Reduced High-Density Lipoprotein Cholesterol Is an Independent Determinant of Altered Bone Quality in Women with Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is associated with an increased fracture risk. Our study aimed to explore differences in bone alterations between T2DM women and controls and to assess clinical predictors of bone impairment in T2DM. For this observational case control study, we recruited 126 T2DM female patients and 117 non-diabetic, age- and BMI-comparable women, who underwent clinical examination, routine biochemistry and dual-energy X-ray absorptiometry (DXA) scans for bone mineral density (BMD) and trabecular bone score (TBS) assessment-derived indexes. These were correlated to metabolic parameters, such as glycemic control and lipid profile, by bivariate analyses, and significant variables were entered in multivariate adjusted models to detect independent determinants of altered bone status in diabetes. The T2DM patients were less represented in the normal bone category compared with controls (5% vs. 12%; p = 0.04); T2DM was associated with low TBS (OR: 2.47, C.I. 95%: 1.19-5.16, p = 0.016) in a regression model adjusted for age, menopausal status and BMI. In women with T2DM, TBS directly correlated with plasma high-density lipoprotein cholesterol (HDL-c) (p = 0.029) and vitamin D (p = 0.017) levels. An inverse association was observed with menopausal status (p < 0.001), metabolic syndrome (p = 0.014), BMI (p = 0.005), and waist circumference (p < 0.001). In the multivariate regression analysis, lower HDL-c represented the main predictor of altered bone quality in T2DM, regardless of age, menopausal status, BMI, waist circumference, statin treatment, physical activity, and vitamin D (p = 0.029; R2 = 0.47), which likely underlies common pathways between metabolic disease and bone health in diabetes.

HypoparaNet: A Database of Chronic Hypoparathyroidism Based on Expert Medical-Surgical Centers in Italy.

Hypoparathyroidism is a rare disease characterized by low serum calcium levels and absent or deficient parathyroid hormone level. Regarding the epidemiology of chronic hypoparathyroidism, there are limited data in Italy and worldwide. Therefore, the purpose of this study was to build a unique database of patients with chronic hypoparathyroidism, derived from the databases of 16 referral centers for endocrinological diseases, affiliated with the Italian Society of Endocrinology, and four centers for endocrine surgery with expertise in hypoparathyroidism, to conduct an epidemiological analysis of chronic hypoparathyroidism in Italy. The study was approved by the Institutional Review Board. A total of 537 patients with chronic hypoparathyroidism were identified. The leading etiology was represented by postsurgical hypoparathyroidism (67.6%), followed by idiopathic hypoparathyroidism (14.6%), syndromic forms of genetic hypoparathyroidism (11%), forms of defective PTH action (5.2%), non-syndromic forms of genetic hypoparathyroidism (0.9%), and, finally, other forms of acquired hypoparathyroidism, due to infiltrative diseases, copper or iron overload, or ionizing radiation exposure (0.7%). This study represents one of the first large-scale epidemiological assessments of chronic hypoparathyroidism based on data collected at medical and/or surgical centers with expertise in hypoparathyroidism in Italy. Although the study presents some limitations, it introduces the possibility of a large-scale national survey, with the final aim of defining not only the prevalence of chronic hypoparathyroidism in Italy, but also standards for clinical and therapeutic approaches.

Diagnostic accuracy of 3T magnetic resonance imaging in the preoperative localisation of parathyroid adenomas: comparison with ultrasound and 99mTc-sestamibi scans.

