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Abstract: Introduction. – Clinical and experimental evidence supports a link between the effects of mechanical loading and those of estrogens on bone. The objective of this study was to compare bone loss induced in female rats by hindlimb unloading, ovariectomy, or both. Materials and methods. – Thirty-six female Wistar rats aged 12 weeks were randomized to bilateral surgical ovariectomy without tail suspension (OV) or with tail suspension for 30 days (OV-TS) or to sham surgery without tail suspension (control group, C) or with tail suspension for 30 days (TS). Bone mineral density (BMD) of the distal femoral metaphysis was measured in g/cm2 by dual X-ray absorptiometry in all 12 animals on days 0, 7, 14, and 30. Results. – On D14 and D30, BMD (mean±S.D.) was significantly lower in the OV, TS, and OV-TS groups than in the control group (D14: 0.239±0.014, 0.243±0.016, and 0.227±0.018, respectively, vs. 0.258±0.005 in the controls; P <0.05; and D30: 0.241±0.011, 0.227±0.015, and 0.200±0.018, respectively, vs. 0.279±0.009 in the controls; P <0.001). On D30, the percentage BMD change versus baseline (mean±S.D.) differed significantly between the combination (OV-TS) group (−14.26±8.14) and the single-intervention groups (OV: +0.99±6.44, P <0.001; and TS: −6.36±4.56, P <0.05). As early as D7, bone loss was significantly greater in the combination (OV + TS) group than in the OV group (−1.79%±7.17 vs. +4.29%±9.55; P <0.05). Conclusion. – In female rats, the rate and severity of bone loss were greater when estrogen deprivation was combined with mechanical unloading than when either intervention was used alone. Mechanical unloading induced a greater degree of bone loss than did estrogen deprivation. In this model of high-rate bone loss, mechanical unloading may predominate over estrogen deprivation in the genesis of bone loss. [Copyright &y& Elsevier]

Résumé: Introduction – Des données cliniques et expérimentales suggèrent que les effets osseux des contraintes mécaniques et ceux des estrogènes sont en partie liés. Cette étude a pour but de comparer la perte osseuse induite chez la ratte par la suspension par la queue, par l''ovariectomie, et par la combinaison des deux méthodes. Matériel et méthodes. – Trente-six rattes Wistar âgées de 12 semaines ont été randomisées en quatre groupes : ovariectomie chirurgicale bilatérale et suspension par la queue pendant 30 jours (OVX-S), ovariectomie sans suspension (OVX), chirurgie factice et suspension (S), chirurgie factice sans suspension (T). La densité minérale osseuse (DMO) de la métaphyse distale du fémur a été mesurée par DXA chez tous les animaux à j0, j7, j14 et j30. Résultats. – À j14 et j30, la DMO (g/cm2 ; moy±ET) était significativement plus basse dans les groupes S, OVX,et OVX-S que dans le groupe T (j14 : S=0,243±0,016, OVX=0,239±0,014, OVX-S=0,227±0,018 vs T=0,258±0,005, p <0,05 ; j30 : S=0,227±0,015, OVX=0,241±0,011, OVX-S=0,200±0,018 vs T=0,279±0,009, p <0,001). À j30, l''évolution de la DMO par rapport à j0 (% ; moy±ET) était significativement différente entre le groupe OVX-S (–14,26±8,14) et les groupes OVX (+0,99±6,44, p <0,001) et S (–6,36±4,56, p <0,05). Pour le groupe S une baisse modérée de DMO (–6,36 %±4,56) a été observée, alors que la DMO a augmenté dans le groupe OVX (+0,99±6,44, p <0,05). De même, dès j7, l''évolution de la DMO était significativement différente dans le groupe OVX-S (–1,79 %±7,17) et dans le groupe OVX (+4,29 %±9,55, p <0,05). Conclusion. – Chez la ratte, la perte osseuse la plus importante et la plus rapide est induite par la combinaison de l''ovariectomie et de la suspension. La perte osseuse induite par la diminution des contraintes mécaniques est plus importante que la perte osseuse induite par l''ovariectomie. Dans ce modèle de perte osseuse rapide, la variation des contraintes mécaniques semble donc prépondérante par rapport au rôle des estrogènes. [Copyright 2006 Elsevier]

