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Effects of selective serotonin reuptake inhibitors on bone mechanical properties in ovariectomized and non-ovariectomized rats
Abstracts / Bone 44 (2009) S339–S450
Results: The right hind limb weight was significantly reduced by 15%, 28%, 36%, 41% (right vs left) and by 22%, 43%, 52%, 54% (BTX vs baseline) after 1, 2, 3, and 4 weeks, respectively. The right rectus femoris weight was significantly reduced by 23%, 47%, 58%, 61% (right vs left) and by 28%, 54%, 64%, 67% (BTX vs baseline) and the right rectus femoris CSA was significantly reduced by 33%, 40%, 53%, 51% (right vs left) and by 19%, 46%, 56%, 56% (BTX vs baseline) after 1, 2, 3, and 4 weeks, respectively. The right femoral BMD was significantly reduced by 2.4%, 3.6%, 5.5%, 7.9% (right vs left) and non-significantly reduced by −1.9%, 1.2%, 3.7% and significantly reduced by 6.2% (BTX vs baseline) after 1, 2, 3, and 4 weeks, respectively. Conclusion: Botox induced a rapid and time-dependent loss of muscle and bone mass. The loss of BMD was delayed compared with the loss of muscle mass. The Botox model is fast and straightforward and is well suited for studying bone and muscle loss induced by immobilization. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.316
P405 Bone mass in women with subclinical hypothyroidism on levothyroxine replacement therapy J.M. Lavado-Garcíaa,*, M.L. Canal-Macíasb, J.F. Calderón-Garcíab, R. Roncero-Martínc, M.C. Costa-Fernándezb, J.D. Pedrera-Zamoranob a Department of Medicine I, Universidad de Extremadura, Cáceres, Spain b Department of Nursing, Universidad de Extremadura, Cáceres, Spain c Department of Nursing, Universidad de Extremadura, Badajoz, Spain Background and aim: The results of studies examining the influence of subclinical hypothyroidism on bone mass have generated considerable interest but also some controversy. The present research aims to evaluate, in different skeletal sites, the effect of levothyroxine replacement therapy on bone mineral density in women. Methods: A group of 262 biochemically and clinically euthyroid women (mean age 55.22 ± 9.73 years old) with subclinical hypothyroidism on levothyroxine replacement therapy for at least six months was compared to 262 controls pair-matched for sex and age. Levothyroxine mean doses were 86.89 ± 37.34 μg/day. Bone mass measurements were assessed using peripheral quantitative computed tomography (pQCT) of the non-dominant distal radius, phalangeal quantitative bone ultrasound (QUS) and dual energy Xray absorptiometry (DXA) in lumbar spine and hip. Results: No differences were observed between patients and control in bone mass measurements (QUS, pQCT and DEXA) and weight, height, body mass index (BMI), menopausal status, age of menarche and years since menopause. Simple linear regression analyses between bone measurements and doses of levothyroxine only showed significant positive relations with total (p = 0.0259) and cortical + subcortical (p = 0.0372) bone density by pQCT. Conclusion: In women biochemically and clinically euthyroid with subclinical hypothyroidism, levothyroxine replacement therapy was accompanied by normal bone mass values. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.317
P406 Effects of selective serotonin reuptake inhibitors on bone mechanical properties in ovariectomized and non-ovariectomized rats J. Folwarczna*, M. Pytlik, B. Nowinska, U. Cegiela, P. Molin, T. Hanke, H.I. Trzeciak Department of Pharmacology, Medical University of Silesia, Sosnowiec, Poland
S407
Administration of selective serotonin reuptake inhibitors (SSRIs), drugs used in the treatment of depression, may be associated with the increased risk of fracture. SSRIs are often prescribed to postmenopausal women. There are a few experimental studies on fluoxetine skeletal effects. To our knowledge, the effects of other SSRIs on bones have not been studied in experimental conditions. The aim of the present study was to investigate how SSRIs (fluoxetine and fluvoxamine) affect the skeletal system of female rats and whether their possible effects depend on estrogen status. The experiments were carried out on 15–17-week-old Wistar rats. The effects of fluoxetine hydrochloride (10 mg/kg p.o.) and fluvoxamine maleate (30 mg/kg p.o.) on bones of normal nonovariectomized rats, bilaterally ovariectomized (OVX, estrogendeficient) rats and OVX rats supplemented with estradiol (0.2 mg/ kg p.o.), in comparison with appropriate control groups, were studied (n = 8–10 per group). The ovariectomy was performed 7–9 days before the start of a four-week period of daily administration of the drugs. Bone geometric