment escalation in the first year of therapy by increasing dose (13.6%), reducing interval (9%), or both (36.3%). The mean infliximab dose administered to all the patients was 3.57 mg/kg and the mean infusion interval was 50 days. Considering all expenditure items, the mean year treatment cost per patient was euro 8454,65. Infliximab vial optimization allows us to reduce this amount to euro 7505,85, with a significant saving of euro 948,80 per patient/year., Conclusions: In this observational study, adjustments in infliximab treatment in the first year of therapy were common. Despite dose escalation, the mean dosing schedule does not significantly differ from those recommended in the product label. The cost of treatment could be reduced by using infliximab vial optimization.

Objective: To analyze the influence of cyclosporine A (CYA) on bone using data from a large multicenter, cross-sectional study on bone mineral density (BMD) in rheumatoid arthritis (RA)., Methods: We selected 558 female patients with RA and divided them into two groups on the basis of CYA use: those who had never used CYA (n = 467) and CYA users (n = 91; users for < 24 months n = 50; users for > 24 months n = 41). Demographic, disease and treatment-related variables were collected for each patient. BMD was measured at the lumbar spine and proximal femur using dual x-ray absorptiometry. Data was analyzed by means of a univariate and multivariate statistical procedure. Osteoporosis (OP) was defined as BMD < -2.5 T score., Results: The frequency of OP among non-CYA users and CYA users was 28.2% and 33.3% (p=NS) for the lumbar spine, and 34.2% and 31.3% (p=NS) for the femoral neck, respectively. The prevalence of fragility fractures was not significantly different between the two groups. Mean values for the T-score at either the lumbar spine or the femoral neck were comparable in the two groups, even after adjustment for age, menopausal status, body mass index (BMI), Health Assessment Questionnaire (HAQ) score and steroid use. The generalized linear model showed that age, BMI and the HAQ score were significant independent predictors of BMD at the lumbar and femoral levels, whereas CYA use was not. Logistic analysis showed that only age, the HAQ score and BMI were significantly associated with the risk of OP. However, the duration of CYA therapy > 24 months was associated with an adjusted decreased lumbar BMD and a significantly decreased femoral neck BMD (p = 0.01). The frequency of femoral neck OP in patients on CYA for > 24 months was significantly higher than in patients on CYA for < 24 months: 46.4% vs. 19.44% (p=0.03), while the prevalence of fragility fractures did not differ significantly: 23.1% vs. 16.6%, respectively (p=NS). Logistic analysis showed that CYA use was an independent predictor of osteoporosis at the femoral site., Conclusion: Long-term CYA therapy may have negative effects on BMD in female RA patients.

Background: High calcium intakes seem to be ineffective at reducing bone loss in early postmenopausal women. However, the inverse relation between calcium intake and body weight can attenuate the negative effect of a low dietary calcium intake., Objective: The objective was to assess the role of dietary calcium and body mass index (BMI) on osteoporosis, defined according to World Health Organization criteria as a lumbar bone density >2.5 SD below the T score., Design: This was a cross-sectional, retrospective, observational study conducted in 1771 healthy, early postmenopausal women, who were not taking calcium supplements at the first densitometric evaluation. Weekly frequency of dairy food consumption was used to estimate the relative intake of dietary calcium. Total dairy intake was classified into 4 categories by quartile cutoffs. Multiple logistic regression analyses were used to study this sample., Results: BMI and prevalence of overweight showed significant inverse trends with increasing dairy intake. Calcium intake was not associated with osteoporosis when overweight was not considered. However, when overweight was considered in the analysis, women with the lowest calcium intake were more likely to have osteoporosis (odds ratio: 1.46; 95% CI: 1.12, 1.89; P = 0.008) than were women with the highest calcium intake., Conclusions: In early postmenopausal women, a low dietary calcium intake may increase the risk of osteoporosis, but its negative effect can be offset by the greater BMI found in women with a low calcium intake.

