Bone and Mineral Metabolism Phenotypes in MEN1-Related and Sporadic Primary Hyperparathyroidism, before and after Parathyroidectomy

Primary hyperparathyroidism (PHPT) is the most common endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Persistent levels of increased parathyroid hormone (PTH) result in a higher incidence of osteopenia and osteoporosis compared to the general population. Surgical removal of hyper-functioning parathyroid tissue is the therapy of choice. This retrospective study evaluated the effect of parathyroidectomy (PTX) on bone metabolism and bone mass in two series of patients with MEN1 PHPT and sporadic PHPT (sPHPT) by comparing bone metabolism-related biochemical markers and bone mineral density (BMD) before and after surgery. Our data confirmed, in a higher number of cases than in previously published studies, the efficacy of PTX, not only to rapidly restore normal levels of PTH and calcium, but also to normalize biochemical parameters of bone resorption and bone formation, and to improve spine and femur bone mass, in both MEN1 PHPT and sPHPT. Evaluation of single-patient BMD changes after surgery indicates an individual variable bone mass improvement in a great majority of MEN1 PHPT patients. In MEN1 patients, PTX is strongly suggested in the presence of increased PTH and hypercalcemia to prevent/reduce the early-onset bone mass loss and grant, in young patients, the achievement of the bone mass peak; routine monitoring of bone metabolism and bone mass should start from adolescence. Therapy with anti-fracture drugs is indicated in MEN1 patients with BMD lower than the age-matched normal values.

Download Full-text

Is Preptin a New Bone Metabolism Parameter in Hemodialysis Patients?

Life ◽

10.3390/life11040341 ◽

2021 ◽

Vol 11 (4) ◽

pp. 341

Author(s):

Małgorzata Kałużna ◽

Krzysztof Pawlaczyk ◽

Krzysztof Schwermer ◽

Krzysztof Hoppe ◽

Aisha Yusuf Ibrahim ◽

...

Keyword(s):

Lumbar Spine ◽

Glucose Tolerance ◽

Bone Metabolism ◽

Mineral Metabolism ◽

Peptide Hormone ◽

Normal Glucose Tolerance ◽

Indirect Measurement ◽

Chronic Hemodialysis ◽

Mineral Density ◽

Patients With Diabetes

Background: Preptin is a bone-anabolic pancreatic peptide hormone. Its role in bone metabolism has been studied in rats and in patients with diabetes, but its levels and significance in bone metabolism in hemodialyzed (HD) patients is unknown. Methods: The relationships between preptin and anthropometric and biochemical parameters related to bone metabolism were studied in 73 patients on chronic hemodialysis (48 males, 25 females; mean age of 57 years; HD vintage of 69.7 months). Of these subjects, 36 patients had diabetes or impaired glucose tolerance (DM/IGT), and 37 patients had normal glucose tolerance (NGT). Dual-energy X-ray absorptiometry of the femoral neck and lumbar spine were also performed. Results: No differences were observed in preptin levels between DM/IGT and NGT HD patients. Preptin was positively correlated with HD vintage (r = 0.312, p = 0.007). Negative correlations between preptin and bone mineral density (BMD), T-score, and Z-score in the lumbar spine (L2-L4) were observed (r = −0.319, p = 0.009; r = −0.341, p = 0.005; r = −0.375, p = 0.002). Preptin was positively correlated with parathormone (PTH) levels (r = 0.379, p < 0.001) and osteocalcin levels (r = 0.262, p = 0.027). Conclusions: The results indicate that preptin may reflect on bone and mineral metabolism disturbances seen in HD patients. The significant correlation of preptin with PTH and osteocalcin suggests that preptin may be important in indirect measurement of bone turnover in HD patients.

