Ileal interposition coupled with duodenal diverted sleeve gastrectomy versus standard medical treatment in type 2 diabetes mellitus obese patients: long-term results of a case-control study.

BACKGROUND: Randomized controlled trials have demonstrated that bariatric surgery is effective in obtaining remission of type 2 diabetes mellitus (T2DM) in obese patients, yet no data exist in the literature from prospective studies with ileal interposition with duodenal diversion sleeve gastrectomy (II-DD-SG). The aim of this case-control study is to investigate if II-DD-SG is superior to medical treatment in T2DM obese patients. METHODS: Thirty obese patients (BMI > 30) affected by T2DM were recruited for surgery (II-DD-SG) between 2008 and 2011 and were matched with an equal control group which received standard medical treatment. Anthropometric measures, glucose metabolism, cardiovascular risk factors were determined baseline and during follow-up. The primary end point was T2DM remission; reduction of body weight, BMI, and cardiovascular risk factors were secondary end-points. RESULTS: Shortly after II-DD-SG, normalization of glucose plasma levels and glycated hemoglobin was observed followed by a significant decrease in body weight and BMI. At one-year follow-up, insulin resistance strongly declined as did insulin plasma levels. Complete remission was observed in 26 patients (86%); 2 (6.6%) had partial remission, and two (6.6%) were still diabetic. After 5 years, 17 of 25 patients on follow-up (68%) showed complete remission of T2DM and 56% had remission of cardiovascular risk factors. Only two patients receiving medical treatment showed complete remission of T2DM (p < 0.0001 versus II-DD-SG). No significant changes of anthropometric parameters and lipid metabolism were recorded. CONCLUSIONS: II-DD-SG is an effective surgical procedure, able to induce complete and prolonged remission of T2DM in obese patients as opposed to medical treatment.

Diabetic retinopathy screening: the first telemedical approach in an Italian hospital.

PURPOSE: To assess the feasibility of a telemedical approach for diabetic retinopathy (DR) screening in the Italian population and to evaluate advantages/disadvantages in comparison to standard slit-lamp funduscopic examination (SFE). METHODS: This 1-year, Italian, single-center, observational study evaluated semiautomatic fundus photography (FP) DR screening, performed during routine type 2 diabetes (T2D) systemic visits and examined remotely. Adults with T2D underwent SFE and 3-field FP. The study was divided into 2 stages (stage 1 validated the screening procedure, stage 2 evaluated the screening impact on the clinical practice). Annual costs of SFE ± FP screening were compared. Patients completed a DR screening questionnaire. RESULTS: Of 1,281 T2D patients enrolled, 61% were male (mean age 65.69 ± 12.64 years). In stage 1, 71% and 15% of patients were considered nongradable when FP was performed before (BPD) versus after pupil dilation (APD). The FP specificity was higher with APD vs BPD (79% vs 25%); therefore, FP APD only was used for stage 2. Of 1,281 patients screened using FP APD, 240 (18.7%) had unreadable images; 64.3% did not have DR, and 17.0% were diagnosed with DR. There was a cost saving of €801.25 when screening was performed using FP. Overall, 98% of patients had a positive opinion of FP screening. CONCLUSIONS: The telemedicine approach provides a convenient, simple test that is well-received by patients and minimizes unnecessary referrals. Telemedicine may also reduce screening costs in our setting.

Duodenal diverted sleeve gastrectomy with ileal interposition does not cause biliary salt malabsorption.

BACKGROUND: Duodenal diverted sleeve gastrectomy with ileal interposition (DDSG-II) is a bariatric-metabolic operation designed to treat type 2 diabetes mellitus (T2DM). It is restrictive (SG) but also acts on the small bowel with functional effects. The objective of the present study was to investigate whether or not it is also a malabsorptive operation. METHODS: Twelve obese patients (9 female and 3 male) affected by T2DM had DDSG-II. Follow-up was every 3 months, and the results after 1 year are reported here. Clinical conditions, related to diabetes and malnutrition, changes in weight, body mass index, fasting glucose plasma levels, HbA1c (glycated hemoglobin %), basal insulin, vitamin B12, folic acid, vitamin D, total proteins, albumin, and hemoglobin were recorded. Basal plasma levels of FGF19 (pg/mL) and of 7α-hydroxy-4-cholesten-3-one (C4) (µg/dL) were also determined for the diagnosis of biliary salt malabsorption. The results were expressed as mean±SEM, and the differences between times compared by the Mann Whitney U test; P<.05 was considered significant. RESULTS: After 1 year, all patients had a significant weight loss (-33.2±3 kg) with T2DM remission according to the American Diabetes Association criteria (11), criteria. No significant changes in total proteins, albumin, hemoglobin, and vitamins (B6, B12, and D) were detected. C4 did not change after the operation (2±.5 µg/dL versus 1.6±.5 µg/dL), whereas FGF19 significantly increased (from 85±11.2 pg/mL to 166.4±28.2 pg/mL, P<.04). Only 2 patients had mild symptoms of malabsorption. CONCLUSIONS: DDSG-II is effective for treatment of T2DM obese patients, increases the enterokine FGF19, and does not cause biliary salt malabsorption.

