Osteocalcin, which is produced by the osteoblast, and the urinary pyridinium compounds (pyridinoline and deoxypyridinoline), which are derived from collagen, are widely used as markers of bone turnover. Osteocalcin was extracted from bone in 20% formic acid and separated using a linear 4-60% acetonitrile gradient containing 0.1% TFA at a flow rate of 1ml/min. The standard curve was linear up to 15 <I>μ</I>g of osteocalcin injected, with inter- and intra-assay coefficients of variation of 6.9 and 8.8% respectively while recovery of osteocalcin added to bone extracts averaged 102.7 ± 6.16 %. Having developed this assay it was then used in a series of experiments designed to study the biological function of osteocalcin in bone. Plasma osteocalcin levels decreased with age and showed large between-animal variations; the variability over 24 h was also large but there was no evidence of consistent circadian rhythm. In bone, changes in osteocalcin levels tended to parallel those for calcium whereas pyridinium crosslink levels tended to increase with age. Neither were sufficiently sensitive to detect differences in bone turnover in lambs of the same age but growing at different rates though osteocalcin levels in blood and in bone were sensitive to P-deficiency in sheep but not in pigs and there was little evidence indicating that osteocalcin plays any direct role in the mineralisation process. In separate studies adult sheep were treated with a bone antiresorptive agent, Ibandronate, and its effects on the metabolism and excretion of the pyridinium crosslinks was examined. At rates which have been shown to be effective in reducing bone resorption in humans this compound had little effect on the overall rate of excretion of these crosslinks in these sheep but did alter the proportions excreted in free or in peptide bound form.

To compare the efficacy and safety of nandrolone decanoate and calcium (NDC) with those of calcium alone (CAL) in men with idiopathic osteoporosis, a 12-month, randomized, prospective, controlled study, was performed in an outpatient clinic. Twenty-one men with idiopathic osteoporosis (as determined by radiological and dual energy x-ray absorptiometry findings) were randomly allocated to either 50 mg nandrolone decanoate intramuscularly (im) weekly and 1,000 mg oral calcium carbonate daily (NDC group) or to 1,000 mg oral calcium carbonate daily (CAL group). Bone densitometry (total body, left femur, and lumbar spine), serum, and urine biochemical parameters were measured at 3-month intervals. In the NDC group, bone mineral density initially increased, reached a plateau, and then decreased to near baseline levels at 12 months. Increases in lean muscle mass mirrored these changes. Free and total testosterone significantly decreased. Hemoglobin increased in all patients in this group. Patients in the CAL group exhibited no significant change in either total body or bone mineral density or biochemical parameters. Thus, nandrolone decanoate, 50 mg im weekly, transiently increases the bone mass of men with idiopathic osteoporosis in this preliminary study. Careful monitoring is necessary.

This thesis examines the overarching theme of inhaled corticosteroid (ICS) dose response effects on a variety of asthma outcome measures; with further importance placed on the application of these findings to personalising ICS dosing for the individual asthmatic. The introduction provides a detailed summary of the current recommendations for the treatment of adult asthma, with particular reference to the mechanism of action and clinical utility of ICS for the treatment of asthma. Current methods of assessing ICS dose response are presented, as well as the common influences that affect these responses. Novel therapeutic theories and the identification of specific asthmatic phenotypes are also introduced, in order to demonstrate the shift towards personalising treatment for asthma. The first two studies examine the dose response of ICS on two specific factors that influence asthma. The third study presents an examination of pharmacological manipulation of the ICS dose response using an additional agent. The following two studies address: how asthma outcomes relate to each other in patients receiving ICS; in addition to an overall assessment of the ICS dose response across a broad range of both ICS moieties and outcome measures. The final study examines for any detrimental effect of an ICS dose ramp on bone metabolism, an important potential long-term adverse effect of higher ICS dosing. The discussion draws together all the results obtained in relation to ICS dose response in asthma, and how these apply to current clinical practice for the individual patient. Furthermore, hypotheses are generated for areas of future study based on the findings from this work.

