Elisa Cairoli

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Patients with adrenal incidentalomas (AIs) and subclinical hypercortisolism (SH) have increased risk of fracture independent of bone mineral density (BMD) and possibly due to reduced bone quality. The trabecular bone score (TBS) has been proposed as a index of bone microarchitecture. The aim of the study was to investigate TBS in AI. In 102 AI patients, SH was diagnosed in the presence of at least two of the following: (1) urinary free cortisol >70u2009µg/24u2009h (193.1u2009nmol/L); (2) cortisol after 1‐mg dexamethasone suppression test (1‐mg DST) >3.0u2009µg/dL (82.8u2009nmol/L); or (3) adrenocorticotropic hormone (ACTH) <10u2009pg/mL (<2.2u2009pmol/L). In patients and in 70 matched controls, BMD was measured at lumbar spine (LS) and femur (neck [FN] and total [FT]) by dual X‐ray absorptiometry and TBS was assessed in the region of LS‐BMD; BMD and TBS data were reported as Z‐scores. In patients, vertebral deformities were assessed by radiograph. Patients with SH (nu2009=u200934) had lower LS‐BMD (−0.31u2009±u20091.17), FT‐BMD (−0.29u2009±u20090.91), and TBS (−3.18u2009±u20091.21) than patients without SH (nu2009=u200968, 0.31u2009±u20091.42, pu2009=u20090.03; 0.19u2009±u20090.97, pu2009=u20090.01; −1.70u2009±u20091.54, pu2009<u20090.0001, respectively) and controls (0.42u2009±u20091.52, pu2009=u20090.02; 0.14u2009±u20090.76, pu2009=u20090.02; −1.19u2009±u20090.99, pu2009<u20090.0001, respectively). TBS was inversely correlated with 1‐mg DST (βu2009=u2009−0.26, tu2009=u2009−2.79, pu2009=u20090.006) regardless of age, LS‐BMD, body mass index (BMI), and gender. The presence of fracture was associated with low TBS alone (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.85–12.42, pu2009=u20090.001) and with the cluster low TBS plus low LS‐BMD (OR, 4.37; 95% CI, 1.71–11.4, pu2009=u20090.002), after adjustment for age, BMI, and gender. Low TBS plus low LS‐BMD showed a good specificity (79%) for predicting fractures, whereas normal TBS (ie,u2009>u2009−1.5) plus normal LS‐BMD high specificity (88.1%) for excluding fractures. Finally, TBS predicted the occurrence of a new fracture in 40 patients followed for 24 months (OR, 11.2; 95%CI, 1.71–71.41, pu2009=u20090.012) regardless of LS‐BMD, BMI, and age. In SH, bone quality, as measured by TBS, is altered. TBS is useful in detecting AI patients at risk of fractures.

Prevalence of Morphometric Vertebral Fractures in Patients With Type 1 Diabetes

OBJECTIVE Several studies showed low bone mineral density (BMD) and elevated risk of symptomatic fractures in patients with type 1 diabetes (T1D). To our knowledge, there has been no investigation on the prevalence of asymptomatic vertebral fractures (VFx) in T1D. In the current study, we assessed BMD and the prevalence of VFx in T1D. RESEARCH DESIGN AND METHODS We evaluated 82 T1D patients (26 males and 56 females, aged 31.1 ± 8.6 years, BMI 23.5 ± 3.3 kg/m2, disease duration 12.8 ± 8.3 years) and 82 controls (22 females and 60 males, aged 32.9 ± 5.8 years, BMI 23.9 ± 4.8 kg/m2). Spinal and femoral BMD (as Z-score, Z-LS and Z-FN, respectively) and the prevalence of VFx were evaluated by dual X-ray absorptiometry. RESULTS T1D patients had lower Z-LS and Z-FN than controls (−0.55 ± 1.3 vs. 0.35 ± 1.0, P < 0.0001, and −0.64 ± 1.1 vs. 0.29 ± 0.9, P < 0.0001, respectively) and a higher prevalence of VFx (24.4 vs. 6.1%, P = 0.002). Age, diabetes duration, age at diabetes manifestation, glycosylated hemoglobin, Z-LS, Z-FN, and the prevalence of chronic complications were similar for patients with and without VFx. In the logistic regression analysis, the presence of VFx was associated with the presence of T1D but not with lumbar spine BMD. Whereas moderate or severe VFx was associated with low lumbar spine BMD in the whole combined group of T1D patients and controls, there was no association between moderate or severe VFx and lumbar spine BMD in the T1D group. CONCLUSIONS T1D patients have low BMD and elevated prevalence of asymptomatic VFx, which is associated with the presence of T1D independently of BMD.

