Applications of Metabolomics in Calcium Metabolism Disorders in Humans.

The pathogenesis of the disorders of calcium metabolism is not fully understood. This review discusses the studies in which metabolomics was applied in this area. Indeed, metabolomics could play an essential role in discovering biomarkers and elucidating pathological mechanisms. Despite the limited bibliography, the present review highlights the potential of metabolomics in identifying the biomarkers of some of the most common endocrine disorders, such as primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), calcium deficiency, osteoporosis and vitamin D supplementation. Metabolites related to above-mentioned diseorders were grouped into specific classes and mapped into metabolic pathways. Furthermore, disturbed metabolic pathways can open up new directions for the in-depth exploration of the basic mechanisms of these diseases at the molecular level.

Calcium Metabolic Disorders in Pregnancy: Primary Hyperparathyroidism, Pregnancy-Induced Osteoporosis, and Vitamin D Deficiency in Pregnancy.

Physiologic changes during pregnancy include calcium, phosphate, and calciotropic hormone status. Calcium metabolic disorders are rare in pregnancy and management with close calcium and vitamin D control and supplementation. Primary hyperparathyroidism is mostly asymptomatic and does not affect conception or pregnancy. It requires control of plasma calcium levels. Surgical intervention may be indicated. Data on severe cases are missing. Osteoporosis in or before pregnancy is rare but usually diagnosed from fractures. Medical treatment other than supplementation is contraindicated. Vitamin D deficiency is common and may affect conception and increase complications. Current evidence does not prove vitamin D supplements effective in improving outcomes.

Hypochlorhydria-induced calcium malabsorption does not affect fracture healing but increases post-traumatic bone loss in the intact skeleton.

Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr-/- mice. However, Cckbr-/- mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr-/- mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1914-1921, 2016.

[Biochemical evaluation of metabolic disorders in the tissues of the locomotor system in patients with occupational diseases caused by physical stress]. / Biokhimicheskaia otsenka metabolicheskikh rasstroistv v tkaniiakh oporno-dvigatel'nogoapparata u bol'nykh professional'nymi zabolevaniiami ot fizicheskogo perenapriazheniia.

A group of patients with occupational disease and female sewing-machine operators were medically examined with a broad set of biochemical techniques aimed at the detection of metabolic disorders in the locomotor system tissues. Noninflammatory dystrophic changes were found. The muscular component was dominating in comparison with the osseous one in the genesis of the degenerative dystrophic processes, which manifested in the clinical course. Laboratory manifestations were revealed related to the lowered energy supply and oxygenation of the skeleton muscles in patients with neuromuscular and osteo-muscular++ syndromes. The metabolic disorders were diagnosed at the early stages of myalgia.

Effects of high protein diet and sodium bicarbonate supplementation on calcium metabolism in rats.

This study was conducted to determine the effect of a high protein diet on calcium metabolism in rat. Wistar strain male rats (50 days old) were divided into 5 groups (day 0): control diet (18% casein); high protein diet (18% casein +20% lactalbumin); high protein and 0.1% sodium bicarbonate diet; high protein and 0.2% sodium bicarbonate diet; and high protein and 0.4% sodium bicarbonate diet. On days 0, 1, 3, 5, 7, 9, urine samples were collected and, at the same time, feces were collected from half of the animals in each group. Urinary titratable acidity (TA-HCO3-), ammonium ion (NH4+), and net acid excretion (NAE) were measured as an index of acid-base balance in rat body. Urinary volume was rapidly increased and the increase of urinary volume continued throughout the study in rats fed the high protein diet. Urinary excretions of calcium and phosphorus were increased after day 3 and day 1, respectively, in rats fed the high protein diet. The high protein diet depressed calcium absorption and elevated phosphorus absorption from the digestive tract in rats fed the high protein diet. The high protein diet decreased TA-HCO3-, which was closely correlated with the decrease of NAE. Sodium bicarbonate supplementation to the high protein diet had little effect on urinary calcium excretion and NAE. This study suggested that there was no relationship between metabolic acidosis and hypercalciuria in rats fed the high protein diet.

Is there a renal phosphorus leak in recurrent renal stone formers with absorptive hypercalciuria?

In ten male hypophosphataemic hypercalciuric recurrent renal stone formers with absorptive hypercalciuria and ten male normophosphataemic normocalciuric control persons, fasting plasma and urine chemistry was studied throughout the day under basal conditions and following an oral phosphorus load. After overnight fasting, plasma phosphorus and TMP/GFR were lower and urinary calcium higher in patients than in controls. Both in patients and controls, plasma phosphorus rose throughout the morning hours. In the afternoon, plasma phosphorus was almost equal in patients and controls. The circadian rise of plasma phosphorus despite no increase of urinary phosphorus argues against the presence of a fixed renal tubular phosphorus leak in absorptive hypercalciuria, at least in the fasting state. Patients differed from controls not only with respect to urinary calcium, but also with respect to fasting absolute and fractional urinary excretion of sodium and chloride. Increased fractional urinary sodium was found both in normotensive and hypertensive patients. Since tubular reabsorption of phosphorus and the setting of fasting plasma phosphorus depend, among other factors, on tubular handling of sodium, the finding may be relevant for the genesis of transient fasting hypophosphataemia in absorptive hypercalciuria.

Is there a disorder of phosphate metabolism in idiopathic hypercalciuria?

Hypophosphatemia either as a consequence of secondary hyperparathyroidism or as a consequence of a primary defect in phosphate metabolism appears to be a well established abnormality among subsets of patients with idiopathic hypercalciuria and nephrolithiasis. The detailed biochemical events that lead to hypophosphatemia in those patients who exhibit a primary abnormality of phosphate metabolism remain to be clarified.

Calcium and phosphorus metabolic changes in children with hepatic bilharziasis.

Investigations were done to study the calcium and phosphorus metabolic changes in 35 children with hepatic bilharziasis, of whom 12 were ascitic. Thirteen normal children served as controls. Despite a normal serum level of both calcium and inorganic phosphate in the Bilharzial group, yet both were increased in urine. The mean values obtained from the ascitic fluid were 70% and 90.2% of their serum levels, respectively. The corrected creatinine clearance was significantly diminished, while PEI was significantly increased, and the % TRP significantly decreased, with still a more marked decrease in the ascitic cases. Following a phosphate lead the serum inorganic phosphate level showed a significantly more rapid lowering in both bilharzial groups, as compared to the control group. On the other hand bilharzial cases responded to the intravenous calcium load by a significant retention of calcium in the serum.