Effects of a diphophonate on calcium metabolism in calcium-deprived rats

1975 ◽  
Vol 228 (6) ◽  
pp. 1750-1756 ◽  
Author(s):  
DB Morgan ◽  
A Gasser ◽  
U Largiader ◽  
A Jung ◽  
H Fleisch
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Bone Formation ◽  
Kinetic Parameters ◽  
Calcium Intake ◽  
Calcium Metabolism ◽  
Published Data ◽  
Efficient Mechanism ◽  
Growing Rats ◽  
Inhibit Bone Resorption

Calcium metabolism was studied in growing rats, submitted to calcium deprivation ofvarious intensity. A decreased intake resulted in decreased net absorption of calcium(V'na), no change in bone formation (V'o+), and an increase in bone resorption (V'o -). In animals given dichloromethylene disphosphate (Cl'2MDP), a compoundknown to inhibit bone resorption, V'o+ was less than in the controls but again the same at all calcium intakes; V'na was below V'o+, V'o- still increased as the calcium intake was reduced. The various kinetic parameters in rats receiving Cl'2MDPwere indistinguishable from published data in parathyroidectomized (PTX) animals, yetblood calcium was low in PTX rats but normal in Cl'2MDP-atreated rats. It appears that the rat has an efficient mechanism for increasing bone resorption which is not inhibited by Cl'2MDP and does not require parathyroid hormone.

Role of parathyroid hormone in regulation of main calcium fluxes in rats.

1977 ◽  
Vol 232 (6) ◽  
pp. E535
Author(s):  
B Haldimann ◽  
J P Bonjour ◽  
H Fleisch
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Linear Correlation ◽  
Constant Amount ◽  
Calcium Fluxes ◽  
Growing Rats

The effect of calcium deprivation on the various calcium fluxes was studied in growing rats either sham-operated (SHAM), thyroparathyroidectomized (TPTX), or thyroparathyroidectomized and supplemented with parathyroid hormone (PTH) (TPTX + PTH). In SHAM rats a decrease in the net absorption of calcium (Vna) has no influence on calcemia or on bone formation (Vo+), but leads to an increase in bone resorption (Vo-). In TPTX rats a decrease in Vna induces a decrease in calcemia and in Vo+ but still causes an increase in Vo-. The same is true in TPTX + PTH rats although all the variables measured are increased. In TPTX rats, both without and with PTH, a linear correlation exists between calcemia and Vo+ suggesting that calcemia influences bone formation. Furthermore, it appears that PTH is important in regulating bone turnover, but that the adaptation of Vo- to a change in Vna can occur in the absence or in the presence of a constant amount of this hormone. The mechanism of regulating this adaptation of bone resorption is still unknown.

scholarly journals SLPI is a critical mediator that controls PTH-induced bone formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Akito Morimoto ◽  
Junichi Kikuta ◽  
Keizo Nishikawa ◽  
Takao Sudo ◽  
Maki Uenaka ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Bone Formation ◽  
Protease Inhibitor ◽  
Bone Metabolism ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Bone Imaging ◽  
Genetic Ablation

AbstractOsteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although it is unclear how these cells are coordinately regulated by PTH. Here, we identify a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a critical mediator that is involved in the PTH-mediated shift to the osteoblastic phase. Slpi is highly upregulated in osteoblasts by PTH, while genetic ablation of Slpi severely impairs PTH-induced bone formation. Slpi induction in osteoblasts enhances its differentiation, and increases osteoblast–osteoclast contact, thereby suppressing osteoclastic function. Intravital bone imaging reveals that the PTH-mediated association between osteoblasts and osteoclasts is disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism.

scholarly journals SIKs control osteocyte responses to parathyroid hormone

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Marc N. Wein ◽  
Yanke Liang ◽  
Olga Goransson ◽  
Thomas B. Sundberg ◽  
Jinhua Wang ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Bone Formation ◽  
Small Molecule ◽  
Nuclear Translocation ◽  
Rna Seq ◽  
Once Daily ◽  
Skeletal Effects ◽  
Stimulation Of

Abstract Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH.

scholarly journals INTAKE OF A VITAMIN-MINERAL COMPLEX IS A RATIONAL WAY TO MAKE UP A CALCIUM DEFICIENCY IN CONDITIONS OF INSUFFICIENT CONSUMPTION OF DAIRY PRODUCTS BY A CHILD

2018 ◽  
Vol 17 (3) ◽  
pp. 200-206 ◽  
Author(s):  
Evgenia V. Shikh ◽  
Anna A. Makhova ◽  
Evgeny E. Emelyashenkov
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Bone Formation ◽  
Calcium Intake ◽  
Dairy Products ◽  
Milk Protein ◽  
Calcium Deficiency ◽  
Food Sources ◽  
Lactase Deficiency ◽  
Milk And Dairy Products

