The effects of ovarian transplantation on bone loss in ovariectomized rats

1994 ◽  
Vol 142 (1) ◽  
pp. 187-192 ◽  
Author(s):  
J H Tobias ◽  
T J Chambers ◽  
A Gallagher

Abstract Although hormone replacement therapy can prevent postmenopausal bone loss, it does not restore bone mass to normal in patients with established osteoporosis. This might reflect a failure to reproduce certain aspects of gonadal function. One method of investigating this possibility would be to examine the effect of ovarian transplantation on the skeleton of osteopaenic ovariectomized rats. However, ovarian transplantation may not fully restore ovarian function to normal, and it is not known whether transplanted ovaries reproduce the action of native ovaries on the skeleton. Therefore, we investigated whether renal capsular or subcutaneous ovarian transplants prevent the effects of ovariectomy on histomorphometric indices of rat tibiae over 44 days. Daily vaginal smears showed that oestrous cycles returned in all but two of 25 animals receiving ovarian transplants. We found that ovarian transplantation prevented the reduction in cancellous bone volume following ovariectomy. While trabecular number was reduced in ovariectomized animals receiving renal capsular ovarian transplants compared to intact animals, trabecular thickness was increased in both transplant groups. Ovarian transplantation also prevented the increase in cancellous and cortical bone formation, cancellous bone resorption and longitudinal growth rate caused by ovariectomy. We conclude that restoration of ovarian function by ovarian transplantation largely prevents the effects of ovariectomy on histomorphometric indices of rat tibiae, suggesting that transplanted ovaries can substitute for the action of native ovaries on the skeleton. Journal of Endocrinology (1994) 142, 187–192

1995 ◽  
Vol 133 (4) ◽  
pp. 483-488 ◽  
Author(s):  
Andrea C Gallagher ◽  
Timothy J Chambers ◽  
Jonathan H Tobias

Gallagher AC, Chambers TJ, Tobias JH. Distinct effects of ovarian transplantation and exogenous 17 β-oestradiol on cancellous bone of osteopenic ovariectomized rats. Eur J Endocrinol 1995;133:483–8. ISSN 0804–4643 Although 17 β-oestradiol (E2) is known to prevent bone loss, prolonged administration of E2 is unable to reverse this in female rats rendered osteopenic by ovariectomy. To determine whether this reflects a failure to replace other components of ovarian function involved in bone metabolism, we compared the effects of administering E2 to osteopenic ovariectomized (ovx) rats with those of ovarian transplantation. Ovariectomy was performed in female rats. After 13 weeks, by which time marked bone loss had occurred, one group of ovx animals received ovaries from donor rats, and, after a delay of 2 weeks to allow oestrus cycles to return, a further group received E2 5 μg · kg−1 · day−1 for 9 weeks. The dose of E2 was chosen as that which in preliminary studies restored mean serum E2 levels to that of intact female rats. The study was terminated 24 weeks after ovariectomy. Both E2 and ovarian transplantation largely restored indices of oestrogenic exposure in ovx rats to those of sham-ovx animals. Animals receiving ovarian transplants also showed a small increase in serum progesterone and full restoration of serum testosterone. However, while ovarian transplantation also returned indices of cancellous bone metabolism to those of sham-ovx animals, there was little increase in bone volume. Interestingly, exogenous E2 caused a greater increase in cancellous bone volume than ovarian transplantation but also caused more marked suppression of bone formation, as assessed at the end of the study. In conclusion, exogenous E2 and ovarian transplantation exerted distinct effects on skeletal metabolism in osteopenic ovx rats, although the basis for this difference is currently unclear. JH Tobias, Department of Histopathology, St George's Hospital Medical School, London SW17 ORE, UK


1994 ◽  
Vol 267 (6) ◽  
pp. E853-E859 ◽  
Author(s):  
J. H. Tobias ◽  
A. Gallagher ◽  
T. J. Chambers

Although androgens are thought to be important for skeletal maintenance in females and males, little is known about the mechanisms involved. To investigate this question further, we examined the effects of administering 0.01, 0.1, or 1.0 mg/kg 5 alpha-dihydrotestosterone (DHT) for 60 days on the skeleton of ovariectomized rats. Treatment was delayed until 90 days after ovariectomy to enable bone loss to stabilize. We found that ovariectomy markedly reduced cancellous bone volume of the proximal tibial metaphysis due to a combination of loss and thinning of trabeculae. Cancellous bone volume was partially restored by all doses of DHT, with trabecular thickness, but not number, returning to that of sham-operated animals. DHT also stimulated longitudinal bone growth and endosteal and periosteal bone formation and suppressed histomorphometric indexes of cancellous bone resorption. This suggests that DHT influences skeletal metabolism in osteopenic ovariectomized rats both by stimulating bone formation and suppressing resorption, although it is unclear which, if any, of these actions predominate at cancellous sites.


