Combination treatment with pioglitazone and fenofibrate attenuates pioglitazone-mediated acceleration of bone loss in ovariectomized rats

Peroxisome proliferator-activated receptor (PPAR) γ agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARα agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10 mg/kg per day)+Feno (25 mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ∼50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (∼45%) and bone mineral density (BMD; ∼60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARγ and PPARα may reduce the negative effects of PPARγ agonism on bone mass.

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Short- and long-term effects of calcium and exercise on bone mineral density in ovariectomized rats

British Journal Of Nutrition ◽

10.1079/bjn2001428 ◽

2001 ◽

Vol 86 (4) ◽

pp. 521-527 ◽

Cited By ~ 18

Author(s):

Joseé Gala ◽

Manuel Di´az-curiel ◽

Concepcioó de la Piedra ◽

Jesu´s Calero

Keyword(s):

Bone Mineral Density ◽

Bone Loss ◽

Bone Mineral ◽

Exercise Programme ◽

Female Rats ◽

Ovariectomized Rats ◽

Standard Diet ◽

Mineral Density ◽

Left Femur ◽

Ovx Rats

At the level of prevention of bone mineral loss produced by ovariectomy, the aim of the present study was to determine the effect produced by supplementation of Ca in the diet and a moderate exercise programme (treadmill), simultaneously or separately, in ovariectomized rats, an experimental model of postmenopausal bone loss. Female Wistar rats (n110, 15 weeks old) were divided into five groups: (1) OVX, rats ovariectomized at 15 weeks of age, fed a standard diet; (2) SHAM, rats sham operated at 15 weeks of age, fed a standard diet; (3) OVX–EX, ovariectomized rats, fed a standard diet and performing the established exercise programme; (4) OVX–Ca, ovariectomized rats fed a diet supplemented with Ca; (5) OVX–EXCa, ovariectomized rats with the exercise programme and diet supplemented with Ca. The different treatments were initiated 1 week after ovariectomy and were continued for 13 weeks for subgroup 1 and 28 weeks for subgroup 2, to look at the interaction of age and time passed from ovariectomy on the treatments. Bone mineral density (BMD) was determined, at the end of the study, in the lumbar spine (L2, L3 and L4) and in the left femur using a densitometer. Bone turnover was also estimated at the end of the study, measuring the serum formation marker total alkaline phosphatase (AP) and the resorption marker serum tartrate-resistant acid phosphatase (TRAP). As expected, OVX rats showed a significant decrease (P<0·05) in BMD, more pronounced in subgroup 2, and a significant increase in AP and TRAP with regard to their respective SHAM group. The simultaneous treatment with Ca and exercise produced the best effects on lumbar and femoral BMD of ovariectomized rats, partially avoiding bone loss produced by ovariectomy, although it was not able to fully maintain BMD levels of intact animals. This combined treatment produced a significant increase in AP, both in subgroups 1 and 2, and a decrease in TRAP in subgroup 1, with regard to OVX group. The exercise treatment alone was able to produce an increase in BMD with regard to OVX group only in subgroup 1 of rats (younger animals and less time from ovariectomy), but not in subgroup 2. In agreement with this, there was an increase of AP in both subgroups, lower than that observed in animals submitted to exercise plus Ca supplement, and a decrease of TRAP in subgroup 1, without significant changes in this marker in the older rats. Ca treatment did not produce any significant effect on BMD in OVX rats in both subgroups of animals, showing a decrease of AP and TRAP levels in the younger animals with no significant variations in markers of bone remodelling in the older female rats compared with their respective OVX group.