Sweden and Norway have the worldwide highest incidence of osteoporotic fractures. As these fractures constitute a tremendous and growing problem, primary prevention is of great importance. The principal causes of an osteoporotic fracture are a fall and a fragile skeleton. The aim of the studies reported in these papers was therefore to determine the genetic and environmental influences on fractures and the genetic influence on the two main reasons to the emergence of osteoporotic fractures; bone mineral density and propensity to fall. In the present thesis, we display that the heritability of fractures is dependent on fracture site and age. With increasing age, lifestyle becomes the dominant explanatory factor. These results indicate that focus should be on lifestyle interventions for the prevention of fractures in the elderly. Although the genetic liability to impaired balance is modest, twins with self-reported impaired balance have a substantially increased risk of osteoporotic fractures compared to their co-twin without impaired balance. Asking a patient about his or her balance might be a simple tool for future risk assessment. The genetic influence on bone phenotypes is under strong genetic influence in Swedish adult twins. These findings are in agreement with the results from previous studies in other countries, with a lower incidence of osteoporotic fractures compared to Sweden. The high heritability of bone phenotypes together with the low heritability of fractures at old age, indicates that bone mineral density has a modest influence on fracture risk at old age. In summary, based on the results in this thesis, more emphasis should be targeted to the prevention of falls, by strength and balance training in order to prevent the occurrence of  low energy fractures in the elderly.

Diets formulated to contain varying ratios of omega 6 to omega 3 fatty acids were fed to exercising yearlings to evaluate bone activity and inflammatory response. Nine Quarter Horse yearlings were arranged within a triplicated 3 X 3 Latin Square experimental design and fed one of three diets. Exercise protocol was designed to stimulate sub-clinical inflammation and normal bone response. Body weight and physical growth measurements were not different between groups (P > 0.05), and feed intake was similar between groups (P > 0.05). Horses consuming soybean oil (SBO) diet had lower fatty acid profiles (% by weight) of C16:0 and C16:1 (P < 0.05) when compared to horses consuming either corn oil (CO) or menhaden/corn oil (MCO) diets. Though numerically different, percentage changes in C16:0 and C16:1 were not different between diets (P < 0.05). Horses consuming MCO had significantly higher measurements of C20:4, C20:5 and C22:6 over the 28 day period when compared to horses consuming SBO or CO. Percent change in mean concentrations of C20:5 were significantly different between the MCO group and the SBO group (P < 0.05) with no observed difference between MCO and CO treatment groups. Overall mean carboxyterminal telopeptide of type I collagen (ICTP) concentrations did not differ between diets (P > 0.05) nor was there a significant change from baseline values when compared to day 28 of the period. Mean Osteocalcin (OC) concentrations did not differ between treatments (P > 0.05). Numerically, OC levels were lower after 14 days, with subsequent increases occurring from day 14 to day 28; however, there was no significant day effect (P > 0.05). Mean measurements of PGE2 and fibrinogen, the two inflammation markers evaluated, did not differ among groups (P > 0.05). However, when fibrinogen data were normalized, horses consuming SBO had a significantly lower change in baseline values of fibrinogen compared to horses fed CO or MCO diets (P< 0.05). In general, horses fed SBO exhibited reduced levels of the inflammatory marker fibrinogen (P< 0.05). No other variable evaluated was influenced by the supplementation of varying ratios of polyunsaturated fatty acids into the equine diet.