A calcium deficiency is detected in more than 80% of children. This is the result of inadequate consumption of milk and dairy products which are the main food sources of calcium. There is a correlation between deficiency of calcium intake with food in childhood and the risk of osteopenia and osteoporosis in subsequent life periods. With insufficient exogenous intake of calcium, its concentration in the blood decreases which stimulates bone resorption. The factors that further limit the consumption of dairy products are lactase deficiency and cow's milk protein allergy. In order to ensure the intake of the necessary amount of calcium, it is advisable to use vitaminmineral complexes in children that contain not only a sufficient amount of calcium and vitamin D but also other micronutrients required for bone formation.

Disuse osteopenia is accompanied by downregulation of gene expression for bone proteins in growing rats

2006 ◽  
Vol 263 (6) ◽  
pp. E1029-E1034
Author(s):  
G. K. Wakley ◽  
J. S. Portwood ◽  
R. T. Turner
Keyword(s):  
Bone Resorption ◽  
Sciatic Nerve ◽  
Bone Formation ◽  
Type I ◽  
Mrna Levels ◽  
Nerve Section ◽  
Bone Formation Rate ◽  
Growing Rats ◽  
Bone Proteins ◽  
Sciatic Neurectomy

Unilateral sciatic neurectomy (USN) resulted in cortical osteopenia in tibiae from the sciatic nerve-sectioned limb of growing rats. The bone deficit resulted from decreased periosteal addition; there were no changes in the indexes of bone resorption. The periosteal bone formation rate was reduced in the nerve-sectioned limb within 7 days of sciatic neurectomy, and this decrease persisted for at least 56 days. Steady-state mRNA levels for bone proteins were determined in periosteum isolated from tibiae and femurs 7 and 14 days after sciatic nerve section. Nerve section resulted in decreased levels of mRNA for osteocalcin, alkaline phosphatase, and possibly the prepro-alpha (I)-subunit of type I collagen (collagen). The effects were more pronounced in tibiae than femurs, corresponding to the greater degree of immobility induced by USN in the former bone. The results demonstrate that decreased bone formation precedes establishment of disuse cortical osteopenia in growing rats with no evidence for a change in bone resorption. Furthermore, the decreased bone formation is associated with, and may be due to, reduced mRNA levels for matrix proteins and other important bone proteins.

scholarly journals Possible evidence of pregnancy and or famine in an ancient nubian female

2005 ◽  
Vol 80 (1) ◽  
Author(s):  
John Denton ◽  
Jennifer Mann ◽  
Ann Rosalie David
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Physical Exercise ◽  
Bone Tissue ◽  
Calcium Intake ◽  
Nutritional Quality ◽  
Bone Cells ◽  
Mechanical Stresses ◽  
Bone Apposition ◽  
Blood Calcium

A female Nubian femur from the Manchester Mummy Collection exhibits periodic features of bone resorption, bone apposition and then bone resorption as demonstrated by bone histology. Bone is a metabolically active, dynamic, structural tissue whose development and maintenance is influenced by many factors, including nutrition, sunlight, hormonal secretions, and physical exercise. When biochemical or mechanical stresses occur bone cells respond either producing or resorbing bone. When food becomes scarce or of poor nutritional quality, for example in times of famine or flood, malnutrition and concurrent low calcium intake occur. In low blood calcium conditions, parathyroid hormone is released. This stimulates osteoclasts to break down bone tissue. When nutritional state normalises, bone is laid down again and this cycle recurs. Additionally, during pregnancy there is profound resorbtion of the maternal skeleton in order that the foetus may thrive. The condition of the observed bone is consistent with such cyclic events.

scholarly journals Sinusoidal electromagnetic fields promote bone formation and inhibit bone resorption in rat femoral tissuesin vitro

2014 ◽  
Vol 35 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Jian Zhou ◽  
Xiao-Ni Ma ◽  
Yu-hai Gao ◽  
Juan-Li Yan ◽  
Wen-Gui Shi ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Electromagnetic Fields ◽  
Inhibit Bone Resorption

scholarly journals Increased calcium intake does not completely counteract the effects of increased phosphorus intake on bone: an acute dose–response study in healthy females

2007 ◽  
Vol 99 (4) ◽  
pp. 832-839 ◽  
Author(s):  
Virpi E. Kemi ◽  
Merja U. M. Kärkkäinen ◽  
Heini J. Karp ◽  
Kalevi A. E. Laitinen ◽  
Christel J. E. Lamberg-Allardt
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Bone Formation ◽  
Dose Response ◽  
Hormone Secretion ◽  
High Serum ◽  
Dietary Guidelines ◽  
Controlled Study ◽  
Bone Resorption Marker ◽  
Type I

