Jessica Pepe

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.

Long-Term Bioavailability After a Single Oral or Intramuscular Administration of 600,000 IU of Ergocalciferol or Cholecalciferol: Implications for Treatment and Prophylaxis

CONTEXT We previously showed that a single high dose of oral (po) cholecalciferol (D₃) sharply increases serum 25-hydroxyvitamin D [25(OH)D]. OBJECTIVE We evaluated the long-term bioavailability and metabolism of a single po or intramuscular (im) high dose of ergocalciferol (D₂) or D₃. DESIGN This was a prospective intervention study. SETTING The study was conducted in an ambulatory care setting. PATIENTS Participants were 24 subjects with hypovitaminosis D. INTERVENTIONS A single dose of 600,000 IU of po or im D₂ or D₃ was administered. MAIN OUTCOME MEASURES Serum 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)₂D] were measured at baseline and at days 30, 60, 90, and 120 by RIA. Serum 1,25(OH)₂D₂, 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], 24,25-hydroxyvitamin D₂ [24,25(OH)D₂], and 24,25-hydroxyvitamin D₃ [24,25(OH)D₃] were measured by liquid chromatography-tandem mass spectrometry in a subgroup of patients receiving the po formulations. RESULTS The areas under the curve of 25(OH)D after D₃ were significantly higher than those after D₂ (P < .0001). Serum 25(OH)D basal difference significantly increased at day 30 with po D₂ and D₃ (P < .01 and P < .0001) and up to day 90 with po D₃ (P < .01). The im formulations produced a slow increased, and values peaked at day 120 relative to the other time points (P < .0001). We found a decrease in 1,25(OH)₂D at day 30 (P < .05) and up to day 120 (P < .001) and an increase in 1,25(OH)₂D₂ at day 30 (P < .01) and up to day 120 (P < .01) after po D₂. Oral D₂ and D₃ produced increases in 24,25(OH)D₂ and 24,25(OH)D₃, respectively, at day 30 (P < .001). CONCLUSIONS A po dose of 600,000 IU of D₂ or D₃ is initially more effective in increasing serum 25(OH)D than the equivalent im dose and is rapidly metabolized. Our RIA assay for 1,25(OH)₂D may not recognize 1,25(OH)₂D₂.

MANAGEMENT OF ENDOCRINE DISEASE: Value and limitations of assessing vitamin D nutritional status and advised levels of vitamin D supplementation

The growing attention to the role of vitamin D in skeletal and extra-skeletal diseases over the last decade induced an increased demand for vitamin D determination as well as a dramatic rise of sales of vitamin D supplement. However, several critical points in this field remain to be clarified. We lack a clear consensus about the definition of vitamin D deficiency, insufficiency, and sufficiency. The identification of different thresholds defining vitamin D status has relevant implications in clinical practice. In fact, the worldwide prevalence of low vitamin D status is highly varying according to the level of 25(OH)D utilized to define sufficiency. Therefore, the assessment of 25-hydroxyvitamin D levels may have a critical role, but a number of different technical problems associated with its determination may interfere in interpreting the results. The hydrophobic nature of vitamin D and the tight binding to its carrier (vitamin D binding protein), the different forms circulating in blood, and the issue of standardization are among the most important factors influencing the measurement of this metabolite. Another controversial point relies on the conflicting guidance on prevention and treatment of vitamin D deficiency endorsed by different medical and scientific communities. In particular, uncertainty exists about how to replete vitamin D stores, how to maintain normal 25(OH)D levels after repletion, which form of vitamin D is preferable for supplementation, and which route of administration and dosing regimens are advisable. Finally, concerns have been raised regarding vitamin D toxicity and its adverse effects.

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.

Prevalence of Kidney Stones and Vertebral Fractures in Primary Hyperparathyroidism Using Imaging Technology

CONTEXT The fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism (PHPT) has recently suggested that skeletal and renal imaging be routinely conducted. So far, no study has systematically assessed this issue. OBJECTIVE The objective was to evaluate the prevalence of kidney stones (KS) and vertebral fractures (VFs) in a cohort of patients with PHPT utilizing noninvasive imaging technology. DESIGN This was a prospective study evaluating patients consecutively diagnosed with PHPT in a single center over a 5-year period (2009-2013). SETTING The setting was a referral center. PATIENTS There were a total of 140 patients with PHPT (127 women [18 premenopausal and 109 postmenopausal] and 13 men; mean age, 63.2 ± 11 y). MAIN OUTCOMES MEASURES Main outcome measures were the prevalence of KS by abdominal ultrasound, osteoporosis by dual-energy x-ray absorptiometry (DXA) (lumbar spine, femoral neck, total hip, and distal 1/3 radius), and VFs by vertebral spine x-ray, with attention to those categorized as symptomatic or asymptomatic. RESULTS Fifty-five percent of all subjects had KS by ultrasound, 62.9% had osteoporosis by T-score at any site, and 35.1% had VFs by x-ray. There was no difference in the incidence of VFs and densitometric osteoporosis between symptomatic and asymptomatic patients (VFs, 34.4 vs 34.7%; osteoporosis by DXA, 59.4 vs 65.8%), whereas more KS were detected in symptomatic (78%) than asymptomatic (35.5%). Twenty-two percent of patients classified as asymptomatic at baseline without osteoporosis by DXA were found to have KS and/or VFs. CONCLUSIONS Nephrolithiasis and VFs are common in asymptomatic subjects with PHPT. The results provide evidence in support of recent recommendations that a more proactive approach be taken to detect silent bone and stone disease in asymptomatic PHPT.

The diagnosis and management of hypercalcaemia.

#### The bottom line Hypercalcaemia is a common finding in the setting of primary care,1 as well as in emergency departments2 and patients admitted to hospital.3 Primary hyperparathyroidism and malignancy are the two most common causes of increased serum calcium levels, together accounting for about 90% of all cases.4 The remaining 10% represent an important figure, and thus the need to consider other disorders in the evaluation of patients with hypercalcaemia. This review aims to give an overview of the diagnosis and clinical management of hypercalcaemia for non-specialist clinicians and health professionals. #### Sources and selection criteria We carried out a search through Medline and PubMed of articles published from 1990 to 2015 using the terms “mild hypercalcaemia” and “severe “hypercalcemia”, “primary hyperparathyroidism”, “hypercalcemia of malignancy”, “parathyroid hormone measurement”, “parathyroidectomy”, and “cinacalcet” and through the National Cancer Institute using the term “hypercalcaemia”. We also retrieved personal archived references to identify …

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.

Vitamin D and its relationship with obesity and muscle

The skin synthesis of vitamin D represents the first step of a metabolic pathway whose features have been extensively studied and clarified in the last decades. In particular, the production of active and inactive forms of the hormone and the actions of the corresponding enzymes have offered new insights into the knowledge of vitamin D metabolism. Additionally, the description of the different organs and tissues expressing the vitamin D receptor and its possible functions, as well as its genetic determinants, have allowed focusing on the interrelationship between vitamin D and many physiological and pathological functions. In this context, many studies reported the association between vitamin D and adipose tissue metabolism, as well as the possible role of the hormone in obesity, weight, and fat mass distribution. Finally, many reports focused on the vitamin D-related effects on skeletal muscle, particularly on the mechanisms by which vitamin D could directly affect muscle mass and strength. This paper is mainly aimed to review vitamin D metabolism and its relationship with obesity and skeletal muscle function.

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

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.