The pharmacokinetic profile of bisphosphonates is complex and depends on their potency in inhibiting bone resorption through their cellular effects and on the physicochemical action related to the interaction of these compounds with bone matrix. Amino-substituted bisphosphonates exert a more potent cellular effect on osteoclast via the inhibition of the mevalonate pathway, whereas non-nitrogen containing compounds exert a weaker effect deriving from the induction of intracellular metabolites in osteoclasts. For nitrogen-containing bisphosphonates there is a correlation between in vitro potency of inhibition of a specific enzyme, farnesyl pyrophosphate synthase, and their antiresorptive potency in vivo. Besides these effects on osteoclasts, bisphosphonates may in part mediate indirectly their antiresoprtive activity through several effects on osteoblasts and osteocytes. Different binding affinities of bisphopshonates to hydroxyapatite depend on both side chains structures and may explain how these drugs reach bone cells and exert their prolonged action in terms of adsorption and desorption processes. Clinical and animal-models derived data indicate that agents with high anti-resorptive potency, favourable bone binding characteristics and good tolerability can be used with long between-dose intervals to optimize therapeutic outcomes.

Much work has been directed at establishing the impact of osteoporosis and related fragility fractures in rheumatic diseases. Several cross-sectional studies reported that disability and reduced motility that are due to functional impairment are among the most important determinants of bone loss in different rheumatic diseases. At the same time, longitudinal studies have confirmed the detrimental effect of uncontrolled disease activity on bone density. In this perspective, the suppression of inflammation probably remains the main concern when considering treatment options. Besides these variables, pharmacologic agents that are used commonly in the treatment of these conditions probably have an adjunctive effect on bone loss in rheumatic patients. Large epidemiologic studies have demonstrated clearly that patients who have RA, SLE, or AS are at an increased risk for fragility fractures. Further studies are required to investigate the effective impact of osteoporosis and fragility fractures in other rheumatic diseases, and to define the relationship between OA and osteoporosis. A better appreciation of the impact and mechanisms of osteoporosis in rheumatic diseases by rheumatologists represents a clinical challenge; however, a greater understanding of this frequent complication will improve the quality of health care and the lives of patients who have rheumatic diseases.

Unlabelled: None of the available osteoporosis therapies have been shown to completely abolish the risk of fractures. In clinical practice, the outcome may be even poorer. In 880 patients prescribed with antiresorptives (alendronate, risedronate, and raloxifene) for >1 year, a fragility fracture was recorded in 8.9%/year of them. This incidence is considerably higher than that observed in randomized clinical trials, and it was significantly related to poor compliance and lack of supplementation with calcium and vitamin D., Introduction: Osteoporotic fracture is one of the most important public health concerns among the elderly. Currently available therapies have been shown to significantly decrease the risk of fracture, although none of them completely abolishes this risk. In clinical practice, poor treatment response may also result from a number of other factors., Materials and Methods: The Incidence and ChAracterization of inadequate clinical Responders in Osteoporosis (ICARO) is a multicenter, observational study carried out in Italy. It aimed to analyze, in postmenopausal women with established osteoporosis, the risk factors for an "inadequate clinical response" to drug therapy, defined as the occurrence of new vertebral or nonvertebral fragility fractures in patients prescribed, for at least 1 year, alendronate, risedronate, or raloxifene, with a compliance >50%., Results: In 880 patients treated with antiresorptive agents for a median of 2.0 years (95% CI: 1.0-4.5) years, the "inadequate clinical responder (ICR)" subjects over the observation period were 220 (25%), with an annual incidence of 8.9%. ICRs, compared with "adequate clinical responders (ACRs)," had more pretreatment fractures and were treated longer (2.8 versus 1.8 years; p < 0.001). After multiple adjustment for these confounding factors, significant determinants of inadequate clinical response were a poorer treatment compliance and a less frequent co-administration of calcium and vitamin D supplements., Conclusions: The incidence of fractures during treatment with antiresorptive agents in a clinical setting is considerably higher than that observed in randomized clinical trials. Inadequate compliance to treatment and lack of supplementation of calcium and vitamin D are major determinants of this poor response.

