Calcium Requirements. The body regulates few functions with greater fidelity than the concentration of ionized calcium in the extracellular fluid. Although extracellular calcium represents less than 1% of the body’s calcium stores, it is the metabolically active component that is critically important for numerous lifesustaining processes that include enzymatic reactions, mitochondrial function, cell membrane maintenance, intracellular and intercellular communication, interneuronal transmission, neuromuscular transmission, muscle contraction, and blood clotting. An elaborate endocrine system maintains the serum calcium concentration within a very narrow physiologic range. When this level falls, even momentarily, it is restored to normal through the parathyroid hormone (PTH)/vitamin D system, which increases calcium absorption in the gastrointestinal tract and reabsorption in the kidneys, and the resorption of bone (see Plate 2-33).

The National Research Council of the National Academy of Sciences has established recommended daily allowances (RDAs) of calcium for all age groups. These values, which may be conservative estimates, reflect the average amount of calcium required to maintain a positive calcium balance and to prevent withdrawal of the mineral stores banked in bone. For young adults, the RDA of calcium is 1000 to 1300 mg. Despite this recommendation, large-scale dietary surveys of women with osteoporosis show that the average American woman consumes less than 500 mg/day. On such a calcium-deficient diet, the body mobilizes calcium from its skeletal reserve for its daily needs by increasing secretion of PTH and 1,25-dihydroxyvitamin D, or 1,25(OH)₂D, the hormonally active metabolite of vitamin D. (Because both D₂ and D₃ isomers are treated identically and act in similar manners, the numeric designator has been omitted.)

Absorption of calcium from the upper gastrointestinal tract becomes less efficient with age because of decreases in baseline levels and secretory reserves of 1,25(OH)₂D; thus, older persons need more dietary calcium to maintain a calcium balance. Healthy premenopausal women older than age 30 may require as much as 1300 mg/day, and pregnant women and women older than age 50 need more than 1500 mg/day. Lactating women need 2000 mg/day to prevent untimely catabolism of bone.

Calcium consumption may be inadequate in persons with lactase deficiency who avoid eating dairy products, the primary source of dietary calcium. Increased protein intake accelerates calcium excretion by the kidney. Therefore, the high-protein diet common in Western industrialized countries may be a contributing factor to accelerated bone loss in these populations.

Vitamin D Requirements. The vitamin D metabolite 1,25(OH)₂D helps to maintain normal serum calcium and phosphate levels by increasing the absorption of these substances from the intestine and the osteoclastic resorption of bone. About half of our vitamin D comes from dietary sources (particularly from vitamin D–enriched milk), and the remainder comes from a reaction in the skin stimulated by ultraviolet radiation. Only a few natural foods, such as fish liver oils, contain vitamin D. Elderly persons frequently have a mild vitamin D deficiency because of their meager exposure to sunlight, decreased intake of milk and other dairy products, and decreased intestinal absorption of vitamin D. The RDA of vitamin D is 600 IU for young adults and 800 IU for elderly persons. Larger amounts may cause hypercalcemia. Premature infants may require 500 to 1000 IU daily.

In addition to age- and sex-related effects on bone loss, endocrine and metabolic changes affect bone homeostasis, leading to osteoporosis. In both osteoporotic and normal elderly women, 1,25(OH)₂D levels are normal. However, in elderly patients, the kidney’s production of 1,25(OH)₂D in response to PTH infusion is impaired. Also, in postmenopausal women, bone-resorbing cells (osteoclasts) appear to be excessively responsive to endogenous PTH. Estrogen receptors have been found in both osteoblasts and osteoclasts. Estrogen decreases the sensitivity of osteoclasts to PTH, making estrogen deficiency the major cause of bone loss in the early postmenopausal period.