Calcium-phosphate homeostasis and insulin resistance in men.

BACKGROUND AND AIMS: Data on P homeostasis in insulin resistance (IR) are still conflicting. We investigated calcium-phosphate homeostasis parameters in men with/without IR. METHODS AND RESULTS: 177 volunteers (aged 61.62 ± 12.11), whose body mass index (BMI) was 29.97 ± 6.35, were studied. On fasting blood and spot urine samples, we measured serum creatinine, sodium (sNa), potassium (sK), chloride (sCl), calcium (sCa), phosphate (sP), alkaline phosphatase total activity (ALP), glucose, insulin, parathyroid hormone (PTH), 25-hydroxy-vitamin D [25(OH)D], and urinary electrolytes corrected for creatinine (uNa/Cr, uK/Cr, uCl/Cr, uCa/Cr, and uP/Cr). Through the QUICKI index, we separated subjects with (IR+, n = 68) or without (IR-, n = 109) IR, and their parameters were compared. Associations were assessed by age-adjusted partial correlation, whose coefficients were compared by Fisher's transform. IR + had higher sP (3.54 ± 0.65 vs. 3.35 ± 0.47, p = 0.044) and lower uCa/Cr levels (0.073 ± 0.056 vs. 0.095 ± 0.072, p = 0.047) than IR-. BMI correlated with sP (r = 0.21, p < 0.05) and PTH (r = 0.29, p < 0.01). QUICKI negatively correlated with sCa (r = -0.22, p < 0.05) and positively with uCa/Cr (r = 0.21, p < 0.05), in turn correlating with uNa/Cr (r = 0.45, p < 0.001). In both groups, uCa/Cr correlated with eGFR and uNa/Cr (p < 0.05 to p < 0.001). In IR + only, sP correlated with BMI, PTH with insulin, and uP/Cr (p < 0.05 for all). IR+ and IR-coefficients differed (p < 0.05 to p < 0.001) for the correlation of sP with BMI and of PTH with insulin and uP/Cr. CONCLUSION: The higher sP and lower uCa/Cr levels found in men with IR + suggest that IR could modulate calcium-phosphate homeostasis, likely by affecting their renal handling.

The degree of cortisol secretion is associated with diabetes mellitus and hypertension in patients with nonfunctioning adrenal tumors.

BACKGROUND: Similarly to cortisol-secreting adrenal tumors, also non-functioning adrenal tumors (NFAT) may be associated with an increased cardiovascular risk. We assessed in NFAT patients: (i) the association between hypertension (HT), diabetes mellitus (DM), obesity (OB), dyslipidemia (DL) and cardiovascular events (CVE) and cortisol secretion; (ii) the cut-off of the cortisol secretion parameters for identifying NFAT patients with a worse cardiometabolic profile. PATIENTS AND METHODS: In 615 NFAT patients (with cortisol levels after 1 mg overnight dexamethasone suppression test, F-1mgDST < 1.8 µg/dL [50 nmol/L]) F-1mgDST and adrenocorticotroph hormone (ACTH) levels and data on HT, DM, OB, DL and CVEs prevalence were retrospectively collected. RESULTS: HT, DM and HT plus DM were associated with F-1mgDST levels (area under the ROC curve: 0.588 ± 0.023, 0.610 ± 0.028, 0.611 ± 0.033, respectively, p < 0.001 for all comparisons) but not with ACTH. The cut-off for identifying patients with either HT or DM or HT plus DM was set at ≥ 1.2 µg/dL (33 nmol/L). As compared with patients with F-1mgDST < 1.2 µg/dL (n = 289), patients with F-1mgDST 1.2-1.79 µg/dL (33-49.4 nmol/L) (n = 326) had lower ACTH levels (17.7 ± 11.9 vs 15.3 ± 10.1 pg/mL, respectively, p = 0.008), older age (57.5 ± 12.3 vs 62.5 ± 10.9 years, respectively, p < 0.001), and higher prevalence of HT (38.1% vs 52.5% respectively p < 0.001), DM (13.1% vs 23.3%, respectively, p = 0.001), HT plus DM (8.3% vs 16.9%, respectively, p < 0.002) and CVE (3.2% vs 7.3%, respectively, p = 0.028). F-1mgDST 1.2-1.79 µg/dL was associated with either HT (odd ratio, OR, 1.55, 95% confidence interval, 95% CI 1.08-2.23, p = 0.018) or DM (OR 1.60, 95% CI 1.01-2.57, p = 0.045) after adjusting for age, gender, OB, DL, and DM (for HT) or HT (for DM), and with the presence of HT plus DM (OR 1.96, 95% CI 1.12-3.41, p = 0.018) after adjusting for age, gender, OB and DL. CONCLUSIONS: In NFAT patients, F-1mgDST 1.2-1.79 µg/dL seems to be associated with a higher prevalence of HT and DM and a worse cardiometabolic profile, even if the poor accuracy of these associations suggests caution in interpreting these results.