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Plasma nitrate+nitrite levels are regulated by ovarian steroids but do not correlate with trabecular bone mineral density in rats

Journal of Endocrinology ◽

10.1677/joe.0.1590027 ◽

1998 ◽

Vol 159 (1) ◽

pp. 27-34 ◽

Cited By ~ 34

Author(s):

RL van Bezooijen ◽

I Que ◽

AG Ederveen ◽

HJ Kloosterboer ◽

SE Papapoulos ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Loss ◽

Trabecular Bone ◽

Bone Mineral ◽

Ovariectomized Rats ◽

No Production ◽

Mineral Density ◽

Trabecular Bone Mineral Density ◽

Oestrogen Treatment ◽

Plasma Nitrate

Nitric oxide (NO) is a mediator of bone metabolism and its production is under the control of gender hormones in several cell types or tissues. Changes in endogenous NO production, measured as plasma nitrate+nitrite levels, may therefore contribute to ovariectomy (OVX)-induced bone loss. We studied plasma nitrate+nitrite levels and trabecular bone mineral density (TBMD) 4 weeks after sham-operation or OVX in rats receiving various hormonal treatments. OVX decreased plasma nitrate+nitrite levels significantly and this was accompanied by a significant decrease in TBMD. Treatment with oral ethinyl oestradiol (EE) and subcutaneous 17beta-oestradiol dose-dependently prevented the decrease in plasma nitrate+nitrite levels after OVX, but treatment with oral 17beta-oestradiol did not. Oestrogen treatment, 17beta-oestradiol (s. c. or orally) or EE (orally), prevented the OVX-induced decrease in TBMD. Treatment of sham-operated rats with the anti-oestrogen ICI164, 384 induced a significant decrease in TBMD that corresponded to 54% of the decrease observed after OVX, but did not affect plasma nitrate+nitrite levels. Treatment of ovariectomized rats with Org 2058, a pure progestagen, did not prevent bone loss, but prevented the decrease in plasma nitrate+nitrite levels dose-dependently. Treatment with tibolone, a synthetic steroid with combined weak oestrogenic, progestagenic, and androgenic properties, or with progestagen in combination with EE completely prevented bone loss after OVX. These treatments, however, only partly prevented the OVX-induced decrease in plasma nitrate+nitrite levels. In conclusion, OVX decreased both TBMD and plasma nitrate+nitrite levels. Although plasma nitrate+nitrite levels were under the control of both oestrogen and progesterone, TBMD was affected by oestrogen only. Decreased systemic production of NO is, therefore, not involved in OVX-induced bone loss in rats.

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Effect of swimming exercise on three-dimensional trabecular bone microarchitecture in ovariectomized rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.00147.2015 ◽

2015 ◽

Vol 119 (9) ◽

pp. 990-997 ◽

Cited By ~ 8

Author(s):

Yong-In Ju ◽

Teruki Sone ◽

Kazuhiro Ohnaru ◽

Kensuke Tanaka ◽

Masao Fukunaga

Keyword(s):

Bone Mass ◽

Trabecular Bone ◽

Bone Microarchitecture ◽

Weight Bearing ◽

Three Dimensional ◽

Ovariectomized Rats ◽

Swimming Exercise ◽

Mineral Density ◽

Geometrical Properties ◽

Ovx Rats

Swimming is generally considered ineffective for increasing bone mass in humans, at least compared with weight-bearing sports. However, swimming exercise has sometimes been shown to have a strong positive effect on bone mass in small animals. This study investigated the effects of swimming on bone mass, strength, and microarchitecture in ovariectomized (OVX) rats. OVX or sham operations were performed on 18-wk-old female Fisher 344 rats. Rats were randomly divided into four groups: sham sedentary (Sham-CON), sham swimming exercised (Sham-SWI), OVX sedentary (OVX-CON), and OVX swimming exercised (OVX-SWI). Rats in exercise groups performed swimming in a water bath for 60 min/day, 5 days/wk, for 12 wk. Bone mineral density (BMD) in right femurs was analyzed using dual-energy X-ray absorptiometry. Three-dimensional trabecular architecture at the distal femoral metaphysis was analyzed using microcomputed tomography (μCT). Geometrical properties of diaphyseal cortical bone were evaluated in the midfemoral region using μCT. The biomechanical properties of femurs were analyzed using three-point bending. Femoral BMD was significantly decreased following ovariectomy. This change was suppressed by swimming. Trabecular bone thickness, number, and connectivity were decreased by ovariectomy, whereas structure model index (i.e., ratio of rod-like to plate-like trabeculae) increased. These changes were also suppressed by swimming exercise. Femurs displayed greater cortical width and maximum load in SWI groups than in CON groups. Together, these results demonstrate that swimming exercise drastically alleviated both OVX-induced decreases in bone mass and mechanical strength and the deterioration of trabecular microarchitecture in rat models of osteoporosis.

