Dietary Calcium Supplementation Suppresses Bone Formation in Magnesium-Deficient Rats

2006 ◽  
Vol 76 (3) ◽  
pp. 111-116 ◽  
Author(s):  
Hiroshi Matsuzaki ◽  
Misao Miwa

The purpose of this study was to clarify the effects of dietary calcium (Ca) supplementation on bone metabolism of magnesium (Mg)-deficient rats. Male Wistar rats were randomized by weight into three groups, and fed a control diet (control group), a Mg-deficient diet (Mg- group) or a Mg-deficient diet having twice the control Ca concentrations (Mg-2Ca group) for 14 days. Trabecular bone volume was significantly lower in the Mg - and Mg-2Ca groups than in the control group. Trabecular number was also significantly lower in the Mg - and Mg-2Ca groups than in the control group. Mineralizing bone surface, mineral apposition rate (MAR), and surface referent bone formation rate (BFR/BS) were significantly lower in the Mg - and Mg-2Ca groups than in the control group. Furthermore, MAR and BFR/BS were significantly lower in the Mg-2Ca group than in the Mg - group. These results suggest that dietary Ca supplementation suppresses bone formation in Mg-deficient rats.

2007 ◽  
Vol 35 (01) ◽  
pp. 89-101 ◽  
Author(s):  
Wenping Zhang ◽  
Masayuki Kanehara ◽  
Yanjun Zhang ◽  
Xiaoming Wang ◽  
Torao Ishida

We investigated whether treatments with beta-blockers or other administrations that have similar actions to β-blockers, such as Chinese herbs or needling, were effective in treating osteoporosis induced by ovariectomy (OVX). Female Wister rats were divided into five groups: a sham-operated control group treated with vehicle (Sham, n = 8), an ovariectomized (OVX) group treated with vehicle (Model, n = 8), an OVX group administered with propranolol (Pro, n = 10), an OVX group administered an ethanol extract of Fructus Citri Sarcodactylis (Fcs, n = 9), and an OVX punctured at Sanyinjiao (SP-6) and Neiguan (PC-6) (Needling, n = 8). The treatment started when rats were 12 weeks old and continued for 24 weeks. Serum osteocalcin and urinary deoxypyridinoline (Dpd) levels were upregulated in rats in response to OVX, together with a significantly decreased BMD and trabecular bone area. The Pro, Fcs and Needling treatment improved the decreased BMD and the trabecular area, increased the trabecular number, lowered the trabecular separation to some extent as well as significantly depressed the urinary Dpd levels ( p < 0.05). The bone formation markers, such as the mineralizing surface, mineral apposition rate and bone formation rate were not significantly changed, along with a slightly higher trend of osteocalcin levels when compared with the Model rats. The slower heart rate and lower plasma NE levels in these therapeutic groups were also found. Our results suggested that propranolol, Fcs and needling on Sanyinjiao (SP-6) and Neiguan (PC-6) may improve the bone mass of OVX rats, and it provides an alternative and potential therapy for the prevention of postmenopausal osteoporosis.


1992 ◽  
Vol 133 (2) ◽  
pp. 189-195 ◽  
Author(s):  
J. W. M. Chow ◽  
J. M. Lean ◽  
T. Abe ◽  
T. J. Chambers

ABSTRACT We have previously demonstrated that administration of oestrogen, at doses sufficient to raise serum concentrations to those seen in late pregnancy, increases trabecular bone formation in the metaphysis of adult rats. To determine whether prostaglandins (PGs), which have been shown to induce osteogenesis in vivo, play a role in the induction of bone formation by oestrogen, 13-week-old female rats were given daily doses of 4 mg 17β-oestradiol (OE2)/kg for 17 days, alone or with indomethacin (1 mg/kg). The rats were also given double fluorochrome labels and at the end of the experiment tibias were subjected to histomorphometric assessment. Treatment with OE2 suppressed longitudinal bone growth and increased uterine wet weight, as expected, and neither response was affected by indomethacin. Oestrogen also induced a threefold increase in trabecular bone formation in the proximal tibial metaphysis, which resulted in a substantial increase in trabecular bone volume. As previously observed, the increase in bone formation was predominantly due to an increase in osteoblast recruitment (as judged by an increase in the percentage of bone surface showing double fluorochrome labels), with only a minor increase in the activity of mature osteoblasts (as judged by the mineral apposition rate). Indomethacin abolished the increase in osteoblastic recruitment, but the activity of mature osteoblastic cells remained high. The bone formation rate and bone volume remained similar to controls. The results suggest that PG production may be necessary for the increased osteoblastic recruitment induced by oestrogen, but not to mediate the effects of oestrogen on the activity of mature osteoblasts. Journal of Endocrinology (1992) 133, 189–195


