Federica Paglia

Quality of life in ambulatory postmenopausal women: the impact of reduced bone mineral density and subclinical vertebral fractures

Health-related quality of life (HRQOL) in postmenopausal women with osteoporosis has hitherto been mainly assessed in patients with clinically recognized vertebral fractures. Our study aimed to investigate the QOL perception in 361 asymptomatic ambulant postmenopausal women who came to our center for an osteoporosis screening program planned with their general practitioners. The Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) was administered to all subjects. The participants underwent bone mineral density (BMD) measurements by DXA of either the lumbar spine and/or the femoral neck, as well as X-ray examination of the thoracolumbar spine to identify subclinical vertebral fractures. According to the WHO definition, where subjects are subdivided by BMD values into three groups (women with normal BMD, osteopenia, and osteoporosis), a significant difference was found only for the domains which explore general health perception (p<0.01 by ANOVA) and mental function (p<0.001 by ANOVA). When we segregated both osteopenic and osteoporotic women according to whether or not they had vertebral fractures, a significant difference was found only in osteoporotic patients for domains which explore physical function (p<0.001), social function (p<0.001), general health perception (p<0.02), and total QUALEFFO score (p<0.01). Stepwise multiple logistic regression analysis of the whole sample showed that both vertebral fractures and a low femoral BMD impairs QOL perception, while age did not exert a significant influence. ROC curves analysis demonstrated a low discriminating capacity of individual domains and total QUALEFFO score for both vertebral deformities and BMD categorization. Our results showed that QUALEFFO is not able to discriminate between patients with or without subclinical vertebral fractures. However, some aspects of QOL appear to be impaired in patients with subclinical vertebral fractures or reduced BMD.

Concurrent Parathyroid Adenomas and Carcinoma in the Setting of Multiple Endocrine Neoplasia Type 1: Presentation as Hypercalcemic Crisis

We describe a patient with multiple endocrine neoplasia type 1 characterized by the simultaneous occurrence of parathyroid cancer, parathyroid adenomas, and pancreatic gastrinoma, who presented with an episode of acute hypercalcemia. The rapid parathyroid hormone assay provided a basis for the diagnosis of parathyroid hyperfunction. Mediastinal metastasis of the parathyroid carcinoma was found at autopsy. However, the staining of pancreatic and gastric tissue for parathyroid hormone-related protein does not make it possible to exclude completely the contribution of this peptide in mediating the hypercalcemia. To our knowledge, this is the first reported case of parathyroid carcinoma as part of the multiple endocrine neoplasia type 1 syndrome.

Vitamin D status in female patients with primary hyperparathyroidism: does it play a role in skeletal damage?

objective  Vitamin D deficiency, even subclinical, has been considered to worsen the skeletal damage in primary hyperparathyroidism (PHPT). Our study aimed to investigate the impact of vitamin D status on skeletal involvement in PHPT.

Gender Differences in Serum Markers of Bone Resorption in Healthy Subjects and Patients with Disorders Affecting Bone

Abstract: To assess how two different serum markers of bone resorption may reflect changes in bone turnover, we compared age- and sex-related changes in serum C-terminal telopeptide of type I collagen (βCTx) and tartrate-resistant acid phosphatase activity (TRAP) in 136 healthy men and 184 normal women. Serum levels of the two markers were also assessed in several groups of patients of both sexes presenting with the most common metabolic and endocrine bone diseases: established osteoporosis (n= 77), primary hyperparathyroidism (n= 44), glucocorticoid excess (n= 17), chronic renal failure (n= 39), active Paget’s disease of bone (n= 5), humoral hypercalcemia of malignancy (n = 3), osteomalacia (n= 3), hyperthyroidism (n= 10), post-surgical hypoparathyroidism (n= 10), acromegaly (active disease, n= 8) and Cushing’s syndrome (n= 10). In men the regression of βCTx with age showed an initial decrease in bone resorption followed by an increase thereafter, starting from the sixth decade of life. No age-related change in serum TRAP activity was observed. In women, by contrast, a slight but significant linear correlation of both serum βCTx and TRAP with age (r= 0.223, p<0.003 and r= 0.333, p<0.0001, respectively) was found, the two markers being positively correlated (r= 0.238, p<0.002). In each class of patients the mean Z-scores of βCTx were significantly higher than those of TRAP activity. Moreover, compared with normal subjects, serum βCTx seems to be characterized by a superior sensitivity relative to TRAP measurement, at least in the disorders studied.

