Components of 25-hydroxyvitamin D in serum of young children in upper midwestern United States.

The relative importance of cholecalciferof (vitamin D3) and ergocalciferol (vitamin D2) in maintaining the vitamin D level in children (1/2 to 6 years old) living in the upper midwestern United States was determined by measurement of total 25-hydroxyvitamin D (25-OH-D), its components, and other indices of calcium homeostasis in serum. In 38 normal children, mean (range) serum total 25-OH-D was 32.8 (less than 5 to 53) ng/ml; in 25 of the 28 sera partitioned, the major component was 25-OH-D3. Significant seasonal variation in serum 25-OH-D3 (mean, range: 35.2, 17 to 51 ng/ml in summer and 15.9, less than 5 to 32 ng/ml in winter) was not accompanied by changes in mean serum 25-OH-D2, calcium, phosphorus, or alkaline phosphatase values. However, individual serum total 25-OH-D values correlated with serum phosphorus values (r = 0.37; P less than 0.05). The proportion of the total represented by 25-OH-D3 varied widely, with a a mean of 83% in summer and 67% in winter. Sources of D3, which include both dermal synthesis and intestinal absorption of D3 added to milk, appear to be more important than sources of D2 in maintaining vitamin D nutrition of young children throughout the year. However, sources of D2 offset the decrease in total 25-OH-D in winter months.

Effects of phosphorus supplementation on serum parathyroid hormone and bone morphology in osteoporosis.

The effect of phosphorus (inorganic phosphate) supplementation was studied in seven postmenopausal women with osteoporosis. Prior to supplementation, all chemical parameters studied in serum and urine were normal. Bone density was below the fifth percentile for age in all but one patient, and the percentage of bone surface involved in resorption was higher than normal. During administration of the phosphorus supplement, fasting serum concentrations of calcium and immunoreactive parathyroid hormone showed no significant changes, while serum phosphorus, urinary calcium, and tubular reabsorption of phosphorus decreased. In four patients studied by balance techniques, calcium balance became positive or less negative. Bone-forming surface decreased and bone-resorbing surface increased in all patients. Bone-resorbing surface was highly correlated with total phosphorus intake. Density of the distal radius changed variably, while density of the midradius increased slightly in all patients.

The effects of calcium and phosphorus in hemodialysis.

Combined use of Ca supplements (orally or by dialysis) to circumvent decreased intestinal Ca absorption and aluminum compounds to reduce plasma [Pi] has been demonstrated to decrease plasma [iPTH], to normal or near normal in many patients, and to decrease the percentage of bone surface involved in bone resorption. A highly significant positive relationship between change in plasma [iPTH] and bone resorbing surface has been reported. It seems evident, therefore, that PTH must be a major factor in the bone resorption of chronic renal failure, despite the relative skeletal resistance to PTH. As a result, correction of factors that increase PTH secretion should be considered a prime goal of therapy in these patients. The osteomalacic element of renal osteodystrophy, on the other hand, is only partially controlled by these maneuvers and probably requires the additional use of vitamin D or one of its active metabolites for full correction.

Osteomalacia associated with anticonvulsant drug therapy in mentally retarded children.

A survey of 289 severely retarded inpatients at a school for retarded children in American Fork; Utah revealed 67 patients with osteomalacia as defined by hypocalcemia, hypophosphatemia, elevated serum alkaline phosphatase levels, and appropriate bone changes. Investigation of the variables which might influence bone mineralization revealed no differences in age, sex, physical activity, sunshine exposure, or dietary intake of vitamin D between the osteomalacia and nonosteomalacia groups. However, all of the patients with osteomalacia were receiving anticonvulsant medications, either phenobarbital, diphenylhydantoin, or both. Duration of anticonvulsant therapy was the most important contributing factor to the development of osteomalacia. Seventy-five percent of patients who had received anticonvulsants for more than ten years had osteomalacia. The single most costly medical problem at the school is the treatment of pathologic bone fractures due to demineralized bone.

Etiology of hyperparathyroidism and bone disease during chronic hemodialysis. 3. Evaluation of parathyroid suppressibility.