The fundamental role of Vitamin D has been long known in regulating calcium homeostasis and bone metabolism. An increased contribution of Vitamin D was recently described in association with a lower incidence of Rheumatoid Arthritis (RA). This must not be surprising, as the immunomodulating effects of Vitamin D are clear, which have been attributed protective effects in autoimmune disorders such as some chronic inflammatory bowel diseases, multiple sclerosis and type I diabetes. An interaction was suggested between Vitamin D metabolism and inflammation indexes through mediation of TNF-alpha which is also especially involved in osteoclastic resorption and therefore in bone loss processes. Some preliminary data would indicate an association between seasonal changes of Vitamin D serum levels, latitude and disease activity (DAS28) in RA patients. Consequently, the Osteoporosis and Metabolic Bone Diseases Study Group of SIR believes that there are grounded reasons for assessing the Vitamin D status of RA patients in order to investigate whether this is to be related to physiopathological and clinical aspects of disease other than those of bone involvement. Primary end point of the study will be to assess the levels of 25 OH Vitamin D in RA patients. Secondary endpoints will include correlation with dis-ease activity, densitometry values and bone turnover. The cross-sectional study will enroll patients of both sex genders, age ranging between 30 and 75 years according to the 1988 ACR criteria, onset of symptoms at least 2 years prior to study enrollment. Patients will be excluded suffering from osteo-metabolic diseases, liver and kidney insufficiency and those administered Vitamin D boli in the previous 12 months. Disease activity will be evaluated with the HAQ. Hemato-chemical tests and femoral and lumbar bone densitometry will be performed, unless recently undergone by patients. Blood levels of 25 OH C Vitamin D and PHT and of the two bone remodelling markers (bone alkaline phosphatase and serum CTX) will be measured, as well. Patient enrollment will start on February 2007 and will last 4 months. By the end of 2007 the study will be concluded and results will be published.

Pancreatic polypeptide (PP) islet cell tumors are usually not associated with a distinct clinical syndrome, although some reports suggest that they can cause a watery diarrhea syndrome similar to vasoactive intestinal polypeptide (VIP) cell tumors. We report the case of a young woman with an unusual presentation of a pancreatic neuroendocrine tumor mainly secreting PP. The patient developed a reversible hypokalemic rhabdomyolysis very likely secondary to the presence of the tumor. The myopathy resolved following the restoration of normokaliemia using potassium supplementation and a partial laparoscopic pancreasectomy. Isolated cases of hypokalemic rhabdomyolysis induced by intestinal diseases have been described in literature but these did not include gastroenteropancreatic neoplasms. We suggest that pancreatic neuroendocrine tumors should be added to the list of intestinal diseases capable of producing hypokalemic myopathy.

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.

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 re-evaluations, 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 gastro-protective 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.

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.

Agranulocytosis is a disorder characterized by a severe decrease in the number of granulocytes in blood, that frequently occurs as an adverse reaction to some drugs. By now, there are no reports in literature of agranulocytosis caused by tumur necrosis factor-alpha blockers. We describe the case of a 20-year-old Caucasian male affected by enteropathic (Crohn's disease) spondyloarthropathy HLA B27 negative, successfully treated with infliximab. After the second infliximab infusion, he was found to have a severe transient neutropenia (0.5 x 10(9)/L). Routine serum chemistry and full blood cell count (apart from neutrophil count) were normal. Serology excluded an active infection. Bone marrow needle aspirate showed a normal trilineage differentiation. Autoantibody assessment showed negative ANA, anti-dsDNA, anti-ENA, and ANCA, but positive granulocyte-bound antibodies (GBA) and neutrophil-specific (CD 16+)-bound antibodies (anti-NA). Ten weeks after infliximab infusion, neutrophil count and GBA and anti-NA assay returned spontaneously within normal range and we observed the same progress after every successive infliximab infusion we performed. These data indicated that infliximab possibly triggered production of granulocyte and neutrophil autoantibodies with resultant autoimmune agranulocytosis.

Objective: To analyze the influence of low dose methotrexate (MTX) on bone using data from a large multicenter, cross-sectional study on bone mineral density (BMD) in women with rheumatoid arthritis (RA)., Methods: We selected 731 female patients with RA divided into 2 groups on the basis of MTX use: never MTX users (n = 485) and MTX users for at least 6 months (n = 246). Demographic, disease, and treatment related variables were collected for each patient. BMD was measured at lumbar spine and proximal femur by dual energy x-ray absorptiometry. Osteoporosis was defined as BMD < -2.5 T-score., Results: The frequency of osteoporosis among never MTX users and MTX users was 29.1% and 28.3% (p = NS) for lumbar spine, and 34.8% and 37.8% (p = NS) for femoral neck, respectively. Mean T-score values at lumbar spine and femoral neck were comparable in the 2 groups, even after adjusting for age, menopausal status, body mass index (BMI), Health Assessment Questionnaire (HAQ) score, and steroid use. The generalized linear model showed that age, menopause, BMI, HAQ score, and steroid use were significant independent predictors of BMD at lumbar or at femoral level, whereas MTX use was not. Logistic procedure showed that only age, HAQ score, and BMI were significantly associated with the risk of osteoporosis., Conclusion: We found no negative effect of low dose MTX on BMD in women with RA.

