Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study.

Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12 months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12 months of GLP-1RAs therapy. After 12 months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12 months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis.

Bone fragility, sarcopenia and cardiac calcifications in an elderly population: a preliminary study.

BACKGROUND: Cardiovascular disease, osteoporosis and sarcopenia are very common age-related conditions. This study aimed at investigating the relationships of cardiac calcifications, as assessed by using GCCS with BMD, fragility fractures and sarcopenia in elderly subjects. METHODS: In a cohort of 106 subjects (age 70.4 ± 5.8 yrs) we measured lumbar (BMD-LS), femoral BMD (femoral neck: BMD-FN, total femur: BMD-TH) and body composition (BMD-WB) with Dual-energy X-ray Absorptiometry (DXA) method. We also evaluated the presence of sarcopenia on the basis of the EWGSOP Consensus. All subjects, simultaneously, underwent to a transthoracic color doppler echocardiography exam to assess the presence of cardiac calcifications. The degree of non coronaric cardiac calcifications was evaluated using the Global Cardiac Calcium Score (GCCS). RESULTS: The degree of cardiac calcification assessed by GCCS was significantly higher in osteoporotic patients (p < 0.001). Furthermore, an inverse correlation emerged between BMD and GCCS, statistical significance was found at lumbar spine and femoral sub-regions in female population (p < 0.01). Moreover by dividing population according to the presence of fragility fractures, we observed that GCCS values were significantly higher in subjects with fractures in respect of non-fractured ones (p < 0.05). Multiple regression models showed that BMD-LS and BMD-FT were independently associated with cardiac calcification. GCCS values were significantly associated with BMI and ASMM in women (p < 0.01 and p < 0.05, respectively) and with handgrip strength in men (p < 0.05). CONCLUSIONS: Our data confirm the presence of a relationship between cardiac calcifications and decreased BMD values. It's also the first study that relates sarcopenia and valvular calcifications.

Osteoporosis and major fragility fractures (MOF) in sarcoidosis patients: association with disease severity.

BACKGROUND: The reports on bone mineral loss or major osteoporosis fracture (MOF) in sarcoidosis are scarce and have conflicting outcomes. This study aimed to evaluate the prevalence and risk factors of MOF in sarcoidosis patients. METHODS: In a single-center cohort of 382 patients with sarcoidosis (55.8 ± 11.6 years) we evaluated bone mineral density at lumbar spine, at femoral neck and at total hip and the presence of MOF. Lung function measurements including diffusion capacity for carbon monoxide (DLCO) were assessed. Chest X-rays were performed and radiological staging was done by Scadding score. RESULTS: Ninety patients (23.6%) with sarcoidosis have history of a MOF. BMD T-scores were lower in sarcoidosis with MOF with respect to those without MOF, but the difference was statistically significant only for BMD at femoral neck (p < 0.05). Moreover, BMD values at total hip was positively correlated with DLCO (%) (p < 0.001). Prevalence of MOF was higher in patients with sarcoidosis with lung parenchymal involvement (radiological stages 2-4) than in patients with sarcoidosis in chest X-ray stages 0 and 1 (28.3 vs 19.2% respectively, p < 0.05). Moreover, multiple regression analyses showed that X-ray Scadding score was positively associated with MOF. CONCLUSIONS: This study shows that MOF represent a common and important complication in patients with moderate/severe sarcoidosis. The chest X-ray evaluation and the pulmonary function test could allow to define the risk of MOF in sarcoidosis patients.

Fragility Score: a REMS-based indicator for the prediction of incident fragility fractures at 5 years.