Download Full-text

Reduction of arrhythmias in primary hyperparathyroidism, by parathyroidectomy, evaluated with 24-h ECG monitoring

Acta Endocrinologica ◽

10.1530/eje-17-0948 ◽

2018 ◽

Vol 179 (2) ◽

pp. 117-124 ◽

Cited By ~ 3

Author(s):

Jessica Pepe ◽

Cristiana Cipriani ◽

Mario Curione ◽

Federica Biamonte ◽

Luciano Colangelo ◽

...

Keyword(s):

Primary Hyperparathyroidism ◽

Mineral Metabolism ◽

Randomized Study ◽

Density Measurement ◽

Mean Value ◽

Ecg Monitoring ◽

Mineral Density ◽

Group A ◽

Group B ◽

The Impact

ObjectiveHypercalcemia may induce arrhythmias. There are no data on the prevalence of arrhythmias in primary hyperparathyroidism (PHPT) in daily life. Aim of the study was to investigate both the prevalence of arrhythmias in patients with PHPT compared to controls and the impact of parathyroidectomy, evaluated by 24-h electrocardiogram (ECG) monitoring.DesignThis is a randomized study.MethodsTwenty-six postmenopausal women with PHPT and 26 controls were enrolled. PHPT patients were randomized to two groups: 13 underwent parathyroidectomy (Group A) and 13 were followed up conservatively (Group B). After 6 months, patients were studied again. Each patient underwent mineral metabolism biochemical evaluation, bone mineral density measurement, standard ECG and 24-h ECG monitoring.ResultsPHPT patients showed higher calcium and parathyroid hormone compared to controls and a higher prevalence of both supraventricular (SVBPs) and ventricular premature beats (VPBs) during 24-h ECG monitoring. Groups A and B showed no differences in mean baseline biochemical values and ECG parameters. Mean value of QTc in PHPT groups was in the normal range at baseline, but significantly shorter than controls. A negative correlation was found between QTc and ionized calcium levels (r = −0.48,P < 0.05). After parathyroidectomy, Group A had a significant reduction in SVPBs and VPBs compared to baseline and restored normal QTc. Group B showed no significant changes after a 6-month period.ConclusionsThe increased prevalence of SVPBs and VPBs is significantly reduced by parathyroidectomy, and it is mainly related to the short QTc caused by hypercalcemia.

Download Full-text

Vitamin D Status in Patients Operated for Primary Hyperparathyroidism: Comparison of Patients from Southern and Northern Europe

International Journal of Endocrinology ◽

10.1155/2013/164939 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Erik Nordenström ◽

Antonio Sitges-Serra ◽

Joan J. Sancho ◽

Mark Thier ◽

Martin Almquist

Keyword(s):

Vitamin D ◽

Primary Hyperparathyroidism ◽

Disease Activity ◽

Vitamin D Deficiency ◽

Urinary Calcium ◽

Vitamin D Status ◽

Mineral Density ◽

Before And After ◽

25 Hydroxy Vitamin D ◽

One Year

Aim. The interaction between vitamin D deficiency and primary hyperparathyroidism (PHPT) is not fully understood. The aim of this study was to investigate whether patients with PHPT from Spain and Sweden differed in vitamin D status and PHPT disease activity before and after surgery.Methods. We compared two cohorts of postmenopausal women from Spain(n=126)and Sweden(n=128)that had first-time surgery for sporadic, uniglandular PHPT. Biochemical variables reflecting bone metabolism and disease activity, including levels of 25-hydroxy vitamin D3(25(OH)D) and bone mineral density, BMD, were measured pre- and one year postoperatively.Results. Median preoperative 25(OH)D levels were lower, and adenoma weight, PTH, and urinary calcium levels were higher in the Spanish cohort. The Spanish patients had higher preoperative levels of PTH (13.5 versus 11.0 pmol/L,P<0.001), urinary calcium (7.3 versus 4.1 mmol/L,P<0.001), and heavier adenomas (620 versus 500 g,P<0.001). The mean increase in BMD was higher in patients from Spain and in patients with vitamin D deficiency one year after surgery.Conclusion. Postmenopasual women with PHPT from Spain had a more advanced disease and lower vitamin 25(OH)D levels. Improvement in bone density one year after surgery was higher in patients with preoperative vitamin D deficiency.