Introdução: Recém-nascidos prematuros hospitalizados costumam receber manuseio mínimo com objetivo de protegê-los de estresse. Como resultado desta inatividade pode ocorrer aumento da reabsorção óssea e desmineralização. Objetivo: Avaliar a formação óssea de recém-nascidos prematuros antes e após um protocolo de fisioterapia motora, por meio dos marcadores bioquímicos fosfatase alcalina óssea específica (FAO) e deoxipiridinolina urinária (DPID). Método: Ensaio clínico randomizado que incluiu 30 recém-nascidos com idades gestacionais de até 35 semanas e peso adequado para a idade gestacional randomizados em grupo controle (GC) e grupo fisioterapia (GF). No GF foi aplicado o protocolo de fisioterapia motora que consistiu de 15 minutos diários de movimentos passivos com compressões articulares suaves, cinco dias por semana. Diariamente foram obtidos dados sobre alimentação e peso corporal. FAO e DPID foram coletados na entrada e na alta hospitalar, em ambos os grupos. Foi realizado teste de ANCOVA para comparar as médias dos grupos. Resultados: No início do estudo a idade gestacional, a idade gestacional corrigida, o peso de nascimento e o gênero foram similares entre os grupos. Na oferta de nutrientes, tempo de uso de nutrição parenteral total e ventilação mecânica os grupos mostraram-se homogêneos. No GF o aumento nos níveis de FAO foi de 22,44 ± 3,49 U/L após a intervenção, ao passo que o GC apresentou aumento de 2,87 ± 3,99 U/L (p= 0,003). No GF houve redução nos níveis de DPID de 28,21 ± 11,05 nmol/mmol, enquanto no GC houve aumento de 49,95 ± 11,05 nmol/mmol (p<0,001). Conclusão: Uma proposta de intervenção fisioterapêutica aplicada por meio de exercícios passivos e por um curto período de tempo (15 minutos), diariamente ao longo de quatro semanas, associada com adequada alimentação, resulta em efeitos favoráveis ao metabolismo ósseo dos recém-nascidos prematuros. Os benefícios da prevenção e do tratamento da doença metabólica óssea da prematuridade, além de uma alimentação adequada, devem incluir estes exercícios passivos com suaves compressões articulares a fim de melhorar a qualidade óssea do prematuro. / Introduction: Preterm infants need minimal handling in order to protect them from stress, resulting in bone resorption and demineralization. Objetives: To evaluate bone formation in newborn preterm infants before and after a physical therapy protocol, by means of biochemical markers bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD). Method: Randomized controlled clinical trials included 30 newborn preterm infants with gestational ages of 35 weeks or less and appropriate weight for gestational age were randomized into control group (CG) and physiotherapy group (PG). Physical therapy protocol consisted of 15 minutes of daily passive movements with gentle joint compression, five days a week. Daily data were obtained on feeding and body weight. BAP and DPD were collected before and after intervention in both groups. ANCOVA test was performed to compare the means of both groups. Results: At baseline, gestational age and corrected gestational age, birth weight and gender were similar between groups. The supply of nutrients, time of use of Total Parenteral Nutrition and mechanical ventilation were similar among groups. The increase of BAP levels for PG was 22.44 ± 3.49 U/L, whereas CG presented an increase of 2.87 ± 3.99 U/L (p= 0.003). There was a reduction on DPD levels for PG of 28.21 ± 11.05 nmol/mmol, and an increase of 49.95 ± 11.05 nmol/mmol (p< 0.001) in GC. Conclusion: Physiotherapy intervention results in beneficial effects to bone metabolism of preterm infants and should be included in the standard care of preterm infants.

Introdução: Recém-nascidos prematuros hospitalizados costumam receber manuseio mínimo com objetivo de protegê-los de estresse. Como resultado desta inatividade pode ocorrer aumento da reabsorção óssea e desmineralização. Objetivo: Avaliar a formação óssea de recém-nascidos prematuros antes e após um protocolo de fisioterapia motora, por meio dos marcadores bioquímicos fosfatase alcalina óssea específica (FAO) e deoxipiridinolina urinária (DPID). Método: Ensaio clínico randomizado que incluiu 30 recém-nascidos com idades gestacionais de até 35 semanas e peso adequado para a idade gestacional randomizados em grupo controle (GC) e grupo fisioterapia (GF). No GF foi aplicado o protocolo de fisioterapia motora que consistiu de 15 minutos diários de movimentos passivos com compressões articulares suaves, cinco dias por semana. Diariamente foram obtidos dados sobre alimentação e peso corporal. FAO e DPID foram coletados na entrada e na alta hospitalar, em ambos os grupos. Foi realizado teste de ANCOVA para comparar as médias dos grupos. Resultados: No início do estudo a idade gestacional, a idade gestacional corrigida, o peso de nascimento e o gênero foram similares entre os grupos. Na oferta de nutrientes, tempo de uso de nutrição parenteral total e ventilação mecânica os grupos mostraram-se homogêneos. No GF o aumento