BACKGROUND: Accurate estimation of the imminent fragility fracture risk currently represents a challenging task. The novel Fragility Score (FS) parameter, obtained during a Radiofrequency Echographic Multi Spectrometry (REMS) scan of lumbar or femoral regions, has been developed for the non-ionizing estimation of skeletal fragility. AIMS: The aim of this study was to assess the performance of FS in the early identification of patients at risk for incident fragility fractures with respect to bone mineral density (BMD) measurements. METHODS: Data from 1989 Caucasians of both genders were analysed and the incidence of fractures was assessed during a follow-up period up to 5 years. The diagnostic performance of FS to discriminate between patients with and without incident fragility fracture in comparison to that of the BMD T-scores measured by both Dual X-ray Absorptiometry (DXA) and REMS was assessed through ROC analysis. RESULTS: Concerning the prediction of generic osteoporotic fractures, FS provided AUC = 0.811 for women and AUC = 0.780 for men, which resulted in AUC = 0.715 and AUC = 0.758, respectively, when adjusted for age and body mass index (BMI). For the prediction of hip fractures, the corresponding values were AUC = 0.780 for women and AUC = 0.809 for men, which became AUC = 0.735 and AUC = 0.758, respectively, after age- and BMI-adjustment. Overall, FS showed the highest prediction ability for any considered fracture type in both genders, resulting always being significantly higher than either T-scores, whose AUC values were in the range 0.472-0.709. CONCLUSION: FS displayed a superior performance in fracture prediction, representing a valuable diagnostic tool to accurately detect a short-term fracture risk.

Ability of radiofrequency echographic multispectrometry to identify osteoporosis status in elderly women with type 2 diabetes.

BACKGROUND: Patients with type 2 diabetes (T2DM) have an increased or normal BMD; however fragility fractures represent one of the most important complications of T2DM. AIMS: This study aimed to evaluate whether the use of the Radiofrequency Echographic multi spectrometry (REMS) technique may improve the identification of osteoporosis in T2DM patients. METHODS: In a cohort of 90 consecutive postmenopausal elderly (70.5 ± 7.6 years) women with T2DM and in 90 healthy controls we measured BMD at the lumbar spine (LS-BMD), at femoral neck (FN-BMD) and total hip (TH-BMD) using a dual-energy X-ray absorptiometry device; moreover, REMS scans were also carried out at the same axial sites. RESULTS: DXA measurements were all higher in T2DM than in non-T2DM women; instead, all REMS measurements were lower in T2DM than in non T2DM women. Moreover, the percentage of T2DM women classified as "osteoporotic", on the basis of BMD by REMS was markedly higher with respect to those classified by DXA (47.0% vs 28.0%, respectively). On the contrary, the percentage of T2DM women classified as osteopenic or normal by DXA was higher with respect to that by REMS (48.8% and 23.2% vs 38.6% and 14.5%, respectively). T2DM women with fragility fractures presented lower values of both BMD-LS by DXA and BMD-LS by REMS with respect to those without fractures; however, the difference was significant only for BMD-LS by REMS (p < 0.05). CONCLUSIONS: Our data suggest that REMS technology may represent a useful approach to enhance the diagnosis of osteoporosis in patients with T2DM.

Could radiofrequency echographic multispectrometry (REMS) overcome the overestimation in BMD by dual-energy X-ray absorptiometry (DXA) at the lumbar spine?

BACKGROUND: Osteoarthritis (OA) and vertebral fractures at the lumbar spine lead to an overestimation of bone mineral density (BMD). Recently, a new approach for osteoporosis diagnosis, defined as radiofrequency echographic multi-spectrometry (REMS), represents an innovative diagnostic tool that seems to be able to investigate bone quality and provide an estimation of fracture risk independent of BMD. The aim of this paper was to evaluate whether the use of REMS technology can favor the diagnosis of osteoporosis in subjects with an apparent increase in BMD. METHODS: In a cohort of 159 postmenopausal (66.2 ± 11.6 yrs) women with overestimated BMD by DXA at the lumbar spine, we performed an echographic scan with the REMS technique. RESULTS: The mean values of BMD at different skeletal sites obtained by the DXA and REMS techniques showed that the BMD T-scores by REMS were significantly lower than those obtained by the DXA technique both at the lumbar spine (p < 0.01) and at all femoral subregions (p < 0.05). In OA subjects, the percentage of women classified as "osteoporotic" on the basis of BMD by REMS was markedly higher with respect to those classified by DXA (35.1% vs 9.3%, respectively). Similarly, the REMS allows a greater number of fractured patients to be classified as osteoporotic than DXA (58.7% vs 23.3%, respectively). CONCLUSIONS: REMS technology by the analysis of native raw unfiltered ultrasound signals appears to be able to overcome the most common artifacts, such as OA and vertebral fracture of the lumbar spine, which affect the value of BMD by DXA.

Relationship between Lymphocyte Subpopulations and Vitamin D Levels in COVID-19 Pneumonia Patients.