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.

Osteoporosis is currently defined on the basis of the T-score by dual-energy X-ray absorptiometry (DXA). Despite its limitations, this definition is applied worldwide. However, the normal values provided by manufacturers may not be fully representative of specific local populations. So far, there are no normative data in the Italian population using Hologic densitometers. The Densitometric Italian Normative Study (DINS) is an ongoing multi-center study that aims to establish reference values for bone densitometry with dual-energy X-ray absorptiometry (DXA) in the male and female Italian population. In this paper we report the results of the lumbar vertebrae (L2-L4) and proximal femur in 1,622 women aged 20-79 years. Bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry (DXA) on Hologic bone densitometers (Hologic, Waltham, Mass.). Most of the subjects were examined with a QDR 4500. The BMD of the lumbar vertebrae was virtually constant between 20 and 49 years (test for trend: P=0.66); the BMD values between 20-45 in premenopausal women (mean 1.036; SD 0.109 g/cm(2)) were thus defined as the peak bone mass values, significantly lower compared to the Hologic reference curve (mean 1.079, SD 0.11 g/cm(2)). The mean BMD values of the femoral neck were virtually identical to those of the NHANES study in the first 3 decades; after the age of 50 the BMD values were slightly greater than those of the NHANES subject. The subject classification according to the WHO criteria was similar using the DINS and NHANES reference values for the femur; for the spine, the Hologic reference values classified a larger proportion of women as osteoporotic (21 vs. 16%) or osteopenic (42 vs. 38%) compared to DINS.

The purpose of this study was to assess whether a migrant population from southern regions of Italy showed differences in osteoporosis (OP) and fracture prevalence in comparison to a population born and living in Milan, a city in northern Italy. The study group consisted of 1764 postmenopausal women born in southern Italy who migrated after age 20 to Milan, where they had lived for at least 15 years. This group was compared with a sample of 4018 postmenopausal women born, raised and living in Milan. Bone mineral density (BMD) was measured at lumbar spine by dual-energy X-ray absorptiometry. Univariate analysis showed a significantly higher BMI, a greater parity, a lower postmenopausal estrogen (HRT) usage and a lower calcium intake in the Southern group (SG). Densitometric values showed a mean lumbar BMD significantly lower in SG ( P<0.001), resulting in a greater prevalence of OP (30.5% versus 24.9%; P<0.001). Consistent with this result, the number of women reporting low energy fractures after menopause was higher in SG (4.8% versus 3.6%; P=0.01). Multiple logistic regression analyses showed that OP was predicted by well-recognized variables, such as age, age at menopause, BMI, HRT, calcium intake together to belonging to SG, which independently increased the risk for OP by 42%. Age, age at menopause, BMI and belonging to SG significantly influenced the fracture risk, but the last variable was no longer associated with an increased fracture risk when BMD was entered in the model. Despite the results of previous epidemiological studies and protective anthropometric measures, a higher OP and fracture prevalence was found in the migrant group from southern Italy to Milan in comparison with the native sample. These differences are not solely explained by lifestyle variables. Our data suggest that changing environmental exposures can influence bone mass and fracture risk.

A case of tumor-induced osteomalacia in a 35-year-old woman suffering from severe bone pain and muscle weakness is described. This uncommon disease is characterized by a reduced serum phosphorus level with elevated urinary phosphate excretion, normocalcemia, high serum bone alkaline phosphatase and a deficiency of 1,25 dihydroxyvitamin D3. The tumors responsible for oncogenic osteomalacia are usually small, benign and commonly located in bone or soft tissues of the head and the limbs, so the diagnosis can often be difficult. In this case a 111In-pentetreotide scintigraphy was able to detect a hemangiopericytoma located in the right mascellar sinus. Removal of the tumor resulted in the reversal of clinical and biochemical abnormalities.