May diabetes patients have trouble sleeping despite not having obesity?

Obstructive sleep apnea (OSA) and periodic limb movements during sleep (PLMs) are sleep-related disorders with a high prevalence in type 2 diabetes. Commonly OSA is considered as a consequence of obesity, but several previous studies have shown the presence of OSA in non-obese diabetic patients. A previous study showed higher PLMs prevalence in patients with type 2 diabetes, compared to age-matched controls. We speculated that both OSA and PLMs may reflect the presence of diabetic autonomic neuropathy. To test this hypothesis, we compared a group of 112 non-obese patients with type 2 diabetes with 66 age-, sex-, and body mass index- matched nondiabetic patients. Both groups have been investigated through a set of tests including the Epworth Sleepiness Scale, polysomnography, and the Orthostatic Grading Scale (OGS), a questionnaire to assess the degree of autonomic dysfunction. Diabetic patients with OSA and PLMs scored higher on the OGS than controls. Our results confirm that both OSA and PLMs are related to dysautonomy and may be unrelated to obesity in type 2 diabetes patients.

Modelling of thermal hyperemia in the skin of type 2 diabetic patients.

The microcirculatory response to thermal stimulation involves both an axon reflex and NO-mediated activation. The analysis of the microcirculatory flow following thermal stimulation may therefore enhance the detection of any impairment of the small unmyelinated fibres that are involved in the axon reflex. The aim of this work is to establish a method of non-invasive measurement of small fibre impairment. The microcirculatory flow in response to local heating is measured by using a laser Doppler instrument, and mathematically modelled to extract a set of quantitative parameters. The results confirm that there is a significant difference in the parameters modelling the axon reflex between diabetic and control subjects, while no significant difference is found in the parameters modelling the NO-mediated activation.

Effect of a mixture of calcium, vitamin D, inulin and soy isoflavones on bone metabolism in post-menopausal women: a retrospective analysis.

OBJECTIVES: Aging might affect the effectiveness of the sole supplementation of calcium and vitamin D in post-menopausal women, due to the development of vitamin D resistance in the gut, which limits calcium absorption. Thus, we wanted to test the efficacy of a mixture of calcium (500 mg), 25-hydroxyvitamin D [25(OH)D; 300 IU], inulin (3 g) and soy isoflavones (40 mg), to improve calcium absorption in this type of population. STUDY DESIGN: It is a retrospective study on otherwise healthy post-menopausal women. MAIN OUTCOME MEASURES: The following parameters were evaluated at baseline and after 3 months of supplementation: daily calciuria as an indirect marker of calcium absorption, serum 25(OH)D, parathormone, insulin-like growth factor 1 (IGF1) as a marker of bone anabolism, collagen telopeptide and osteocalcin as markers of bone resorption and bone turnover, respectively. RESULTS: Twenty-eight women (median age 67 years) were included in the analysis. The supplementation markedly increased daily calciuria (+60 %; p = 0.00009), while reducing parathormone levels (-18 %; p = 0.02) and leaving 25(OH)D unaltered. An increase in IGF1 (+16 %; p = 0.01) and a reduction in collagen telopeptide (-17 %; p = 0.04) were observed, too, as well as a modest trend towards osteocalcin reduction, although not significant. CONCLUSIONS: These results suggest that the considered mixture improved intestinal calcium absorption and bone metabolism in post-menopausal women. Since the amount of supplemented calcium was relatively low and 25(OH)D levels were unchanged, the observed effects are likely due to the combined contributions of inulin and soy isoflavones.

One night on-call: sleep deprivation affects cardiac autonomic control and inflammation in physicians.