Download Full-text

Iron Status Independently Associates With Bone Mineral Density At Population Level. Insights From The Val Borbera Study

Blood ◽

10.1182/blood.v122.21.4672.4672 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4672-4672

Author(s):

Nicola Martinelli ◽

Michela Traglia ◽

Fabiana Busti ◽

Marcella Sirtori ◽

Natascia Campostrini ◽

...

Keyword(s):

Bone Loss ◽

Bone Mass ◽

Iron Overload ◽

Bone Metabolism ◽

Iron Status ◽

Population Level ◽

Mineral Density ◽

Major Health Problem ◽

T Score ◽

Serum Hepcidin

Background and Aims Osteoporosis is a multifactorial major health problem affecting over 200 million people worldwide. It is long known as a complication of marked iron overload, both primary (i.e. genetic hemochromatosis) and secondary (i.e. transfusional iron overload), but only recently cellular and animal models have shed some light on the pathogenetic link between iron and bone metabolism. Iron has been shown to activate osteoclasts (Ishii KA, Nat Med 2009) and to inhibit osteoblasts (Yamasaki K, Toxicol Lett 2009), which express ferroportin regulated by hepcidin (Xu Y, Inflammation 2012). A murine model has shown that iron overload causes bone loss through induction of Reactive Oxygen Species (ROS) (Tsay J, Blood 2010). Of note, a recent longitudinal study in a Korean population has demonstrated that serum ferritin, even at concentrations generally not considered as “iron overload”, is an independent predictor of bone mass deterioration and incident vertebral fractures (Kim BJ, J Bone Miner Res 2012), an effect most prominent in women ≥ 45 years of age (Kim BJ, Osteoporos Int 2013). Taking advantage from the recently completed iron section of the Val Borbera Study (Traglia M, J Med Genet 2011), this study aimed to evaluate for the first time the association between iron status (including serum hepcidin levels) and bone mass in a Caucasian population. Subjects and Methods This survey included 921 subjects (564 females, 357 males) aged 53.8 ± 16.3 years for whom complete data regarding bone mass (measured by transportable Quantitative Ultrasonography, QUS-based approach) and iron status (including serum hepcidin-25 levels measured by Mass Spectrometry) were available. Subjects with known inflammatory and renal disorders, as well as hereditary hemochromatosis had been previously excluded. Analyses were performed separately in males and females, due to known gender-related differences in either iron or bone metabolism. Main Results No significant association was found in males, while in females both ferritin (r= -0.42, P<0.001) and hepcidin (r= -0.30, P<0.001) were inversely correlated with T-score at univariate analyses. However, after including both ferritin and hepcidin in an age-adjusted linear regression model, only ferritin remained a significant predictor of T-score variability (beta coefficient= -0.115, P=0.042). Subsequent regression models adjusted for age, BMI, and C-Reactive Protein highlighted ferritin levels as independent predictors of T-score in females. After stratification for age and ferritin categories, T-score decreased linearly with increasing ferritin levels especially in females aged 50-75 years (n=293), i.e. the age known to be at major risk of accelerated bone loss (P<0.001 – Figure 1). Conclusions This study confirms that iron status significantly associates with bone loss at population level even in Caucasians, particularly in post-menopausal women. Increasing iron stores, even not clearly “pathologic”, may influence bone metabolism through increased ROS and/or hepcidin-mediated altered iron handling of osteoblasts and osteoclasts. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Bone Involvement in Primary Hyperparathyroidism and Changes After Parathyroidectomy

European Endocrinology ◽

10.17925/ee.2014.10.01.84 ◽

2010 ◽

Vol 10 (1) ◽

pp. 84 ◽

Cited By ~ 5

Author(s):

Lars Rolighed ◽

Lars Rejnmark ◽

Peer Christiansen ◽

◽

...