Factors associated with bisphosphonate treatment failure in postmenopausal women with primary osteoporosis

SummaryAmong 97 postmenopausal women with primary osteoporosis, adequate calcium and vitamin D supplementation, and good compliance to a 36-month bisphosphonate treatment, the 25.8xa0% of patients are inadequate responders. Current smoking and a bone turnover in the upper part of the normal range increase the risk of treatment failure.IntroductionTo evaluate the prevalence of the bisphosphonate treatment failure and its possible associated factors in women with primary osteoporosis (PO).MethodsWe studied 97 previously untreated postmenopausal women with PO and fragility fractures and/or a FRAX® 10-year probability of a major osteoporotic fracture ≥7.5xa0%, before and after a 36-month treatment with alendronate or risedronate and adequate vitamin D supplementation with good compliance. At baseline and after 36xa0months, lumbar spine (LS) and femoral bone mineral density (BMD) were assessed by Dual X-ray absorptiometry and vertebral fractures by spinal radiographs. Spinal deformity index (SDI) was calculated. Treatment failure was defined by the presence of ≥2 incident fragility fractures and/or a BMD decrease greater than the least significant change.ResultsBisphosphonate treatment failure was observed in 25.8xa0% of patients. Age, body mass index, years since menopause, familiar history of hip fracture, number of falls, type of bisphosphonate used, 25-hydroxyvitamin D levels (25OHVitD), BMD, SDI, and FRAX® score at baseline were not different between responders and inadequate responders. Treatment failure was associated with current smoking (OR 3.22, 95xa0% CI 1.10–9.50, Pu2009=u20090.034) and baseline alkaline phosphatase total activity levels ≥66.5xa0U/L (OR 4.22, 95xa0% CI 1.48–12.01, Pu2009=u20090.007), regardless of age, number of falls, LS BMD, and baseline SDI.ConclusionsThe 25.8xa0% of PO postmenopausal women inadequately responds to bisphosphonates, despite a good compliance to therapy and normal 25OHVitD levels. The current smoking and bone turnover in the upper part of the normal range are associated with the inadequate response to bisphosphonates.

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 fractures 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 SDIu200a=u200a0. Methodology We compared ANNs prognostic performance with that of LR in identifying SDI≥1/SDI≥5 in 372 women with postmenopausal-osteoporosis (SDI≥1, nu200a=u200a176; SDIu200a=u200a0, nu200a=u200a196; SDI≥5, nu200a=u200a51), 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 SDIu200a=u200a0 (first) and SDI≥5 vs SDIu200a=u200a0 (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.

The utility of lumbar spine trabecular bone score and femoral neck bone mineral density for identifying asymptomatic vertebral fractures in well-compensated type 2 diabetic patients

SummaryThe objective of the study was to evaluate the usefulness of trabecular bone score (TBS) and bone mineral density (BMD) for identifying vertebral fractures (VFx) in well-compensated type 2 diabetic (T2D) patients. TBS and femoral neck BMD below certain cutoffs may be useful for identifying VFx in well-compensated T2D patients.IntroductionIn T2D, the prevalence of VFx is increased, especially in poorly compensated and complicated diabetic patients. The possibility of predicting the fracture risk in T2D patients by measuring BMD and TBS, an indirect parameter of bone quality, is under debate. Therefore, the objective was to evaluate the usefulness of TBS and BMD for identifying VFx in well-compensated T2D patients.MethodsNinety-nine T2D postmenopausal women in good metabolic control (glycosylated haemoglobin 6.8u2009±u20090.7xa0%) and 107 control subjects without T2D were evaluated. In all subjects, we evaluated the following: the BMD at the lumbar spine (LS) and the femoral neck (FN); the TBS by dual X-ray absorptiometry; and VFx by radiography. In T2D subjects, the presence of diabetic retinopathy, neuropathy, and nephropathy was evaluated.ResultsT2D subjects had increased VFx prevalence (34.3xa0%) as compared to controls (18.7xa0%) (pu2009=u20090.01). T2D subjects presented higher BMD (LS −0.8u2009±u20091.44, FN −1.06u2009±u20091.08), as compared to controls (LS −1.39u2009±u20091.28, pu2009=u20090.002; FN −1.45u2009±u20090.91, pu2009=u20090.006, respectively). TBS was not different between diabetics and controls. In fractured T2D patients, LS-BMD, FN-BMD, and TBS were reduced (−1.2u2009±u20091.44; −1.44u2009±u20091.04; 1.072u2009±u20090.15) and the prevalence of retinopathy (15.4xa0%) was increased than in nonfractured T2D subjects (−0.59u2009±u20091.4, pu2009=u20090.035; −0.87u2009±u20091.05, pu2009=u20090.005; 1.159u2009±u20090.15, pu2009=u20090.006; 1.8xa0%, pu2009=u20090.04, respectively). The combination of TBS ≤1.130 and FN-BMD less than −1.0 had the best diagnostic accuracy for detecting T2D fractured patients (SP 73.8xa0%, SN 63.6xa0%, NPV 78.9xa0%, PPV 56.8xa0%).ConclusionsTBS and FN-BMD below certain cutoffs may be useful for identifying VFx in well-compensated T2D patients.