BACKGROUND: Some studies have shown that patients who are hospitalized with severe COVID-19 also have low levels of vitamin D. It is known that vitamin D can reduce the risk of infections and down regulate the immune/inflammatory reaction. OBJECTIVES: To investigate the association between vitamin D status and lymphocyte subpopulations in hospitalized pneumonia COVID-19 patients. METHODS: In 33 positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients with radiologic evidence of interstitial pneumonia and in 16 healthy control subjects matched for age, sex, and seasonality lymphocyte subpopulations and vitamin D levels were evaluated. RESULTS: The majority of patients with COVID-19 pneumonia (70.8%) presented vitamin D deficiency. The percentages of neutrophils presented a negative correlation (r = -0.74; P < 0.001), whereas the percentages of lymphocytes presented a positive correlation (r = 0.43; P < 0.01) with 25(OH)D. Moreover, vitamin D levels were positively correlated with CD3+ (r = 0.37, P < 0.05), CD4+ (r = 0.41, P < 0.05), CD8+ (r = 0.32, P < 0.07), and CD19+ (r = 0.38, P < 0.05). CONCLUSIONS: This preliminary study confirms the high prevalence of vitamin D deficiency in patients with COVID-19 pneumonia and that vitamin D deficiency is associated with a reduction of lymphocyte subsets and altered T-lymphocyte activation. This finding may contribute to clarify the mechanisms by which vitamin D influences the course and outcome of COVID-19 pneumonia.

Radiofrequency echographic multispectrometry (REMS): an innovative technique for the assessment of bone status in young women with anorexia nervosa.

PURPOSE: Reduced bone mineral density (BMD) and increase risk of fragility fracture are common complication of anorexia nervosa (AN). BMD by dual-energy X-ray absorptiometry (DXA) present several limits in subjects with AN. This study aimed to evaluate the usefulness of the new Radiofrequency echographic multispectrometry (REMS) technique in the assessment of bone status in young women with AN. METHODS: In a cohort of 50 subjects with restrictive AN and in 30 healthy controls, we measured BMD at the lumbar spine (LS-BMD), at femoral neck (FN-BMD) and total hip (TH-BMD) using both DXA and REMS technique. RESULTS: BMD evaluated by DXA and REMS technique at all measurement sites were all significantly (p < 0.01) lower in subjects suffering from AN subjects than in controls. Good correlations were detected between BMD by DXA and BMD by REMS measurements at LS (r = 0.64, p < 0.01) at FN (r = 0.86, p < 0.01) and at TH (r = 0.84, p < 0.01) in subjects suffering from AN. Moreover, Bland-Altman analysis confirmed the good agreement between the two techniques. The subjects suffering from AN with previous vertebral fragility fractures presented lower values of both BMD-LS and BMD-TH by DXA and by REMS with respect to those without fractures; however, the difference was significant only for BMD-TH by REMS (p < 0.05). CONCLUSIONS: Our data suggest that REMS technique due to its characteristic of precision and reproducibility may represent an important tool for the evaluation of the changes in bone status in AN young women, especially during the fertile age and in case of pregnancy and breastfeeding. LEVEL OF EVIDENCE: Level of evidence: level III cohort study.

Could Radiofrequency Echographic Multi-Spectrometry (REMS) Overcome the Limitations of BMD by DXA Related to Artifacts? A Series of 3 Cases.

Dual-energy X-ray absorptiometry (DXA) is considered the gold standard in the evaluation of bone mineral density (BMD) and in the diagnosis of osteoporosis.The diagnostic sensitivity of BMD at lumbar spine is frequently reduced by the presence of artifacts. This study aimed to show the usefulness of radiofrequency echographic multi-spectrometry (REMS) in determining lumbar BMD in the presence of artifacts with DXA measurements. We present 3 cases in which REMS technology, by the analysis of native raw unfiltered ultrasound signals, appears to be able to recognize and overcome the most common artifacts that affect the value of the BMD by DXA, thus allowing a better assessment of fracture risk.

Pharmacokinetic profile and effect on bone markers and muscle strength of two daily dosage regimens of calcifediol in osteopenic/osteoporotic postmenopausal women.