Sympathetic innervation has been demonstrated in bone. Adrenergic stimulation is one of the transmitters of bone loss by uncoupling between decreased bone formation and increased bone resorption.Objective. – By using a non specific antagonist of β-adrenergic pathway (propranolol per os), we hypothesized that we could rescue the uncoupling induced mechanical unloading bone loss in the rat model of tail-suspension.Materials and methods. – Twenty-two female rats Wistar, 12 week-old, have been divided into three groups: eight tail-suspended rats (SR), six tail-suspended rats treated by propranolol (SRP) and eight non suspended rats (NSR) during 30 days. Bone mineral density (BMD, g/cm2) has been measured by DXA (Hologic QDR-4500A) at D0 and D30 of the study, in the distal femoral metaphysis (DFM), the femoral diaphysis (FD), the whole body (WB, g) and body composition.Results. – Between D0 and D30, in DFM a significant variation in BMD is observed between NSR and SR (% BMD change: NSR +15.6 ± 3.1% vs. SR –1.0 ± 1.4%, P < 0.0001) and BMD rescue in SRP group (% BMD change SRP +5.3 ± 1.5% vs. SR –1.0 ± 1.4%, P = 0.03). In FD, gain of BMD is significant in NSR compared to SR (+17.5 ± 1.5% vs. +8.2 ± 2.8%, P = 0.007), and to SRP (+17.5 ± 1.5% vs + 10.1 ± 2.4%, P = 0.046). Gain in SRP group is not significant compared to SR group (P = 0.6). In WB SRP gain more BMD than NSR (+14.0 ± 1.8% vs. +5.4 ± 0.7%, P = 0.0002) and than SR (+14.0 ± 1.8% vs. +7.8 ± 1.4%, P = 0.0043). There is no difference between NSR and SR groups (P = 0.19).Conclusion. – We demonstrate that β-adrenergic pathway of sympathetic nervous system is a major transmitter pathway of mechanical loading in rat bone. A specific study is necessary to analyse a possible systemic effect of propranolol in rat bone. Propranolol could be used to prevent induced mechanical unloading bone loss as weightlessness. [Copyright &y& Elsevier]

Unlabelled: Sympathetic innervation has been demonstrated in bone. Adrenergic stimulation is one of the transmitters of bone loss by uncoupling between decreased bone formation and increased bone resorption.Objective: By using a non-specific antagonist of -adrenergic pathway (propranolol per os), we hypothesized that we could rescue the uncoupling induced mechanical unloading bone loss in the rat model of tail-suspension.Materials and Methods: Twenty-two female Wistar rats, 12 week-old, have been divided into three groups: eight tail-suspended rats (SR), six tail-suspended rats treated by propranolol (SRP) and eight non-suspended rats (NSR) during 30 days. Bone mineral density (BMD, g/cm2) has been measured by DXA (Hologic QDR-4500A) at D0 and D30 of the study, in the distal femoral metaphysis (DFM), the femoral diaphysis (FD), the whole body (WB, g) and body composition.Results: Between D0 and D30, in DFM a significant variation in BMD is observed between NSR and SR (% BMD change: NSR +15.6 +/- 3.1% vs SR -1.0 +/- 1.4%, P < 0.0001) and BMD rescue in SRP group (% BMD change SRP +5.3 +/- 1.5% vs SR -1.0 +/- 1.4%, P = 0.03). In FD, gain of BMD is significant in NSR compared to SR (+17.5 +/- 1.5% vs +8.2 +/- 2.8%, P = 0.007) and to SRP (+17.5 +/- 1.5% vs +10.1 +/- 2.4%, P = 0.046). Gain in SRP group is not significant compared to SR group (P = 0.6). In WB, SRP gain more BMD than NSR (+14.0 +/- 1.8% vs +5.4 +/- 0.7%, P = 0.0002) and than SR (+14.0 +/- 1.8% vs +7.8 +/- 1.4%, P = 0.0043). There is no difference between NSR and SR groups (P = 0.19).Conclusion: We demonstrate that -adrenergic pathway of sympathetic nervous system is a major transmitter pathway of mechanical loading in rat bone. A specific study is necessary to analyse a possible systemic effect of propranolol in rat bone. Propranolol could be used to prevent the induced mechanical unloading bone loss as weightlessness [ABSTRACT FROM AUTHOR]