Validation of the clinical consensus recommendations on the management of fracture risk in postmenopausal women with type 2 diabetes.

BACKGROUND AND AIMS: Bone fragility is recognized as a complication of type 2 diabetes (T2D). However, the fracture risk in T2D is underestimated using the classical assessment tools. An expert panel suggested the diagnostic approaches for the detection of T2D patients worthy of bone-active treatment. The aim of the study was to apply these algorithms to a cohort of T2D women to validate them in clinical practice. METHODS AND RESULTS: The presence of T2D-specific fracture risk factors (T2D ≥ 10 years, ≥1 T2D complications, insulin or thiazolidinedione use, poor glycaemic control) was assessed at baseline in 107 postmenopausal T2D women. In all patients at baseline and in 34 patients after a median follow-up of 60.2 months we retrospectively evaluated bone mineral density and clinical and morphometric vertebral fractures. No patient was treated with bone-active drug. Following the protocols, 34 (31.8%) and 73 (68.2%) patients would have been pharmacologically and conservatively treated, respectively. Among 49 patients without both clinical fractures and major T2D-related risk factors, who would have been, therefore, conservatively followed-up without vertebral fracture assessment, only one showed a prevalent vertebral fracture (sensitivity 90%, negative predictive value 98%). The two patients who experienced an incident fracture would have been pharmacologically treated at baseline. CONCLUSIONS: The clinical consensus recommendations showed a very good sensitivity in identifying T2D postmenopausal women at high fracture risk. Among those with treatment indication as many as 13% of patients experienced an incident fracture, and, conversely, among those without treatment indication no incident fractures were observed.

Secondary Osteoporosis: A Still Neglected Condition.

The condition of "secondary osteoporosis" is defined as a bone loss that results from specific well-defined clinical disorders [...].

Management of bone fragility in type 2 diabetes: Perspective from an interdisciplinary expert panel.

AIM: Bone fragility is increasingly recognized as a relevant complication of type 2 diabetes (T2D) and diabetic patients with fragility fractures have higher mortality rates than non diabetic individuals or diabetic patients without fractures. However, current diagnostic approaches for fracture risk stratification, such as bone mineral density measurement or the use of risk assessment algorithms, largely underestimate fracture risk in T2D patients. A multidisciplinary expert panel was established in order to in order to formulate clinical consensus recommendations on bone health assessment and management of fracture risk in patients with T2D. DATA SYNTHESIS: The following key questions were addressed: a) which are the risk factors for bone fragility in T2D?, b) which diagnostic procedures can be currently used to stratify fracture risk in T2D patients?, c) which are the effects of antidiabetic treatments on bone?, and d) how to prevent and treat bone fragility in T2D patients? Based on the available data members of this panel suggest that the stratification of fracture risk in patients with diabetes should firstly rely on the presence of a previous fragility fracture and on the individual risk profile, with the inclusion of T2D-specific risk factors (namely T2D duration above 10 yrs, presence of chronic T2D complications, use of insulin or thiazolidinediones and persistent HbA1c levels above 8% for at least 1 year). Two independent diagnostic approaches were then suggested in the presence or the absence of a prevalent fragility fracture, respectively. CONCLUSIONS: Clinical trials in T2D patients at risk for fragility fractures are needed to determine the efficacy and safety of available antiresorptive and anabolic agents in this specific setting.

