Circadian rhythm of parathyroid hormone (PTH) is well documented, but its physiological role is not fully understood. In healthy individuals, biochemical markers of bone remodeling follow a similar circadian rhythm to PTH with a nocturnal rise in bone resorption and formation. The loss of PTH diurnal variation was observed not only in primary hyperparathyroidism, but also in patients with postmenopausal osteoporosis. Continuously elevated concentrations of PTH lead to excessive stimulation of bone resorption, whereas intermittent PTH administration has a strong osteoanabolic effect in patients with osteoporosis. It has not been examined whether the skeletal sensitivity to PTH action depends also on the time of its application. The aim of our study was to verify the hypothesis that the application of teriparatide (TPTD, recombinant human PTH [1-34]) at different times of the day in the context of its diurnal variability affects the physiological circadian rhythm of bone remodeling and also the bone mineral density (BMD) after the long-term TPTD treatment. Fourteen women with postmenopausal osteoporosis treated with 20 micrograms of TPTD daily, applied subcutaneously either in the morning or evening, were included in the first study. The concentration of serum C-terminal telopeptide of type I collagen...

Orientador: Marcelo Rocha Marques / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-22T08:55:24Z (GMT). No. of bitstreams: 1 Nicoli_NaianaVianaViola_D.pdf: 2862352 bytes, checksum: 850ee3538e25d4ffd9574bbd24d8529e (MD5) Previous issue date: 2013 / Resumo: A deteriorização do tecido ósseo representa um dos efeitos colaterais da irradiação ionizante nas estruturas adjacentes às regiões irradiadas. O PTH (hormônio da paratireóide) é um hormônio vital na homeostase, de forma que é o principal regulador do metabolismo do íon cálcio. A administração intermitente deste hormônio pode induzir aumentos acentuados na formação de osso. Considerando a necessidade da regularização aos danos provocados ao tecido ósseo pela irradiação, o objeto deste estudo foi avaliar o efeito da administração intermitente de PTH no tecido ósseo de ratos submetidos à irradiação de corpo inteiro. Foram utilizados 27 ratos divididos 3 grupos de 9 animais cada: Grupo Controle (CONT), Grupo Irradiado (RAD) e Grupo Irradiado+PTH (RAD+PTH). Após irradiação do corpo inteiro, com dose única, não letal de 8 Gy, foi administrado PTH de forma intermitente (dia sim/dia não) por 24 dias. Transcorridos os 24 dias de tratamento intermitente com PTH, os animais foram sacrificados e as tíbias, hemimandíbulas e fêmures removidos. Foi realizada a pesagem da tíbia e hemimandíbula direita, depois foram congeladas a -20ºC para posterior análise em microtomografia computadorizada (?CT). Na tíbia e hemimandíbula esquerda, foi realizada a análise histológica morfométrica da área óssea, número de osteócitos e osteoclastos; os fêmures foram submetidos aos ensaios mecânicos de microdureza Knnop, resistência à compressão e flexão. Os resultados mostraram que o Grupo CONT apresentou maior área óssea da cortical lingual do segundo molar que o Grupo RAD e RAD+PTH, e maior número de osteoclastos e área óssea da região de furca do primeiro molar em comparação ao Grupo RAD. Em uma análise histológica qualitativa da tíbia, o Grupo RAD e RAD+PTH apresentaram tecido adiposo em meio ao tecido medular. Grupo RAD+PTH apresentou melhor resposta no ensaio de resistência à compressão, necessitando de uma maior força (Newton) para causar a deformação no fêmur em comparação ao Grupo CONT e Grupo RAD. Na pesagem (grama) das peças, as tíbias apresentaram-se mais pesadas no RAD+PTH em relação ao RAD e CONT. Entretanto, houve uma queda acentuada no número de animais somente no Grupo RAD+PTH durante o tratamento com PTH, ocorrendo à morte de 6 dos 9 animais iniciais. Na análise por ?CT, os animais do Grupo RAD+PTH apresentaram maior volume ósseo da tíbia que os dos demais grupos. Estes resultados mostram que o PTH promove melhora nas propriedades ósseas pós-irradiação, entretanto a associação da administração de PTH com a irradiação de corpo inteiro pode ser letal / Abstract: The deterioration of bone tissue adjacent to the irradiated regions is a common effect of ionizing radiation. PTH is the main regulator of the metabolism of calcium ion. The intermittent administration of this hormone can induce marked increases in bone formation. Considering the necessity of settling the damage caused by radiation to bone, the object of this study was to evaluate the effect of intermittent PTH administration on bone tissue quality of rats subjected to whole body irradiation. It was used 27 rats which were assigned in 3 groups of 9 animals: a Control group (CONT), Irradiantion Group (RAD) and Irradiantion+PTH Group (RAD+PTH). After whole body irradiation of single-dose non-lethal of 8 Gy, during 24 days it was administered PTH intermittently (one time per 48hs) to the RAD+PTH group, and placebo was administered to the other groups (CONT and RAD). After 24 day of treatment, the animals were sacrificed and tibias, femurs and mandible removed. Were weighed righ hemimandible and tibia, and then were frozen at -20 º C for further analysis in computed microtomography (?CT). Lefts tibias and hemimandibles were prepared to morphometric analysis of bone area, number of osteocytes and osteoclasts. Both femurs were submitted to mechanical tests: Knnop microhardness, compressive and bending test. The results showed that the CONT group showed greater cortical bone area in the hemimandibles and the RAD Group and RAD+PTH and increased number of osteoclasts and bone area of the furcation region of the first molar in compared to the RAD Group. In a qualitative histological analysis, RAD and RAD+PTH group showed that medullar tissue is replaced by adipose tissue. RAD+PTH group showed a better response in the compressive test, requiring more force (Newton) to cause deformation in the femur compared to the CONT and RAD Group. When the weighing (g) of the parts, the tibia showed up in the heavier RAD+PTH compared to RAD and CONT group. However, there was a large decrease in the number of animals only at RAD+PTH group during treatment with PTH, occurring 6 deaths of the 9 initial animals. The analysis by ?CT, animals of Group RAD+PTH had higher bone volume of the tibia that of other groups. These results show that PTH promotes improvement in bone quality after irradiation. However the association of PTH administration with whole body irradiation can be lethal / Doutorado / Histologia e Embriologia / Doutora em Biologia Buco-Dental

