Effect of etidronate on bone in orchidectomized and sciatic neurectomized adult rats

Iwamoto, Jun; Takeda, Tsuyoshi; Katsumata, Takashi; Tanaka, Tomoyuki; Ichimura, Shoichi; Toyama, Yoshiaki

doi:10.1016/s8756-3282(01)00687-1

Cited by 29 publications

(18 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, maturation-related gains in bone mass could not be ignored in ORX rats. Furthermore, the effect of ALN and/or ALF on cortical porosity, which could be observed in aged ORX rats (5,20), was not assessed. Therefore, the results of the present study can not be translated into human in terms of men with primary osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Combined Administration of Alendronate and Alfacalcidol on Cancellous Bone Mass of the Tibia in Orchidectomized Rats: A Bone Histomorphometry Study

Iwamoto

Takeda

Matsumoto

et al. 2008

J Nutr Sci Vitaminol

View full text Add to dashboard Cite

SummaryThe purpose of the present study was to examine the effects of combined administration of alendronate (ALN) and alfacalcidol (ALF) on the cancellous and cortical bone mass of the tibia in orchidectomized rats. Fifty male Sprague-Dawley rats, 3 mo of age, were randomized by the stratified weight method into five groups: age-matched control, orchidectomy, and orchidectomy with administration of ALN (2.5 g/kg, s.c., 5 times a week), ALF (0.05 g/kg, p.o., 5 times a week), or ALN ϩ ALF. The total experimental period was 12 wk. Orchidectomy reduced the cancellous bone mass of the proximal tibial metaphysis and maturation-related cortical bone gain of the tibial diaphysis as a result of increased trabecular bone resorption and decreased periosteal bone formation and also increased endocortical bone erosion and formation. ALN suppressed trabecular bone resorption and endocortical bone erosion and formation and increased periosteal bone formation, while ALF increased the number of osteoblasts and suppressed trabecular bone resorption and markedly increased periosteal and endocortical bone formation. Thus, both ALN and ALF prevented the orchidectomy-induced reduction in the cancellous bone mass and maturation-related cortical bone gain. Combined administration of ALN and ALF increased the cancellous bone mass as compared with the values observed in age-matched controls by causing more marked suppression of trabecular bone resorption. The present study showed the beneficial effects of combined administration of ALN and ALF on the cancellous bone mass of the tibia in orchidectomized rats. Key Words orchidectomy, osteopenia, alendronate, alfacalcidol, rat Testosterone is important for skeletal growth during the period of linear growth in males, and is also responsible for maintenance of the skeletal mass in the later stage of life ( 1-3 ). Testosterone deficiency, caused by orchidectomy (ORX), has been reported to induce highturnover cancellous osteopenia and cortical osteopenia with decreased periosteal bone formation in rats ( 4 , 5 ). We clarified, based on the findings in bone specimens obtained from 3-mo-old male Sprague-Dawley (SD) rats, that ORX induced cancellous osteopenia of the proximal tibial metaphysis as a result of increased bone resorption, and reduced maturation-related gain in the cortical bone mass of the tibial diaphysis as a result of decreased periosteal bone formation ( 6 ).Bone growth, bone modeling, and Basic Multi-Cellular Unit (BMU)-based bone remodeling differ between the cortical and cancellous bones. Typically, bone growth and modeling drifts are predominant in cortical bone and can increase the bone mass, whereas bone remodeling occurs primarily in the cancellous bone, and can either conserve or remove bone in contact with the marrow in rats ( 7 ). Bone modeling may add bone mass but can never result in a reduction in the bone mass, whereas bone remodeling usually results in a zero or negative balance of the bone mass. Thus, it was suggested that ORX in 3-mo-old male SD rats resulted in ...

show abstract

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Combined Administration of Alendronate and Alfacalcidol on Cancellous Bone Mass of the Tibia in Orchidectomized Rats: A Bone Histomorphometry Study

Iwamoto

Takeda

Matsumoto

et al. 2008

J Nutr Sci Vitaminol

View full text Add to dashboard Cite

show abstract

“…Also, increased glucocorticoid released as a result of elevated stress may occur in the NX rat, which is not necessarily seen in patients. However, we do not think that increased stress levels increased the degree of bone loss substantially, as aged rats lose 12% of bone 4 weeks after sham NX surgery, 35 while young animals still show increasing bone mass after sham NX surgery as a result of normal growth. 36 Another limitation in our study was the absence of a sham operated group.…”

Section: Discussionmentioning

confidence: 72%

Comparison of bone loss induced by ovariectomy and neurectomy in rats analyzed by in vivo micro‐CT