nos níveis de FAO foi de 22,44 ± 3,49 U/L após a intervenção, ao passo que o GC apresentou aumento de 2,87 ± 3,99 U/L (p= 0,003). No GF houve redução nos níveis de DPID de 28,21 ± 11,05 nmol/mmol, enquanto no GC houve aumento de 49,95 ± 11,05 nmol/mmol (p<0,001). Conclusão: Uma proposta de intervenção fisioterapêutica aplicada por meio de exercícios passivos e por um curto período de tempo (15 minutos), diariamente ao longo de quatro semanas, associada com adequada alimentação, resulta em efeitos favoráveis ao metabolismo ósseo dos recém-nascidos prematuros. Os benefícios da prevenção e do tratamento da doença metabólica óssea da prematuridade, além de uma alimentação adequada, devem incluir estes exercícios passivos com suaves compressões articulares a fim de melhorar a qualidade óssea do prematuro. / Introduction: Preterm infants need minimal handling in order to protect them from stress, resulting in bone resorption and demineralization. Objetives: To evaluate bone formation in newborn preterm infants before and after a physical therapy protocol, by means of biochemical markers bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD). Method: Randomized controlled clinical trials included 30 newborn preterm infants with gestational ages of 35 weeks or less and appropriate weight for gestational age were randomized into control group (CG) and physiotherapy group (PG). Physical therapy protocol consisted of 15 minutes of daily passive movements with gentle joint compression, five days a week. Daily data were obtained on feeding and body weight. BAP and DPD were collected before and after intervention in both groups. ANCOVA test was performed to compare the means of both groups. Results: At baseline, gestational age and corrected gestational age, birth weight and gender were similar between groups. The supply of nutrients, time of use of Total Parenteral Nutrition and mechanical ventilation were similar among groups. The increase of BAP levels for PG was 22.44 ± 3.49 U/L, whereas CG presented an increase of 2.87 ± 3.99 U/L (p= 0.003). There was a reduction on DPD levels for PG of 28.21 ± 11.05 nmol/mmol, and an increase of 49.95 ± 11.05 nmol/mmol (p< 0.001) in GC. Conclusion: Physiotherapy intervention results in beneficial effects to bone metabolism of preterm infants and should be included in the standard care of preterm infants.

Submitted by Tatiane Souza dos Santos null (tatianesouza7@hotmail.com) on 2016-06-30T14:20:04Z No. of bitstreams: 1 Dissertação Tatiane Final.pdf: 1307496 bytes, checksum: 89e3b2f7bd2c32edaab8538b65c7914f (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-06-30T19:06:01Z (GMT) No. of bitstreams: 1 santos_ts_me_bot.pdf: 1307496 bytes, checksum: 89e3b2f7bd2c32edaab8538b65c7914f (MD5) / Made available in DSpace on 2016-06-30T19:06:01Z (GMT). No. of bitstreams: 1 santos_ts_me_bot.pdf: 1307496 bytes, checksum: 89e3b2f7bd2c32edaab8538b65c7914f (MD5) Previous issue date: 2016-06-24 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Este estudo objetivou avaliar o efeito de três fitases comerciais derivadas da Escherichia coli, em dietas com níveis reduzidos de fósforo disponível, sobre o desempenho, fosfatase alcalina e ácida no soro, cálcio e fósforo no plasma e nos parâmetros ósseos (densitometria óssea, resistência óssea e cinzas) de frangos de corte aos 35 dias de idade. Dois mil e cem pintos machos de um dia de idade da linhagem Cobb®500 foram alojados em 70 boxes em delineamento experimental inteiramente casualizado em esquema fatorial, criados até 35 dias de idade dividido em fase inicial (I) e fase de crescimento (C). Nos tratamentos Controle positivo*(CP*) e Controle negativo*(CN*) foi praticada a valorização nutricional da fitase preconizada pelos fabricantes (0,12% Pd) em relação aos tratamentos Controle positivo (CP) e Controle negativo (CN). O esquema fatorial foi 2x4+2: dois níveis de fósforo disponível (Pd) (CP* - 0,33% (I) e 0,28% (C)) e (CN* - 0,23% (I) e 0,18% (C)) × fitases (A, B, C, ausente) + CP (0,45 (I) e 0,40% (C) Pd, sem fitase) e CN (redução de 0,10% de Pd: 0,35 (I) e 0,30% (C) Pd, sem fitase) totalizando 10 tratamentos com sete repetições. A ausência de fitase na dieta CN* promoveu os piores resultados para desempenho e qualidade óssea, além de elevar o nível de fosfatase alcalina e cálcio no sangue como resposta ao baixo nível de fósforo disponível na dieta. A inclusão de fitases nas dietas CP* melhorou o desempenho, com maior disponibilidade de minerais para o desenvolvimento ósseo. Desta forma, a