BACKGROUND: Sleep loss is associated with increased cardiovascular morbidity and mortality. It is known that chronic sleep restriction affects autonomic cardiovascular control and inflammatory response. However, scanty data are available on the effects of acute sleep deprivation (ASD) due to night shifts on the cardiovascular system and its capability to respond to stressor stimuli. The aim of our study was to investigate whether a real life model of ASD, such as "one night on-call", might alter the autonomic dynamic response to orthostatic challenge and modify the immune response in young physicians. METHODS: Fifteen healthy residents in Internal Medicine were studied before and after one night on-call at Rest and during a gravitational stimulus (head up-tilt test, HUT). Heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were analyzed during Rest and HUT before and after ASD. Plasmatic hormones (epinephrine, norepinephrine, cortisol, renin, aldosterone, ACTH) and tissue inflammatory cytokines were measured at baseline and after ASD. RESULT: HRV analysis revealed a predominant sympathetic modulation and a parasympathetic withdrawal after ASD. During HUT, the sympathovagal balance shifted towards a sympathetic predominance before and after ASD. However, the magnitude of the autonomic response was lower after ASD. BPV and BRS remained unchanged before and after ASD as the hormone levels, while IFN-γ increased after ASD compared to baseline. CONCLUSION: In summary, one night of sleep deprivation, at least in this real-life model, seems to affect cardiovascular autonomic response and immune modulation, independently by the activation of the hypothalamic-pituitary axis.

Different PTH response to oral peptone load and oral calcium load in patients with normocalcemic primary hyperparathyroidism, primary hyperparathyroidism, and healthy subjects.

BACKGROUND: Normocalcemic primary hyperparathyroidism (PHPT-N) is a condition that may have similar long-term implications to primary hyperparathyroidism (PHPT); however, differential diagnosis and treatment for parathyroid disorders are not clearly defined. We investigated the effect of an oral peptone and an oral calcium load on calcium-regulating hormones in PHPT-N compared with PHPT and healthy controls to provide a new potential diagnostic tool. DESIGN: Case-control study. METHODS: We evaluated serum gastrin, PTH, ionized calcium, and phosphate responses to oral calcium (1 g) and peptone (10 g) load in 22 PHPT and 20 PHPT-N patients matched for PTH serum values. Moreover, 30 healthy subjects were enrolled as controls. In 12 patients for each group, we also performed the oral peptone test adding aluminum hydroxide (AH) to suppress phosphate absorption. RESULTS: In PHPT patients, PTH increased significantly 30 min after the oral peptone load, while no significant increase was found in PHPT-N and controls. After oral calcium load, PTH remained stable in PHPT while it decreased dramatically in PHPT-N patients, and ionized calcium increased significantly in each of the three groups. Peptones plus AH induced a blunted PTH increase in the three groups. CONCLUSIONS: Considering the marked difference in PTH response elicited by peptones in PHPT compared with PHPT-N, we suggest that the oral peptone test could be added to the diagnostic evaluation of PHPT patients. In case of absent response to peptones, patients should have their serum calcium levels assessed twice a year in accordance with recent guidelines.

Recognition of morphometric vertebral fractures by artificial neural networks: analysis from GISMO Lombardia Database.

BACKGROUND: It is known that bone mineral density (BMD) predicts the fracture's risk only partially and the severity and number of vertebral fractures are predictive of subsequent osteoporotic fractures (OF). Spinal deformity index (SDI) integrates the severity and number of morphometric vertebral fractures. Nowadays, there is interest in developing algorithms that use traditional statistics for predicting OF. Some studies suggest their poor sensitivity. Artificial Neural Networks (ANNs) could represent an alternative. So far, no study investigated ANNs ability in predicting OF and SDI. The aim of the present study is to compare ANNs and Logistic Regression (LR) in recognising, on the basis of osteoporotic risk-factors and other clinical information, patients with SDI≥1 and SDI≥5 from those with SDI = 0. METHODOLOGY: We compared ANNs prognostic performance with that of LR in identifying SDI≥1/SDI≥5 in 372 women with postmenopausal-osteoporosis (SDI≥1, n = 176; SDI = 0, n = 196; SDI≥5, n = 51), using 45 variables (44 clinical parameters plus BMD). ANNs were allowed to choose relevant input data automatically (TWIST-system-Semeion). Among 45 variables, 17 and 25 were selected by TWIST-system-Semeion, in SDI≥1 vs SDI = 0 (first) and SDI≥5 vs SDI = 0 (second) analysis. In the first analysis sensitivity of LR and ANNs was 35.8% and 72.5%, specificity 76.5% and 78.5% and accuracy 56.2% and 75.5%, respectively. In the second analysis, sensitivity of LR and ANNs was 37.3% and 74.8%, specificity 90.3% and 87.8%, and accuracy 63.8% and 81.3%, respectively. CONCLUSIONS: ANNs showed a better performance in identifying both SDI≥1 and SDI≥5, with a higher sensitivity, suggesting its promising role in the development of algorithm for predicting OF.