OBJECTIVES: To evaluate the diagnostic performance of 3TMRI in comparison with ultrasound (US) and 99mTc-sestamibi scan for presurgical localisation of parathyroid adenomas (PTAs) in patients with primary hyperparathyroidism (PHPT). METHODS: Fifty-seven patients affected by PHPT were prospectively enrolled and underwent US, 99mTc-sestamibi and 3TMRI. T2-weighted and post-contrast T1-weighted Iterative decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL) sequences were acquired. Diagnostic performance of US, 99mTc-sestamibi and MRI in localising PTAs to correct quadrant were compared according to surgical and pathological findings. RESULTS: According to surgical findings, US correctly localised 41/46 PTAs (sensitivity of 89.1%; specificity 97.5%; PPV 93.1% and NPV 95.6%); 99mTc-sestamibi correctly localised 38/46 PTAs (sensitivity 83.6%, specificity 98.3%, PPV 95% and NPV 93.7%). US and 99mTc-sestamibi combined had a sensitivity of 93.4% (43/46 PTAs), specificity of 98.3%, PPV 95% and NPV 98.3%. MRI correctly localised 45/46 PTAs (sensitivity 97.8%; specificity 97.5%; PPV 93.7% and NPV 99.2%). MRI was able to detect six adenomas missed by 99mTc-sestamibi and two adenomas missed by US. MRI and US were able to detect all enlarged parathyroid glands in patients with multiglandular disease. MRI identified six of seven ectopic adenomas. CONCLUSIONS: Our study demonstrated high diagnostic performance of 3T MRI in the preoperative PTAs quadrant localisation, as well as in patients with multiglandular disease and ectopic PTAs. MRI may be preferred to adequately select patient candidates for minimally invasive parathyroidectomy (MIP). KEY POINTS: • PTA(s) quadrant localisation by 3TMRI was more accurate than US+99mTc-sestamibi. • MRI identified all enlarged glands in multiglandular disease similarly to US. • MRI identified 6/7 ectopic PTAs similarly to 99mTc-sestamibi. • Presurgical PTA(s) localisation by 3TMRI select the optimal candidates for MIP.

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.

Vitamin D supplementation: when and how?

The multiple effects of vitamin D on skeletal and extra-skeletal tissues increased the attention of scientists and public to the possible relationship between hypovitaminosis D and a variety of acute and chronic diseases. However, several points are still largely debated. In particular, the definition of optimal vitamin D status [as assessed by the circulating levels of 25-hydroxyvitamin D (25(OH)D)] remains controversial, and experts still disagree about several related outcomes: how to estimate the prevalence of vitamin D deficiency, when to start treatment, how to reach optimal 25(OH)D levels, which type of vitamin is preferable for supplementation, which dosing strategy is the better option. In this context, a matter of major debate is represented by the measurement of circulating level of 25(OH)D, whose determination is affected by the lack of standardization and by several technical problems. It has been recently hypothesized that free and bio-available, rather than total 25(OH)D, mostly determine its biological action. However, further evaluation of directly measured free 25(OH)D levels is needed, in order to establish its role in research and clinical practice. Finally, it is not yet defined if a threshold of optimal vitamin D status for reducing the risk of extra-skeletal diseases exists. Actually, it is plausible that the desired 25(OH)D level may vary widely, depending on the health outcome in question. However, this topic is uncertain, partly due to the lack of randomized controlled trials assessing the effect of vitamin D supplementation on extra-skeletal end-points.

Development of high-efficiency molecular adsorbent recirculating system: preliminary report.

Molecular Adsorbent Recirculating System (MARS) is a liver support system widely employed in the treatment of liver failure. The method is normally well tolerated. To develop a liver support system combining high efficiency and tolerability, we modified the MARS albumin circuit with the insertion of double adsorption units in parallel. Four patients have been treated with this modified method (high-efficiency MARS, HE MARS): two had very high serum bilirubin and two had very high total bile acids. After a single MARS session bilirubin was reduced more with HE MARS than standard MARS (from 27.6 to 52.3% in patient A and from 27.9 to 49.1% in patient B), and bile acid reduction increased from 40 to 59.8% in patient C and from 39.9 to 60% in patient D. The results of this preliminary investigation in only a very small number of patients do support the possibility of developing a liver support system that combines good tolerability and high efficacy.

Cinacalcet in the management of primary hyperparathyroidism: post marketing experience of an Italian multicentre group.