densidade óssea da tíbia e do fêmur aumentaram, proporcionando ossos mais resistentes e com maior porcentagem de cinzas. Recomenda-se, quando da utilização das fitases para frangos de corte, utilizar apenas a valorização nutricional da enzima (-0,12% Pd), sem redução adicional de fósforo disponível nas dietas. / This study aimed to evaluate the effect of three commercial phytases derived from Escherichia coli, in diets with reduced levels of available phosphorus, on performance, alkaline and acid phosphtases in serum, calcium and phosphorus in plasma and bone parameters (bone density, bone strength and ash) of broilers at 35 d old. Two thousand one hundred male Cobb®500 broilers were housed in 70 pens in a completely randomized design in factorial arrangement, reared to 35 d old divided into starter phase (I) and the grower phase (G). In treatments positive control* (PC*) and negative control*(NC*) was practiced nutritional value of phytase recommended by the manufacturer (0.12% aP) in relation to positive control (PC) and negative control (NC) treatments. The factorial design was 2x4+2: two levels of available phosphorus (aP) (PC* - 0.33% (S) and 0.28 % (G)) and (NC* - 0.23% (S) and 0.18% (G)) × phytases (A, B, C, without) + PC (0.45 (S) and 0.40% (G) aP without phytase) and NC (decrease of 0.10 of aP: 0.35 (S) and 0.30% (G) aP without phytase) for a total 10 treatments with seven replicates. The absence of phytase in the diet NC* promoted the worst results for performance and bone quality, and increased the level of alkaline phosphatase and calcium in the blood in response to low levels of available phosphorus in diet. The inclusion of phytase in diets PC* improve the performance and increased availability of minerals for bone development. Thus, increased the bone density of the tibia and femur, bone strenght and bone ash. It is concluded that the inclusion phytase in diets PC* was sufficient to ensure good performance and bone quality. It is recommended, while the use of phytases for broiler use only the nutritional value of phytase (-0.12% aP) without additional reduction of available phosphorus in the diets. / FAPESP: 2014/27175-8

Orientador: José Roberto Sartori / Resumo: Este estudo objetivou avaliar o efeito de três fitases comerciais derivadas da Escherichia coli, em dietas com níveis reduzidos de fósforo disponível, sobre o desempenho, fosfatase alcalina e ácida no soro, cálcio e fósforo no plasma e nos parâmetros ósseos (densitometria óssea, resistência óssea e cinzas) de frangos de corte aos 35 dias de idade. Dois mil e cem pintos machos de um dia de idade da linhagem Cobb®500 foram alojados em 70 boxes em delineamento experimental inteiramente casualizado em esquema fatorial, criados até 35 dias de idade dividido em fase inicial (I) e fase de crescimento (C). Nos tratamentos Controle positivo*(CP*) e Controle negativo*(CN*) foi praticada a valorização nutricional da fitase preconizada pelos fabricantes (0,12% Pd) em relação aos tratamentos Controle positivo (CP) e Controle negativo (CN). O esquema fatorial foi 2x4+2: dois níveis de fósforo disponível (Pd) (CP* - 0,33% (I) e 0,28% (C)) e (CN* - 0,23% (I) e 0,18% (C)) × fitases (A, B, C, ausente) + CP (0,45 (I) e 0,40% (C) Pd, sem fitase) e CN (redução de 0,10% de Pd: 0,35 (I) e 0,30% (C) Pd, sem fitase) totalizando 10 tratamentos com sete repetições. A ausência de fitase na dieta CN* promoveu os piores resultados para desempenho e qualidade óssea, além de elevar o nível de fosfatase alcalina e cálcio no sangue como resposta ao baixo nível de fósforo disponível na dieta. A inclusão de fitases nas dietas CP* melhorou o desempenho, com maior disponibilidade de minerais para o desenvolviment... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This study aimed to evaluate the effect of three commercial phytases derived from Escherichia coli, in diets with reduced levels of available phosphorus, on performance, alkaline and acid phosphtases in serum, calcium and phosphorus in plasma and bone parameters (bone density, bone strength and ash) of broilers at 35 d old. Two thousand one hundred male Cobb®500 broilers were housed in 70 pens in a completely randomized design in factorial arrangement, reared to 35 d old divided into starter phase (I) and the grower phase (G). In treatments positive control* (PC*) and negative control*(NC*) was practiced nutritional value of phytase recommended by the manufacturer (0.12% aP) in relation to positive control (PC) and negative control (NC) treatments. The