Circadian rhythm of parathyroid hormone (PTH) is well documented, but its physiological role is not fully understood. In healthy individuals, biochemical markers of bone remodeling follow a similar circadian rhythm to PTH with a nocturnal rise in bone resorption and formation. The loss of PTH diurnal variation was observed not only in primary hyperparathyroidism, but also in patients with postmenopausal osteoporosis. Continuously elevated concentrations of PTH lead to excessive stimulation of bone resorption, whereas intermittent PTH administration has a strong osteoanabolic effect in patients with osteoporosis. It has not been examined whether the skeletal sensitivity to PTH action depends also on the time of its application. The aim of our study was to verify the hypothesis that the application of teriparatide (TPTD, recombinant human PTH [1-34]) at different times of the day in the context of its diurnal variability affects the physiological circadian rhythm of bone remodeling and also the bone mineral density (BMD) after the long-term TPTD treatment. Fourteen women with postmenopausal osteoporosis treated with 20 micrograms of TPTD daily, applied subcutaneously either in the morning or evening, were included in the first study. The concentration of serum C-terminal telopeptide of type I collagen...

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Les effets des agents anti-ostéoporotiques sur le tissu osseux sont évalués au niveau de la crête iliaque (CI) mais les réponses aux traitements peuvent varier selon le site osseux. Le but de cette étude était de comprarer les effets de l’acide zolérodronique (ZOL) et du tériparatide (TPTD) au niveau de la crête iliaque et de la vertèbre lombaire L1 (VL1) chez la brebis âgée. Le ZOL a induit une forte diminution du remodelage osseux et une augmentation des microendommagements au niveau des deux sites et une modification des crosslinks du collagène surtout au niveau de l’os cortical de la CI. Trois mois de TPTD ont augmenté le remodelage osseux uniquement au niveau de la VL1. En conclusion, les délais et les amplitudes de réponses au ZOL ou au TPTD diffèrent entre la CI et la VL1 chez la brebis. Ces résultats montrent l’importance de prendre en compte le site osseux pour évaluer les effets des agents anti-ostéoporotiques / The effects of anti-osteoporotic agents on bone tissue are evaluated on iliac crest (IC) but the answers to treatments may vary according to the skeletal site. The purpose of this study was to compare the effect of zoledronic acid (ZOL) and teriparatide (TPTD) on IC and lumbar vertebrae (LV1) in ewes. ZOL has induced a high decrease of bone remodeling, an increase in microdamages in both sites and a modification of collagen crosslinks mainly in cortical bone of IC. Three months of TPTD has increased the bone remodeling only in LV1. In conclusion, the delays and the magnitudes of responses to ZOL or to TPTD differ between IC and LV1 in ewes. These results show that the distinction of bone sites to study the early effects of antiosteoporotic therapies appears meaningful