ABSTRACT
Rat parathyroid hormone (PTH) 1-34 (4 microg/kg/day) was applied for 2.5 months to 9 month-old rats immediately after ovariectomy or orchidectomy or to 15 month-old rats with low bone mass which had been castrated 6 months before in order to know the effects on serum biochemistry parameters, lumbar and femoral bone mineral density, histology, cancellous and cortical bone histomorphometry, mineralisation content profile in cortical bone by backscattered-electron microscopy, and femoral torsion biomechanical testing. In ovariectomised rats, preventive PTH treatment avoided cancellous bone loss in tibial metaphysis and partially in lumbar vertebra, while in cortical bone, PTH increased endosteal resorption and periosteal formation. In intervention study, PTH did not restore cancellous bone but a strong endosteal and periosteal new bone formation was detected. In orchidectomised rats, PTH, in preventive study, avoided cancellous bone loss in metaphysis and lumbar vertebra, and a mild new bone formation in cortical bone was found. In intervention study, PTH maintained baseline cancellous bone mass, but in cortical bone a strong endosteal and periosteal new bone formation was detected. The PTH-induced new bone formation was confirmed by histology and by mineral content profiles. After castration, biomechanical properties were affected in females but not in male rats and PTH reverted this effect.
Subject(s)
Androgens/deficiency , Estrogens/deficiency , Osteogenesis/drug effects , Osteoporosis/drug therapy , Parathyroid Hormone/therapeutic use , Androgens/blood , Animals , Biomechanical Phenomena , Bone Density , Bone and Bones/drug effects , Bone and Bones/radiation effects , Bone and Bones/ultrastructure , Calcium/blood , Disease Models, Animal , Estrogens/blood , Female , Male , Rats , Rats, WistarABSTRACT
La calidad ósea viene determinada por una serie de factores diversos entre los que presentan especial importancia la propia densidad mineral ósea (DMO), el remodelado óseo y las propiedades biomecánicas del hueso. El objetivo de este trabajo es el estudio de las variaciones producidas por la orquidectomía o la ovariectomía sobre estos factores, así como los efectos producidos por la administración de hormona paratiroidea (PTH) (4 x 10-6 g/kg/día) vía subcutánea, tanto a nivel preventivo como curativo. Se han estudiado 97 ratas Wistar macho (M) y 92 ratas hembra (H) de 9 meses de edad, que fueron SHAM-operadas (SHAM), orquidectomizadas (OQX) u ovariectomizadas (OVX), tratadas y no tratadas con PTH; y se repartieron en dos estudios: preventivo y curativo. Se determinaron la DMO en columna y fémur por absoriometría de rayos X de doble energía (DEXA). estudios histomorfométricos de volumen trabecular, marcadores de formación y resorción ósea y propiedades biomecánicas (momento torsor, rigidez, ángulo girado, energía absorbida y tensión cortante máxima). Tanto la OQX como la OVX produjeron disminución significativa en la DMO, que se detectaron con mayor sensibilidad con la histomorfometría que con la DEXA, aumento general del remodelado y variaciones en los parámetros biomecánicos en el caso de la OVX. Nuestros resultados mostraron que la depleción estrogénica tiene consecuencias más graves sobre la pérdida de calidad del hueso que la androgénica. La administración de PTH, tanto por prevención como por tratamiento, restaura los niveles de la DMO en las ratas OQX, aunque los niveles de remodelado óseo, especialmente los de formación, de los animales tratados sufren un incremento significativo frente a los controles. Las propiedades biomecánicas del hueso en ratas OQX u OVX tratadas son similares a las de las ratas control, sugiriendo que la PTH no tiene efectos negativos sobre la calidad del hueso. En el caso de las ratas OVX, la administración de PTH restaura los niveles de calidad ósea en el estudio preventivo, pero no es capaz de hacerlo totalmente en el curativo, lo que sugiere que existe un límite en el nivel de pérdida ósea a partir del cual no es posible recuperar los valores normales
Bone quality is determined by a variety of factors, among which bone mineral density (BMD), bone remodelling and biomechanical properties of bone have special importance. The purpose of this work is to study changes produced by orchidectomy and ovariectomy on these factors, and the effects produced by subcutaneous PTH-administration (4x10-6g/kg/day), at preventive and treatment level. Ninety-seven male Wistar rats (M) and 92 female Wistar rats (H), 9 months old, SHAM-operated (SHAM), orchidectomized (OQX) or ovariectomized (OVX); treated and non-treated with PTH were studied; and they were distributed into two studies: prevention and treatment. Lumbar BMD and femoral BMD were measured by DEXA, trabecular-volume histomorphometric assays, formation and resorption markers and biomechanical properties (maximum torque, angular deformation, rigidity and absorbed energy) were also measured. Both orchidectomy and ovariectomy produced a significant decrease in BMD, that was detected with more sensitivity with histomorphometric assays than with DEXA, a general increase in bone remodeling and changes in biomechanical parameters in the case of OVX rats. Our results showed that estrogenic depletion produces higher bone quality decrease than the androgenic one. PTH administration on a preventive and treatment level restores BMD levels in OQX rats, although bone remodeling levels, especially formation markers, in treated animals suffered a significant increase with respect to control group. Biomechanical properties of bone in OQX and OVX treated-rats were similar to those of the control group, suggesting that PTH do not produce negative effects on bone quality. In the case of OVX rats, PTH administration restores bone quality levels in the preventive study, but it could not restore these levels in the treatment study, a fact that suggests that there is a limit in bone loss level from which normal levels cannot be recovered