BACKGROUND: At present, although cholecalciferol represents the form of vitamin D of choice for the treatment of vitamin D deficiency, there is a growing interest in calcifediol. AIMS: This study aimed to evaluate the efficacy and the safety of two different daily doses of calcifediol. METHODS: Fifty osteopenic/osteoporotic women with serum levels of 25-hydroxyvitamin D (25OHD) between 10 and 20 ng/ml were randomized to a 6-month treatment with oral calcifediol 20 µg/day (n = 25) or oral calcifediol 30 µg/day (n = 25). In all, we measured the time course of the levels of 25OHD and other biochemical parameters. Moreover, we evaluated handgrip strength and serum levels of myostatin. RESULTS: The peak increase in 25OHD levels was reached after 90 days of treatment in group 1 (59.3 ng/ml) and after only 60 days in group 2 (72.3 ng/ml); thereafter in both groups, the levels of 25OHD showed a tendency towards stabilization. After 30 days, all the patients treated with 30 µg/day had values of 25OHD > 30 ng/ml. Handgrip strength showed a modest but progressive increase which reached the statistical significance in the 30 µg/day group. This latter group also presented a modest and non-significant decrease in serum levels of myostatin. CONCLUSIONS: Calcifediol is able to rapidly normalize the vitamin D deficiency, and the 30 µg daily dosage could be suggested in those patients who need to rapidly reach optimal 25OHD levels. Moreover, the 6-month treatment with calcifediol at a dose of 30 µg results in a modest but significant increase in upper limb strength.

Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with bone disease severity in Rett syndrome.

BACKGROUND: More than 95% of individuals with RTT have mutations in methyl-CpG-binding protein 2 (MECP2), whose protein product modulates gene transcription. The disorder is caused by mutations in a single gene and the disease severity in affected individuals can be quite variable. Specific MECP2 mutations may lead phenotypic variability and different degrees of disease severity. It is known that low bone mass is a frequent and early complication of subjects with Rett syndrome. As a consequence of the low bone mass Rett girls are at an increased risk of fragility fractures. This study aimed to investigate if specific MECP2 mutations may affects the degree of involvement of the bone status in Rett subjects. METHODS: In 232 women with Rett syndrome (mean age 13.8 ± 8.3 yrs) we measured bone mineral density at whole body and at femur (BMD-FN and BMD-TH) by using a DXA machine (Hologic QDR 4500). QUS parameters were assessed at phalanxes by Bone Profiler-IGEA (amplitude dependent speed of sound: AD-SoS and bone transmission time: BTT). Moreover, ambulation capacity (independent or assisted), fracture history and presence of scoliosis were assessed. We divided the subjects with the most common point mutations in two group based on genotype-phenotype severity; in particular, there has been consensus in recognising that the mutations R106T, R168X, R255X, R270X are considered more severe. RESULTS: As aspect, BMD-WB, BMD-FN and BMD-TH were lower in subjects with Rett syndrome that present the most severe mutations with respect to subjects with Rett syndrome with less severe mutations, but the difference was statistically significant only for BMD-FN and BMD-TH (p < 0.05). Also both AD-SoS and BTT values were lower in subjects that present the most severe mutations with respect to less severe mutations but the difference was not statistically significant. Moreover, subjects with Rett syndrome with more severe mutations present a higher prevalence of scoliosis (p < 0.05) and of inability to walk (p < 0.05). CONCLUSION: This study confirms that MECP2 mutation type is a strong predictor of disease severity in subjects with Rett syndrome. In particular, the subjects with more severe mutation present a greater deterioration of bone status, and a higher prevalence of scoliosis and inability to walk.

The Role of Urinary Calcium and Chitotriosidase in a Cohort of Chronic Sarcoidosis Patients.

BACKGROUND: Calcium metabolism alterations are quite common in sarcoidosis and have been correlated with disease activity. OBJECTIVES: The aim of the study was to investigate the clinical significance of calcium metabolism alterations in patients with chronic sarcoidosis. We paid particular attention to associations with specific disease phenotypes and chitotriosidase (CTO) expression. METHODS: 212 chronic sarcoidosis patients (mean age 56.07 ± 12 years; 97 males) were retrospectively recruited. Demographic, clinical, functional, and radiological data, and serum-urinary calcium metabolism were entered into an electronical database for analysis. Levels of CTO and angiotensin-converting enzyme (ACE) were measured and bone mineral density and lung function tests were conducted. RESULTS: Hypercalciuria and hypercalcemia were observed in 18.8 and 1.8% of patients, respectively. Urinary calcium levels correlated with CTO activity (r = 0.33, p = 0.0042). Patients with worsening persistent disease showed the highest levels of urinary calcium. Diffusing capacity of the lung for carbon monoxide (DLCO) percentage correlated inversely with urinary calcium (r = 0.1482; p = 0.0397). CONCLUSIONS: Calcium metabolism alteration, particularly hypercalciuria, was observed in a significant percentage of patients of sarcoidosis. Urinary calcium was correlated with clinical status, DLCO, and serum CTO activity, suggesting its potential role as a biomarker of the activity and severity of sarcoidosis.

