In a 40-year-old man with bone pain, hypophosphatemia, normocalcemia, elevated serum alkaline phosphatase and increased renal phosphate clearance, and radiologic evidence of osteomalacia, ...

Tertiary Hyperparathyroidism and Apparent Cure of Vitamin-D-Resistant Rickets after Removal of an Ossifying Mesenchymal Tumor of the Pharynx

Calcium and osteoporosis.

A new model of calcium (Ca) homeostasis is proposed. It is based on the kinetics of restoration of the plasma Ca level following positive or negative Ca loads in animals of different endocrine status. As others, we can account for the kinetics of plasma Ca restoration as being the result of a very rapid dilution of Ca into extracellular water (t1/2<1 minute) and an uptake or release by bone (t1/2=14–80 minutes) that occurs as the fraction of cardiac output directed to bone is partially cleared of or repleted with Ca. In this model, bone surfaces have Ca-binding sites that demonstrate a range of affinities and whose average Km determines the plasma Ca level. Acute regulation is brought about by controlling access to subpopulations of Ca binding sites in bone, comprising the extremes of high and low affinity. Osteoblasts, when active and extended, block the low affinity sites, and osteoclasts, when active and extended, block the high affinity sites. Exposure of low- or high-affinity sites is brought about when these cells respond to hormonal signals by contraction, parathyroid hormone (PTH), and vitamin D leading to osteoblast, and calcitonin to osteoclast, contraction. These reciprocal cell shape changes are the first in a cascade of metabolic events that lead to bone formation and resorption, as well as changes in the number or affinity of the binding sites. The model also accounts for the prolongation of the response time to Ca loads in animals deprived of PTH, calcitonin, or vitamin D.

Modulation of bone calcium-binding sites regulates plasma calcium: an hypothesis.

The major components of calcium metabolism, as evaluated by a dual-tracer stable isotope method, were determined in 100 studies of 68 healthy girls, aged 5-18 y and analyzed from a developmental and regulatory viewpoint. Bone calcium deposition and removal rates were closely correlated with the size of the exchangeable bone calcium compartment. All three quantities, as well as intestinal calcium absorption, peaked at or near menarche. Both bone calcium deposition and removal rates were positively and linearly correlated with calcium absorption. However, in this correlation, because bone calcium deposition increased 70% faster than calcium absorption, most of the increase in the bone calcium compartment and its turnover must have occurred in response to something other than intestinal calcium input; presumably this occurred in response to developmental signals. Nevertheless, the constancy of the serum calcium in the face of a large intestinal calcium input and the modest way in which excretion overcame the calcium load in this population point to the importance of the exchangeable bone calcium compartment, in dynamic equilibrium with the bone mineral, as the site at which most of the load is taken up. In this population of girls, as in older women, this increase in the skeletal calcium balance resulted from a decrease in the bone calcium removal rate that was greater than the corresponding increase in the bone calcium deposition rate.

Development and Regulation of Calcium Metabolism in Healthy Girls

The term "bioavailability" attempts to include in a single concept the effect of a sequence of metabolic events, i.e., digestibility, solubilization, absorption, organ uptake and release, enzymatic transformation, secretion and excretion. Each of these events is difficult to measure experimentally, and, with the possible exception of digestibility and solubilization, all are age-dependent and subject to nutritional and hormonal controls. In the case of calcium, the body's demand increases and then decreases with age; it also increases with pregnancy and lactation. Age, pregnancy and lactation each affect the regulatable component of the intestinal absorption of calcium. The passive component of calcium absorption is a function of the amount of calcium solubilized and of intestinal transit time. Inasmuch as digestibility and solubilization of calcium are very difficult to determine separately, even a reliable measure of calcium absorption includes a measure of uncertainty. If one wishes to include in the term "calcium bioavailability" rates of net deposition in bone, as well as rates of excretion from the body, quantitative information on calcium pool size, turnover and the effects thereon of age, sex, endocrine and nutritional status are needed. In the case of other nutrients, rates of enzymatic transformation and organ utilization need also to be taken into account. It will therefore require major research programs before the term "bioavailability" of a nutrient can become a quantitative concept useful for clinical, nutritional or managerial evaluation and counseling.

Bryan D. Hall

Papers

Vitamin D-Resistant Rickets and High Fecal Endogenous Calcium Output A Report of Two Cases