Dietary calcium intake in a cohort of individuals evaluated for low bone mineral density: a multicenter Italian study.

BACKGROUND: A low calcium intake is a well-known factor that influences the bone mineral density (BMD) maintenance. In the presence of inadequate calcium intake, secondary hyperparathyroidism develops, leading to an increased bone turnover and fracture risk. AIMS: To assess the dietary calcium intake in relation with osteoporosis and fragility fracture in a cohort of Italian individuals evaluated for low BMD. METHODS: A 7-day food-frequency questionnaire was administered to 1793 individuals, who were consecutively referred at the Centers of the Italian Society for Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS) for low BMD. RESULTS: In 30.3% and 20.9% of subjects, the calcium intake was inadequate (< 700 mg/day) and adequate (> 1200 mg/day), respectively. As compared with patients with adequate calcium intake, those with inadequate calcium intake were younger (65.5 ± 10.8 vs 63.9 ± 11.5 years, p = 0.03) and they more frequently reported adverse reactions to food (3.2% vs 7.2% p = 0.01) and previous major fragility fractures (20.8% vs 27.0%, p = 0.03). Patients with calcium intake < 700 mg/day showed a higher prevalence of diabetes mellitus, idiopathic hypercalciuria and food allergy/intolerance (8.1%, 5.1%, 7.2%, respectively) than patients with calcium intake > 700 mg/day (5.3%, 3.0%, 4.1%, respectively, p < 0.04 for all comparisons), also after adjusting for age, gender and body mass index. In 30.3% of fractured subjects, the calcium intake was < 700 mg/day. DISCUSSION: In Italy, a low calcium intake is highly prevalent in individuals at risk for low BMD. Importantly, an inadequate calcium intake is highly prevalent even in patients with history of fragility fractures. CONCLUSIONS: Only about a fifth of patients being assessed for low BMD in an Italian SIOMMMS referral Centre have an adequate calcium intake.

Energy Metabolism and Ketogenic Diets: What about the Skeletal Health? A Narrative Review and a Prospective Vision for Planning Clinical Trials on this Issue.

The existence of a common mesenchymal cell progenitor shared by bone, skeletal muscle, and adipocytes cell progenitors, makes the role of the skeleton in energy metabolism no longer surprising. Thus, bone fragility could also be seen as a consequence of a "poor" quality in nutrition. Ketogenic diet was originally proven to be effective in epilepsy, and long-term follow-up studies on epileptic children undergoing a ketogenic diet reported an increased incidence of bone fractures and decreased bone mineral density. However, the causes of such negative impacts on bone health have to be better defined. In these subjects, the concomitant use of antiepileptic drugs and the reduced mobilization may partly explain the negative effects on bone health, but little is known about the effects of diet itself, and/or generic alterations in vitamin D and/or impaired growth factor production. Despite these remarks, clinical studies were adequately designed to investigate bone health are scarce and bone health related aspects are not included among the various metabolic pathologies positively influenced by ketogenic diets. Here, we provide not only a narrative review on this issue, but also practical advice to design and implement clinical studies on ketogenic nutritional regimens and bone health outcomes. Perspectives on ketogenic regimens, microbiota, microRNAs, and bone health are also included.

Suppressive effects of tenofovir disoproxil fumarate, an antiretroviral prodrug, on mineralization and type II and type III sodium-dependent phosphate transporters expression in primary human osteoblasts.

Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug commonly used for the management of Human Immunodeficiency Virus (HIV) in highly active antiretroviral therapy (HAART) and of chronic Hepatitis B Virus (HBV) infections. Long-term TDF-treated subjects present decrease of bone mineral density and rarely severe osteomalacia. Although these adverse effects have been attributed to the impaired proximal tubule function, a possible direct involvement of TDF on osteoblasts should be taken into account. The aim of this study was to evaluate whether sodium phosphate transporters NPT2A (sodium-dependent phosphate transport protein 2A), NPT2C (sodium-dependent phosphate transport protein 2C), PIT1 (sodium-dependent phosphate transporter 1), and PIT2 (sodium-dependent phosphate transporter 2) were expressed in primary human osteoblasts (HOBs), whether their expression was related to HOBs differentiation and whether TDF could affect mineralization and gene expression. PIT1 and PIT2 were expressed under proliferating conditions and increased after induction of mineralization, while NPT2A and NPT2C were almost undetectable. In HOBs TDF exposure induced a significant dose-dependent decrease in mineralization. Moreover, TDF caused a reduction of COL1A1 and of ATF4 expression in differentiated HOBs. In summary, HOBs do not express NPT2A and NPT2C and do express PIT1 and PIT2, suggesting a role of these two latter in human osteoblast mineralization. TDF impairs osteoblast mineralization, confirming a direct negative effect on bone. Therefore, in clinical practice, bone damage must be suspected and evaluated also in patients receiving TDF without kidney function alterations.

Prompt clinical and biochemical response to denosumab in a young adult patient with craniofacial fibrous dysplasia.

BACKGROUND: We report on the clinical and biochemical outcomes in a 20-year-old male suffering from active craniofacial monostotic fibrous dysplasia (MFD) of the left mandible treated with the RANK-L inhibitor, denosumab, following unsatisfactory responses to prior long-term bisphosphonates therapy. RESULTS: The patient had been treated over 9 years with pamidronate (cumulative dose of 810 mg) with incomplete control of pain. Following initiation of denosumab 60 mg subcutaneously, bone pain and bone turnover markers (osteocalcin, total and bone alkaline phosphatase and carboxy-terminal cross-linking telopeptide of type I collagen) were monitored over a 27 months period. Few hours after the first administration, the patient demonstrated a complete pain disappearance and after 4 weeks bone turnover markers fell within the normal range. Three months after denosumab initiation the patient reported a pain reactivation that required a second administration, which again led to the pain disappearance. Subsequently, denosumab was administered according to the pain reappearance and the injection was always followed by complete pain relief. However, a gradual shortening of the pain-free interval between administrations was observed, ranging from 90 to 75 days. All bone turnover markers stayed in the lower half of the normal range, even at the moment of pain reappearance, suggesting that the effect of denosumab on pain depends on mechanisms other than bone resorption suppression. No side effects were reported by the patient during the follow-up. CONCLUSION: Denosumab appears to be effective in reducing bone turnover and bone pain in adult patients with active MFD.

Assessment of fracture risk by the FRAX algorithm in men and women with and without type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: The FRAX algorithm is a diffuse tool to assess fracture risk, but it has not been clinically applied in European patients with diabetes. We investigated FRAX-estimated fracture risk in patients with type 2 diabetes mellitus (DM), compared with concomitantly enrolled control subjects. METHODS: In our multicentric cross-sectional study, we assessed the FRAX scores of 974 DM and 777 control subjects from three Italian diabetes outpatient clinics, and in DM. We tested the association between parameters and complications of the disease and FRAX scores. RESULTS: DM had significantly lower FRAX-estimated probability of both major osteoporotic fracture (MOF) and hip fracture (HF) than control subjects (6.35 ± 5.07% versus 7.75 ± 6.93%, p < 0.001, and 2.17 ± 3.07% versus 2.91 ± 4.56%, p = 0.023, respectively). When grouping by gender, such differences were found only in men. In DM, the frequency of previous fracture was higher than in control subjects (29.88% versus 20.46%, p < 0.001). In diabetic patients, age, sex, body mass index, HbA1c and hypoglycaemia are significantly associated with FRAX scores; gender-specific regression models differed. Among DM, the tree-based regression (classification and regression tree (CART)) analysis identified groups of patients with different mean FRAX scores. In female DM aged > 65 years with or without obesity, MOF > 20% was found in 5.66% and 13.53% and H > 3% in 40.57% and 63.91% of patients, respectively. CONCLUSIONS: Patients with DM had mean FRAX scores lower than control subjects, despite the higher number of previous fractures. Some features and complications of DM did associate with FRAX scores. Among DM patients, the CART analysis identified subgroups with higher FRAX scores. However, despite its potential utility, concerns still remain for using FRAX in DM patients.