Quantitative ultrasound (QUS) techniques have been shown to be as good as bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA), in predicting fracture risk: QUS technique could increase substantially the accessibility to a reliable bone osteoporosis risk evaluation, but little is know regarding the relationship of QUS to risk factors that have been found to predict DXA-BMD values and this is even more true in men. We studied 6,811 postmenopausal women 40 to 80 years of age and 4,981 men 60-80 years of age representative of the general population of all regions of Italy. All participants were questioned on lifestyle habits and on their medical history. After a physical examination "bone stiffness" (called here for simplicity, stiffness), which is derived from the values of broadband ultrasound attenuation (BUA) and speed of sounds (SoS) was measured by a heel QUS device (Achilles apparatus, Lunar, Madison, USA). The most common recognized determinants of bone mass (either categorical or continuous variables) were modeled with stiffness by multiple regression analysis or ANOVA. Stiffness was strongly related to age and weight. After adjusting for these variables, the women who had taken hormone replacement therapy for more than a year had significantly higher stiffness values. The difference versus nonusers remained significant for up to 20 years-since-menopause (YSM). This effect was so strong that for further analysis these women were excluded. By multivariate analysis, stiffness was then found to be significantly related to recalled body weight at 25 years of age, actual and past cigarettes smoked per day, and dairy calcium intake. Stiffness was also associated with a number of categorial factors adjusted for age, weight, and YSM: prior ovariectomy, history of more than 2 months confined to bed, outdoor physical activity, smoking, chronic use of any drug, and past corticosteroid use. All these categorial and continuous variables predicted stiffness equally in men and women. In conclusion, QUS bone measurements discriminate postmenopausal women according to past use of hormone replacement therapy. Risk factors usually associated to BMD as measured by DXA are also associated to calcaneal bone stiffness as measured by QUS, and most risk factors for osteoporosis usually observed in women are equally applicable to men.

Objective: To define the frequency of the exon 6 tumor necrosis factor-alpha (TNF-alpha) receptor II (TNFRII) gene polymorphism in severe and mild-moderate rheumatoid arthritis (RA) and its possible influence on anti-TNF-alpha treatment responsiveness., Methods: Two cohorts of patients with RA, the first (n = 97) defined as methotrexate responders (MTX-R) with mild-moderate synovitis, and the second (n = 78) defined as nonresponders to combination therapy and receiving anti-TNF-alpha treatment because of their severe and aggressive disease (TNF-T), were studied retrospectively and compared to age, sex, and ethnically matched controls (n = 84). In the prospective study, 66 patients with severe RA were followed over the first 6 months of anti-TNF-alpha therapy and their response was examined according to genotype., Results: We observed a trend towards an increased frequency of the GG genotype in patients with severe RA (6.4%) in comparison with patients with mild-moderate disease (3.1%) and controls (1.2%). When looking at the response to anti-TNF-alpha therapy, we observed that after 12 weeks of treatment, 37.8% of the TT versus 10.7% of the TG/GG patients passed from high to medium-low disease activity (p = 0.03)., Conclusion: In our cohorts of patients selected by response to the conventional therapy and by disease severity, our preliminary study results showed a trend towards a higher prevalence of the GG genotype for the exon 6 TNFRII polymorphism in the less responsive patients with more aggressive disease. We also found a lower degree of response to anti-TNF-alpha treatments in patients carrying the G allele.

The aim of this study was to evaluate the efficacy of intravenous pamidronate in patients with transient osteoporosis of the hip (TOH). Thirteen men and three women (mean age 38.3 years, range 30-49) were recruited. The diagnosis was made by means of radiographs, bone scintigraphy, and magnetic resonance imaging (MRI). Pamidronate (45 mg) was intravenously administered three times, once every third day. The outcome measures included a clinical assessment using a pain visual analog scale (VAS; range 0-100), and the WOMAC functional impairment score (FUI; range 0-100). The bone mineral density (BMD) of the total hip and femoral neck was measured using dual-energy X-ray absorptiometry (DXA). Clinical assessments were made before treatment (T(0)) and 1 month later (T(1)), and the densitometric measurements at T(0), and then after 2 (T(2)) and 4 months (T(4)). A further MRI scan was made 3 months after treatment. In comparison to the unaffected side, there was a significant decrease at T(0) in the BMD of both the total hip (median 16.6%, range 8.5%-29.1%, p < 0.00001) and femoral neck (median 22.5%, range 12.0%-34.2%, p < 0.00001). By T(1), both VAS and FUI had decreased significantly (p < 0.00001). By T(2), the total hip and femoral neck BMD had increased by 10.9% (range 2.7%-23.6%, p < 0.00001) and 12.3% (range 7.8%-26.9%, p < 0.00001), respectively, and all patients were asymptomatic. By T(3), the MRI findings had normalized in all patients and, at T(4), there was a further increase in BMD. None of the patients experienced symptom relapse during the follow-up of 39.5 +/- 17.7 months. These results suggest that a short course of pamidronate is effective in treating TOH, and leads to a prompt and long-lasting recovery.