1998 ◽  
Vol 12 (1) ◽  
pp. 71-75 ◽  
Author(s):  
S. Williams ◽  
A. Wakisaka ◽  
Q.Q. Zeng ◽  
J. Barnes ◽  
S. Seyedin ◽  
...  

The effect of oral minocycline on osteopenia in ovariectomized (OVX) old rats was examined in this study. Rats were divided into 4 groups: sham-operated, OVX followed by treatment with vehicle, minocycline, or 17β-estradiol. The treatment was initiated one day after OVX and proceeded for 8 wks. OVX reduced bone mineral density (BMD) in the whole femur and in the femoral regions that are enriched in trabecular bone. Treatment with minocycline or estrogen prevented a decrease in BMD. Femoral trabecular bone area, trabecular number, and trabecular thickness were reduced, and trabecular separation was increased by OVX. Treatment with minocycline or estrogen abolished the detrimental effects induced by OVX. OVX also reduced indices that reflect the interconnectivity of trabecular bone, and the loss of trabecular connectivity was prevented by treatment with minocycline or estrogen. Based on the levels of urinary pyridinoline, we showed that the effect of estrogen, but not minocycline, was primarily through its inhibitory effect on bone resorption. Analysis of bone turnover activity suggests that OVX increased parameters associated with bone resorption (eroded surface) and formation (osteoid surface, mineralizing surface, mineral apposition rate, and bone formation rate). Treatment with minocycline reduced bone resorption modestly and stimulated bone formation substantially. In contrast, treatment with estrogen drastically reduced parameters associated with both bone resorption and formation. We have concluded that oral minocycline can effectively prevent the decrease in BMD and trabecular bone through its dual effects on bone resorption and formation.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ima Nirwana Soelaiman ◽  
Wang Ming ◽  
Roshayati Abu Bakar ◽  
Nursyahrina Atiqah Hashnan ◽  
Hanif Mohd Ali ◽  
...  

Postmenopausal osteoporosis is the commonest cause of osteoporosis. It is associated with increased free radical activity induced by the oestrogen-deficient state. Therefore, supplementation with palm-oil-derived tocotrienols, a potent antioxidant, should be able to prevent this bone loss. Our earlier studies have shown that tocotrienol was able to prevent and even reverse osteoporosis due to various factors, including oestrogen deficiency. In this study we compared the effects of supplementation with palm tocotrienol mixture or calcium on bone biomarkers and bone formation rate in ovariectomised (oestrogen-deficient) female rats. Our results showed that palm tocotrienols significantly increased bone formation in oestrogen-deficient rats, seen by increased double-labeled surface (dLS/Bs), reduced single-labeled surface (sLS/BS), increased mineralizing surface (MS/BS), increased mineral apposition rate (MAR), and an overall increase in bone formation rate (BFR/BS). These effects were not seen in the group supplemented with calcium. However, no significant changes were seen in the serum levels of the bone biomarkers, osteocalcin, and cross-linked C-telopeptide of type I collagen, CTX. In conclusion, palm tocotrienol is more effective than calcium in preventing oestrogen-deficient bone loss. Further studies are needed to determine the potential of tocotrienol as an antiosteoporotic agent.


1999 ◽  
Vol 276 (1) ◽  
pp. E62-E69 ◽  
Author(s):  
Walter Dehority ◽  
Bernard P. Halloran ◽  
Daniel D. Bikle ◽  
Tracy Curren ◽  
Paul J. Kostenuik ◽  
...  