parameters, mass, mass of bone mineral in the tibia, femur and L-4 vertebra, as well as mechanical properties of tibial metaphysis and femoral diaphysis in three-point bending tests and femoral neck in a compression test were assessed (Instron 3342 500N apparatus). In OVX control rats, the ratio of bone mineral mass to bone mass was decreased and mechanical properties of tibial metaphysis and femoral neck were worsened in comparison with sham-operated control rats. Supplementation with estradiol improved bone mineralization, but did not improve mechanical properties of bones in OVX rats. Fluoxetine worsened mechanical properties of the tibial metaphysis both in OVX and non-ovariectomized rats; moreover, it decreased bone mass and mass of bone mineral (not affecting the bone mineral/bone mass ratio) in OVX rats. Fluoxetine did not significantly affect mechanical properties of the femoral neck and diaphysis. Fluvoxamine did not affect bone mass, mineralization and mechanical properties in female rats. Concluding, effects of the investigated SSRIs on rat bone mechanical properties do not depend on estrogen status. Results of the present study also indicate that the skeletal effects of different SSRIs should be considered separately. Acknowledgments: This study was supported by grant No N401 059 32/1412 from the Ministry of Science and Higher Education, Poland. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.318
P407 Serotonin effects on the skeletal system may depend on estrogen status: Differential effects on bone mechanical properties in non-ovariectomized and ovariectomized rats J. Folwarczna*, T. Hanke, P. Molin, H.I. Trzeciak Department of Pharmacology, Medical University of Silesia, Sosnowiec, Poland Serotonin has been recently reported to be involved in regulation of bone metabolism in vitro and in vivo. Estradiol has been shown to interact with serotonergic system. The aim of the present study was to investigate how elevated peripheral levels of serotonin or inhibition of serotonin synthesis by p-chlorophenylalanine affects the skeletal system of female rats and whether the serotonin effects on bones depend on estrogen status. The experiments were carried out on 15–17-week-old Wistar rats. The effects of serotonin (serotonin creatinine sulfate complex, 10 mg/ kg/day, s.c.) and p-chlorophenylalanine (a tryptophan hydroxylase inhibitor, 100 mg/kg/day, i.p.) on bones of normal non-ovariecto-
Results: The right hind limb weight was significantly reduced by 15%, 28%, 36%, 41% (right vs left) and by 22%, 43%, 52%, 54% (BTX vs baseline) after 1, 2, 3, and 4 weeks, respectively. The right rectus femoris weight was significantly reduced by 23%, 47%, 58%, 61% (right vs left) and by 28%, 54%, 64%, 67% (BTX vs baseline) and the right rectus femoris CSA was significantly reduced by 33%, 40%, 53%, 51% (right vs left) and by 19%, 46%, 56%, 56% (BTX vs baseline) after 1, 2, 3, and 4 weeks, respectively. The right femoral BMD was significantly reduced by 2.4%, 3.6%, 5.5%, 7.9% (right vs left) and non-significantly reduced by −1.9%, 1.2%, 3.7% and significantly reduced by 6.2% (BTX vs baseline) after 1, 2, 3, and 4 weeks, respectively. Conclusion: Botox induced a rapid and time-dependent loss of muscle and bone mass. The loss of BMD was delayed compared with the loss of muscle mass. The Botox model is fast and straightforward and is well suited for studying bone and muscle loss induced by immobilization. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.316
P405 Bone mass in women with subclinical hypothyroidism on levothyroxine replacement therapy J.M. Lavado-Garcíaa,*, M.L. Canal-Macíasb, J.F. Calderón-Garcíab, R. Roncero-Martínc, M.C. Costa-Fernándezb, J.D. Pedrera-Zamoranob a Department of Medicine I, Universidad de Extremadura, Cáceres, Spain b Department of Nursing, Universidad de Extremadura, Cáceres, Spain c Department of Nursing, Universidad de Extremadura, Badajoz, Spain Background and aim: The results of studies examining the influence of subclinical hypothyroidism on bone mass have generated considerable interest but also some controversy. The present research aims to evaluate, in different skeletal sites, the effect of levothyroxine replacement therapy on bone mineral density in women. Methods: A group of 262 biochemically and clinically euthyroid women (mean age 55.22 ± 9.73 years old) with subclinical hypothyroidism on levothyroxine replacement therapy for at least six months was compared to 262 controls pair-matched for sex and age. Levothyroxine mean doses were 86.89 ± 37.34 μg/day. Bone mass measurements were assessed using peripheral quantitative computed tomography (pQCT) of the non-dominant distal radius, phalangeal quantitative bone ultrasound (QUS) and dual energy Xray absorptiometry (DXA) in lumbar spine and hip. Results: No differences were observed between patients and control in bone mass measurements (QUS, pQCT and DEXA) and weight, height, body mass index (BMI), menopausal status, age of menarche and years since menopause. Simple linear regression analyses between bone measurements and doses of levothyroxine only showed significant positive relations with total (p = 0.0259) and cortical + subcortical (p = 0.0372) bone density by pQCT. Conclusion: In women biochemically and clinically euthyroid with subclinical hypothyroidism, levothyroxine replacement therapy was accompanied by normal bone mass values. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.317
P406 Effects of selective serotonin reuptake inhibitors on bone mechanical properties in ovariectomized and non-ovariectomized rats J. Folwarczna*, M. Pytlik, B. Nowinska, U. Cegiela, P. Molin, T. Hanke, H.I. Trzeciak Department of Pharmacology, Medical University of Silesia, Sosnowiec, Poland
S407
Administration of selective serotonin reuptake inhibitors (SSRIs), drugs used in the treatment of depression, may be associated with the increased risk of fracture. SSRIs are often prescribed to postmenopausal women. There are a few experimental studies on fluoxetine skeletal effects. To our knowledge, the effects of other SSRIs on bones have not been studied in experimental conditions. The aim of the present study was to investigate how SSRIs (fluoxetine and fluvoxamine) affect the skeletal system of female rats and whether their possible effects depend on estrogen status. The experiments were carried out on 15–17-week-old Wistar rats. The effects of fluoxetine hydrochloride (10 mg/kg p.o.) and fluvoxamine maleate (30 mg/kg p.o.) on bones of normal nonovariectomized rats, bilaterally ovariectomized (OVX, estrogendeficient) rats and OVX rats supplemented with estradiol (0.2 mg/ kg p.o.), in comparison with appropriate control groups, were studied (n = 8–10 per group). The ovariectomy was performed 7–9 days before the start of a four-week period of daily administration of the drugs. Bone geometric parameters, mass, mass of bone mineral in the tibia, femur and L-4 vertebra, as well as mechanical properties of tibial metaphysis and femoral diaphysis in three-point bending tests and femoral neck in a compression test were assessed (Instron 3342 500N apparatus). In OVX control rats, the ratio of bone mineral mass to bone mass was decreased and mechanical properties of tibial metaphysis and femoral neck were worsened in comparison with sham-operated control rats. Supplementation with estradiol improved bone mineralization, but did not improve mechanical properties of bones in OVX rats. Fluoxetine worsened mechanical properties of the tibial metaphysis both in OVX and non-ovariectomized rats; moreover, it decreased bone mass and mass of bone mineral (not affecting the bone mineral/bone mass ratio) in OVX rats. Fluoxetine did not significantly affect mechanical properties of the femoral neck and diaphysis. Fluvoxamine did not affect bone mass, mineralization and mechanical properties in female rats. Concluding, effects of the investigated SSRIs on rat bone mechanical properties do not depend on estrogen status. Results of the present study also indicate that the skeletal effects of different SSRIs should be considered separately. Acknowledgments: This study was supported by grant No N401 059 32/1412 from the Ministry of Science and Higher Education, Poland. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.318
P407 Serotonin effects on the skeletal system may depend on estrogen status: Differential effects on bone mechanical properties in non-ovariectomized and ovariectomized rats J. Folwarczna*, T. Hanke, P. Molin, H.I. Trzeciak Department of Pharmacology, Medical University of Silesia, Sosnowiec, Poland Serotonin has been recently reported to be involved in regulation of bone metabolism in vitro and in vivo. Estradiol has been shown to interact with serotonergic system. The aim of the present study was to investigate how elevated peripheral levels of serotonin or inhibition of serotonin synthesis by p-chlorophenylalanine affects the skeletal system of female rats and whether the serotonin effects on bones depend on estrogen status. The experiments were carried out on 15–17-week-old Wistar rats. The effects of serotonin (serotonin creatinine sulfate complex, 10 mg/ kg/day, s.c.) and p-chlorophenylalanine (a tryptophan hydroxylase inhibitor, 100 mg/kg/day, i.p.) on bones of normal non-ovariecto-