Objective: To examine whether severe rheumatoid arthritis (RA) carries a -238 or +489 tumor necrosis factor-alpha (TNF-alpha) genotype different from mild-moderate RA., Methods: We investigated 163 patients (66 with severe disease) and 67 healthy blood donor controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism., Results: Patients with severe RA (all active disease despite disease modifying antirheumatic drug combination therapy) disclosed the -238 GG genotype in 100% of cases versus 92.8% of the mild-moderates and 92.5% of controls (OR 11.7, Cl 0.6-216, p = 0.03). The +489 AA genotype was seen less often in patients than in controls (OR 4.2. CI 0.97-18.4, p = 0.045), and the contribution to this trend appeared predominant in the anti-TNF treated subgroup., Conclusion: The -238 AG genotype was absent in severe RA; in contrast, patients with mild-moderate RA disclosed the same frequency as controls. Thus -238 GG homozygosity is associated with severe RA. The +489 AA genotype might instead protect against worse outcome in RA.

Objectives: To study -238 and +489 TNF-alpha polymorphisms in severe-unresponsive (more than 6 swollen joints and still active disease despite at least 6 months of DMARDs combination therapy) and mild-responsive (less than 3 swollen joints and good response to MTX or other conventional DMARDs) rheumatoid arthritis (RA)., Methods: We investigated 100 RA patients (56 with severe and 44 with mild disease activity) and 45 healthy blood donors (HBDs). Genotyping was performed by PCR-restriction fragment length polymorphism procedure. Several clinical and serological parameters were also examined., Results: Severe RA patients disclosed the -238 GG genotype in 100% of the cases versus 95.5% in the mild-responsive patients and 91.2% in the HBDs. The +489 GG genotype disclosed only a trend towards a prevalence in severe RA patients. However the +489 A allele seems to associates with early onset, longer disease duration and longer responsiveness to conventional therapy., Conclusion: The -238 AG genotype is absent in severe-unresponsive RA, but present in mild-responsive RA subjects. Thus -238 GG homozygosity associates with severity and unresponsiveness. In contrast the +489 polymorphism does not segregate differently between responsive and unresponsive RA patients.

The diagnostic approach in clinical practice in Rheumatology is mainly based on the recognition of pain origin. Patient's experience of pain may be similar in different diseases involving bones, joints, tendons, muscles or peripheral nervous system. The analysis of some characteristics of pain may be helpful in the diagnostic approach. In this perspective pain must be analysed according to the type, localization, occurrence, elicitation and concomitant clinical signs. In the majority of cases this analysis allows a preliminary differential diagnosis which is essential to drive further assessments. The diagnostic approach to arthropaties is based on a group of indicative criteria which include diffusion of the arthropathy, the involved sites, the course of the joint disease, the joint damage, the history of preceding events and the presence of extra-articular features which accompany joint disease. This kind of clinical approach helps the clinician in saving time and reducing costs of diagnosis by driving any further investigation.

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.