Keyword(s):

Primary Hyperparathyroidism ◽

Fracture Risk ◽

Bone Metabolism ◽

Plasma Calcium ◽

Parathyroid Glands ◽

Elevated Plasma ◽

Mineral Density ◽

High Bone Turnover ◽

Normal Bone ◽

High Bone

Parathyroid hormone (PTH) is produced and secreted by the parathyroid glands and has primary effects on kidney and bone. During the pathological growth of one or more parathyroid glands, the plasma level of PTH increases and causes primary hyperparathyroidism (PHPT). This disease is normally characterised by hyperparathyroid hypercalcaemia. In PHPT a continuously elevated PTH stimulates the kidney and bone causing a condition with high bone turnover, elevated plasma calcium and increased fracture risk. If bone resorption is not followed by a balanced formation of new bone, irreversible bone loss may occur in these patients. Medical treatment can help to minimise the loss of bone but the cure of PHPT is by parathyroidectomy. After operation, bone mineral density increases during the return to normal bone metabolism. Supplementation with calcium and vitamin D after operation may improve the normalisation to normal bone metabolism with a secondary reduction in fracture risk.

Download Full-text

Prediction of bone mass changes after successful parathyroidectomy using biochemical markers of bone metabolism in primary hyperparathyroidism: is it clinically useful?

Archives of Endocrinology and Metabolism ◽

10.20945/2359-3997000000154 ◽

2019 ◽

Author(s):

Monique Nakayama Ohe ◽

Teresa Cristina Piscitelli Bonanséa ◽

Rodrigo Oliveira Santos ◽

Murilo Catafesta das Neves ◽

Livia Marcela Santos ◽

...

Keyword(s):

Primary Hyperparathyroidism ◽

Bone Mass ◽

Bone Metabolism ◽

Biochemical Markers

Download Full-text

Selenium: A Trace Element for a Healthy Skeleton - A Narrative Review

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200628030913 ◽

2020 ◽

Vol 20 ◽

Author(s):

Fabio Vescini ◽

Iacopo Chiodini ◽

Andrea Palermo ◽

Roberto Cesareo ◽

Vincenzo De Geronimo ◽

...

Keyword(s):

Bone Mass ◽

Bone Metabolism ◽

Bone Cells ◽

Fragility Fractures ◽

Serum Selenium ◽

Mineral Density ◽

Increased Risk ◽

Serum Selenium Levels ◽

Essential Nutrient ◽

The Relationship

: Inadequate serum selenium levels may delay the growth and the physiological changes in bone metabolism. In humans, reduced serum selenium concentrations are associated with both increased bone turnover and reduced bone mineral density. Moreover, a reduced nutritional intake of selenium may lead to an increased risk of bone disease. Therefore, selenium is an essential nutrient playing a role in bone health, probably due to specific selenium-proteins. Some selenium-proteins have an anti-oxidation enzymatic activity and participate in maintaining the redox cellular balance, regulating inflammation and proliferation/differentiation of bone cells too. At least nine selenium-proteins are known to be expressed by fetal osteoblasts and appear to protect bone cells from oxidative stress at bone microenvironment. Mutations of selenium-proteins and reduced circulating levels of selenium are known to be associated with skeletal diseases such as the Kashin-Beck osteoarthropathy and postmenopausal osteoporosis. In addition, the intake of selenium appears to be inversely related to the risk of hip fragility fractures. Recent data suggest that an altered selenium state may affect bone mass even in males and seleniumproteins and selenium concentrations were positively associated with the bone mass at femoral, total and trochanteric site. However, selenium, but not selenium-proteins, seems to be associated with femoral neck bone mass after adjustment for many bone fracture risk factors. The present review summarizes the findings of observational and interventional studies, which have been designed for investigating the relationship between selenium and bone metabolism.