Bone status in relation to ambulatory performance in girls with Rett syndrome: a 10-year longitudinal study.

BACKGROUND: Low bone mass is a frequent and early complication of girls with Rett syndrome. As a consequence of the low bone mass, Rett patients are at an increased risk of fragility fractures. This study aimed to investigate the long-term influences of mobility on bone status in girls with Rett syndrome. METHODS: In 58 girls with Rett syndrome, biochemical parameters and quantitative ultrasound parameters at phalanges (amplitude-dependent speed of sound: AD-SoS and bone transmission time: BTT) were measured at baseline and after 5 and 10 years. The subjects were divided into two groups: nonambulatory (n = 28) and ambulatory (n = 30). RESULTS: In nonambulatory Rett subjects, the values of AD-SoS and BTT were significantly lower than in ambulatory Rett subjects at each time point. However, during the 10-year follow-up both ambulatory and nonambulatory Rett patients showed a similar worsening in their bone status. CONCLUSION: This longitudinal study suggests that both ambulatory and nonambulatory Rett subjects present a progressive deterioration of bone status as assessed by quantitative ultrasound parameters, and the ambulatory impairment and the nutritional status seem to play a key role in the deterioration of bone status.

Retrospective evaluation of persistence in osteoporosis therapy with oral bisphosphonates in Italy: the TOBI study.

The patients' persistence with osteoporosis treatments is low. This retrospective, multicenter survey showed that almost 30% of osteoporotic patients discontinued the treatment within the first 6 months and that those taking drinkable bisphosphonates were less likely to interrupt the therapy; instead, the use of generic bisphosphonates was associated to a more precocious interruption. PURPOSE: Low persistence with osteoporosis medications is associated with higher fracture risk. This study aimed to assess the persistence to treatment with oral bisphosphonates among Italian osteoporotic patients under treatment for at least 6 months and to evaluate whether the different oral formulations of bisphosphonates may influence the interruption of the therapy. METHODS: 723 consecutive osteoporotic patients, aged 50 years or over, referred as outpatients for a follow-up visit after receiving a prescription of an oral bisphosphonate for the first time for at least 6 months were enrolled in this retrospective, multicenter survey carried out under conditions of usual clinical practice. All the patients enrolled were submitted to a standardized interview. RESULTS: 191 patients turned out to have discontinued treatment (28.7%), the more common causes for interruption being the adverse events (43.9%), fear of adverse events (23.3%) and perceived absence of efficacy of the treatment (15.8%). The osteoporotic patients taking drinkable bisphosphonate or on treatment with aromatase inhibitors or under the age of 70 years were less likely to interrupt the treatment. However, these associations were no longer significant when the pharmaceutical formulation (generic vs branded) was included into the multivariate logistic regression model. CONCLUSION: This study suggests that the new drinkable formulations of bisphosphonates could be an interesting option able to reduce upper GI adverse events, thus increasing persistence; whereas the generic formulations of bisphosphonates were associated to a premature discontinuation.

In Type-2 Diabetes Subjects Trabecular Bone Score is Better Associated with Carotid Intima-Media Thickness than BMD.

