Parathyroid Hormone and Experimental Osteosclerosis

Kalu, Dike N.; Pennock, J. M.; Doyle, F. H.; Foster, G. V.

doi:10.1016/s0140-6736(70)91271-7

Cited by 138 publications

(33 citation statements)

References 17 publications

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“…PTH was also shown to modulate phospholipid metabolism [21]. It promotes bone formation at low doses in vivo [22][23][24], in addition to its effects on resorption; the net effect of the hormone on bone mass must, therefore, be determined by the balance between these two processes [25,26]. Using histological techniques, it was found that there was an increase in the bone apposition rate, accompanied by an increase in the formation surface, without any increase in the resorption surface, after daily injection of PTH-(1-84) into rats [27].…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, it has been shown that PTH, together with vitamin D3, can be used at low doses for treatment of osteoporosis [30]. Moreover, increased bone formation in hyperparathyroid states in man [31] and animals [23,24] has also been demonstrated. Recently we have shown that the central portion of the PTH molecule increases cell proliferation in chondrocytes [32] and in osteoblasts [33] without affecting cyclic AMP production.…”

Section: Introductionmentioning

confidence: 99%

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Stimulation of cell proliferation in skeletal tissues of the rat by defined parathyroid hormone fragments

Sömjen

Schlüter

Wingender

et al. 1991

Biochemical Journal

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We have found, in previous studies in vitro using skeletal derived cell cultures, that mid-region fragments of human parathyroid hormone (hPTH) stimulate [3H]thymidine incorporation into DNA and increase the specific activity of the brain-type isoenzyme of creatine kinase (CK). These changes occurred without an increase in cyclic AMP formation which is linked to bone resorption. In this study, we found that the mid-region fragment hPTH-(28-48) stimulated CK activity in diaphysis, epiphysis and kidney in a time-and dose-dependent manner, parallel to the effects of the whole molecule bovine (b)PTH-(1-84) and the fully active fragment hPTH-(1-34). The increase caused by hPTH-(28-48) at a dose of 1.25,ug/rat was not less than the 2-fold increase caused by a roughly equimolar concentration of bPTH-(1-84). A significant increase was reached at 1 h after intraperitoneal injection in all cases. All three sequences of PTH caused an increase in [3H]thymidine incorporation into DNA in diaphysis and epiphysis, but not in kidney, 24 h after injection. A fragment further towards the C-terminal, hPTH-(34-47), was inactive compared with an equimolar concentration of the fragment hPTH-(25-39), which stimulated both CK activity and DNA synthesis. These results in vivo are in line with previous findings in vitro; they provide further support for the suggestion that mid-region fragments of the PTH molecule could be used to induce bone formation without incurring the deleterious effect of bone resorption.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stimulation of cell proliferation in skeletal tissues of the rat by defined parathyroid hormone fragments

Sömjen

Schlüter

Wingender

et al. 1991

Biochemical Journal

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“…47CaCl2 dissolved in 5-10 ml of sterile acidified isotonic saline was given by rapid injection into an antecubital vein. Plasma samples were taken from the opposite antecubital vein through an indwelling catheter at 2, 4,6,8,11,15,20,25,30,35,45,60,80, 100, 120, 180, 240, 300, 360, 480, 600, and 720 min, and at 1, 1.5, 2, 3, and 4 d after the isotopic injection. These samples were then analyzed for radioactivity and stable calcium.…”

Section: Methodsmentioning

confidence: 99%

“…It is well known that high doses of parathyroid hormone are catabolic to bone in animals, and excessive secretion of endogenous hormone reduces bone mass in humans and animals. The dose dependence of parathyroid hormone's effects upon bone metabolism in the human skeleton has not been adequately investigated, but multiple investigators have shown that low doses of parathyroid hormone are anabolic for trabecular bone in young rats (3)(4)(5)(6)(7). Repeated injections of the hormone increase trabecular bone in such animals whether they are intact or previously thyroparathyroidectomized (6).…”

mentioning

confidence: 99%

“…The dose dependence of parathyroid hormone's effects upon bone metabolism in the human skeleton has not been adequately investigated, but multiple investigators have shown that low doses of parathyroid hormone are anabolic for trabecular bone in young rats (3)(4)(5)(6)(7). Repeated injections of the hormone increase trabecular bone in such animals whether they are intact or previously thyroparathyroidectomized (6). It has been impossible to evaluate the effects of low doses of parathyroid hormone on trabecular bone mass in humans in the past because the only available material was bovine parathyroid hormone, which provokes neutralizing antibodies in humans after several weeks of injections (8).…”

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confidence: 99%

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Short-term effects of synthetic human parathyroid hormone-(1--34) administration on bone mineral metabolism in osteoporotic patients.

Dm¹,

Neer²,

Potts³

1981

J. Clin. Invest.

120

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A B S T R A C T Since studies in animals and humans have shown that parathyroid hormone can stimulate bone formation and increase trabecular bone, and patients with primary and secondary hyperparathyroidism may exhibit osteosclerosis, we evaluated the effect of short-term administration of human parathyroid hormone, hPTH-(1-34), in patients with osteoporosis.Six patients with osteoporosis underwent detailed studies including blood and urinary measurements of calcium, phosphate, and magnesium; 47Ca kinetic studies; and 18-d balance studies before and during the short-term administration (3-4 wk) of a daily subcutaneous injection of hPTH fragment 1-34 given as 450 or 750 U/dose.The mean fasting plasma calcium values rose slightly after hPTH-(1-34) administration, primarily in the high-dose group. There was no difference in the mean fasting plasma inorganic phosphate levels. The mean daily urinary excretion of calcium and phosphate was significantly increased in patients given the higher dose.In patients given 450 U, net intestinal calcium absorption increased, phosphate absorption increased, calcium balance improved, and phosphate balance improved. In patients given 750 U, calcium balance and phosphate balance worsened.47Ca kinetic studies showed a minimal increase in bone accretion rate, a decrease in the mean transit time of calcium in the exchangeable pools, and a decrease in the exchangeable-pool size. In all six patients there was an increased renal clearance of 47Ca as a result of hPTH-(1-34) administration.These studies indicate that low doses of parathyroid

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The Sclerotic Vertebral Body

Resnick¹

1983

JAMA

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Parathyroid Hormone and Experimental Osteosclerosis

Cited by 138 publications

References 17 publications

Stimulation of cell proliferation in skeletal tissues of the rat by defined parathyroid hormone fragments

Stimulation of cell proliferation in skeletal tissues of the rat by defined parathyroid hormone fragments

Short-term effects of synthetic human parathyroid hormone-(1--34) administration on bone mineral metabolism in osteoporotic patients.

The Sclerotic Vertebral Body

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