O tecido ósseo é afetado tanto pela obesidade como por tratamentos radicais, com acentuada perda de peso. A Cirurgia Bariátrica (CB) tem se mostrado mais efetiva para o tratamento da obesidade grave, mas com dados de deterioração de massa óssea e até aumento de risco de fraturas. Este estudo visou avaliar o impacto da perda rápida de peso induzida por CB em períodos recente (um ano) e tardio (cinco anos) sobre a massa óssea de sujeitos obesos. Em particular, houve interesse em investigar a associação da Adiposidade de Medula Óssea (AMO) com a massa óssea, sendo avaliados três grupos: um formado por indivíduos normais controles; um por obesos após o 1º ano de CB; e o grupo de obesos após o 5º ano de CB. Realizaram-se exames de densitometria óssea; espectroscopia por ressonância magnética de coluna e abdome; exames bioquímicos para avaliação da massa óssea, AMO, e gordura visceral e hepática; e avaliação hormonal e de fatores sistêmicos que influenciam o metabolismo ósseo e energético. Foi feito um ajuste da Densidade Mineral Óssea (DMO) pelo peso a partir do cálculo da taxa de DMO, dividido por quilo de peso, sendo a DMO QT maior no grupo Controle, intermediária no grupo 1º Ano CB e menor no grupo 5º Ano CB. Houve associação do peso com a DMO, mostrando a influência daquele sobre a massa óssea e presença de fratura por fragilidade nos grupos operados. Notaram-se o incremento de Paratormônio (PTH), a redução de calcemia em longo prazo e a correlação negativa de PTH com DMO de antebraço também em longo prazo. O telopeptídeo do colágeno tipo I (CTX) se correlacionou negativamente com a DMO L1-L4 no grupo 5º Ano CB, e não houve correlação entre os valores de insulina, osteocalcina, leptina, adiponectina e grelina com a massa óssea. Foi documentado o aumento de AMO nos pacientes submetidos à CB em longo prazo (cinco anos), além de associação negativa do constituinte saturado da AMO com a DMO L3. Constataram-se maiores valores de Tecido Adiposo Subcutâneo (TAS) nos obesos cirúrgicos, a despeito de quantidades semelhantes de Tecido Adiposo Visceral (TAV) em todos os grupos, sinalizando uma melhor composição corporal após a CB. A partir de um comportamento diferente de AMO, TAS e TAV, propõe-se a hipótese de que a AMO pode servir de depósito de energia nesse estado de deprivação/disabsorção. / Bone tissue is affected by both obesity and radical treatments, with marked loss of weight. Bariatric Surgery (BS) has been shown to be more effective for the treatment of severe obesity, but with data on bone mass deterioration and even an increased risk of fractures. The study aimed to evaluate the impact of rapid weight loss induced by BS in recent (one year) and late (five years) periods on the bone mass of obese subjects. In particular, there was an interest in investigating the association of Bone Marrow Adiposity (BMA) with bone mass, and three groups were evaluated: one was formed by normal control individuals; one for obese patients after the first year of BS; and the obese group after the 5th year of BS. Bone densitometry tests; magnetic resonance spectroscopy of spine and abdomen; biochemical tests for evaluation of bone mass, BMA, visceral and liver fat; and evaluation of hormonal and systemic factors that influence the bone and energy metabolism were performed. Bone Mineral Density (BMD) was adjusted by weight from the calculation of BMD rate, divided by kilogram of weight, with BMD QT being higher in the Control group, intermediate in the 1styear BS group and lower in the 5th-year BS group. There was an association between weight and BMD, showing its influence on bone mass and the presence of fracture by fragility in the operated groups. The increase in Parathormone (PTH), the reduction of calcemia in the long term and the negative correlation of PTH with the BMD of forearm were also noted in the long term. Telopeptide of type I procollagen (CTX) correlated negatively with L1-L4 BMD in the 5th-year BS group, and there was no correlation between insulin, osteocalcin, leptin, adiponectin and ghrelin levels with bone mass. It was documented the increase of BMA in patients submitted to BS in the long term (five years), besides a negative association of the saturated constituent of BMA with L3 BMD. Greater values of Subcutaneous Adipose Tissue (SAT) were observed in obese patients, despite similar amounts of Visceral Adipose Tissue (VAT) in all groups, signaling a better body composition after BS. From a different behavior of BMA, SAT and VAT, the proposed hypothesis is that BMA can serve as a deposit of energy in this state of deprivation/disabsorption.