Evidence for vitamin D deficiency and increased prevalence of fractures in autoimmune bullous skin diseases.

Backgroundu2002 Vitamin D deficiency plays a role in autoimmune diseases and risk of fractures. No data are available on vitamin D levels and vertebral fractures in autoimmune bullous skin diseases.

Bone health in type 1 diabetes: focus on evaluation and treatment in clinical practice

IntroductionType 1 diabetes (T1D) is an autoimmune disease with chronic hyperglycemic state, which incidence has been globally rising during the past decades. Besides the well-known diabetic complications such as retinopathy, nephropathy and neuropathy, T1D is characterized also by poor bone health. The reduced bone mineralization, quality and strength lead to vertebral and hip fractures as the most important clinical manifestations. Suppressed bone turnover is the main characteristic of T1D-associated bone disorder.ResultsThis is thought to be due to hyperglycemia, hypoinsulinemia, autoimmune inflammation, low levels of insulin-like growth factor-1 and vitamin D. Young age of T1D manifestation, chronic poor glycemic control, high daily insulin dose, low body mass index, reduced renal function and the presence of diabetic complications are clinical factors useful for identifying T1D patients at risk of reduced bone mineral density. Although the clinical risk factors for fracture risk are still unknown, chronic poor glycemic control and the presence of diabetic complications might raise the suspicion of elevated fracture risk in T1D. In the presence of the above-mentioned risk factors, the assessment of bone mineral density by dual-energy X-ray absorptiometry and the search of asymptomatic vertebral fracture by vertebral fracture assessment or lateral X-ray radiography of thorax-lumbar spine should be recommended.ConclusionThere is no consensus about the treatment of diabetic bone disorder. However, the improvement of glycemic control has been suggested to have a beneficial effect on bone in T1D. Recently, several experiments showed promising results on using anabolic pharmacological agents in diabetic rodents with bone disorder. Therefore, randomized clinical trials are needed to test the possible use of the bone anabolic therapies in humans with T1D.

Perspectives on osteoporosis therapies

AbstractnOsteoporosis is a skeletal disease which predisposes to fragility fractures with high morbidity and economic impact, and, therefore, the goal of any osteoporosis treatment is to reduce the fracture risk. In the various forms of osteoporosis an imbalance between bone resorption and apposition is present, that generally leads to a reduction of bone mineral density and bone quality, and finally to the increased fracture risk. Nowadays, several drugs are available with a demonstrated anti-fracturative effect obtained by inhibiting bone resorption or stimulating bone formation. However, their use is not free from limitations and side effects. Importantly, to date, the available antiresorptive drugs have also an inhibiting, though to a lesser extent, effect on bone apposition and, similarly, the anabolic drugs lead to an increase also of bone resorption. Advances in our knowledge about bone biology, with molecular insights into mechanisms underlying osteoblast, osteoclast, and osteocyte activity, have led to the recognition of new potential targets and consequently to the formulation of new therapeutic agents to treat osteoporosis. New potential developments among the antiresorptive drugs include cathepsin K inhibitors and among the osteoanabolic drugs those activating the Wnt signaling pathway, such as the monoclonal antibodies against sclerostin. The novelty of these compounds is that their mechanism of action gives the exciting possibility to uncouple bone resorption and bone formation, and data available so far appear to be promising. Finally, several new therapeutic targets are under investigation in preclinical studies which could open further approaches to treat osteoporosis in the future.

Bone involvement in adult patients affected with Ehlers-Danlos syndrome.