Secondary hyperparathyroidism in HIV patients: is there any responsibility of highly active antiretroviral therapy?

Secondary hyperparathyroidism may develop in the presence of hypovitaminosis D in order to maintain calcium homeostasis. We conducted a cross-sectional analysis in a cohort of 371 patients, identifying secondary hyperparathyroidism in 65 patients. This high prevalence (17.5%) was in part justified by the high prevalence of hypovitaminosis D (77.4%) in the whole sample, but we also identified an independent association with the use of tenofovir.

Vitamin D and inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are the main forms of inflammatory bowel disease (IBD), chronic relapsing-remitting inflammatory conditions of uncertain origin affecting the gastrointestinal tract. Much effort has recently been made both in defining the mechanisms underlying the development of IBD, and in broadening the spectrum of effective treatment. Substantial progress has been made in characterising immune-cell populations and inflammatory mediators in IBD. 1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], the bioactive form of Vitamin D(3), besides having well-known control findings of calcium and phosphorus metabolism, bone formation and mineralization, also has a role in the maintenance of immune- omeostasis. The immune-regulatory role of vitamin D affects both the innate and adaptive immune system contributing to the immune-tolerance of self-structures. Impaired vitamin D supply/regulation, amongst other factors, leads to the development of autoimmune processes in animal models of various autoimmune diseases, including IBD. The administration of vitamin D in these animals leads to improvement of immune-mediated symptoms. Future studies now need to focus on the potential of vitamin D and its derivatives as therapeutic adjuncts in the treatment of IBD.

Different vitamin D substrate-product relationship after oral vitamin D supplementation in familial benign hypercalcemia, primary hyperparathyroidism, and healthy controls.

CONTEXT: In healthy subjects and in patients with primary hyperparathyroidism (PH), the administration of a low dose of 25(OH)D (25 µg/day) increases the serum levels of both 25(OH)D and 1,25(OH)(2)D. It is unknown whether this relationship is present in patients affected by familial benign hypocalciuric hypercalcemia (FBH). OBJECTIVE: To evaluate the different vitamin D substrate-product relationship after oral vitamin D supplementation in familial benign hypercalcemia, PH, and healthy controls. DESIGN: We evaluated the main physiological regulators of 1α-hydroxylase and the substrate-product relationship of 25(OH)D and 1,25(OH)(2)D in 20 patients with PH, 25 with FBH, and 122 healthy sex- and age-matched controls before and after administration of 25(OH)D for 2 weeks. RESULTS: 25(OH)D increased significantly in all subjects, whereas 1,25(OH)(2)D serum levels increased significantly in PH patients and healthy controls but not in patients with FBH. Therefore, a significant positive substrate-product relationship of 25(OH)D-1,25(OH)(2)D was found in PH and healthy controls, but not in FBH. Monomeric calcitonin (hCT-M) was significantly lower at baseline and after 25(OH)D supplementation in the FBH group compared with the other two groups. CONCLUSIONS: The lack of 1,25(OH)(2)D increase in FBH may be due to a direct inhibitory effect on 1α-hydroxylase of hypercalcemia per se, increased metabolic clearance of 1,25(OH)(2)D, or a decreased stimulus of 1α-hydroxylase related to persistently low levels of hCT.

Acute parathyroid hormone increase by oral peptones administration after roux-en-Y gastric bypass surgery in obese subjects: role of phosphate in the rapid control of parathyroid hormone release.

