Ralph S. Goldsmith

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.

Etiology of Hyperparathyroidism and Bone Disease during Chronic Hemodialysis. III. 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.

Serum Parathyroid Hormone and Blood Minerals: Interrelationships in Normal Children

Extract: Simultaneous measurements of immunoreactive parathyroid hormone (iPTH), calcium, magnesium, phosphorus, and alkaline phosphatase in serum were performed in 120 normal subjects who ranged from 6 months to 20 years of age. When plotted as a function of age, these extracellular indices of calcium homeostasis showed changes throughout the growth period and differences in their interrelationships in early childhood, middle childhood, and adolescence. Mean serum concentration of minerals was highest during early childhood and decreased parallel to decreases in iPTH and alkaline phosphatase. Between the ages of 6 and 12 years, calcium, magnesium, and phosphorus tended to plateau, iPTH was lower, and alkaline phosphatase increased. During adolescence, calcium, phosphorus, and alkaline phosphatase decreased to adult values, magnesium showed no change, and iPTH increased to adult values.Plasma ionized calcium, which was higher in middle childhood (mean, 4.59 mg/100 ml) than at ages 12 to 20 years (mean, 4.33 mg/100 ml), showed the expected negative correlation with iPTH (P < 0.005). Total serum calcium did not correlate with iPTH; however, the pattern of decrease of serum calcium with age was similar to growth velocity curves, especially in girls, in whom mean serum calcium was higher (9.93 mg/100 ml) between 8 and 16 years than in boys (9.75 mg/100 ml).Speculation: Parathyroid hormone is important in maintaining the concentration of plasma ionized calcium in normal children, but the regulation of total serum calcium is different from that in adults. The total serum calcium or factors regulating it may have a direct or indirect influence on the growth process.

Effects of Hydralazine and High Molecular Weight Dextran upon the Circulatory Responses to Severe Thermal Burns

The greatly depressed cardiac output observed in untreated burned dogs appears to be due to a combination of two factors: (1) a decrease in venous return to the heart associated with a decrease in effective circulating fluid volume and (2) an increase in peripheral resistance. This hypothesis is supported by the observations that administration of a peripheral vasodilator (hydralazine) and minimal fluid volume replacement (high molecular weight dextran in isotonic saline) restore the cardiac output to preburn levels by the fourth postburn hour.

The Chicken or the Egg—Idiopathic Hypercalciuria

Excerpt Ever since the syndrome known as idiopathic hypercalciuria was identified by Flocks (1) and Henneman and associates (2), concern over the possibility that the syndrome was caused by underly...