GH secretion reserve in subclinical hypercortisolism.

PURPOSE: In overt hypercortisolism, growth hormone (GH) secretion is decreased and normalizes after surgery. In subclinical hypercortisolism (SH), GH secretion has been scarcely investigated. We assessed GH reserve in patients with and without SH and, in the former, also after recovery. METHODS: We enrolled 24 patients with adrenal adenomas, 12 with SH (SH+, 8 females, 58.3 ± 6.5 years) and 12 without SH (SH-; 11 females, 61.8 ± 10.6 years). SH was diagnosed in the presence of ≥ 2 out of: 1 mg overnight dexamethasone suppression test >83 nmol/L, urinary free cortisol (UFC) >193 nmol/day and ACTH levels <2.2 pmol/L. GH secretion was assessed by GHRH + Arginine test (GHRH-ARG) and age-adjusted serum IGF-I levels, expressed as SDS (IGF-I SDS). Eight SH+ patients were re-evaluated after the recovery from SH. RESULTS: Age, gender, body mass index (BMI) and IGF-I SDS were comparable between SH+ and SH- patients. After GHRH-ARG the mean GH peak levels (GH-P) and GH response (as Area Under Curve, GH-AUC) were lower in SH+ than in SH- patients (15.2 ± 8.1 vs 44.5 ± 30.9 µg/L, P = 0.004 and 1,418 ± 803 vs 4,028 ± 2,476 µg/L/120 min, P = 0.002, respectively), after adjusting for age and BMI. The GH-AUC and GH-P levels were negatively associated with UFC after adjusting for age and BMI (ß = -0.39, P = 0.02 and ß = -0.4, P = 0.020 respectively). After recovery, GH-P levels and GH-AUC increased as compared to baseline (23.7 ± 16.3 vs 15.8 ± 10.2 µg/L, P = 0.036 and 2,549 ± 1,982 vs 1,618 ± 911 µg/L/120 min, P = 0.012, respectively). CONCLUSIONS: GH secretion reserve is decreased in SH patients and increases after the recovery.

Zoledronate After Denosumab Discontinuation: Is Repeated Administrations More Effective Than Single Infusion?

BACKGROUND: After denosumab (Dmab) discontinuation C-terminal telopeptide (CTX) levels increase, bone mineral density (BMD) decreases and multiple vertebral fractures (FX) may occur with relevant impacts on women's health. A sequential therapy with bisphosphonates is recommended, and the European Calcified Tissue Society (ECTS) proposed repeated zoledronate (ZOL) administrations in patients with persistently high CTX levels, although the efficacy of this schedule is unknown. In this retrospective study, we describe BMD changes and FX rate in 52 patients managed according to the ECTS recommendations. METHODS: We measured CTX levels and administered ZOL after 1 month from Dmab withdrawal (t0). After 6 months (t1), we administered a second ZOL infusion, if CTX levels were ≥280 ng/L. BMD changes and FX rate were assessed on average after 17 months from Dmab withdrawal. RESULTS: Seventy-five percent of patients repeated ZOL infusion. In this group, spine BMD declined significantly (-5.5 ± 5.6%), while it remained stable in the group with CTX levels <280 ng/L (-0.1 ± 5.5%, P = 0.008). All fractured patients (9.6%) had received >5 Dmab injections and 2 ZOL infusions. The BMD worsening after Dmab withdrawal was associated with CTX t1 [odds ratio (OR) 2.9, interquartile range (IQR) 1.3-6.6, P = .009] and spine BMD gain during Dmab therapy corrected for the number of Dmab injections (OR 3.0, IQR 1.2-7.2, P = .014). A CTX level at t1 > 212 ng/L had 100% sensitivity in predicting the BMD loss. CONCLUSION: In patients with uncontrolled CTX levels after Dmab withdrawal, 2 ZOL infusions 6 months apart do not prevent BMD loss and FX.