OBJECTIVE: To report the Italian experience on cinacalcet use following its approval by the European Medical Agency (EMA) to control hypercalcaemia in patients with primary hyperparathyroidism (PHPT). DESIGN: Retrospective data collection from 100 patients with sporadic (sPHPT) and 35 with familial PHPT (fPHPT) followed in eight Italian centres between October 2008 and March 2011. MEASUREMENTS: Albumin-adjusted serum calcium, PTH, 25OHD, daily cinacalcet dose and adverse events were recorded during the follow-up (1-46 months). RESULTS: Baseline serum calcium was 2·90 ± 0·27 nmol/l in sPHPT and 2·75 ± 0·17 nmol/l in fPHPT patients (P = 0·007). The cinacalcet EMA labelling was met in 53% sPHPT and 26% fPHPT patients. High surgical risk (34%), negative preoperative imaging (19%), control of hypercalcaemia before parathyroidectomy (PTx) (24%), and refusal of PTx (19%) accounted for cinacalcet prescription in 96% of sPHPT patients. Conversely, initial treatment (34%), persistent/relapsing PHPT after surgery (31%), and refusal of PTx (14%) were the indications in 79% fPHPT patients. Cinacalcet was started at 30 mg/daily in 64% of sPHPT and 91% of fPHPT and increased until normocalcaemia was reached or side effects occurred. The final daily dose ranged between 15 and 120 mg. The majority of patients (65% of sPHPT and 80% of fPHPT) become normocalcaemic. Treatment was withdrawn in six patients because of side effects. CONCLUSIONS: There is a wide heterogeneity in the prescription of cinacalcet in PHPT patients in Italy and the EMA labelling is not always followed, particularly in fPHPT patients. Cinacalcet effectively reduces serum calcium in patients with either sPHPT or fPHPT.

Arrhythmias in primary hyperparathyroidism evaluated by exercise test.

BACKGROUND: Hypercalcemia induces arrhythmias and shortening of QT. The aim of this study was to investigate risk factors for occurrence of arrhythmias in patients with primary hyperparathyroidism (PHPT) during bicycle ergometer exercise test (ET). METHODS: Thirty PHPT postmenopausal women (mean age, 60·9 ± 8·0 years) and 30, sex and age-matched, controls underwent ET, echocardiogram and mineral metabolism biochemical evaluation. The following stages were considered during ET: rest, peak exercise, recovery (early recovery, 2 and 10 min after peak exercise). QT was corrected with Bazett's formula (QTc). RESULTS: Compared with controls, PHPT patients showed an increased occurrence of ventricular premature beats (VPBs) during ET (26·6% vs. 6·6%, P = 0·03). Being affected by PHPT predicted the onset of VPBs at peak exercise (P = 0·04) and recovery (P = 0·03), as shown by logistic regression analysis. In PHPT patients, serum calcium level was a predictor of VPBs at peak exercise (P = 0·05). QTc in patients with PHPT was in the normal range. Serum calcium level showed a negative correlation with QTc (P = 0·01) in whole sample. Compared with controls, PHTP patients had QTc significantly shorter for every stage of ET, except at peak exercise. Physiological reduction of QTc interval from rest to peak exercise was not seen in patients with PHPT, QTc at rest being the only predictor of QTc in every stage, as shown by multivariate regression analysis. CONCLUSIONS: In patients with PHPT, an increased occurrence of VPBs and a different QTc adaptation during ET were observed and may represent risk factors for major arrhythmias.

Effects of strontium ranelate administration on calcium metabolism in female patients with postmenopausal osteoporosis and primary hyperparathyroidism.

We investigated possible changes of parameters of calcium metabolism induced by strontium ranelate (SR). Twenty-three patients with postmenopausal osteoporosis (PO) and 14 with primary hyperparathyroidism (PHPT) were studied while taking 2 g/day of SR. Women with PO and 10 healthy age-matched control women were also daily supplemented with 1,000 mg calcium and 800 IU vitamin D. All subjects were studied at baseline and after 7 and 30 days; PO women and controls were also investigated at 180 and 360 days of treatment. Serum ionized calcium (iCa), phosphate (sP), magnesium, creatinine, 25-hydroxycholecalciferol (25[OH]D), 1,25-dihydroxycholecalciferol (1,25[OH](2)D), serum parathyroid hormone (PTH) were measured. In spot urine, we assessed calcium and phosphate over creatinine ratios (uCa/Cr, uP/Cr), calcium excretion (Ca ex) and renal phosphate threshold (TmP/GFR); in 24-h urine, calcium and magnesium over creatinine clearance ratios (CaCl/CrCl and MgCl/CrCl). In PO, SR administration was associated with a significant decrease of PTH and 1,25(OH)(2)D levels but an increase of sP (p < 0.001). SR also significantly increased Ca/Cr, Ca ex, and TmP/GFR in spot urine and CaCl/CrCl in both spot and 24-h urine (p = 0.004 to <0.001). In PHPT, SR significantly decreased iCa and increased sP, slightly modifying PTH, 25(OH)D, and 1,25(OH)(2)D values. Also in PHPT, Ca ex and CaCl/CrCl of spot and 24-h urine, as TmP/GFR, significantly increased (all p < 0.02). SR influenced the main parameters of calcium homeostasis, probably through the calcium-sensing receptor.