Uneven Deficits in Vertebral Bone Density in Postmenopausal Patients with Primary Hyperparathyroidism as Evaluated by Posterior–Anterior and Lateral Dual-Energy Absorptiometry

Abstract: This investigation was undertaken to determine whether the preservation of bone mass in patients with mild primary hyperparathyroidism (PHPT) could be detected when measuring spine density in the lateral projection. We compared the bone mineral density (BMD) of L2–L4 utilizing the posterior–anterior (PA) and lateral projections in postmenopausal patients with PHPT and in a group of 27 postmenopausal normal women. Thirty-three consecutive postmenopausal patients with PHPT were studied; 25 were asymptomatic whereas the remaining 8 suffered complications related to the disease. Based upon the criteria established by the Consensus Conference on the Management of Asymptomatic PHPT, only 10 of the 25 asymptomatic patients could be considered affected by mild disease; the remaining patients were classified as having moderate disease. Patients with mild disease had mean lateral total BMD values (0.682 ± 0.113 g/cm2) significantly higher than normal women (0.588 ± 0.076, p<0.02) and patients with moderate disease (0.599 ± 0.077, p<0.05). There were significant differences among the three groups in both PA L2–L4 and L1–L4 levels: patients with mild disease had significantly higher mean BMD values than patients with moderate disease and normal women, when either three or four vertebrae were considered. Interestingly, at this latter site, patients with moderate disease had significantly (p<0.05) lower values than normal women. Our results indicate that patients with mild PHPT have a preservation of vertebral mass when compared with the other hyperparathyroid patients and normal women, when taking into account both the mainly trabecular portion and the whole vertebra. The finding that when the PA projection was assessed, BMD values of patients with moderate disease were significantly lower than those of normal women, might be attributed to the detrimental effect of raised parathyroid hormone levels on the cortical component of the vertebral body.

Short-term effects of surgery in post-menopausal patients with primary hyperparathyroidism and normal bone turnover.

The most common clinical presentation of primary hyperparathyroidism (PHPT) is nowadays characterized by a slight skeletal involvement. We studied 5 consecutive female patients with PHPT presenting with bone turnover marker levels within the reference range of our Center and whose bone mineral density values were above the usual fracture risk threshold. In each patient we measured, both in basal conditions and daily, for the first 5 days after surgery, the following indexes: serum total (T-ALP) and bone-specific (B-ALP) alkaline phosphatase activity, osteocalcin (BGP, by two different assays), together with the 24-hour urinary excretions of total pyridi-noline (Pyr/Cr) and deoxypyridinoline (D-Pyr/Cr), free deoxypyridinoline (FD-Pyr/Cr), cross-linked N-telopeptide of type I collagen (NTx/Cr), and type I C-telopeptide (CTx/Cr). The markers of both bone formation and resorption significantly decreased after surgery (p<0.001 by multiple ANOVA). Individual post-surgical markers changes were all significant but T-ALP and FD-Pyr, the most pronounced percent reductions being shown by NTx and CTx. The time-course of such variations substantially differed among the various indexes. These results show that bone formation and resorption markers are up-regulated also in PHPT patients with mild skeletal involvement; acute removal of parathyroid hormone excess differently affected the markers of bone turnover in terms of both entity and time-course.

Dehydroepiandrosterone sulfate and bone resorption rates as reflected by serum levels of C-terminal telopeptide of type I collagen : A study in healthy men

Sex steroid hormones contribute to the physiological regulation of bone turnover in males. To address this issue, we investigated serum estradiol (E2), total testosterone (T), and DHEAS concentrations, along with serum levels of carboxy-terminal telopeptide of type I collagen (sCTx), in a sample of 76 healthy men aged 23 to 87. The concentration of sCTx declined with age. Both T and DHEAS, at variance with E2, showed a significant age-related decline. T, DHEAS and sCTx significantly (p<0.01) correlated with each other. DHEAS and T were significantly associated after correcting for age (r=0.35, p=0.002) or body mass index (r=0.65, p<0.0001). DHEAS, but not T, significantly correlated with sCTx after correcting for age (r=0.26, p=0.026, and r=0.20, p=0.08, respectively). Stepwise multiple regression analysis showed that only DHEAS (but not T or E2) was a significant independent predictor of sCTx (p=0.0001). Our results show that adrenal androgens play a crucial role in regulating bone resorption in aging men.