Objective: To determine the frequency of osteoporosis in a large cohort of women with rheumatoid arthritis (RA) and to investigate the main determinants of bone mineral density (BMD) and risk factors for vertebral fractures in this population., Methods: We recruited 925 consecutive female patients with RA at 21 Rheumatology Centers in Italy. For each patient pre-registered demographic, disease, and treatment-related variables were collected. BMD was measured at lumbar spine and proximal femur by dual x-ray absorptiometry technique. Collected variables underwent a univariate and multivariate statistical procedure. Osteoporosis was defined as BMD > -2.5 T score., Results: The frequency of osteoporosis in the whole sample was 28.8% at lumbar spine and 36.2% at femoral neck and increased linearly from Steinbrocker's functional stage I to IV (p = 0.0001). Patients with spinal or femoral osteoporosis were significantly older (p = 0.0001), had a lower body mass index (BMI) (p < 0.02), a significantly longer disease duration (p < 0.02) and a significantly higher Health Assessment Questionnaire (HAQ) score (p = 0.0001). These differences were significant, even after adjusting for age. Steroid use was associated with significantly lower lumbar and femoral BMD (p = 0.0001) even after adjusting for the main confounding covariates. Analysis of lateral spine radiographs revealed 74 women with at least one vertebral fracture. These women had a significantly lower lumbar and femoral BMD (p = 0.0001). The generalized linear model showed that steroid use, menopause, BMI, age, and HAQ were all significant independent predictors of lumbar and femoral BMD. The logistic procedure showed that age (OR 1.05, 95% CI 1.03-1.07), HAQ (OR 1.3, 95% CI 1.07-1.7), menopause (OR 1.9, 95% CI 1.1-3.2), use of steroids (OR 1.5, 95% CI 1.07-2.1), and BMI (OR 0.8, 95% CI 0.8-0.9) were significantly associated with the risk for osteoporosis. The only variables associated with an increased risk for vertebral fracture were age (OR 1.04, 95% CI 1.01-1.08), HAQ (OR 1.7, 95% CI 1.08-2.09), and cumulative steroid intake (OR for 1 g of prednisone 1.03, 95% CI 1.006-1.07)., Conclusion: To prevent osteoporosis and its dramatic complications in RA the therapeutic challenge is to preserve functional capacity using the lowest possible dosage of corticosteroids.

Objective: To evaluate the efficacy of intravenous (i.v.) clodronate in patients with reflex sympathetic dystrophy syndrome (RSDS) and to assess the urinary excretion of type I collagen crosslinked N-telopeptide (NTx) before and after the treatment., Methods: Thirty-two patients with RSDS were randomized to receive either i.v. clodronate 300 mg daily for 10 consecutive days or placebo. Forty days later, the placebo treated patients received the clodronate treatment. Outcome measures included as a primary endpoint the visual analog scale of pain (VAS, range 0-100); secondary endpoints were a clinical global assessment (CGA, range 0-3) and an efficacy verbal score (EVS, range 0-3). Clinical and biochemical assessments were performed before the treatment, 40 (T40), 90 (T90), and 180 (T180) days later., Results: At T40 the 15 patients randomized to clodronate treatment showed significant decreases of VAS and CGA (p = 0.002, p = 0.001, respectively). Compared with the placebo group (17 patients), significant differences were found in all clinical variables (VAS: p = 0.001; CGA: p = 0.001; EVS: p<0.0001). A further clinical improvement was observed throughout the study. Pooling the results of all 32 patients after clodronate treatment, at T180 the overall percentage decrease of VAS was 93.2+/-15.6%, with 30 patients significantly improved or asymptomatic. Significant inverse correlations between baseline NTx values and decreases of VAS were found at T90 (p = 0.03) and T180 (p = 0.01). No adverse events related to treatment occurred., Conclusion: A 10 day i.v. clodronate course is better than placebo and effective in the treatment of RSDS. NTx seems to be a predictive factor for clodronate efficacy.

Many pathological processes, including those causing allergies and autoimmune diseases, are associated with the presence of specialized subsets of T helper cells at the site of inflammation. Understanding the genetic program that controls the functional properties of T helper type 1 (Th1) versus T helper type 2 (Th2) cells may provide insight into the pathophysiology of inflammatory diseases. We compared the gene-expression profiles of human Th1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6,000 human genes. Here we analyse the data sets derived from five independent experiments using statistical algorithms. This approach resulted in the identification of 215 differentially expressed genes, encoding proteins involved in transcriptional regulation, apoptosis, proteolysis, and cell adhesion and migration. A subset of these genes was further upregulated by exposure of differentiated Th1 cells to interleukin-12 (IL-12), as confirmed by kinetic PCR analysis, indicating that IL-12 modulates the effector functions of Th1 cells in the absence of antigenic stimulation. Functional assays and in vivo expression of selected genes have validated the biological relevance of our study. Our results provide new insight into the transcriptional program controlling the functional diversity of subsets of T helper cells.