The effect of parathyroidectomy on chronic constipation in patients affected by primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is usually associated with chronic constipation; however, its prevalence is not defined by standardized criteria. The aim of the study was to evaluate both the prevalence of chronic constipation, defined by the standardized Rome diagnostic criteria III (Rome III) in PHPT, and the effect of parathyroidectomy (PTx). Fifty postmenopausal PHPT patients and 50 sex- and age-matched controls were studied. Each patient underwent mineral metabolism biochemical evaluation and completed a questionnaire and a 2-week diary card about bowel habits. PHPT patients were reevaluated after 6 months. According to Rome III, 40 % of PHPT patients had chronic constipation compared with 12 % of controls (p = 0.0002). The only difference between constipated PHPT patients (group A, n = 20) and those without constipation (group B, n = 30) was higher mean PTH values (79.9 ± 18.7 ng/l vs. 65.4 ± 26.0 ng/l; p = 0.03), which predicted the presence of constipation (p = 0.004, OR 1.059, CI 1.011-1.059). Forty percent of PHPT patients had undergone PTx. In group A, constipation was resolved in 80 % of patients after PTx compared to none of the same group who had not undergone PTx (p = 0.0007). In group B, 17.6 % of patients who had not undergone PTx became, after 6 months, constipated. According to Rome III, a higher prevalence of chronic constipation in PHPT patients was observed compared with controls. PTH levels predicted constipation. A significant reduction of chronic constipation was reported following successful surgery.

The combination of FRAX and Ageing Male Symptoms scale better identifies treated HIV males at risk for major fracture.

OBJECTIVE: Osteoporosis and hypogonadism are common in men with HIV infection. Ageing Male Symptoms (AMS) scale measures symptoms related to hypogonadism. FRAX provides 10-year probability of major fractures. We investigated the role of AMS scale combined with FRAX without bone mineral density (BMD), in identifying HIV men with bone fragility. DESIGN: Cross-sectional observational study. METHODS: Fifty HIV-positive men treated with highly active antiretroviral therapy and 27 controls underwent hormonal evaluation, BMD scan and spine X-ray. The AMS questionnaire was administered. RESULTS: Osteoporosis was found in 24·0% of HIV patients and in 3·7% of controls (P = 0·05). In HIV patients, 9 radiological vertebral fractures were found (none in controls, P = 0·04). Calculated free testosterone suggested hypogonadism in 26% of HIV patients vs 4% of controls (P = 0·04); an abnormal AMS score (≥27) was found in 62% HIV patients compared with 41% controls (P = 0·04). ROC curves showed that FRAX for major fracture had a 23% sensitivity and a 100% specificity in identifying HIV patients with bone fragility (P = 0·002, with the threshold of 7% at which bisphosphonate therapy is cost-effective). Considering a value of AMS ≥27, we obtained an 82·6% sensitivity and a 42·9% specificity (P = 0·04). The combination of AMS and FRAX score achieved a 77·3% sensitivity and a 69% specificity (P = 0·02, cut-off 34). CONCLUSION: Combination of FRAX (without BMD) and AMS improved sensitivity of FRAX alone in identifying HIV patients at fracture risk, at the expense of reduced specificity.

Diagnostic performance of vertebral fracture assessment by the lunar iDXA scanner compared to conventional radiography.

