Jenifer Jowsey

Skeletal Resistance to Parathyroid Hormone in Renal Failure: Studies in 105 Human Subjects

Abstract The effects of an infusion of parathyroid extract on serum calcium and urinary phosphate levels were evaluated in 105 individuals—normal persons, patients with renal failure, patients trea...

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.

Effect of sex hormones on bone in primary osteoporosis

The effect of sex hormones on bone tissue was studied in 12 osteoporotic patients. Surfaces of bone undergoing formation and resorption were determined by quantitative microradiography of iliac crest biopsy samples before and after treatment with estrogens in 11 postmenopausal women and with testosterone in one gonadally competent man. Before treatment, bone resorption was greater than normal in all but one patient and bone formation was normal. After treatment, bone resorption decreased to within the normal range in all patients, and bone formation did not change significantly. Biochemical studies showed significant decreases in serum calcium, phosphorus, and alkaline phosphatase levels and in urinary excretion of calcium and hydroxyproline. These changes are believed to be the consequence of the effect of the hormones on bone. The data indicate that the major effect of sex hormones in osteoporosis is an inhibition of bone resorption.

Femoral Trabecular-Pattern Index for Evaluation of Spinal Osteoporosis

Abstract A simple and universally applicable index based on the roentgenographic pattern of trabecular bone in the upper end of the femur was used to evaluate bone loss in 316 randomly selected con...

Bone and soft tissue changes with oral phosphate supplements

Oral phosphate supplements in divided doses were given to adult dogs for a period of 10 months. Bone density, bone turnover, serum chemistry values, and the calcium content of soft tissues were determined initially and at the end of the experimental period. Serum calcium remained the same; serum phosphate decreased slightly but significantly. The decrease in phosphate was related to an increase, compared with pre-experimental values, in bone resorption which was seen in the terminal ulna and iliac crest bone samples from all dogs. Serum immunoreactive parathyroid hormone was increased (compared with pre-experimental values) after 5 and 10 months of phosphate supplementation; this increase was related to the bone loss and the decrease in serum phosphate. Soft-tissue calcification could be demonstrated histologically in the kidney and in the lens of the eye where it resulted in cataracts. Calcium content increased in the thoracic aorta, kidney, heart, and tendon but not in skeletal muscle. Phosphate supplements in adult dogs appear to produce secondary hyperparathyroidism, bone loss, and calcification of soft tissues.

Hypophosphatemic Osteomalacia Associated with Nonendocrine Tumors

Abstract Two adult men with severe adult-onset hypophosphatemic osteomalacia made spectacular recoveries after removal of small benign sclerosing hemangiomas. In both cases removal of the tumor was followed by an increase in the serum inorganic phosphate to high-normal levels, relief of clinical symptoms and roentgenographic evidence of healing of the osteomalacia. In the second case, removal of the tumor increased serum immunoreactive parathyroid hormone. Some cases of adult-onset hypophosphatemic osteomalacia apparently are directly related to the presence of nonendocrine tumors that elaborate a humoral substance (other than parathyroid hormone) that markedly increases the renal clearance of phosphate, resulting in hypophosphatemia and failure of skeletal mineralization.

Calcium Release from the Skeletons of Rachitic Puppies

The experiment was carried out on 3-month old puppies. Control animals received a diet normal in calcium and vitamin D. The diet for one group of experimental animals was deficient in both calcium and vitamin D, while another experimental group was fed a diet deficient in calcium but with adequate vitamin D. The response of these animals to injected parathyroid extract was evaluated over a 4 month period. The serum calcium response fell after approximately 20 days in both the calcium-deficient (vitamin D-replete) and the calcium- and vitamin D-deficient animals. The effect on the parathyroid response of the addition of calcium or vitamin D in vitamin D- and calcium-deficient animals was also evaluated. The addition of vitamin D to rachitic animals did not restore the response to parathyroid extract; however, in calcium- and vitamin D-deficient animals with normal calcium levels there was a restored response to parathyroid extract. Morphologic studies were made of the bone at various times during the experimental period; the presence of osteoid tissue correlated with the absence of a response to injected parathyroid extract. The results suggest that parathyroid hormone acts independently and requires the presence of mineralized bone for its action in raising the serum calcium. Vitamin D appears to be important in the mineralization of new bone tissue.

Adult-onset vitamin-D-resistant hypophosphatemic osteomalacia. Effect of total parathyroidectomy.

Abstract A 27-year-old man with disabling adult-onset hypophosphatemic osteomalacia was studied in 1947. Because of the failure of large doses of vitamin D, with oral calcium and phosphate supplements, to induce calcium retention on prolonged metabolic balance studies, total parathyroidectomy was performed. Bone healing ensued and subsequently tetany has been easily controlled with modest doses of vitamin D. On restudy in 1968 (after vitamin D had been discontinued) both serum phosphate and renal phosphate clearance were in the range expected in hypoparathyroidism. Intravenous administration of parathyroid hormone reproduced the high phosphate clearance that had been present before parathyroidectomy. The data indicate a causal or permissive role of parathyroid hormone in the renal phosphate leak, hypophosphatemia and osteomalacia in this patient.

Percutaneous biopsy of the iliac crest.

By use of a percutaneous trephine, a relatively large (7.5-mm diameter), full-thickness bone sample can be obtained from the iliac crest under local anesthesia. Such a specimen can be used for histologic evaluation as well as small-volume, bone-grafting procedures. Patient acceptance has been excellent.

New Concept in the Treatment of Osteoporosis

Newly developed technics for investigating osteoporosis have allowed evaluation of therapeutic control. Many agents potentially useful for treatment have been studied. The most promising therapeutic program for postmenopausal and senile osteoporosis is one combining fluoride, calcium and vitam in D.