Brouwers

Lambers

Rietbergen

et al. 2009

Journal Orthopaedic Research

View full text Add to dashboard Cite

ABSTRACT:We hypothesized that osteoporosis due to estrogen deficiency progresses faster than due to disuse and that at the same amount of bone loss, disuse leads to less favorable bone structure and mechanical properties than estrogen deficiency. Adult rats were either ovariectomized (OVX) (n ¼ 9) or neurectomized (NX) (n ¼ 8). At week 0, 1, 2, 3, and 4, in vivo micro-CT scans were made of the proximal tibia. Segmented CT-scans at weeks 0 and 4 were used to build a 3D voxel-based micro finite element model (FEM). Displacement in the longitudinal direction was prescribed at the proximal end leading to a compression step of 1%. The severe reduction in metaphyseal bone volume fraction was not significantly different between OVX and NX. Epiphyseal bone loss was less severe in both groups, and BV/TV was significantly lower after NX. Trabecular separation and degree of anisotropy in the metaphysis and connectivity and trabecular number in the epiphysis were significantly more deteriorated after NX. FEM-derived stiffness decreased in both groups, but more after NX. Osteoporosis due to estrogen-deficiency progressed overall at a rate similar to osteoporosis due to disuse. At the same amount of induced bone loss, disuse led to more deteriorated bone structure and mechanical properties than estrogen deficiency. Keywords: estrogen deficiency; disuse; osteoporosis; rats; in vivo micro-CT Osteoporosis is a degenerative bone disease that can develop with reduced estrogen levels during and after menopause and after long periods of disuse. The rat has been used to study osteoporosis, with estrogen deficiency-associated bone loss induced by ovariectomy (OVX), 1-4 and disuse-associated bone loss induced by sciatic neurectomy (NX), tail suspension, or leg taping. 5,6 Both can severely deteriorate bone structure in these models. Differences exist in cellular activity with these forms of bone loss. 7,8 OVX leads to an increased bone formation and resorption rate, disuse leads to decreased turnover rates and increased bone resorption. [9][10][11] This would suggest that bone loss after OVX might proceed faster than that resulting from disuse.Differences also exist in the resulting deterioration of bone mass and microstructure. 9-17 After estrogen deficiency, bone loss is concentrated in the central part of the metaphysis, whereas disuse leads to overall bone loss. 11,13,17 This finding supports the hypothesis that OVX-induced estrogen deficiency increases the mechanostat threshold, 9 leading to low loaded regions being resorbed first, whereas the main loaded structures would remain. With disuse, however, all bone tissue is unloaded, so a more random pattern of bone loss would be expected. 9 This would suggest that disuse-induced osteoporosis would lead to a more severe loss of the main trabecular structures and thus a more severe loss of stiffness and strength in the main loading direction. Upon reloading, distribution of loads in immobilized bones would be very inhomogeneous, because the adaptation to the loading direction is lost. ...

show abstract

“…However, very few studies have reported the alteration of cancellous bone in the DTM of orchidectomized adult rats, and the comparative response of cancellous bone in the DTM and PTM to antiresorptive agents has rarely been reported, although it was reported that etidronate treatment prevented loss of bone mineral density in the proximal tibia, distal femur, and LVB in ORX rats. 12 The aim of the present study was to compare the response of cancellous bone to ORX and short-term etidronate treatment for ORX-induced cancellous osteopenia among the three skeletal sites, the LVB, PTM, and DTM in adult rats.…”

Section: Introductionmentioning

confidence: 99%

Differential effect of short-term etidronate treatment on three cancellous bone sites in orchidectomized adult rats

Iwamoto

Takeda

Ichimura³

2004

Keio J. Med.

View full text Add to dashboard Cite

Abstract. The aim of the present study was to analyze the effects of short-term treatment with the antiresorptive agent, etidronate, on orchidectomized adult rats, via comparison of three cancellous bone sites, the lumbar vertebral body (LVB), proximal tibial metaphysis (PTM), and distal tibial metaphysis (DTM). Thirty-five male Wistar rats, aged 10 months, were randomly divided into four groups: baseline control (BLC, n F 10), age-matched sham-operated control (AMC, n F 9), orchidectomy (ORX, n F 9), and ORXBetidronate treatment (n F 7). Etidronate treatment (10 mg/kg, daily subcutaneous injection) was initiated 2 weeks after surgery and was continued for 2 weeks. Four weeks after surgery, the 5th LVB, PTM, and DTM were processed for histomorphometric analysis of cancellous bone (secondary spongiosa). ORX resulted in a decrease in body weight. No significant difference in cancellous bone volume (BV/TV) was found between the BLC and AMC groups at any skeletal site. The cancellous BV/TV loss was attributable to increased eroded surface (ES/BS) with no significant alteration in the mineral apposition rate (MAR), at all skeletal sites and etidronate treatment in ORX rats significantly decreased ES/BS to a level not significantly different from that in the AMC group, resulting in complete prevention of ORX-induced cancellous BV/TV loss. The MAR was markedly decreased in the PTM and LVB, but maintained in the DTM by etidronate treatment. The present study showed that etidronate treatment could completely prevent ORX-induced cancellous bone loss regardless skeletal sites by suppressing bone resorption. In particular, suppression of bone formation in terms of osteoblastic activity by etidronate treatment was not evident only in the DTM.

show abstract

Effect of etidronate on bone in orchidectomized and sciatic neurectomized adult rats

Cited by 29 publications

References 33 publications

Beneficial Effects of Combined Administration of Alendronate and Alfacalcidol on Cancellous Bone Mass of the Tibia in Orchidectomized Rats: A Bone Histomorphometry Study

Beneficial Effects of Combined Administration of Alendronate and Alfacalcidol on Cancellous Bone Mass of the Tibia in Orchidectomized Rats: A Bone Histomorphometry Study

Comparison of bone loss induced by ovariectomy and neurectomy in rats analyzed by in vivo micro‐CT

Differential effect of short-term etidronate treatment on three cancellous bone sites in orchidectomized adult rats

Contact Info

Product

Resources

About