The purpose of this study was to evaluate the diagnostic performance of vertebral fracture assessment (VFA) using the Lunar iDXA scanner. Conventional spinal radiographs and images acquired by dual-energy X-ray absorptiometry (DXA) of 350 subjects (269 females, 81 males) were evaluated by two different readers. We visualized 4,476/4,550 (98.4 %) vertebrae from T4 to L4 on VFA images compared to 4,535/4,550 (99.7 %) on radiographs. Among the visualized vertebrae, 205/4,535 (4.5 %) and 190/4,476 (4.2 %) were identified as nonfracture deformities by reading of radiographs and VFA, respectively. Vertebral fractures (VFs) were 231 in 126 patients and 228 in 125 patients by semiquantitative assessment of radiographs (SQ-Rx) and by VFA, respectively. There was excellent agreement between the two techniques and high diagnostic performance of VFA both on a per-vertebra basis (k score = 0.984, 95 % CI 0.972-0.996, sensitivity 98.68 %, specificity 99.91 %, PPV 98.25 %, NPV 99.93 %) and on a per-patient basis (k score = 0.957, 95 % CI 0.925-0.988, sensitivity 96.83 %, specificity 98.66 %, PPV 97.60 %, NPV 98.22 %). In older patients (≥65 years) affected by moderate or severe osteoarthritis, SQ-Rx and VFA identified 96 VFs and 95 versus 90 vertebral deformities, respectively. This study demonstrates that most vertebrae are evaluable using the iDXA scanner, with improved VFA diagnostic performance even in discriminating mild VFs from vertebral deformities. Therefore, VFA may be appropriate as an alternative to conventional radiography in patients at high risk of VF who are undergoing DXA bone densitometry and in the follow-up of osteoporotic patients on treatment.

Acute and chronic effects of hypercalcaemia on cortical excitability as studied by 5 Hz repetitive transcranial magnetic stimulation.

We designed the present study to disclose changes in cortical excitability in humans with hypercalcaemia, by delivering repetitive transcranial magnetic stimulation (rTMS) over the primary motor area (M1). In 22 patients with chronic hypercalcaemia related to primary hyperparathyroidism and 22 age-matched healthy subjects 5 Hz-rTMS was delivered at rest and during a sustained voluntary contraction of the target muscle. Changes in the resting motor threshold (RMT), motor evoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured and compared in patients and healthy controls. Two of the 22 patients were re-tested after parathyroidectomy when serum calcium had normalized. In a subgroup of healthy subjects, changes in the rTMS parameters were tested before and after acute hypercalcaemia. No significant difference between healthy normocalcaemic subjects and chronic hypercalcaemic patients was found in the RMT values and MEP amplitude and CSP duration evoked by the first stimulus of the trains. During the course of 5 Hz-rTMS trains, MEP size increased significantly less in patients with chronic hypercalcaemia than in healthy subjects, whereas the CSP duration lengthened to a similar extent in both groups. In the two patients studied after parathyroidectomy, rTMS elicited a normal MEP amplitude facilitation. Our findings indicate that acute hypercalcaemia significantly decreased the MEP amplitude facilitation. Given that 5 Hz-rTMS modulates cortical excitability through mechanisms resembling short-term synaptic enhancement, the reduction of MEP amplitude facilitation by hypercalcaemia may be related to Ca2+-dependent changes in synaptic plasticity.

Metabolic changes following 500 µg monthly administration of calcidiol: a study in normal females.