Le but de ce travail était de déterminer les effets de la pratique d'activité physique sur le phénotype osseux et l'adiposité médullaire en cas d'insuffisance pondérale selon deux approches complémentaires, chez l'humain et chez les souris. La première étude a été menée sur 24 femmes normo-pondérées et 13 femmes en sous-poids âgées entre 20 et 35 ans. Cette étude a montré que les femmes en sous-poids présentent une faible masse osseuse au niveau du corps entier, rachis lombaire et col fémoral et une altération de la géométrie du col fémoral par rapport aux femmes normo-pondérées, et un score de l'os trabéculaire sur la limite inférieure de la normale. La VO₂ₘₐₓ (L/min) était parmi les principaux déterminants des paramètres osseux chez les jeunes femmes quel que soit leur indice de masse corporelle. Les résultats de cette première étude suggèrent que l'augmentation de la VO₂ₘₐₓ (L/min) sont essentiels pour prévenir la perte osseuse chez les jeunes femmes en sous-poids. La deuxième étude a été menée sur des souris femelles jeunes adultes soumises à un exercice physique volontaire dans une roue combinée à une restriction alimentaire (restriction de 50% de l'apport ad libitum) pendant 15 et 55 jours. Cette étude a démontré que la perte pondérale liée à la restriction alimentaire présente des répercussions négatives sur l'os cortical avec peu d'effets néfastes sur l'os trabéculaire et est associée à une augmentation du nombre des adipocytes médullaires dès 15 jours de restriction. Cette étude a également démontré que l'exercice physique volontaire dans une roue ne protège pas contre les modifications de l'architecture osseuse et l'accumulation de l'adiposité médullaire liées à la restriction alimentaire. Parce que la ghréline est apparue comme régulateur potentiel de l'adiposité médullaire, la troisième étude a été menée sur des souris femelles jeunes adultes dépourvues du récepteur de la ghréline (Growth Hormone Secretagogue Receptor, Ghsr-/-) soumises à une restriction alimentaire (restriction de 50% de l'apport ad libitum) combinée à un exercice physique volontaire dans une roue de 21 jours. Cette étude a démontré que la ghréline est un médiateur clé de l'expansion de l'adiposité médullaire associée à la restriction alimentaire suite à l'activation du GHSR et que la restriction alimentaire est nécessaire pour révéler certaines différences dans la microarchitecture osseuse associée à l'invalidation du GHSR. / The aim of this work was to determine the effects of physical activity on bone phenotype and bone marrow adiposity in underweight conditions using two complementary approaches, on human and on mice. The first study was conducted on 24 normal weight women and 13 underweight women aged 20-35 years. This study showed that underweight women have appropriately lower bone mass at the whole body, lumbar spine and femoral neck and altered femoral neck geometry compared to normal weight women, and a trabecular bone score on the lower limit of normal. VO₂ₘₐₓ (L/min) was considered as strong determinant of bone parameters in young adult women regardless of their body mass index. The results of this first study suggest that increasing VO₂ₘₐₓ (L/min) is essential to prevent bone loss in underweight young women. The second study was conducted on young adult female mice subjected to voluntary wheel running and food restriction (50% of ad libitum intake) during 15 and 55 days. This study demonstrated that weight loss related to food restriction has a negative impact on cortical bone with few adverse effects on trabecular bone and is associated with an increase in the number of bone marrow adipocytes already after 15 days of restriction. This study also showed that voluntary wheel running exercise does not protect against changes in bone architecture and accumulation of bone marrow adiposity related to food restriction. Because ghrelin appeared as a potential regulator of bone marrow adiposity, the third study was conducted on young adult mice lacking the ghrelin receptor (Growth Hormone Secretagogue Receptor, Ghsr-/-) subjected to voluntary wheel running and food restriction (50% of ad libitum intake) during 21 days. This study demonstrated that ghrelin is a key mediator of food restriction - associated bone marrow adiposity expansion through activation of GHSR and that food restriction is necessary to reveal some differences in bone microarchitecture associated to GHSR invalidation.