A high dietary P intake is suggested to have negative effects on bone through increased parathyroid hormone secretion, as high serum parathyroid hormone (S-PTH) concentration increases bone resorption. In many countries the P intake is 2- to 3-fold above dietary guidelines, whereas Ca intake is too low. This combination may not be optimal for bone health. In a previous controlled study, we found that dietary P dose-dependently increased S-PTH and bone resorption and decreased bone formation. The aim of the present study was to investigate the dose–response effects of Ca intake on Ca and bone metabolism with a dietary P intake higher than recommended. Each of the twelve healthy female subjects aged 21–40 years attended three 24-h study sessions, which were randomized with regard to a Ca dose of 0 (control day), 600 or 1200 mg, and each subject served as her own control. The meals on each study day provided 1850 mg P and 480 mg Ca. S-PTH concentration decreased (P < 0·001) and serum ionized Ca concentration increased (P < 0·001) with increasing Ca doses. The bone formation marker, serum bone-specific alkaline phosphatase, did not differ significantly (P = 0·4). By contrast, the bone resorption marker, urinary N-terminal telopeptide of collagen type I, decreased significantly with both Ca doses (P = 0·008). When P intake was above current recommendations, increased Ca intake was beneficial for bone, as indicated by decreased S-PTH concentration and bone resorption. However, not even a high Ca intake could affect bone formation when P intake was excessive.

Effect of 1α,24(R)-dihydroxyvitamin D3 on calcium metabolism in the rat

1986 ◽  
Vol 111 (4) ◽  
pp. 572-576 ◽  
Author(s):  
S. Yamada ◽  
J.-P. Bonjour ◽  
H. Fleisch
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Bone Formation ◽  
Urinary Excretion ◽  
Intestinal Absorption ◽  
Calcium Metabolism ◽  
Significant Rise ◽  
Whole Body ◽  
Dihydroxyvitamin D3 ◽  
Vitamin D Analogue

Abstract. It has been suggested that 1α,24(R)-dihy droxyvitamin D3 (1,24(OH)2D3), a chemically synthesized vitamin D analogue, may have the property to enhance whole-body Ca retention and may thus be of use in osteoporosis. In order to test this hypothesis the main fluxes of Ca metabolism were measured in vitamin D-replete rats injected ip with 1,24(OH)2D3 at daily doses of 25, 50 and 100 pmol for 10 days. As compared with pair fed control animals, rats treated with 1,24(OH)2D3 displayed a significant rise in net intestinal absorption of Ca and in urinary excretion of Ca, and increase in bone resorption but no significant change in bone formation. Whole body Ca retention was not changed at 25 pmol/day and showed a trend to decrease at 50 and 100 pmol/day. In conclusion these results do not suggest that among available vitamin D analogues, 1,24(OH)2D3 would be particularly useful for increasing bone Ca retention in osteoporosis.

Disuse osteopenia is accompanied by downregulation of gene expression for bone proteins in growing rats

1992 ◽  
Vol 263 (6) ◽  
pp. E1029-E1034 ◽  
Author(s):  
G. K. Wakley ◽  
J. S. Portwood ◽  
R. T. Turner
Keyword(s):  
Bone Resorption ◽  
Sciatic Nerve ◽  
Bone Formation ◽  
Type I ◽  
Mrna Levels ◽  
Nerve Section ◽  
Bone Formation Rate ◽  
Growing Rats ◽  
Bone Proteins ◽  
Sciatic Neurectomy

Unilateral sciatic neurectomy (USN) resulted in cortical osteopenia in tibiae from the sciatic nerve-sectioned limb of growing rats. The bone deficit resulted from decreased periosteal addition; there were no changes in the indexes of bone resorption. The periosteal bone formation rate was reduced in the nerve-sectioned limb within 7 days of sciatic neurectomy, and this decrease persisted for at least 56 days. Steady-state mRNA levels for bone proteins were determined in periosteum isolated from tibiae and femurs 7 and 14 days after sciatic nerve section. Nerve section resulted in decreased levels of mRNA for osteocalcin, alkaline phosphatase, and possibly the prepro-alpha (I)-subunit of type I collagen (collagen). The effects were more pronounced in tibiae than femurs, corresponding to the greater degree of immobility induced by USN in the former bone. The results demonstrate that decreased bone formation precedes establishment of disuse cortical osteopenia in growing rats with no evidence for a change in bone resorption. Furthermore, the decreased bone formation is associated with, and may be due to, reduced mRNA levels for matrix proteins and other important bone proteins.

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