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Drug-induced prevention of gastrectomy- and ovariectomy-induced osteopaenia in the young female rat

Journal of Endocrinology ◽

10.1677/joe.0.1750695 ◽

2002 ◽

Vol 175 (3) ◽

pp. 695-703 ◽

Cited By ~ 15

Author(s):

N Andersson ◽

VV Surve ◽

D Lehto-Axtelius ◽

C Ohlsson ◽

R Hakanson ◽

...

Keyword(s):

Bone Loss ◽

Trabecular Bone ◽

Bone Mineral ◽

Lumbar Vertebra ◽

Underlying Mechanism ◽

Female Rat ◽

Mineral Density ◽

Drug Induced ◽

Ovx Rats ◽

Trabecular Bone Loss

Both ovariectomy (Ovx) and gastrectomy (Gx) induce osteopaenia in rats and humans. While the effect of Ovx has been ascribed to oestrogen deficiency, the underlying mechanism behind Gx is poorly understood. Alendronate, oestrogen and parathyroid hormone (PTH) are known to prevent the osteopaenia induced by Ovx in rats. The purpose of the present study was to determine whether alendronate, oestrogen or PTH could also prevent Gx-evoked osteopaenia. Rats were Ovx-, Gx-, or were sham-operated (Sham) and were then treated with alendronate (50 micro g/kg/day), oestrogen (10 micro g/kg/day) or PTH(1-84) (75 micro g/kg/day) for eight weeks. At sacrifice, serum PTH was unaffected by surgery (Ovx, 64+/-8 pg/ml; Gx, 75+/-13 pg/ml; Sham, 58+/-11 pg/ml). The bone mineral density (BMD) of the fifth lumbar vertebra (L5) was analysed. Ovx and Gx reduced the BMD (ash weight/Volume) of the L5 by 15+/-4% and 22+/-3% respectively. Trabecular BMD and the cortical bone mineral content (BMC) of the femur were assessed using peripheral computed tomography. Both Ovx and Gx markedly reduced trabecular BMD in the metaphyseal area of the distal femur (Ovx, -37+/-7%; Gx, -49+/-7%). The cortical BMC of the femur was only slightly reduced. Alendronate prevented trabecular bone loss after both Ovx and Gx, while oestrogen and PTH prevented trabecular bone loss after Ovx but not after Gx. In conclusion, the bisphosphonate alendronate prevented both Ovx- and Gx-induced trabecular bone loss. In contrast, PTH and oestrogen prevented Ovx-induced but not Gx-induced trabecular bone loss, suggesting that the mechanism behind the trabecular bone loss in Ovx rats differs from that in Gx rats. The results support the notion that the mechanism of action for the bone-sparing effect of these drugs differs. The ability of alendronate, and probably also other bisphosphonates, to prevent Gx-evoked osteopaenia in the rat might be of potential clinical interest when dealing with post-Gx osteopaenia in humans.

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Effects of the Peroxisome Proliferator-Activated Receptor (PPAR)-δ Agonist GW501516 on Bone and Muscle in Ovariectomized Rats

Endocrinology ◽

10.1210/en.2013-1166 ◽

2014 ◽

Vol 155 (6) ◽

pp. 2178-2189 ◽

Cited By ~ 7

Author(s):

M. P. Mosti ◽

A. K. Stunes ◽

M. Ericsson ◽

H. Pullisaar ◽

J. E. Reseland ◽

...