Literature data reported that in elderly subjects, carotid intima-media thickness (IMT) was negatively associated with bone mineral density (BMD). Paradoxically, type-2 diabetes (T2DM) patients, despite having higher BMD, present an increased risk of fragility fractures and cardiovascular complications. Some studies have reported trabecular bone score (TBS), an index of trabecular bone quality, as possibly being reduced in T2DM. This study aimed to evaluate whether in T2DM subjects TBS was better associated with IMT with respect to BMD. In 131 consecutive T2DM subjects (55 men and 76 women; mean age: 60.0 ± 7.3 years) and 265 consecutive non-T2DM subjects (107 men and 158 women; mean age: 58.9 ± 7.8 years) we measured carotid IMT by high-resolution ultrasonography and BMD at lumbar spine (LS-BMD), at femoral neck FN-BMD and total hip TH-BMD; TBS was calculated using TBS iNsight software. LS-BMD, FN-BMD, and TH-BMD were all significantly higher in T2DM than in non-T2DM subjects, whereas TBS was significantly lower in T2DM subjects than in controls and inversely correlated with diabetes duration. In T2DM subjects multiple regression analysis showed that IMT was positively associated with age (b = 0.017; p < 0.001) and inversely associated with TBS (b = -0.473; p = 0.038). In non-T2DM subjects, only age was positively associated with IMT. To sum up, T2DM subjects present higher values of BMD and lower values of TBS with respect to non-diabetic controls. Moreover, in T2DM subjects TBS was found to be independently associated with carotid IMT. These findings suggest that TBS may not only capture bone fragility-related factors, but also some information associated with greater risk of developing cardiovascular diseases.

Prescription of anti-osteoporosis medications after hospitalization for hip fracture: a multicentre Italian survey.

PURPOSE: Literature data indicate that the proportion of patients with recent hip fracture who receive a prescription for anti-osteoporotic drugs is low and does not seem to increase over time. This study aimed to obtain data on the prescription for anti-osteoporotic drugs in Italian patients discharged after a recent hip fracture and to assess which variables could have influenced the decision for prescribing osteoporosis medication. METHODS: A total of four Italian centres located in four different geographical areas (Siena, Verona, Naples and Palermo) participated in this retrospective study. In each centre, experienced clinicians gathered the data of up to 200 consecutive patients discharged after a recent low-trauma hip fracture. The analysis was carried out on 697 patients (540 women and 157 men; mean age 81.9 ± 8.6 years). RESULTS: The percentage of patients who were receiving any type of treatment for osteoporosis before the hip fracture was 8.8% (ranging from 2.4% in Naples to 17.4% in Verona). After the index hip fracture, only 23.2% of patients (namely 10.5% of men and 27.2% of women) received prescription for any pharmacological treatments for osteoporosis. Both female gender and previous use of medications for osteoporosis were positively associated with the likelihood of receiving prescription for anti-osteoporotic treatment at discharge. CONCLUSIONS: This study showed that less than 25% of the elderly Italian patients discharged after a hip fracture received a prescription for any type of treatment for osteoporosis and highlights the urgent need for implementing new strategies in the management of hip fracture patients.

How the knowledge of fracture risk might influence adherence to oral therapy of osteoporosis in Italy: the ADEOST study.

UNLABELLED: The patients' adherence to osteoporosis treatments is low. In our study population a history of osteoporotic fractures was associated to better compliance and persistence; however, a 12-month randomized study carried out on 816 osteoporotic women showed that providing the patients with their individual fracture risk information did not prove effective. PURPOSE: Several drugs are currently available for the treatment of osteoporosis, but the patients' compliance and persistence with these treatments are low. This study aimed to both analyze the adherence to oral osteoporosis medications among Italian osteoporotic patients (cross-sectional study) and evaluate if providing patients with their individual fracture risk information may improve compliance and persistence (prospective study). METHODS: A total of 3379 osteoporotic patients referred as outpatients for a visit 1 year after receiving a prescription of oral osteoporosis medications for the first time, were enrolled for the retrospective study. Moreover, 816 postmenopausal women receiving an oral prescription for osteoporosis for the first time, were randomized into two groups: group 1 (managed according to standard clinical practice) and group 2 (managed with greater patient involvement and information on the individual risk of major osteoporotic fractures calculated by DeFRA algorithm). RESULTS: In the retrospective study, a history of osteoporotic fractures, the frequency of drug administration and a condition of being overweight/obese had a significant influence on both compliance and persistence. Of the 816 patients enrolled in the longitudinal study, 731 (374 of group 1 and 357 of group 2) attended the 1 year follow-up visit. The percentage of women with high compliance or persistence was greater in group 2 (64.2 vs. 58.1 % and 66.8 vs. 62.6 %, respectively), but without reaching any statistical significance. CONCLUSIONS: Although providing the patients with their individual fracture risk information was not statistically effective, further studies on additional interventions able to improve the patients' perceived risk of fracture are warranted.

Abaloparatide.

