The Aged Rat Model of Ovarian Hormone Deficiency Bone Loss*

Kalu, Dike N.; Liu, Chung-Ching; Hardin, Robert R.; Hollis, Bruce W.

doi:10.1210/endo-124-1-7

Cited by 348 publications

(151 citation statements)

References 28 publications

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“…MK-4 has been shown to inhibit bone resorption in a mouse calvaria culture system (22) and en hance the mineralization of osteoblasts in a human cell culture system (23). It is well known that calcium absorp tion from the intestine decreases in ovariectomized rats (24) and in rats that have been treated with steroids (25). In this study, the reduction in calcium balance tended to induce the decrease in bone density, suggesting that cal cium balance plays an important role in bone metabo lism.…”

Section: Discussionmentioning

confidence: 50%

Effects of Menatetrenone on the Decrease in Calcium Balance Induced by Vitamin K-Deficient Diet and Sodium Loading in Rats.

et al. 1994

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ABSTRACT-The effects of menatetrenone (2-methyl-3-tetraprenyl-1,4-naphthoquinone, MK-4) on cal cium balance were studied in male Sprague-Dawley rats. Experiment 1: Rats in metabolic cages that were fed a vitamin K-deficient diet and injected daily with latamoxef (100 mg/kg, i.p.) were either treated or untreated with MK-4 for 7 days. Daily food intake, urine volume and feces weight were determined, and calcium concentration in these samples was measured. Calcium balance was calculated as the difference between calcium intake and urinary and fecal calcium excretion. Cumulative calcium balance in the vitamin K-deficient group treated with latamoxef was lower than that in normal rats; this balance was significantly improved by MK-4 (1 and 10 mg/kg, s.c.) administered for 7 days. Experiment 2: Rats were fed a vitamin K-deficient diet containing 4.6°1o sodium chloride for 6 weeks. MK-4 was administered as a dietary supple ment. Forty-eight-hour calcium balance, determined once a week, was significantly reduced compared with that of normal rats after 3 and 5 weeks; the balance was restored dose-dependently by MK-4 administration (1 and 10 mg/kg). Experiment 3: Rats were subjected to the same experimental conditions as experiment 2 for 6 weeks, and intestinal calcium transport was determined using an everted gut-sac technique. Calcium transport was reduced by the high sodium, vitamin K-deficient diet, and this reduction was restored by MK 4 administration (10 mg/kg). These results suggest that MK-4 improves the reduced calcium balance by increasing intestinal calcium absorption in these rats.

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Section: Discussionmentioning

confidence: 50%

Effects of Menatetrenone on the Decrease in Calcium Balance Induced by Vitamin K-Deficient Diet and Sodium Loading in Rats.

et al. 1994

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“…The present study therefore differed from our previous study (34) which showed a preventive effect of the combination of etidronate and 1a (OH)D 3 on bone loss starting 1 week after OVX in 14-week-old rats. In the present study we ovariectomized 40-week-old rats in whom bone growth and maturation have been completed (35,36), and treatment started 15 weeks after surgery. As a bisphosphonate, this study used alendronate, a more potent and prevalent bisphosphonate than etidronate.…”

Section: Discussionmentioning

confidence: 99%

“…However, the effect shown in the previous study was not curative but preventive for bone loss by OVX, because the application of etidronate and /or 1a (OH)D3 started only one week after the operation. In addition, the rats used in the study were 14-week-old when bone growth and maturation had not yet been completed (35,36). To investigate the curative effect of the combined treatment with bisphosphonates and 1a (OH)D3 on established postmenopausal osteoporosis, in the present study we ovariectomized 40-week-old rats and the application of agents started 15 weeks after the surgery.…”

mentioning

confidence: 99%

Curative Effect of Combined Treatment With Alendronate and 1 α-Hydroxyvitamin D3 on Bone Loss by Ovariectomy in Aged Rats

Ito

Azuma

Takagi

et al. 2002

Japanese Journal of Pharmacology

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ABSTRACT-We investigated the combined effects of alendronate and 1a-hydroxyvitamin D3 (1a(OH)D3) on the bone mass and strength in aged ovariectomized rats and compared them with those of single treatments. Forty-week-old female rats underwent ovariectomy or sham operation, and after 15 weeks, ovariectomized rats were daily administered vehicle alone, alendronate (0.2 or 1.0 mg /kg, p.o.), 1a(OH)D 3 (0.02 mg/kg, p.o.), or the combinations of 0.2 or 1.0 mg /kg of alendronate and 1a(OH)D 3 . After 12 weeks, the groups receiving combined treatments had significantly increased bone density and mechanical strength of the 4th lumbar vertebral body and the midfemur compared to the vehicle-treated group, and the effects were almost equal to or slightly less than the addition of those of the respective single treatments. The increase in mechanical strength was proportional to that in bone mineral density, suggesting that the stimulatory effects of these treatments on bone strength are ascribable primarily to those on bone mass. Analyses of histology, computed tomography, and biochemical markers confirmed the strong effect of the combined treatment on trabecular bone in particular, which was associated with increased trabecular number and decreased bone turnover. We propose that the combination of daily alendronate and 1a (OH)D 3 is clinically promising as a curative treatment of established postmenopausal osteoporosis.Keywords: Combined treatment, Alendronate, 1a -Hydroxyvitamin D3, Ovariectomy, Osteoporosis Estrogen deficiency after menopause is associated with bone loss leading to fractures that constitute a serious health problem in many countries (1). Many bone-sparing drugs have successively been developed for the treatment of postmenopausal osteoporosis (2). However, the effects of the combined treatments of these drugs have not been well investigated despite the fact that postmenopausal osteoporosis is frequently treated with combination therapy.Bisphosphonates, potent anti-resorptive agents, are known to be one of the most reliable and prevalent drugs in osteoporosis treatment. Alendronate (sodium 4-amino-1-hydroxybutilidene-1,1-bisphosphonate trihydrate), an aminobisphosphonate, is well known as a potent inhibitor of osteoclastic bone resorption (3 -5). The efficacy of bisphosphonates has been demonstrated in osteoporosis (6 -8) as well as in various other metabolic bone disorders such as Paget's disease (9) and hypercalcemia of malignancy (10). Alendronate has also been reported to increase the bone mass and strength in ovariectomized (OVX) rats (11 -13). The modes of action of alendronate include suppression of the differentiation of osteoclast precursors (14 -16) and the activation of mature osteoclast function (17), resulting in the decrease in bone turnover. Recent studies on its molecular mechanism show that aminobisphosphonates such as alendronate can inhibit enzymes of the mevalonate pathway (18).Vitamin D and vitamin D derivatives may also have a role in osteoporosis (19), and the activated form of vitam...

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“…Although the ovariectomized rat has been used frequently to demonstrate the loss of trabecular bone volume in the tibia, vertebra, and femur due to aging and estrogen depletion (15)(16)(17), only one study included the rat maxilla (18), and one other (19) included the rat mandible.…”

Section: Discussionmentioning

confidence: 99%