Modulation of vitamin d status and dietary calcium affects bone mineral density and mineral metabolism in göttingen minipigs.

Calcium and vitamin D deficiency impairs bone health and may cause rickets in children and osteomalacia in adults. Large animal models are useful to study experimental osteopathies and associated metabolic changes. We intended to modulate vitamin D status and induce nutritional osteomalacia in minipigs.

Recent developments in intestinal calcium absorption.

Calcium absorption proceeds by transcellular and paracellular flux, with the latter accounting for most absorbed calcium when calcium intake is adequate. Vitamin D helps regulate transcellular calcium transport by increasing calcium uptake via a luminal calcium channel and by inducing the cytosolic calcium transporting protein, calbindinD(9k). Recent studies utilizing knockout mice have challenged the functional importance of the channel and calbindin.

A model of the kinetics of lanthanum in human bone, using data collected during the clinical development of the phosphate binder lanthanum carbonate.

Objective: Lanthanum carbonate (Fosrenol) is a non-calcium phosphate binder that controls hyperphosphataemia without increasing calcium intake above guideline targets. The biological fate and bone load of lanthanum were modelled with the aid of a four-compartment kinetic model, analogous to that of calcium.

Methods: The model used data from healthy subjects who received intravenous lanthanum chloride or oral lanthanum carbonate, and bone lanthanum concentration data collected from dialysis patients during three long-term trials (up to 5 years).

Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions.

Objective: To investigate whether the abnormal expression of matrix metalloproteinases (MMPs) 3, 9, and 13 and ADAMTS-4 by human osteoarthritic (OA) chondrocytes is associated with epigenetic "unsilencing."

Methods: Cartilage was obtained from the femoral heads of 16 patients with OA and 10 control patients with femoral neck fracture. Chondrocytes with abnormal enzyme expression were immunolocalized.

Mechanisms and functional aspects of intestinal calcium absorption.

Calcium absorption, in terms of mechanisms and function, is well adapted to meet the calcium needs of mammals. When calcium levels in the food are low, the active, mediated transcellular calcium transport assumes primary importance. This process is vitamin D-dependent, largely localized in the duodenum, and involves three steps: entry across the brush border, mediated by a molecular structure, CaT1, with two components; a facilitated transport that saturates at low luminal calcium concentration; and a channel component through which most calcium enters the cell at the higher luminal concentrations.

Founding editorial--bone biology.

The skeleton is a complicated vertebrate structure, comprised of bone cells that form, modulate, and resorb the extracellular structure of bone. It is the extracellular structure, made up of the bone mineral (largely calcium phosphate) and the bone matrix, which constitutes the visible skeleton and the mechanical support for the vertebrate body. The matrix is the protein structure on which the bone mineral is laid down, many components of which have been identified in recent years.

Calcium nutrition and metabolism.

An adequate calcium intake throughout life is essential for maintenance of the skeleton, by far the largest body reservoir of calcium. Appropriately high calcium intake is particularly important in the first two decades, when the body calcium mass increases to near maximum. In subsequent decades, because calcium absorption is relatively modest, typically 25% or less, calcium intake must be kept near 1000 mg per day in order to minimize the possibility that the skeleton will be mined for its mineral content.

Mechanisms of intestinal calcium absorption.

Calcium is absorbed in the mammalian small intestine by two general mechanisms: a transcellular active transport process, located largely in the duodenum and upper jejunum; and a paracellular, passive process that functions throughout the length of the intestine. The transcellular process involves three major steps: entry across the brush border, mediated by a molecular structure termed CaT1, intracellular diffusion, mediated largely by the cytosolic calcium-binding protein (calbindinD(9k) or CaBP); and extrusion, mediated largely by the CaATPase. Chyme travels down the intestinal lumen in approximately 3 h, spending only minutes in the duodenum, but over 2 h in the distal half of the small intestine.