Abaloparatide is an investigational analog of human PTHrP (1-34) being developed for the treatment of osteoporosis. The amino-acid sequence of abaloparatide is identical to that of PTHrP in the first 20 amino-acids, while over half of the remaining amino-acids are different. Some studies in animals and in humans reported that abaloparatide presented a potent anabolic activity with reduced effects on bone resorption as compared to that observed with teriparatide. This may be due to a more transient signaling response of abaloparatide related to differing affinities of the two drugs to the specific conformations of the PTH1 receptor. In the ACTIVE study, a phase 3 fracture prevention trial, 2460 postmenopausal osteoporotic women at high risk for fracture were randomized to receive 18-months of either daily abaloparatide 80 µg s.c., placebo or teriparatide 20 µg s.c. The reduction in vertebral fracture rate with respect to placebo was 86% in the abaloparatide group and 80% in the teriparatide group. Abaloparatide also produced a significant 43% reduction in the rate of nonvertebral fractures (2.7 vs 4.0% with placebo, p=0.04) whereas teriparatide determined a 28% reduction (2.9 vs 4.0% with placebo, p=NS). Abaloparatide or teriparatide showed similar increases in BMD at lumbar spine, while the patients of the abaloparatide group showed significantly greater increases in BMD at both total hip (4.18 vs 3.26%) and femoral neck (3.60 vs 2.66%). Therefore, if the preliminary data of the ACTIVE study is confirmed, abaloparatide may become an important option for the anabolic treatment of postmenopausal osteoporosis.

The Trochanteric Localization is a Mediator of Slower Short-Term Functional Recovery in Overweight and Obese Elderly Women with Recent Hip Fracture: The BREAK Study.

The hypothesis tested in this study, carried out on elderly Italian women with recent hip fracture, was to assess the extent to which the effect of a condition of being overweight/obese on short-term functional recovery as evaluated by the "time to permitted load" could be explained by a mediator variable (type of hip fracture). We studied 727 women aged 60 years or over with a recent low trauma surgically treated hip fracture and for whom an information on post-surgery complications and on the time to permitted load was available. To assess for mediation, the statistical analyses were carried out following the procedure described by Baron and Kenny. In this study, 46 % of women with hip fracture presented a time to permitted load of ≥ 10 days. The women with a post-surgery time to permitted load of ≥ 10 days showed a significantly higher proportion of trochanteric fracture localization (72.1 vs 42 %), of total overweight/obesity (46.5 vs 36.8 %) and of post-surgery complications (38.8 vs 18.8 %). The mediating effect of hip fracture localization on the association between overweight/obesity and the time of permitted load was demonstrated and confirmed in a multivariate logistic regression model. This study, carried out using a "mediator" statistical analysis, suggests that in elderly women with hip fracture being overweight/obese is associated with a slower short-term functional recovery as evaluated by the time to permitted load and that this association is mediated by the trochanteric localization of hip fracture.

The prevention of fragility fractures in diabetic patients.

Patients with diabetes mellitus (DM) are at greater risk of fractures mostly due to not only extraskeletal factors, such as propensity to falls, but also to bone quality alteration, which reduces bone strength. In people with DM, insulin deficit and hyperglycemia seem to play a role in determining bone formation alteration by AGE accumulation which directly influences osteoblast activity. Although there are conflicting data in the literature, adequate glycemic control with hypoglycemic treatment may be an important element in preventing bone tissue alterations in both type 1 and type 2 DM. Diabetes status is a predictive of future hip and major osteoporosis fractures independently of BMD and FRAX probability. Attention should be paid to the use of thiazolidinediones, especially in older women, because the direct negative effect on bone could exceed the positive effect of glycemic control. Systematic screening for complications and fall prevention efforts, along with calcium and vitamin D repletion and adequate physical activity, represents the mainstay of fracture prevention in DM patients. All anticatabolic drugs (raloxifene, bisphosphonates, denosumab) seem to be effective in DM patients. On the basis of pathophysiological evidence that suggests low bone formation in DM patients, osteoanabolic therapies such as teriparatide might represent an important therapeutic option for DM patients with severe osteoporosis and/or multiple fractures. The search for better methods for the identification of fragility fracture risk in the growing population of adult and elderly subjects with DM might be considered a clinical priority which could improve the prevention of fracture in DM patients.