Carotid intima-media thickness in surgically or conservatively managed patients with primary hyperparathyroidism.

CONTEXT: Current evidence of cardiovascular (CV) risk in primary hyperparathyroidism (PHPT) is still inconsistent. OBJECTIVE: To prospectively investigate changes of early atherosclerosis in patients with PHPT undergoing parathyroidectomy (PTx) or conservative management, according to Consensus criteria. METHODS: Biochemical parameters of PHPT, CV risk factors (systolic and diastolic blood pressure-BP-, total-, HDL- and LDL-cholesterol, triglyceride, glycosilated hemoglobin, and HOMA-IR), and carotid intima-media thickness (IMT) and plaque were assessed in 52 consecutive postmenopausal PHPT patients both at baseline and ≥24 months after surgery (PTx: n = 22) or conservative management (no-PTx: n = 30). RESULTS: At baseline, PTx and no-PTx showed comparable age, BMI, renal function, 25(OH)D levels, and did not differ for CV risk factors, IMT and plaques, nor for the prevalence of smoking, diabetes mellitus, antihypertensive or statin therapy, while differing for all parameters characterizing PHPT. Follow-up length in PTx was longer (p = 0.004) than in no-PTx. Parameters characterizing PHPT significantly improved ≥24 months after surgery, whereas in no-PTx serum phosphate slightly decreased and PTH increased. Systolic and diastolic BP increased at follow-up in both groups, while other CV risk factors did not significantly vary. In PTx IMT did not significantly vary after surgery (0.85 ± 0.14 to 0.89 ± 0.22 mm, p = 0.366), whereas it significantly increased in no-PHPT (0.80 ± 0.18 to 0.93 ± 0.23 mm, p = 0.008), even adjusting for BP values. Plaque prevalence and incidence did not significantly differ in the two groups. CONCLUSION: Our results suggest that in postmenopausal PHPT patients subclinical atherosclerosis could be halted by PTx, whereas it worsens over time in not operated patients with milder disease.

Increased Risk of Vertebral Fractures in Patients With Mild Autonomous Cortisol Secretion.

CONTEXT: The risk of vertebral fractures (VFx) in patients with adrenal incidentalomas (AI) and mild autonomous cortisol secretion (MACS) is debated. OBJECTIVE: To evaluate the VFx prevalence and incidence in patients with AI and MACS. METHODS: This cross-sectional and longitudinal study using retrospective data from 4 Italian endocrinology units included 444 patients (cross-sectional arm) and 126 patients (longitudinal arm, 24.9 ± 5.3 months follow-up) to evaluate prevalent and incident VFx, respectively, in patients with MACS (MACS-yes) and without MACS (MACS-no). The main outcome measures were serum cortisol after a 1-mg dexamethasone test (F-1mgDST), bone mineral density (BMD) by dual-energy x-ray absorptiometry at spine (LS) and femur (FN), and VFx presence by x-ray. RESULTS: Cross-sectional arm: 214 and 230 patients were MACS-yes and MACS-no, respectively, based on F-1mgDST >1.8 µg/dL (50 nmol/L). Patients with MACS had higher VFx prevalence (62.6%) than those without MACS (22.9%, P < .001); MACS was associated with prevalent VFx (odds ratio, 5.203; 95% CI, 3.361-8.055; P < .001; relative risk [RR] 2.07), regardless of age, body mass index, gender distribution, LS-BMD, and presence of type 2 diabetes mellitus (T2D). Longitudinal arm: 66 and 60 patients were MACS-no and MACS-yes, respectively. Patients without MACS showed higher number of incident VFx (36.4%) than patients without MACS (10.0%, P < .001); MACS was associated with the presence of an incident VFx (RR 4.561; 95% CI, 1.600-13.003; P = .005) regardless of age, LS-BMD, gender distribution, presence of prevalent VFx, and T2D. Results were confirmed in women and men when separately evaluated. CONCLUSION: Women and men with AI and MACS are at higher risk of VFx.