BACKGROUND: It is generally considered that changes in serum phosphate levels do not alter parathyroid hormone (PTH) secretion in the absence of concomitant changes in ionized serum calcium level in humans. An acute rise in PTH was shown after phosphate administration by intraduodenal gavage in rats. We aimed to study gastrin, phosphate, PTH, ionized calcium (iCa), and blood pH responses to oral peptones in morbidly obese patients before and after roux-en-Y gastric bypass (RYGB) surgery. METHODS: These parameters were evaluated in response to an oral peptone load in 24 (18 male and 6 female) obese subjects before and 6 months after RYGB surgery. In 12 gastric bypass patients, we also evaluated PTH and phosphate after peptones plus aluminum hydroxide administration to suppress phosphate absorption. RESULTS: Before RYGB, peptones increased gastrin (P < .001), and decreased iCa (P < .01) without changes in PTH or pH. Both phosphate and PTH markedly increased after RYGB with the peptones oral load (P < .01), without changes in pH, iCa, or gastrin. There was a significant, direct relationship between the increase of phosphate and the increase of PTH in the patients treated with aluminum hydroxide (r(2) = 0.78; P < .0001). CONCLUSION: Rapid delivery of peptones in the jejunum in bypassed obese patients results in a significant rise in phosphate and PTH, in the absence of changes of other PTH regulators, possibly mediated by a signaling from the gastrointestinal tract. RYGB patients provide an opportunity to study the control of PTH secretion, with potential relevant clinical implications.

Osteoporosis after stroke: a review of the causes and potential treatments.

Osteoporosis is a known consequence of stroke, associated with an increased incidence of fractures, mainly of the hip, leading to further disability. The pattern of bone loss seen in stroke patients is different from that usually encountered with postmenopausal osteoporosis, since it is limited to the paretic side and more evident in the upper extremities. Several factors appear to have an influence on bone mass in stroke patients, such as the degree of paresis, gait disability and the duration of immobilization. The pathogenesis of osteoporosis after stroke remains unclear. Paresis, reduced mobility and reduced bone load seem to play a major role. Other factors such as nutritional and iatrogenic ones may also play an important part. In this paper, the clinical evidence, pathophysiology and possible treatments of post-stroke osteoporosis will be reviewed.

Insulin Resistance and the cardiometabolic syndrome in HIV infection.

Highly active antiretroviral therapy (HAART) has dramatically improved the prognosis of HIV-positive patients. However, long-term adverse effects of this therapy include dyslipidemia, insulin resistance (IR), changes in body fat distribution (lipodystrophy), and cardiometabolic syndrome (CMS). IR in HIV-positive patients does not seem to represent a significant independent risk factor for the development of cardiovascular disease; nevertheless, the association with other metabolic complications (dyslipidemia, fat redistribution) and CMS may increase the risk of type 2 diabetes and cardiovascular disease. The use of nucleoside analogue reverse transcriptase inhibitors is associated with the development of upper trunk and visceral fat accumulation and may cause IR. The progression of IR toward diabetes may be impeded with the choice of HAART regimens with less IR effects and encouraging patients to adhere to a healthy lifestyle. For patients with marked IR but relatively preserved fat, the use of metformin may consent the improvement of CMS and lipodystrophy, especially when combined with an appropriate exercise program. Therapy with rosiglitazone is not indicated in these patients.

Vitamin D substrate-product relationship in idiopathic hypercalciuria.

Absorptive hypercalciuria (AH) is associated with elevated levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D). While no increase of 1,25(OH)(2)D after oral administration of 25-hydroxyvitamin D (25OHD) at high doses has been claimed in normal subjects, a substrate-product relationship has been reported in normal children, young people after UV irradiation, older persons, postmenopausal women, primary hyperparathyroidism, renal failure, osteomalacia, and sarcoidosis. No data of this relationship in AH is available. To investigate 25OHD-1,25(OH)(2)D substrate-product relationship in AH, 161 AH patients (mean age 60.9+/-11.7 years) and 110 age- and sex-matched controls (mean age 61.5+/-12.4 years) were studied. In 57 controls and 52 AH subjects 25OHD-1,25(OH)(2)D relationship in basal conditions and after 2-week oral 25OHD (25 microg/day) administration were evaluated. In basal conditions 25OHD and 1,25(OH)(2)D were correlated in both, controls and AH; 25OHD treatment was followed by an increase in serum 25OHD and 1,25(OH)(2)D in both groups. However, delta responses of 25OHD and 1,25(OH)(2)D to 25OHD were higher in AH suggesting an enhanced activity of 1 alpha-hydroxylase. In conclusion, the higher response of 1,25(OH)(2)D after oral 25OHD in AH patients suggests a differential capacity between both groups in handling the increases in 1,25(OH)(2)D.