This study was performed to investigate the effect of monthly oral administration of 500 µg of calcidiol (25-hydroxyvitamin D(3)) for 4 months on both serum vitamin D levels and sequential changes of parameters of calcium metabolism; 18 normal women aged 24-72 years were investigated. There was a significant increase of serum 25(OH)D after the first administration; thereafter all values persisted significantly higher compared to the basal value (P < 0.001). Mean 1,25(OH)(2)D serum levels peaked at day 3 and then tended to stabilize following day 30. During the first month, all mean values observed following the initial administration were significantly higher than basal values. The first calcidiol dose produced a significant reduction of serum PTH levels (P < 0.001), which then remained constant over time. Concerning serum calcium and phosphorus, we were not able to demonstrate any significant change during the entire observation period. Considering the single values for both serum ionized and total calcium, the values of Ca(2+) exceeded upper limits of normal on only two occasions. Regarding biochemical markers of bone remodeling, mean changes of serum bone isoenzyme of alkaline phosphatase activity showed a significant trend to decrease, starting at day 30. No significant changes of serum CTX values were noted. Overall, 24-h urinary excretion of calcium did not change, seven values exceeding the threshold of 4 mg/kg body weight. Monthly administration of 500 µg of 25-hydroxyvitamin D(3) may be considered an alternative for vitamin D repletion, without any detrimental effect.

Impaired Immune Function in Patients With Chronic Postsurgical Hypoparathyroidism: Results of the EMPATHY Study.

CONTEXT: Despite the pivotal role of calcium signaling in immune response, little is known about immune function in patients affected by hypoparathyroidism. OBJECTIVE: This work aimed to evaluate immune function in hypoparathyroidism. METHODS: The Evaluation of iMmune function in Postsurgical and AuToimmune HYpoparathyroidism (NCT04059380) is a case-control, cross-sectional study set in an Italian referral center. Participants included 20 patients with postsurgical hypoparathyroidism (12 females) and 20 age- and sex-matched controls. Main outcome measures included calcium metabolism assessment, peripheral blood mononuclear cells (PBMC) profiling via flow cytometry, parathyroid hormone receptor 1 (PTHr1) expression analysis using immunofluorescence and PrimeFlow RNA assay, gene expression analysis via real-time polymerase chain reaction, cytokine measurement, and evaluation of infectious disease frequency and severity. RESULTS: Immune cell profiling revealed decreased monocytes, regulatory, naive, and total CD4+ T lymphocytes, which correlated with total calcium, ionized calcium, and PTH levels, in patients with hypoparathyroidism. Patients with hypoparathyroidism had a higher CD3-CD56+ natural killer (NK) cell count, which inversely correlated with calcium, PTH, and vitamin D levels. Furthermore, they exhibited decreased tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor gene expression and decreased circulating TNF levels. Gene expression and immunofluorescence analysis confirmed PTHr1 expression in all PBMC lineages; however, the percentage of cells expressing PTHr1 was lower, whereas the intensity of PTHr1 expression in monocytes, total T lymphocytes, CD8+CD4+ and CD4+ T lymphocytes, and total NK cells was higher in patients with hypoparathyroidism. CONCLUSIONS: This study describes for the first time the immune alterations in patients with hypoparathyroidism receiving conventional therapies, supporting the immunoregulatory role of PTH and proposing an explanation for the increased susceptibility to infections observed in epidemiological studies.

Sex hormones and bone health in males.

Sex steroids play a key role in maintaining skeletal integrity lifelong, through a complex variety of endocrine, but also paracrine and possibly autocrine actions. The current knowledge that androgens may act as pro-hormones for estrogens has seriously challenged many traditional views, so that, at least for their skeletal actions, these can no longer be considered exclusively "male" or "female" hormones.

The effect of recombinant PTH(1-34) and PTH(1-84) on serum ionized calcium, 1,25-dihydroxyvitamin D, and urinary calcium excretion: a pilot study.

We investigated the frequency of hypercalcemia and/or hypercalciuria following parathyroid hormone (PTH) 1-34 and 1-84 administration in a crossover trial. Ten postmenopausal osteoporotic women previously treated with bisphosphonates were subdivided into two groups of five patients each. A 24-h urine collection to determine baseline calcium (Ca) and creatinine (Cr) the day before administration of PTH was followed by determination of serum ionized Ca (Ca(2+)), Cr, 25(OH)D, and 1,25(OH)(2)D at baseline. Thereafter, 100 mcg of PTH(1-84) or 20 mcg of PTH(1-34) was administered. A 24-h urinary collection and blood samples 2, 4, and 24-h after each PTH administration were again taken. One week after the first PTH administration patients were rechallenged with the second PTH. The PTH peptides did not differ with respect to changes in Ca(2+) at 2, 4, and 24 h postinjection; at the last time point the values were virtually identical to the initial values. There was no difference in urinary Ca on the day following PTH injection compared to baseline, in terms both of Ca/Cr and of Ca excretion. The two PTH peptides did not differ with respect to changes in 1,25(OH)(2)D at 2, 4, and 24 h considering both the absolute values and the percent changes with respect to baseline (24-h 1-84 = 125.6 + or - 58.6 pg/ml, 153% increase; 1-34 = 124.1 + or - 64.7, 130%). Our results indicate no difference in postinjection serum Ca(2+), 1,25(OH)(2)D, or urinary Ca excretion after a single dose of either PTH(1-84) or PTH(1-34) in patients previously treated with bisphosphonates.