SummaryThe Ehlers-Danlos syndrome is characterized by abnormal connective tissue but bone involvement is debated. We found a reduced BMD and bone quality and increased prevalence of asymptomatic vertebral fractures in eugonadal patients with Ehlers-Danlos syndrome. These findings suggest the need of a bone health evaluation in these patients.IntroductionThe Ehlers-Danlos (EDS) syndrome is characterized by abnormalities of the connective tissue leading to ligamentous laxity and skin and tissue fragility. We evaluated the bone metabolism, bone mineral density (BMD) and bone quality (measured by trabecular bone score, TBS), and the prevalence of vertebral fractures (VFx) in a group of eugonadal adult EDS patients.MethodsFifty consecutive Caucasian patients, aged 30–50xa0years (36 females, 14 males) with classical or hypermobility EDS and 50 age-, gender-, and body mass index (BMI)-matched control subjects were enrolled. In all subjects’ calcium-phosphorous metabolism, bone turnover, BMD at the lumbar spine (LS) and femur (femoral neck, FN and total femur, FT) and TBS by dual-energy X-ray absorptiometry, and the VFx presence by spine radiograph were assessed.ResultsPatients showed reduced BMD (Z-scores LS −0.45u2009±u20091.00, FN −0.56u2009±u20091.01, FT −0.58u2009±u20090.92) and TBS (1.299u2009±u20090.111) and increased prevalence of morphometric VFx (32xa0%) than controls (Z-scores LS 0.09u2009±u20091.22, FN 0.01u2009±u20090.97, FT 0.08u2009±u20090.89; TBS 1.382u2009±u20090.176; VFx 8xa0%, p <0.05 for all comparisons), while vitamin D levels, calcium-phosphorous metabolism, and bone turnover were comparable. Fractured EDS patients showed lower TBS values than non-fractured ones (1.245u2009±u20090.138 vs 1.325u2009±u20090.086, pu2009<u20090.05), despite comparable BMD. In EDS patients, the VFx presence was significantly associated with TBS even after adjusting for sex, age, BMD, EDS type, and falls frequency.ConclusionsEDS patients have reduced BMD and bone quality (as measured by TBS) and increased prevalence of VFx.

Vitamin D and skeletal health in autoimmune bullous skin diseases: a case control study

BackgroundThe presence of hypovitaminosis D in patients with autoimmune bullous skin diseases, such as pemphigus vulgaris (PV) and bullous pemphigoid (BP), is debated. In a previous study we found an increased prevalence of vertebral fractures (VFx) and hypovitaminosis D in PV and BP patients. The present study extends the sample size of the previous one, for investigating the 25-hydroxyvitamin D (25OHVitD) levels in relation with the skeletal health and disease intensity in these patients.MethodsThe previous study was performed in 13 PV and 15 BP patients and 28 controls. Data from 39 additional patients (22 PV and 17 BP) were now added. Eventually, we studied 67 patients (35 PV, 32 BP, 51 females), aged 64.7u2009±u200916.9xa0years and 67 age- gender- and body mass index-matched controls. In all subjects, serum 25OHVitD, calcium and alkaline phosphatase (ALP) levels were measured, bone mineral density (BMD) was evaluated by Dual-energy X-ray. Absorptiometry at lumbar spine (LS) and femoral neck (FN) and the presence of VFx were ascertained by visual assessment from spinal radiographs. In patients, the disease intensity was evaluated by the autoimmune bullous skin disorder intensity score (ABSIS).ResultsAs compared with controls, both PV and BP patients showed lower 25OHVitD (22.2u2009±u200911.1 vs 13.9u2009±u20098.3xa0ng/mL, pu2009<u20090.001 and 22.4u2009±u200914.9 vs 9.5u2009±u20097.7xa0ng/mL, pu2009<u20090.0001, respectively) and higher prevalence of severe hypovitaminosis D (22.9 vs 48.6%, pu2009<u20090.02 and 31.1 vs 75.0%, pu2009<u20090.0001, respectively) and VFx (28.6 vs 57.1%, pu2009=u20090.03 and 34.4 vs 62.5%, Pu2009=u20090.02, respectively). In both PV and BP patients, LS and FN BMD did not differ from controls. In the whole patients’ group, ABSIS score was inversely associated with 25OHVitD levels (Ru2009=u2009−0.36, pu2009<u20090.005), regardless of age (βu2009=u2009−3.2, Pu2009=u20090.009).ConclusionsPV and BP patients have an increased prevalence of hypovitaminosis D and VFx. The extended study shows, for the first time, that the 25OHVitD levels are inversely associated with disease intensity and that VFx occur in spite of a not reduced BMD.