Download Full-text

Bone Mineral Density and Biochemical Markers of Bone Metabolism in Women Engaging in Recreational Horseback Riding

Journal of Physical Activity and Health ◽

10.1123/jpah.2015-0131 ◽

2016 ◽

Vol 13 (5) ◽

pp. 520-524 ◽

Cited By ~ 1

Author(s):

Agnieszka Kaczmarek ◽

Alicja Nowak ◽

Piotr Leszczynski

Keyword(s):

Physical Activity ◽

Bone Mineral Density ◽

Bone Mass ◽

Bone Turnover ◽

Bone Metabolism ◽

Bone Mineral ◽

Bone Turnover Markers ◽

Horseback Riding ◽

Mineral Density ◽

Turnover Markers

Background:An increased occurrence of lifestyle-related diseases such as osteoporosis indicates the necessity for taking preventive action, including regularly engaging in physical activity. The aim of the study was to assess the areal bone mineral density (aBMD) and bone turnover markers levels in young adult women engaging in recreational horseback riding and to determine the relationship between training characteristics and bone metabolism indices.Methods:The study involved 43 women: 23 equestrians and 20 age- and body mass index–matched controls. The hip and spine aBMD and serum levels of the bone turnover markers: osteocalcin and collagen type I cross-linked C-telopeptide were measured.Results:No significant differences were found in somatic features, concentrations of bone turnover markers, or bone mass variables. Correlation analysis of the equestrian participants showed significant relationship between body mass and BMDL1–L4 (P < .05) as well as between BMI and BMDL1–L4 (P ≤ .01) and z-score L1–L4 (P < .05).Conclusions:The study showed no differences in bone mass and levels of bone metabolic indices between groups of women practicing horseback riding at the recreational level and subjects who do not participate in frequent systematic physical activity. No relationship between training characteristics and bone turnover markers were found.

Download Full-text

Persistent increase of osteoprotegerin levels after cortisol normalization in patients with Cushing's syndrome

Acta Endocrinologica ◽

10.1530/eje-09-0800 ◽

2010 ◽

Vol 162 (1) ◽

pp. 85-90 ◽

Cited By ~ 12

Author(s):

Valentina Camozzi ◽

Francesca Sanguin ◽

Nora Albigier ◽

Carla Scaroni ◽

Franco Mantero ◽

...

Keyword(s):

Bone Metabolism ◽

Cushing’S Syndrome ◽

Osteoclast Differentiation ◽

Serum Levels ◽

Cushing's Syndrome ◽

Mineral Density ◽

Receptor Activator ◽

Before And After ◽

Design And Methods ◽

Gonadal Status

ObjectiveOsteoprotegerin (OPG) has been identified as a decoy receptor that inhibits osteoclast differentiation and, more recently, as a paracrine regulator of vascular calcification. OPG is suppressed by glucocorticoids (GC); however, results from experimental and clinical studies are not univocal. The aim of this study was to evaluate OPG and bone metabolism in patients with Cushing's syndrome (CS) before and after cure.Design and methodsTwenty-six patients with CS (all women, mean age: 39.1±11.9 years) and 24 age- and gonadal status-matched healthy women were studied for bone mineral density, bone metabolism, OPG, and receptor activator of nuclear factor-kB ligand at baseline. Twelve patients were also studied 6–18 months after surgery, with persistent normalization of cortisol levels.ResultsOPG was significantly higher and osteocalcin (OC) was significantly lower in CS patients than in controls (OPG: 4.17±1.23 vs 2.95±0.79 pmol/l, P=0.00001; OC: 15.0±6.1 vs 18.8±6.8 ng/ml, P=0.04 in CS and controls respectively). After cure, we found no difference in OPG levels, despite a significant increase in OC levels (from 16.4±11 to 37.2±15 ng/ml, P=0.03).ConclusionPatients with CS showed increased OPG serum levels that remained unchanged after recovery, despite a restoration of bone formation. We speculate that high levels of OPG could reflect the persistent damage of the GCs on cardiovascular system.

Download Full-text