factorial design was 2x4+2: two levels of available phosphorus (aP) (PC* - 0.33% (S) and 0.28 % (G)) and (NC* - 0.23% (S) and 0.18% (G)) × phytases (A, B, C, without) + PC (0.45 (S) and 0.40% (G) aP without phytase) and NC (decrease of 0.10 of aP: 0.35 (S) and 0.30% (G) aP without phytase) for a total 10 treatments with seven replicates. The absence of phytase in the diet NC* promoted the worst results for performance and bone quality, and increased the level of alkaline phosphatase and calcium in the blood in response to low levels of available phosphorus in diet. The inclusion of phytase in diets PC* improve the performance and increased availability of minerals for bone development. Thus, increased the bone density of the ti... (Complete abstract click electronic access below) / Mestre

Introdução: Recém-nascidos prematuros hospitalizados costumam receber manuseio mínimo com objetivo de protegê-los de estresse. Como resultado desta inatividade pode ocorrer aumento da reabsorção óssea e desmineralização. Objetivo: Avaliar a formação óssea de recém-nascidos prematuros antes e após um protocolo de fisioterapia motora, por meio dos marcadores bioquímicos fosfatase alcalina óssea específica (FAO) e deoxipiridinolina urinária (DPID). Método: Ensaio clínico randomizado que incluiu 30 recém-nascidos com idades gestacionais de até 35 semanas e peso adequado para a idade gestacional randomizados em grupo controle (GC) e grupo fisioterapia (GF). No GF foi aplicado o protocolo de fisioterapia motora que consistiu de 15 minutos diários de movimentos passivos com compressões articulares suaves, cinco dias por semana. Diariamente foram obtidos dados sobre alimentação e peso corporal. FAO e DPID foram coletados na entrada e na alta hospitalar, em ambos os grupos. Foi realizado teste de ANCOVA para comparar as médias dos grupos. Resultados: No início do estudo a idade gestacional, a idade gestacional corrigida, o peso de nascimento e o gênero foram similares entre os grupos. Na oferta de nutrientes, tempo de uso de nutrição parenteral total e ventilação mecânica os grupos mostraram-se homogêneos. No GF o aumento nos níveis de FAO foi de 22,44 ± 3,49 U/L após a intervenção, ao passo que o GC apresentou aumento de 2,87 ± 3,99 U/L (p= 0,003). No GF houve redução nos níveis de DPID de 28,21 ± 11,05 nmol/mmol, enquanto no GC houve aumento de 49,95 ± 11,05 nmol/mmol (p<0,001). Conclusão: Uma proposta de intervenção fisioterapêutica aplicada por meio de exercícios passivos e por um curto período de tempo (15 minutos), diariamente ao longo de quatro semanas, associada com adequada alimentação, resulta em efeitos favoráveis ao metabolismo ósseo dos recém-nascidos prematuros. Os benefícios da prevenção e do tratamento da doença metabólica óssea da prematuridade, além de uma alimentação adequada, devem incluir estes exercícios passivos com suaves compressões articulares a fim de melhorar a qualidade óssea do prematuro. / Introduction: Preterm infants need minimal handling in order to protect them from stress, resulting in bone resorption and demineralization. Objetives: To evaluate bone formation in newborn preterm infants before and after a physical therapy protocol, by means of biochemical markers bone-specific alkaline phosphatase (BAP) and urinary deoxypyridinoline (DPD). Method: Randomized controlled clinical trials included 30 newborn preterm infants with gestational ages of 35 weeks or less and appropriate weight for gestational age were randomized into control group (CG) and physiotherapy group (PG). Physical therapy protocol consisted of 15 minutes of daily passive movements with gentle joint compression, five days a week. Daily data were obtained on feeding and body weight. BAP and DPD were collected before and after intervention in both groups. ANCOVA test was performed to compare the means of both groups. Results: At baseline, gestational age and corrected gestational age, birth weight and gender were similar between groups. The supply of nutrients, time of use of Total Parenteral Nutrition and mechanical ventilation were similar among groups. The increase of BAP levels for PG was 22.44 ± 3.49 U/L, whereas CG presented an increase of 2.87 ± 3.99 U/L (p= 0.003). There was a reduction on DPD levels for PG of 28.21 ± 11.05 nmol/mmol, and an increase of 49.95 ± 11.05 nmol/mmol (p< 0.001) in GC. Conclusion: Physiotherapy intervention results in beneficial effects to bone metabolism of preterm infants and should be included in the standard care of preterm infants.