Keyword(s):

Skeletal Muscle ◽

Bone Loss ◽

Ovariectomized Rats ◽

Whole Body ◽

Control Group ◽

High Dose ◽

Peroxisome Proliferator ◽

Mineral Density ◽

Muscle Morphology ◽

Ovx Rats

Estrogen deficiency promotes bone loss and skeletal muscle dysfunction. Peroxisome proliferator-activated receptors (PPARs) have 3 subtypes (α, δ, and γ). PPARγ agonists induce bone loss, whereas PPARα agonists increase bone mass. Although PPARδ agonists are known to influence skeletal muscle metabolism, the skeletal effects are unsettled. This study investigated the musculoskeletal effects of the PPARδ agonist GW501516 in ovariectomized (OVX) rats. Female Sprague Dawley rats, 12 weeks of age, were allocated to a sham-operated group and 3 OVX groups; high-dose GW501516 (OVX-GW5), low-dose GW501516 (OVX-GW1), and a control group (OVX-CTR), respectively (n = 12 per group). Animals received GW501516 or vehicle (methylcellulose) daily for 4 months by gavage. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry at the femur, spine, and whole body. Bone microarchitecture at the proximal tibia was assessed by microcomputed tomography, and dynamic histomorphometry was performed. Quadriceps muscle morphology and the relative expression of mitochondrial proteins were analyzed. Bone metabolism markers and metabolic markers were measured in plasma. After 4 months, the OVX-GW5 group displayed lower femoral BMD than OVX-CTR. Trabecular separation was higher in the GW-treated groups, compared with OVX-CTR. The OVX-GW5 group also exhibited lower cortical area fraction and a higher structure model index than OVX-CTR. These effects coincided with impaired bone formation in both GW groups. The OVX-GW5 group displayed elevated triglyceride levels and reduced adiponectin levels, whereas no effects on muscle morphology or mitochondrial gene expression appeared. In summary, the PPARδ agonist GW501516 negatively affected bone properties in OVX rats, whereas no effects were detected in skeletal muscle.

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Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice

Journal of Endocrinology ◽

10.1530/joe-18-0153 ◽

2018 ◽

Vol 238 (1) ◽

pp. 13-23 ◽

Cited By ~ 12

Author(s):

Thomas Funck-Brentano ◽

Karin H Nilsson ◽

Robert Brommage ◽

Petra Henning ◽

Ulf H Lerner ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

Bone Mass ◽

Trabecular Bone ◽

Cortical Bone ◽

Bone Strength ◽

Bending Test ◽

Bone Homeostasis ◽

Mineral Density

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.

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The Preventive Effect of Biochanin A on Bone Loss in Ovariectomized Rats: Involvement in Regulation of Growth and Activity of Osteoblasts and Osteoclasts

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/594857 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Shu-Jem Su ◽

Yao-Tsung Yeh ◽

Huey-Wen Shyu

Keyword(s):

Bone Loss ◽

Mrna Expression ◽

Biological Effects ◽

Biochanin A ◽

Ovariectomized Rats ◽

Tartrate Resistant Acid Phosphatase ◽

Type I ◽

Mineral Density ◽

Ovx Rats

Biochanin A (BCA) is a major isoflavone abundant in red clover (Trifolium pretense). The protective effect of BCA on bone loss in an ovariectomized (OVX) animal model has never been clarified. The objective of this study was to investigate the biological effects of BCA on bone loss in OVX ratsin vivoand on the development of osteoblasts and osteoclastsin vitro. Ovariectomy resulted in a marked increase in body weight and a decrease in femoral bone mineral density and trabecular bone volume that was prevented by BCA or 17β-estradiol (E2) treatment. However, an increase in uterine weight was observed in E2-treated OVX rats, but not in response to BCA treatment. Treatment with BCA increased the mRNA expression of osterix, collagen type I, alkaline phosphatase (ALP), and osteocalcin and decreased the mRNA expression of tartrate-resistant acid phosphatase (TRAP) and the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in the femur of OVX rats. Treatment with BCA or E2 prevented the OVX-induced increase in urinary deoxypyridinoline (DPD) and serum tumor necrosis factorα(TNF-α) and interleukin-1β(IL-1β).In vitro, BCA induced preosteoblasts to differentiate into osteoblasts and increased osteoblast mineralization. BCA inhibited preosteoclasts and osteoclast proliferation and decreased osteoclast bone resorption. These findings suggest that BCA treatment can effectively prevent the OVX-induced increase in bone loss and bone turnover possibly by increasing osteoblastic activities and decreasing osteoclastic activities.