Objective: To evaluate bone mineral density (BMD) in young ambulatory female patients with systemic lupus erythematosus (SLE) and to assess the influence of disease related variables and use of corticosteroids., Methods: Lumbar and femoral BMD were measured by dual x-ray absorptiometry (DXA) in 84 premenopausal patients with SLE (age 30.5+/-7.5 years). All patients were receiving corticosteroids at the time of the study. Variables evaluated were: disease duration, clinical pattern, disease activity (SLEDAI), cumulative damage index (SLICC/ACR), current and cumulative prednisone dose, duration of steroid treatment, and use of immunosuppressive agents. Osteoporosis was defined as a t score below 2.5 SD compared to a reference population of healthy women in at least one region of measurement., Results: Vertebral and femoral BMD were significantly lower in patients with SLE than in age matched controls. Osteoporosis was detected in 22.6% of patients. No significant differences in BMD were detected between patients according to clinical pattern or activity index, whereas patients with damage index > 0 (n = 46) had a significantly lower BMD at both the lumbar (p = 0.008) and the femoral (p = 0.05) level. Compared with non-osteoporotic patients with SLE, women with osteoporosis had similar age, lower body mass index, significantly longer disease duration (p < 0.0001), higher cumulative steroid intake (p < 0.006), and higher SLICC/ACR score (p < 0.01). Stepwise logistic regression analysis showed that disease duration is independently associated with osteoporosis (OR 1.2 for each year of disease, 95% CI 1.07-1.33). Since disease duration and duration of steroid treatment were highly correlated, a new stepwise logistic model was run without disease duration, which revealed that prednisone was associated with an increased risk for osteoporosis (OR 1.16 for each year of treatment, 95% CI 1.05-1.29)., Conclusion: Osteoporosis is a frequent feature in young patients with SLE. Disease duration is associated with an increased risk for osteoporosis, but the role of glucocorticoid treatment seems to be crucial. Steroid exposure was the only treatment related variable exerting an influence on the development of osteoporosis.

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.

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.

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.

The unusual case of reflex sympathetic dystrophy syndrome caused by an acute attack of gout is reported. The syndrome, involving the left ankle and hindfoot, developed twelve days after a classical gouty attack involving the first metatarso-phalangeal joint of the same foot. Diagnosis was based on X-ray and scintigraphic and MRI changes A prompt clinical remission was achieved with a short course of i.v. clodronate.

Objective: To investigate the relationship between lactation and bone mineral density (BMD) of the lumbar spine in a cohort of 540 healthy, postmenopausal women., Study Design: Women were selected who experienced long-term lactation (n = 155, median 18 months) or short-term lactation (n = 168, median 3 months) or who were parous, nonlactating subjects (n = 217). The groups were homogeneous in age and differed in body mass index, parity and age at menopause. Vertebral BMD was measured by x-ray absorptiometry., Results: No statistically significant difference in BMD was found between groups or after adjusting for body mass index, number of live births and age at menopause. Even when the 86 women with the longest lactation history (median 22 months) were matched with 112 parous women with the same parity who did not lactate, we could not find any significant difference., Conclusion: Long-term lactation did not significantly affect postmenopausal vertebral BMD in a cohort of healthy women.

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.

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.

Various pleuropulmonary manifestations are reported to occur in the course of systemic lupus erythematosus (SLE). Among these, pulmonary hypertension is one of the most uncommonly observed. The natural course of this involvement can be independent of the primary disease, and resembles primitive pulmonary hypertension. Various pathogenetic mechanisms might be responsible for this picture. In the case here reported, the pathological data were strongly suggestive of pulmonary vasculitis, emphasizing that SLE, like other connective tissue diseases, can be responsible for fatal pulmonary hypertension.

The uricosuric effect of tiaprofenic acid was evaluated in a group of normouricaemic inpatients with various rheumatic disorders. Six patients aged 26 to 60 years were maintained on a standardised low-purine diet and, after a washout period of 72 hours, tiaprofenic acid was administered in 3 oral doses of 300 mg 12-hourly. A normal renal function, as assessed by serum creatinine and creatinine clearance determinations, was considered mandatory for entry into the study. The following parameters were evaluated before and after treatment: haematological values, blood urea nitrogen (BUN), serum and urinary creatine concentrations, serum uric acid concentration and the fractional excretion rate of uric acid. Our preliminary results showed a substantial increase of urinary uric acid excretion in the samples collected after treatment, especially in the first 4 hours.