Diagnosing and managing thyroid disease in the nursing home.

Thyroid disorders occur at any age, but hypothyroidism is more common in older than in younger adults. In fact, the prevalence of thyroid disorders increases with age, and it is higher in old-old frail residents in nursing homes. Since thyroid diseases in older age, both overt reduced and increased function, may manifest as disorders of other organs, physicians need a high index of suspicion to detect thyroid dysfunction in an older person with multiple comorbidities and chronic polypharmacy. This is particularly true for residents of long-term facilities, where multiple chronic diseases may make it less attractive to direct attention to thyroid function. Subclinical hyperthyroidism and hypothyroidism, more frequently seen in older populations, have been linked to increased total and cardiovascular mortality. Since chronic diseases are more prevalent in old age, nonthyroidal illness is also seen frequently in this age group. Although, there is still debate on the decision to treat or not to treat subclinical thyroid disorders, current recommendations state the necessity of considering treatment on an individual basis according to symptomatology and to the possible benefit that the older person may obtain with treatment, discouraging extended screening and treatment in the community population of subjects older than 65. However, in the long-term setting, the possibility of thyroid dysfunction can be more often investigated, and the consideration of treatment and follow-up is needed to improve quality of life of affected older people.

Increased complexity of short-term heart rate variability in hyperthyroid patients during orthostatic challenge.

Hyperthyroidism is a pathological condition characterized by an altered autonomic cardiovascular control, resulting in an increase of the sympathetic and a decrease of the parasympathetic modulation of heart rate variability. Recently, the entropy-based indices derived from short-term heart period variability have been proved to be helpful in evaluating the autonomic cardiovascular modulation. The aim of our study was to evaluate the autonomic cardiovascular modulation of hyperthyroid subjects at rest and during standing using spectral parameters and corrected conditional entropy indices derived from short-term heart period variability in 12 hyperthyroid (HYPTH) and 9 normal healthy (N) females. Mean heart period was significantly decreased by standing both in N and HYPTH and the LF power expressed in normalized units was increased. The respiratory rate was faster in the HYPTH group compared to N and complexity was significantly greater in HYPTH compared to N during standing. Results suggested an enhanced complexity of cardiovascular control in HYPTH, more evident in a condition of sympathetic activation. The increased complexity of the cardiovascular regulation is probably not completely due to autonomic control but also to other influences, such as metabolic effects of thyroid hormones impinging upon respiratory control mechanisms and, therefore, on cardiorespiratory coupling.

Bosentan and sildenafil: should the combination therapy be a valid alternative in childhood to prostacyclin infusion?

We report a case of a seven-yr-old girl with a PAH treated with continuation therapy of bosentan and sildenafil. The combination therapy revealed safety and efficacy in long-term follow up.

Quality of life in osteoporotic women with inadequate clinical response to antiresorptive drugs: results from the ICARO study.

BACKGROUND AND AIMS: Osteoporotic fractures are a major public health problem notably affecting quality of life. The observational, multicenter study ICARO was designed to evaluate inadequate clinical response to antiresorptive drugs. The aim of the present study was to evaluate the impact of the clinical response to treatment on the health-related quality of life in women with postmenopausal osteoporosis. METHODS: 880 osteoporotic women (mean age 68.0+/-8 years; range 53-79) in treatment with antiresorptive drugs for at least one year were analyzed. All subjects had at least 50% compliance to treatment (i.e., patients took >50% of prescribed doses). The "inadequate clinical response" (ICR), as opposed to "adequate clinical response" (ACR), was defined as the Xrays revealing evident new vertebral or non-vertebral fragility fractures at least 6 months after initiation of antiresorptive therapy. The QUALEFFO- 41 questionnaire was used to evaluate changes in quality of life prospectively. RESULTS: 220 subjects (25%) had an ICR. Non-responders had a higher incidence of multiple vertebral fractures compared with responders. The quality of life data in the study subjects showed a significantly increased score (indicative of lower quality of life) in the total mean score (37.89+/-16.7 vs 45.84+/-18.2, p<0.01), as well as in all the domains/subdomains examined in the QUALEFFO-41 questionnaire in ICR, when compared with ACR. CONCLUSIONS: Inadequate clinical response in subjects on antiresorptive drugs is associated with increased severity of the disease and with a significant reduction in the quality of life.