To determine whether the rat hindlimb elevation model can be used to study the effects of spaceflight and loss of gravitational loading on bone in the adult animal, and to examine the effects of age on bone responsiveness to mechanical loading, we studied 6-mo-old rats subjected to hindlimb elevation for up to 5 wk. Loss of weight bearing in the adult induced a mild hypercalcemia, diminished serum 1,25-dihydroxyvitamin D, decreased vertebral bone mass, and blunted the otherwise normal increase in femoral mass associated with bone maturation. Unloading decreased osteoblast numbers and reduced periosteal and cancellous bone formation but had no effect on bone resorption. Mineralizing surface, mineral apposition rate, and bone formation rate decreased during unloading. Our results demonstrate the utility of the adult rat hindlimb elevation model as a means of simulating the loss of gravitational loading on the skeleton, and they show that the effects of nonweight bearing are prolonged and have a greater relative effect on bone formation in the adult than in the young growing animal.


2006 ◽  
Vol 101 (3) ◽  
pp. 881-886 ◽  
Author(s):  
Russell T. Turner ◽  
Sutada Lotinun ◽  
Theresa E. Hefferan ◽  
Emily Morey-Holton

Intermittent treatment with parathyroid hormone (PTH) increases bone formation and prevents bone loss in hindlimb-unloaded (HLU) rats. However, the mechanisms of action of PTH are incompletely known. To explore possible interactions between weight bearing and PTH, we treated 6-mo-old weight-bearing and HLU rats with a human therapeutic dose (1 μg·kg−1·day−1) of human PTH(1–34) (hPTH). Cortical and cancellous bone formation was measured in tibia at the diaphysis proximal to the tibia-fibula synostosis and at the proximal metaphysis, respectively. Two weeks of hindlimb unloading resulted in a dramatic decrease in the rate of bone formation at both skeletal sites, which was prevented by PTH treatment at the cancellous site only. In contrast, PTH treatment increased cortical as well as cancellous bone formation in weight-bearing rats. Two-way ANOVA revealed that hPTH and HLU had independent and opposite effects on all histomorphometric indexes of bone formation [mineral apposition rate (MAR), double-labeled perimeter (dLPm), and bone formation rate (BFR)] at both skeletal sites. The bone anabolic effects of weight bearing and hPTH on dLPm and BFR at the cortical site were additive, as were the effects on MAR at the cancellous site. In contrast, weight bearing and hPTH resulted in synergistic increases in cortical bone MAR and cancellous bone dLPm and BFR. We conclude that weight bearing and PTH act cooperatively to increase bone formation by resulting in site-specific additive and synergistic increases in indexes of osteoblast number and activity, suggesting that weight-bearing exercise targeted to osteopenic skeletal sites may improve the efficacy of PTH therapy for osteoporosis.


1993 ◽  
Vol 264 (2) ◽  
pp. E182-E189 ◽  
Author(s):  
J. K. Yeh ◽  
C. C. Liu ◽  
J. F. Aloia

The influence of physical activity on bone formation and resorption was studied in the following three groups of 6-wk-old female rats: 30 controls, 24 sciatic denervation immobilized, and 28 treadmill exercised. Bone formation and resorption were determined from 45Ca retention, 45Ca excretion, bone calcium content, bone volume, and resorbing surface and bone formation rate assessed by tetracycline labeling. 45Ca (30 microCi) was administered intravenously to each animal before study, and the excretion of isotope in the urine and feces was then determined during the 6-wk experimental period. Exercise resulted in an initial increase in total excretion of 45Ca (P < 0.01) followed by a drop to below control levels (P < 0.001). The femoral 45Ca retention and calcium content of the exercised group were higher than that of the control group at week 6. Periosteal bone formation rate in the tibia was enhanced during days 32–41 (P < 0.01). With immobilization, the weekly excretion of 45Ca was persistently higher (P < 0.01), and the femoral 45Ca retention (P < 0.05) and calcium content (P < 0.01) were lower than the control group. Periosteal and endosteal bone formation rates were lower than in the controls over the first 31 days. In conclusion, exercise in young growing rats is associated with an initial increase and then a decrease in bone resorption while active bone formation is sustained. Immobilization for 6 wk results in an increase in bone resorption and a rapid fall in bone formation.


