The Effect of Ethinyloestradiol on Calcium and Phosphorus Metabolism of Post-Menopausal Women with Primary Hyperparathyroidism

Gallagher, J. Christopher; Wilkinson, Robert H.

doi:10.1042/cs0450785

Cited by 32 publications

(20 citation statements)

References 8 publications

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“…This observation supports the general concept that estrogen inhibits bone resorption in vivo (2,3,22,24,28,(35)(36)(37)(38), although in vitro studies showed OVX rats that were infused with 17,3E2 (C and F). Fourteen days after ovariectomy, rats were infused with PBS or 1 nM 1713E2 into the metaphyseal region of the femur for 8 days, 24 ,ul/day.…”

Section: Discussionsupporting

confidence: 69%

“…A major unanswered question is whether estrogen action on bone in vivo is direct or indirect (4,(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). It has been suggested that in vivo estrogen promotes the systemic production of growth factors, so-called estromedins, or the removal of growth inhibitors, estrocolyons, elsewhere in the body (42).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Direct effects of 17 beta-estradiol on trabecular bone in ovariectomized rats.

Takano‐Yamamoto

Rodan

1990

Proc. Natl. Acad. Sci. U.S.A.

163

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High-affinity nuclear binding sites for 17 (3-estradiol (17(3E2) were recently found in bone cells; however, the mechanism by which estrogen exerts its effect on bone in vivo is still unknown. To study if estrogen acts on bone directly, we used an experimental model in which test substances are infused locally into rat femur trabecular bone. SpragueDawley rats weighing 150-160 g were ovariectomized (OVX) and 14 days later a polyethylene tube (1 mm in diameter) connected to an Alzet osmotic minipump was implanted into the distal femur 9 mm from the joint. 17fiE2 (24 pl/day at 0.01-1 nM), 17a-estradiol (17aE2) (24 pl/day at 1 nM), or phosphatebuffered saline (NaCl, 8 g/liter; KCI, 0.2 g/liter; KH2PO4, 0.2 g/liter; Na2HPO4-7H2O, 2.16 g/liter) was infused for 8 days.The contralateral limb remained intact. Animals were sacrificed and bones were examined by histomorphometry. Ovariectomy caused a 50% loss in trabecular bone volume (TBV) in the secondary spongiosa (from 20.3% ± 1.7% to 9.6% + 1.1%; mean ± SEM), a 2-fold increase in osteoclast number (to 4.0 ± 0.4 per mm), a 3-fold increase in relative resorption surfaces (to 24.8% ± 2.9%), a 9-fold increase in osteoblast number (to 11.3 ± 2.1 per mm), and an 8-fold increase in relative osteoid surface (to 9.6% ± 1.7%). The local infusion of 17fiE2 for 8 days into OVX rats (t) restored the TBV dose dependently to 75% and 85% of control (non-OVX) levels, at 0.1 nM and 1 nM 17(3E2, respectively; (it) decreased osteoclast number and the relative resorption surface to control (non-OVX) levels; and (iii) further increased osteoblast number and the relative osteoid surface dose dependently (by 5-fold at 1 nM 173E2). Phosphate-buffered saline infusion was without effect.Infusion of 17ciE2 had no effect on TBV, osteoclast number, or resorption surface but increased slightly the osteoblast number and the osteoid surface. Its potency was 1/100 that of 1713E2. The local infusion of 17fiE2 or 17aE2 had no effect on body or uterine weight. We conclude from these rmdings that estrogen delivered directly to the bone of OVX rats in vivo at 2.4 and 24 fmol/day acted locally to inhibit bone resorption and stimulate bone formation.About 50 years ago, Albright et al.(1) suggested a link between postmenopausal osteoporosis and estrogen deficiency. The lack of estrogen is associated with increased bone remodeling rates, accelerated bone loss, and a negative calcium balance (2). Estrogen replacement therapy decreases bone turnover and the rate ofbone resorption and reduces the occurrence of fractures in postmenopausal osteoporosis. However, the mechanism by which estrogen exerts its effects on bone is still unknown (3,4 2172The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Direct effects of 17 beta-estradiol on trabecular bone in ovariectomized rats.

Takano‐Yamamoto

Rodan

1990

Proc. Natl. Acad. Sci. U.S.A.

163

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“…Oestrogens and androgens rather than progesterone have been shown to affect the skeletal metabolism during its maturation and the bone loss which accompanies ageing (Silberberg & Silberberg, 1971;Dequeker, 1975). Most studies have supported the view that oestrogens and androgens act as inhibitors of bone resorption in vivo (Cmess & Hong, 1976;Gallagher & Wilkinson, 1973). In vitro studies are not conclusive (Atkins, Zanelly, Peacock & Nordin, 1972).…”

Section: Discussionmentioning

confidence: 99%

Effects of pregnancy on bone matrix proteins in Wistar rats

Mbuyi-Muamba

Dequeker

1984

Lab Anim

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SummaryUsing an EDT A extraction procedure, bones from pregnant Wistar rats were analyzed for their content of collagen and non-collagenous components (sialoprotein, proteoglycan and carbohydrate). The bone matrix size was found to be smaller in pregnant rats than in normal rats (19,5% vs 17,5% of the dry weight bone). The EDT A extractability of the bone protein from pregnant rats was higher than that from controls (2'6% vs 1,9% dry weight bone). EDT A extracts from pregnant rats contained higher amounts of soluble collagen (1'6% vs 0·5% of dry weight tissue) and lower amounts of non-collagenous components (1,65% vs 2·23% for hexoses, 2,38% vs 3·95% for sialic acid and 1·24% vs 1,73% for uronic acid). In bone matrix, collagen content was lower in the pregnant rats (9·45% vs 10,6%). Similarly, the amounts of non-collagenous components were slightly decreased in the bone matrix from the pregnant rats. The respective values were: 0·91% vs 0,93% for hexoses, 0·45% vs 0·52% for sialic acid and 0·39% vs 0,50% for uronic acid. These results suggest that in pregnancy collagen and non-collagenous protein content in bone is decreased while the total mineral content is increased.That sex steroids are implicated in bone metabolism is a well known phenomenon (Silberberg & Silberberg, 1971). Oestrogens and androgens rather than progesterone have been shown to affect the skeletal metabolism during its maturation and the bone loss which accompanies ageing (Silberberg & Silberberg,

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“…More frequent administration of parathyroid hormone may be needed to increase intestinal calcium and phosphate absorption. Patients with primary hyperparathyroidism have increased phosphate absorption (56,57), whereas the acute administration of parathyroid hormone to normal subjects does not alter radiophosphorus absorption (58).…”

Section: Discussionmentioning

confidence: 99%

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

show abstract

The Effect of Ethinyloestradiol on Calcium and Phosphorus Metabolism of Post-Menopausal Women with Primary Hyperparathyroidism

Cited by 32 publications

References 8 publications

Direct effects of 17 beta-estradiol on trabecular bone in ovariectomized rats.

Direct effects of 17 beta-estradiol on trabecular bone in ovariectomized rats.

Effects of pregnancy on bone matrix proteins in Wistar rats

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

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