1999 ◽  
pp. 70-74 ◽  
Author(s):  
P Morley ◽  
JF Whitfield ◽  
GE Willick ◽  
V Ross ◽  
S MacLean ◽  
...  

OBJECTIVE: Daily injections of human parathyroid hormone (hPTH) increase bone volume in various animal species and in osteoporotic women. For hPTH to be widely accepted as an anabolic therapy for treating postmenopausal osteoporosis alternative delivery options need to be explored to replace the need for daily patient subcutaneous self-injection. Among these are inhalation, oral delivery and the use of programmable implanted minipumps to deliver the peptide. While infusion of high doses of PTH causes bone loss and hypercalcemia, no studies have assessed the effects of prolonged infusion of low doses of PTH on bone growth. DESIGN AND METHODS: [Leu(27)]-cyclo(Glu(22)-Lys(26))-hPTH-(1--31)NH(2) was delivered by Alzet minipumps to ovariectomized rats for 6 weeks after which histomorphometric indices (cancellous bone volume, trabecular thickness, mean trabecular number) of bone formation were measured in distal femurs. RESULTS: Infusing low doses (0.05 and 0.1 nmole/100g body weight/day) of the hPTH analog, [Leu(27)]-cyclo(Glu(22)-Lys(26))-hPTH-(1--31)NH(2), for 6 weeks does not prevent the ovariectomy-induced loss of rat femoral cancellous bone volume, trabecular thickness or trabecular number. CONCLUSION: These results support the absolute requirement of daily injections for the osteogenic action of hPTH on bone.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lingxiao Wang ◽  
Zhenhua Gao ◽  
Yucheng Su ◽  
Qian Liu ◽  
Yi Ge ◽  
...  

AbstractThis study aimed to compare and verify the osseointegration performance of a novel implant (NI) in vivo, which could provide a useful scientific basis for the further development of NIs. Thirty-two NIs treated with hydrofluoric acid and anodization and sixteen control implants (CIs) were placed in the mandibles of 8 beagles. Micro-CT showed that the trabecular number (Tb.N) significantly increased and trabecular separation (Tb.Sp) significantly decreased in the NIs at 2 weeks. Significant differences were found in the trabecular thickness, Tb.N, Tb.Sp, bone surface/bone volume ratio, and bone volume/total volume ratio between the two groups from the 2nd–4th weeks. However, there were no significant differences between the two groups in the bone volume density at 2, 4, 8, or 12 weeks or bone-implant contact at 2 or 4 weeks, but the BIC in the CIs was higher than that in the NIs at the 8th and 12th weeks. Meanwhile, the histological staining showed a similar osseointegration process between the two groups over time. Overall, the NIs could be used as new potential implants after further improvement.


1998 ◽  
Vol 274 (2) ◽  
pp. E328-E335 ◽  
Author(s):  
C. K. Lea ◽  
A. M. Flanagan

The effect of androstenedione (ADIONE) slow-release pellets on cancellous bone volume (BV/TV) at the tibial metaphysis was investigated in ovariectomized (OVX) rats at various times from 21 to 180 days. Plasma levels of ADIONE and testosterone (T) in OVX rats were significantly reduced at 21 days and were restored close to levels in the sham rats with the 1.5-mg ADIONE pellet. OVX animals with and without ADIONE pellets resulted in close to a 50% reduction in BV/TV by day 21. By day 180, OVX rats had only ∼5% BV/TV, whereas that in ADIONE-treated OVX rats was significantly greater at ∼12%. The reduced BV/TV was associated with increased bone resorption and formation. In a separate 90-day experiment, we found that the antiandrogen, Casodex, abrogated the ADIONE-induced skeletal-protective effect in OVX rats, whereas the antiaromatase, Arimidex, had no effect. This provides evidence that ADIONE protects against the development of osteopenia in the estrogen-deficient rat and mediates its effect through androgens and not estrogens.