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The bone-sparing effects of estrogen and WNT16 are independent of each other

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1520408112 ◽

2015 ◽

Vol 112 (48) ◽

pp. 14972-14977 ◽

Cited By ~ 24

Author(s):

Sofia Movérare-Skrtic ◽

Jianyao Wu ◽

Petra Henning ◽

Karin L. Gustafsson ◽

Klara Sjögren ◽

...

Keyword(s):

Bone Loss ◽

Bone Mass ◽

Trabecular Bone ◽

Cortical Bone ◽

Integration Site ◽

Mineral Density ◽

Trabecular Bone Mass ◽

Sparing Effect ◽

Total Body ◽

Cortical Bone Mass

Wingless-type MMTV integration site family (WNT)16 is a key regulator of bone mass with high expression in cortical bone, and Wnt16−/− mice have reduced cortical bone mass. As Wnt16 expression is enhanced by estradiol treatment, we hypothesized that the bone-sparing effect of estrogen in females is WNT16-dependent. This hypothesis was tested in mechanistic studies using two genetically modified mouse models with either constantly high osteoblastic Wnt16 expression or no Wnt16 expression. We developed a mouse model with osteoblast-specific Wnt16 overexpression (Obl-Wnt16). These mice had several-fold elevated Wnt16 expression in both trabecular and cortical bone compared with wild type (WT) mice. Obl-Wnt16 mice displayed increased total body bone mineral density (BMD), surprisingly caused mainly by a substantial increase in trabecular bone mass, resulting in improved bone strength of vertebrae L3. Ovariectomy (ovx) reduced the total body BMD and the trabecular bone mass to the same degree in Obl-Wnt16 mice and WT mice, suggesting that the bone-sparing effect of estrogen is WNT16-independent. However, these bone parameters were similar in ovx Obl-Wnt16 mice and sham operated WT mice. The role of WNT16 for the bone-sparing effect of estrogen was also evaluated in Wnt16−/− mice. Treatment with estradiol increased the trabecular and cortical bone mass to a similar extent in both Wnt16−/− and WT mice. In conclusion, the bone-sparing effects of estrogen and WNT16 are independent of each other. Furthermore, loss of endogenous WNT16 results specifically in cortical bone loss, whereas overexpression of WNT16 surprisingly increases mainly trabecular bone mass. WNT16-targeted therapies might be useful for treatment of postmenopausal trabecular bone loss.

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New Bone Formation with Teriparatide [Human Parathyroid Hormone-(1–34)] Is Not Retarded by Long-Term Pretreatment with Alendronate, Estrogen, or Raloxifene in Ovariectomized Rats

Endocrinology ◽

10.1210/en.2002-221061 ◽

2003 ◽

Vol 144 (5) ◽

pp. 2008-2015 ◽

Cited By ~ 76

Author(s):

Yanfei L. Ma ◽

Henry U. Bryant ◽

Qingqiang Zeng ◽

Allen Schmidt ◽

Jennifer Hoover ◽

...