Fragility Fractures and Cortisol Secretion in Patients With Nonfunctioning Adrenal Incidentalomas.

Context: The risk of vertebral fractures (VFx) in patients with nonfunctioning adrenal incidentalomas (NFAI) is unknown. Objective: This work aimed to assess in NFAI patients the prevalence and incidence of VFx and a hormonal marker to identify patients at risk. Methods: A retrospective, cross-sectional, and longitudinal study of outpatients was conducted. A total of 306 NFAI patients (cross-sectional arm) and 213 controls were evaluated for VFx prevalence; 85 NFAI patients (longitudinal arm, follow-up 30.3 ± 17.5 months) were evaluated for VFx incidence. Main outcome measures included serum cortisol after 1 mg-dexamethasone test (F-1mgDST), lumbar spinal (LS), and femoral neck (FN) bone mineral density (BMD) and VFx presence, by radiograph of the spine. Results: Cross-sectional arm: prevalent VFx associated with F-1mgDST with a cutoff of 1.2 µg/dL (33 nmol/L, area under the curve 0.620 ± 0.39; P = .002). Compared with controls and NFAI patients with F-1mgDST less than 1.2 µg/dL (group A), NFAI patients with F-1mgDST greater than or equal to 1.2 µg/dL (group B) showed a higher VFx prevalence (10.8%, 12.6%, and 29.5%, respectively; P < .001 all comparisons), which was associated with F-1mgDST greater than or equal to 1.2 µg/dL (odds ratio 3.02; 95% CI, 1.63-5.58; P < .001) accounting to confounders. Longitudinal arm: the VFx incidence was higher in group B than in group A (19.3% vs 3.6%; P = .05). In group B, all incident VFx occurred in patients without low BMD. The F-1mgDST cutoff for predicting an incident VFx was 1.2 µg/dL, although statistical significance was not reached after adjustment for confounders (P = .061). Conclusion: In NFAI patients, F-1mgDST levels greater than or equal to 1.2 µg/L (33 nmol/L) are associated with prevalent VFx and may identify patients at risk of incident VFx.

Parathyroid carcinoma and atypical parathyroid tumor: analysis of an Italian database.

OBJECTIVE: Atypical parathyroid tumor (aPT) and parathyroid carcinoma (PC) are extremely rare parathyroid neoplasms, accounting together for <2% of all parathyroid tumors. They often present an overlapping clinical phenotype, sharing clinical, biochemical, and some histological features. They are distinguished only by the presence of local invasion, and lymph nodes or distant metastasis, which are all absent in aPTs. To date, only few studies have compared clinical presentation and features between aPTs and PCs. Our purpose was to conduct a retrospective study on a multicenter Italian database of aPT and PC patients. DESIGN AND METHODS: We comparatively analyzed main features of aPT (n = 57) and PC (n = 74) patients collected at 15 major endocrinology and endocrine surgery centers in Italy. RESULTS AND CONCLUSIONS: Atypical parathyroid tumors and PCs showed no significant differences in many clinical features and presented similar values of elevated parathyroid hormone and total serum calcium. Renal complications, namely nephrolithiasis and nephrocalcinosis, appeared to be more common in PC, with a significantly higher rate of renal colic, regardless of total serum calcium levels and 24-h calciuria. Parathyroid carcinomas showed significantly higher postoperative disease persistence and recurrence rates, presumably due to an uncomplete resection of the primary tumor in 23.5% of cases and/or presence of unremoved active metastasis, but they had similar disease-free mean time after surgery than aPT. To deepen the study of malignant parathyroid tumors, the institution of a novel Italian retro-prospective multicenter registry of aPTs and PCs is currently ongoing, and a dedicated PC European registry has been recently activated.

Italian Guidelines for the Management of Sporadic Primary Hyperparathyroidism.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for the clinical practice recommendations. RESULTS: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. CONCLUSION: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.