1994 ◽  
Vol 142 (1) ◽  
pp. 119-125 ◽  
Author(s):  
J M Lean ◽  
J W M Chow ◽  
T J Chambers

Abstract We have recently found that administration of oestradiol-17β (OE2) to rats stimulates trabecular bone formation. It is not known, however, whether oestrogen has a similar action on bone formation rate under physiological circumstances. Oestrogen is known to suppress bone resorption, and oestrogen-deficient states in the rat, as in humans, are associated with an increase in bone resorption that entrains an increase in bone formation. To see if the latter masks a relative reduction in bone formation, due to oestrogen deficiency, we measured bone formation very early after ovariectomy, before the resorption-induced increase in bone formation becomes established. To do this, rats were administered fluorochrome labels before and after ovariectomy, spaced at weekly intervals in the first, and 3-day intervals in the second experiment. In both experiments there was a decrease in indices of bone formation in the labelling interval immediately following ovariectomy such that, using the shorter fluorochrome intervals, the mineral apposition rate fell to 69%, the double-labelled surface to 45%, and the bone formation rate to 36% of sham-ovariectomized levels. The reduction was not sustained in the subsequent label intervals, presumably masked by the increase in bone formation attributable to increased resorption. These results suggest that if bone formation is assessed before this resorption-entrained increase in bone formation occurs, oestrogen deficiency is associated with a reduction in dynamic indices of bone formation. Thus, these experiments suggest that oestrogen stimulates bone formation under physiological circumstances, and that the osteopaenia that follows oestrogen deficiency may be attributable not only to an increase in bone resorption, but also to a relative deficiency in bone formation. Journal of Endocrinology (1994) 142, 119–125


2008 ◽  
Vol 104 (4) ◽  
pp. 1086-1093 ◽  
Author(s):  
Kyunghwa Baek ◽  
Alicia A. Barlow ◽  
Matt R. Allen ◽  
Susan A. Bloomfield

Leptin is responsible for linking energy metabolism to bone mass. Because astronauts are commonly in negative energy balance during spaceflight, this study was designed to assess individual and combined effects of food restriction and simulated microgravity on bone mass and serum leptin. Six-month-old male Sprague-Dawley rats were randomly assigned to four groups ( n = 12 each): two hindlimb-unloading (HU) groups fed 100% (HU100) and 70% (HU70) and two cage-activity control (CC) groups fed 100% (CC100) and 70% (CC70) of their baseline food requirement. After 28 days, CC100 rats gained body weight, whereas all other groups lost body weight; this loss was greater in HU70 than in CC70 and HU100 rats. Serum leptin decreased in CC70 and HU100 (−60% and −27%, respectively) and was not detectable in HU70 animals. Percent osteoid surface in CC70 and HU100 was lower than that of CC100 (7.80%, 8.60% vs. 10.70%, respectively), and this decrease was more pronounced in HU70 animals (4.38%). Mineral apposition rate of CC70, HU100, and HU70 rats was lower than that of CC100 (1.5, 1.6, and 1.5 vs. 2.1 μm/day, respectively). Bone formation rate of CC70, HU100, and HU70 rats was lower than that of CC100 (13.4, 13.1, and 12.2 vs. 40.8 mm3·mm−2·day−1, respectively). The change in bone formation rate was correlated with the change in serum leptin value over 28 days ( r2 = 0.69, P = 0.0007). We conclude that moderate caloric restriction may cause bone loss at susceptible bone sites to a similar degree as does the unloading effect of microgravity; serum leptin may be an important endocrine regulator contributing to this change in skeletal integrity.


2000 ◽  
Vol 88 (6) ◽  
pp. 1943-1948 ◽  
Author(s):  
D. M. Cullen ◽  
R. T. Smith ◽  
M. P. Akhter

Increased mechanical loading of bone with the rat tibia four-point bending device stimulates bone formation on periosteal and endocortical surfaces. With long-term loading cell activity diminishes, and it has been reported that early gains in bone size may reverse. This study examined the time course for bone cellular and structural response after 6, 12, and 18 wk of loading at 1,200–1,700 microstrain (με). Bone formation rates, measured by histomorphometry, were compared within groups, between loaded and contralateral nonloaded tibiae, and between weeks. Formation surface, mineral apposition rate, and bone formation rate on periosteal and endocortical surfaces were elevated after 6 wk of loading. By 12 wk of loading, periosteal and endocortical formation surface and endocortical mineral apposition rates were elevated. By 18 wk of loading, periosteal adaptation appeared complete, whereas endocortical mineral apposition rate remained elevated. No periosteal resorption was observed. Average thickness of new bone formed, from baseline to collection, was greater in loaded than nonloaded tibiae by week 6 and was maintained through week 18. Early increases in bone formation result in periosteal apposition of new bone that persists after formation ceases.


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