Keyword(s):

Bone Loss ◽

Bone Formation ◽

Formation Rate ◽

Prior Exposure ◽

Ovariectomized Rats ◽

Mineral Density ◽

Bone Formation Rate ◽

Teriparatide Treatment ◽

Antiresorptive Agents ◽

Ovx Rats

With the ready availability of several osteoporosis therapies, teriparatide [human PTH-(1–34)] is likely to be prescribed to postmenopausal women with prior exposure to agents that prevent bone loss, such as bisphosphonates, estrogen, or selective estrogen receptor modulators. Therefore, we evaluated the ability of once daily teriparatide to induce bone formation in ovariectomized (Ovx) rats with extended prior exposure to various antiresorptive agents, such as alendronate (ABP), 17α-ethinyl estradiol (EE), or raloxifene (Ral). Sprague Dawley rats were Ovx and treated with ABP (28 μg/kg, twice weekly), EE (0.1 mg/kg·d), or Ral (1 mg/kg·d) for 10 months before switching to teriparatide 30 μg/kg·d for another 2 months. Analysis of the proximal tibial metaphysis showed that all three antiresorptive agents prevented ovariectomy-induced bone loss after 10 months, but were mechanistically distinct, as shown by histomorphometry. Before teriparatide treatment, ABP strongly suppressed activation frequency and bone formation rate to below levels in other treatment groups, whereas these parameters were not different from sham values for EE or Ral. Trabecular area for ABP, EE, and Ral were greater than that in Ovx controls. However, the trabecular bone effects of ABP were attributed not only to effects on the secondary spongiosa, but also to the preservation of primary spongiosa, which was prevented from remodeling. After 2 months of teriparatide treatment, lumbar vertebra showed relative bone mineral density increases of 18%, 7%, 11%, and 10% for vehicle/teriparatide, ABP/teriparatide, EE/teriparatide, and Ral/teriparatide, respectively, compared with 10 month levels. Histomorphometry showed that trabecular area was increased by 105%, 113%, 36%, and 48% for vehicle/teriparatide, ABP/teriparatide, EE/teriparatide, and Ral/teriparatide, respectively, compared with 10 month levels. Teriparatide enhanced mineralizing surface, mineral apposition rate, and bone formation rate in all groups. Compression testing of vertebra showed that teriparatide improved strength (peak load) and toughness in all groups to a proportionately similar extent compared with 10 month levels. These data showed a surprising ability of the rat skeleton to respond to teriparatide despite extensive pretreatment with ABP, EE, or Ral. Therefore, the mature skeleton of Ovx rats remains highly responsive to the appositional effects of teriparatide regardless of pretreatment status in terms of cancellous bone area or rate of bone turnover.

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Long-Term Therapy with a New Chemically Modified Tetracycline (CMT-8) Inhibits Bone Loss in Femurs of Ovariectomized Rats

Advances in Dental Research ◽

10.1177/08959374980120012501 ◽

1998 ◽

Vol 12 (1) ◽

pp. 76-81 ◽

Cited By ~ 6

Author(s):

T. Sasaki ◽

N.S. Ramamurthy ◽

L.M. Golub

Keyword(s):

Bone Loss ◽

Bone Formation ◽

Trabecular Bone ◽

Female Rats ◽

Ovariectomized Rats ◽

Term Therapy ◽

Ovx Rats ◽

Trabecular Bone Loss ◽

Bone Trabeculae

The effect of a new non-antimicrobial analog of tetracycline (CMT-8) on bone loss in ovariectomized (OVX) rats was examined. Three-month-old female rats were ovariectomized, and one week later, were distributed into 3 groups: sham-operated non-OVX controls, vehicle-treated OVX controls, and CMT-8-treated OVX rats. After 145 days of daily CMT-8 administration, the intact femurs were dissected and examined by several histological and histomorphometric techniques. OVX significantly (p < 0.01) decreased trabecular bone volume by 53.4% in the metaphyses compared with sham-operated controls. CMT-8 therapy produced a significant (p < 0.05) inhibition of trabecular bone loss and also induced bone formation in the OVX rats. Of interest, the newly synthesized bone in the CMT-treated OVX rats was found to increase the "connectivity" of the trabecular "struts" by bridging the adjacent longitudinal bone trabeculae, forming dense, platelike bone trabeculae. These results strongly suggest that long-term CMT-8 therapy effectively inhibits bone loss after OVX, not only by inhibiting bone resorption but also by inducing new bone formation in the trabecular areas of long bones.

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