Parathyroid function was assessed by calcium infusions (4-8 h) in 16 patients with chronic renal insufficiency being treated by long-term hemodialysis. The concentrations of two immunoreactive species of parathyroid hormone in plasma (iPTH-9, mol wt 9500; iPTH-7, mol wt 7000) were estimated by radioimmunoassays utilizing two relatively specific antisera. Control values of the smaller species, iPTH-7, were uniformly high, whereas values of iPTH-9 were normal in 12 of 19 studies. Response of iPTH-7 to calcium infusions was variable, with significant decreases occurring only five times in 27 infusions. Concentrations of iPTH-9, however, decreased during every calcium infusion. In contrast to these acute responses, five of six patients studied during periods of dialysis against both low (< 6 mg/100 ml) and high (7-8 mg/100 ml) calcium concentrations in the dialyzate showed a decrease in values of iPTH-7 during the period of dialysis against the higher calcium concentration. It is concluded that plasma concentrations of iPTH-9 reflect primarily the moment-to-moment secretory status of the parathyroid glands, while concentrations of iPTH-7 reflect more closely chronic parathyroid functional status. It is further concluded that the failure of iPTH-7 to decrease during induced hypercalcemia should not be equated with autonomy of parathyroid gland function.

Parathyroid function in primary osteoporosis.

Two major species of serum immunoreactive parathyroid hormone (iPTH) were measured in 47 untreated patients with primary osteoporosis by using two highly specific radioimmunoassays. Mean iPTH was normal with one antiserum but was lower than normal (P < 0.001) with the other, iPTH values did not correlate with biochemical parameters or with the proportion of bone-resorbing surfaces in iliac crest bone biopsy specimens. These data suggest that the increased bone resorption is not due to increased parathyroid function in most osteoporotic patients. However, seven of our patients (15%) appear to represent a separate population because they had increased values with one or the other of the antisera.

Short- and long-term effects of estrogen and synthetic anabolic hormone in postmenopausal osteoporosis.

In 29 women with postmenopausal osteoporosis, the proportion of total bone surface undergoing resorption or formation was evaluated by microradiography of iliac crest biopsy samples before and after short-term (2(1/2)-4 months) and long-term (26-42 months for estrogen and 9-15 months for anabolic hormone) treatment. After estrogen administration, values for bone-resorbing surfaces decreased, although less prominently after long-term than after short-term therapy. The magnitude of this decrease was positively correlated with the pretreatment value for bone-resorbing surfaces (P < 0.001). When the pretreatment value for bone-resorbing surfaces was used as a covariable, estrogen and anabolic hormone appeared to be equally effective. For bone-forming surfaces, short-term therapy with either hormone had no effect but long-term therapy significantly decreased the values. Serum immunoreactive parathyroid hormone (IPTH) increased significantly after estrogen therapy; the change in IPTH was inversely related to the change in serum calcium (P < 0.001, sign test). We conclude that the primary effect of sex hormones in postmenopausal osteoporosis is to decrease the increased level of bone resorption, perhaps by decreasing the responsiveness of bone to endogenous parathyroid hormone. However, this favorable effect, at least in part, is negated after long-term treatment by a secondary decrease in bone formation. Our data are consistent with the concept that the maximal benefit that can be derived from sex hormone therapy in postmenopausal osteoporosis is arrest or slowing of the progession of bone loss.

Calcium metabolism under stress and in repose.

Derangement of calcium metabolism, although perhaps not as dramatic as that of the cardiovascular or vestibular systems, constitutes one of the major threats to the health of participants in exploration of space. On the basis of studies in immobilized subjects, the clinical disorders most likely to be encountered during prolonged space flight are primarily the consequence of an imbalance between bone formation and resorption (favoring the latter): (1) loss of skeletal mass, leading to osteoporosis; (ii) hypercalcemia; and (iii) hyper-calciuria, with the attendant risk of nephrolithiasis. By itself, loss of skeletal mass would not be expected to pose an in-flight hazard, but hypercalcemia or nephrolithiasis could jeopardize lives or mission success. Such data as are available from in-flight studies tend to support the use of immobilization as a terrestrial model for alterations in calcium metabolism during space flight. A variety of prophylactic measures have been attempted with this model in an effort to modify the observed disorders. Although there is some evidence that hypercalcemia and hypercalciuria can be reduced or prevented, negative calcium balance has not been completely reversed. Perhaps the most successful prophylactic measure utilized to date has been dietary supplementation of both calcium and inorganic phosphate. With the wide variety of excellent study tools which are currently available for application to this field, significantly increased efforts are clearly required both to define the basic mechanism of immobilization-induced skeletal losses and to devise new prophylactic or therapeutic approaches.