2010 ◽  
Vol 2010 ◽  
pp. 1-6
Author(s):  
Zelieann R. Craig ◽  
Samuel L. Marion ◽  
Janet L. Funk ◽  
Mary L. Bouxsein ◽  
Patricia B. Hoyer

Previous work showed that retaining residual ovarian tissue protects young mice from accelerated bone loss following ovarian failure. The present study was designed to determine whether this protection is also present in aged animals. Aged (9–12 months) C57BL/6Hsd female mice were divided into: CON (vehicle), VCD (160 mg/kg; 15d), or OVX (ovariectomized). Lumbar BMD was monitored by DXA andμCT used to assess vertebral microarchitecture. BMD was not different between VCD and CON at any time point but was lower (P<.05) than baseline, starting 1 month after ovarian failure in VCD and OVX mice. FollowingμCT analysis there were no differences between CON and VCD, but OVX mice had lower bone volume fraction, trabecular thickness, and a trend for decreased connectivity density. These findings provide evidence that retention of residual ovarian tissue may protect aged follicle-depleted mice from accelerated bone loss to a lesser extent than that observed in young mice.


Bone ◽  
1995 ◽  
Vol 17 (5) ◽  
pp. 491-496 ◽  
Author(s):  
H.Z. Ke ◽  
H.K. Chen ◽  
H. Qi ◽  
C.M. Pirie ◽  
H.A. Simmons ◽  
...  

2020 ◽  
Author(s):  
Toni L. Speacht ◽  
Charles H. Lang ◽  
Henry J. Donahue

ABSTRACTWe examined the hypothesis that exaggerating unloading-induced bone loss using a combination of hindlimb suspension (HLS) and exogenous injections of receptor activator of nuclear factor kappa-B ligand (RANKL) also exaggerates muscle loss. Forty, male C57Bl/6J mice (16 weeks) were subjected to HLS or normal ambulation (ground control, GC) for 14 days. Mice received 3 intraperitoneal injections of either human recombinant soluble RANKL or PBS as control (n=10/group) at 24 hour intervals starting on Day 1 of HLS. GC + RANKL and HLS mice exhibited similar decreases in trabecular bone volume and density in both proximal tibias and distal femurs. However, RANKL affected trabecular number, separation, and connectivity density, while HLS decreased trabecular thickness. The combination of RANKL and HLS exacerbated these changes. Similarly, GC + RANKL and HLS mice saw comparable decreases in cortical bone volume, thickness, and strength in femur midshafts, and combination treatment exacerbated these changes. Plasma concentrations of P1NP were increased in both groups receiving RANKL, while CTX concentrations were unchanged. HLS decreased gastrocnemius weight and was associated with a reduction in global protein synthesis, and no change in proteasome activity. This change was correlated with a decrease in S6K1 and S6 phosphorylation, but no change in 4E-BP1 phosphorylation. Injection of RANKL did not alter muscle protein metabolism in GC or HLS mice. Our results suggest that injection of soluble RANKL exacerbates unloading-induced bone loss, but not unloading-induced muscle loss. This implies a temporal disconnect between muscle and bone loss in response to unloading.


1994 ◽  
Vol 76 (5) ◽  
pp. 1999-2005 ◽  
Author(s):  
S. Bourrin ◽  
C. Genty ◽  
S. Palle ◽  
C. Gharib ◽  
C. Alexandre

To investigate the manner in which cancellous bone in different skeletal sites and within a bone site adapts to strenuous training, 5-wk-old male rats were subjected to intensive treadmill running [80% of maximal O2 consumption (VO2max)] for 11 wk. VO2max, tibia length, and bone mineral density were measured. Histomorphometric analysis was performed in the epiphysis, primary spongiosa (1 zero sp) and secondary spongiosa (2 zero sp) of the contralateral proximal tibia, and the 2 zero sp of thoracic and lumbar vertebrae. VO2max was increased by 39%. No changes were observed in vertebrae. Tibia length, 1 zero sp bone volume, and number of trabeculae were significantly decreased, indicating a retarded longitudinal bone growth. Bone mineral density in the proximal tibia was significantly decreased. In the epiphysis, a trabecular thinning and an increase of trabecular number were shown. In the 2 zero sp, bone volume and number of trabeculae were significantly decreased. The increased total eroded surfaces could indicate an early but transient increase in bone resorption activity. Osteoid thickness was reduced, whereas osteoclast number and osteoid surfaces were unchanged, suggesting that the observed bone loss was mostly due to an impaired osteoblastic activity. In conclusion, 1) strenuous training in young rats reduces longitudinal bone growth and induces bone loss, 2) the cancellous bone adaptation is site specific, and 3) the bone loss is mainly due to decreased osteoblastic activity rather than a global adaptation of bone remodeling.


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