Phalangeal quantitative ultrasound and bone mineral density in evaluating cortical bone loss: a study in postmenopausal women with primary hyperparathyroidism and subclinical iatrogenic hyperthyroidism.

Twenty-five postmenopausal women with primary hyperparathyroidism (PHPT) and 30 age-matched women with subclinical hyperthyroidism (sHTH) were studied to assess cortical bone loss. One hundred two healthy women were also recruited. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at lumbar spine (LS), femoral neck (FN) and femoral total (FT), and at one-third of the radius (R). Amplitude-dependent speed of sound (ADSoS) and Ultrasound Bone Profile Index (UBPI) were also evaluated using phalangeal quantitative ultrasound (QUS). A significant correlation was found between QUS and BMD at LS (ADSoS, p < 0.05) and R (ADSoS and UBPI, p < 0.001) in controls. QUS significantly correlated with BMD at LS, FN (p < 0.01), and FT (p < 0.001) in sHTH. No correlations were found in the PHPT group. Mean T-score values of all parameters were significantly lower in patients compared with controls (p < 0.001); however, they did not differ between PHPT and sHTH patients. T-score of R, ADSoS, and UBPI was reduced compared with other sites (p < 0.001) in both diseases. In postmenopausal women with PHPT and sHTH, bone loss is mainly detectable at cortical level. However, qualitative and/or structural changes of bone could account for the lack of correlations between these 2 techniques at cortical sites.

Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly.

CONTEXT: In humans, few studies have compared the potencies of ergocalciferol and cholecalciferol in improving and maintaining vitamin D status. OBJECTIVE: Our objective was to evaluate the effects of a single very large dose of both calciferols on serum changes of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], ionized calcium, and parathyroid hormone (PTH) at baseline, and at 3, 7, 30, and 60 d. DESIGN: This was a prospective randomized intervention study. SETTING: The study was performed in a nursing home residence. PARTICIPANTS: A total of 32 elderly female patients (age range 66-97 yr), with vitamin D deficiency was included in the study. INTERVENTION: Participants were randomized into four groups of eight to receive a single dose of 300,000 IU ergocalciferol or cholecalciferol by oral (os) or im route. RESULTS: 25(OH)D levels sharply increased at d 3 only when vitamins were given os. The 30-d basal difference in serum 25(OH)D was significantly greater after cholecalciferol os administration (47.8 +/- 7.3 ng/ml) compared with other forms (D(3) im: 15.9 +/- 11.3; D(2) os: 17.3 +/- 4.7; D(2) im: 5 +/- 4.4; all P < 0.001). The area under the curve (AUC) of the serum 25(OH)D against time (AUC(60)) was: D(3) os, 3193 +/- 759 ng x d/ml vs. D(2) os, 1820 +/- 512, P < 0.001; and D(3) im, 1361 +/- 492 vs. D(2) im, 728 +/- 195, P < 0.01. 25(OH)D significantly influences PTH levels at 3 (P < 0.03), 7 (P < 0.01), 30 (P < 0.01), and 60 d (P < 0.05). At 60 d, the form of vitamin (cholecalciferol) significantly lowers PTH levels (P = 0.037). CONCLUSIONS: Cholecalciferol is almost twice as potent as ergocalciferol in increasing serum 25(OH)D, when administered either by mouth or im. 25(OH)D plays a role in modulating serum PTH.