RESUMO
The cortical structure of human fibula varies widely throughout the bone suggesting a more selective adaptation to different mechanical environments with respect to the adjacent tibia. To test this hypothesis, serial-pQCT scans of the dominant fibulae and tibiae of 15/15 men/women chronically trained in long-distance running were compared with those of 15/15 untrained controls. When compared to controls, the fibulae of trained individuals had similar (distally) or lower (proximally) cortical area, similar moments of inertia (MI) for anterior-posterior bending (xMI) and lower for lateral bending (yMI) with a lower "shape-index" (yMI/xMI ratio) throughout, and higher resistance to buckling distally. These group differences were more evident in men and independent of group differences in bone mass. These results contrast with those observed in the tibia, where, as expected, structural indicators of bone strength were greater in trained than untrained individuals. Proximally, the larger lateral flexibility of runners' fibulae could improve the ability to store energy, and thereby contribute to fast-running optimization. Distally, the greater lateral fibular flexibility could reduce bending strength. The latter appears to have been compensated by a higher buckling strength. Assuming that these differences could be ascribed to training effects, this suggests that usage-derived strains in some bones may modify their relative structural resistance to different kinds of deformation in different regions, not only regarding strength, but also concerning other physiological roles of the skeleton.
RESUMO
Para analizar el impacto directo de la musculatura sobre la estructura ósea se determinaron el área (CtA), la densidad mineral ósea volumétrica (vDMOc) y los momentos de inercia corticales para flexión anteroposterior y lateral (MIap, MIlat) ajustados a CtA, y las relaciones entre MI y vDMOc (de Ê»distribución/calidadʼ, d/c, que describen la eficiencia de la optimización biomecánica del diseño cortical por el mecanostato) en 18 cortes seriados a lo largo de todo el peroné del lado hábil (pQCT), y la fuerza de salto y de rotación externa del pie (dinamometría computarizada) de 22 hombres sanos de 18 a 33 años entrenados en fútbol competitivo por más de 4 años, y de 9 controles etarios no entrenados. Los entrenados tuvieron valores más altos de MI en función de la fuerza de rotación del pie (no de salto), con un ajuste homogéneo para MIap pero variable (más pobre distalmente y más alto proximalmente, en la región de inserción de los peroneos) para MIlat, coincidiendo este último con pobres ajustes de las relaciones d/c (efecto arquitectónico independiente de la rigidez del tejido). Esto evidencia la influencia directa de la tracción de la musculatura peronea sobre la estructura cortical proximal subyacente del hueso y también sugiere que el mecanostato procedería, en este caso, fuera de su conocida concepción como mecanismo regulatorio de la resistencia ósea. (AU)
To analyze the direct impact of muscle contractions on the structure of bones, we determined the cortical cross-sectional area (CtA), volumetric mineral density (vBMDc) and the CtA-adjusted moments of inertia for anterior-posterior and lateral bending (MIap, MIlat), and the ʻdistribution/qualityʼ (d/c) relationships between MIs and vBMDc (which describe the efficiency of the biomechanical optimization of cortical design by bone mechanostat) in 18 serial scans taken throughout the fibula of the dominant side (pQCT), and the jump and the foot-lateral-rotation forces (computed dynamometry) of 22 healthy men aged 18-33 years, who had been trained in competitive soccer for more than 4 years, and of 9 untrained, agematched controls. Trained individuals showed higher MI values as a function of the rotative force of the foot (not the jumping force). The adjustment of these relationships was homogeneous for MIap throughout the bone, but variable (poorer distally and higher proximally, at the insertion area of peroneus muscles) for MIlat, this latter being paralleled by poor adjustments of the corresponding, d/c relationships (architectural effect independent of tissue stiffness). These findings,1. Show the direct influence of the traction force of peroneal muscles on proximal fibula structure close to the insertion area, and 2. Suggest that, in the studied conditions, the bone mechanostat would proceed beyond its known conception as a regulatory mechanism of structural bone strength. (AU)
Assuntos
Fíbula/fisiopatologia , Sistema Musculoesquelético/diagnóstico por imagem , Fenômenos Fisiológicos Musculoesqueléticos , Futebol , Fenômenos Biomecânicos/fisiologia , Osso e Ossos/fisiopatologia , Exercício Físico , Fraturas Ósseas/prevenção & controle , Fíbula/anatomia & histologia , Pé/diagnóstico por imagem , Músculos/fisiopatologiaRESUMO
This study describes the structural features of fibula cortical shell as allowed by serial pQCT scans in 10/10 healthy men and women aged 20-40years. Indicators of cortical mass (mineral content -BMC-, cross-sectional area -CSA-), mineralization (volumetric BMD, vBMD), design (perimeters, thickness, moments of inertia -MIs-) and strength (Bone Strength Indices, BSIs; polar Strength-Strain Index, pSSI) were determined. All cross-sectional shapes and geometrical or strength indicators suggested a sequence of five different regions along the bone, which would be successively adapted to 1. transmit loads from the articular surface to the cortical shell (near the proximal tibia-fibular joint), 2. favor lateral bending (central part of upper half), 3. resist lateral bending (mid-diaphysis), 4. favor lateral bending again (central part of the lower half), and 5. resist bending/torsion (distal end). Cortical BMC and the cortical/total CSA ratio were higher at the midshaft than at both bone ends (p<0.001). However, all MIs, BSIs and pSSI values and the endocortical perimeter/cortical CSA ratio (indicator of the mechanostat's ability to re-distribute the available cortical mass) showed a "W-shaped" distribution along the bone, with maximums at the mid-shaft and at both bone's ends (site effect, p<0.001). The correlation coefficient (r) of the relationship between MIs (y) and cortical vBMD (x) at each bone site ("distribution/quality" curve that describes the efficiency of distribution of the cortical tissue as a function of the local tissue stiffness) was higher at proximal than distal bone regions (p<0.001). The results from the study suggest that human fibula is primarily adapted to resist bending and torsion rather than compression stresses, and that fibula's bending strength is lower at the center of its proximal and distal halves and higher at the mid-shaft and at both bone's ends. This would favor, proximally, the elastic absorption of energy by the attached muscles that rotate or evert the foot, and distally, the widening of the heel joint and the resistance to excessive lateral bending. Results also suggest that biomechanical control of structural stiffness differs between proximal and distal fibula.
Assuntos
Osso Cortical/anatomia & histologia , Osso Cortical/fisiologia , Fíbula/anatomia & histologia , Fíbula/fisiologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Fenômenos Biomecânicos , Densidade Óssea , Osso Cortical/diagnóstico por imagem , Feminino , Fíbula/diagnóstico por imagem , Humanos , Masculino , Tamanho do Órgão , Adulto JovemRESUMO
Se define como estrés (stress) tanto la fuerza que una carga externa ejerce sobre un cuerpo sólido como la fuerza reactiva que acompaña a la primera (Ley de Newton), por unidad de área imaginaria transversal a su dirección. Las cargas internas reactivas inducen deformaciones proporcionales del cuerpo. La resistencia del cuerpo a deformarse se llama rigidez. La deformación puede resquebrajar el cuerpo y, eventualmente, producir una fractura por confluencia de trazos. La resistencia del cuerpo a separarse en fragmentos por esa causa se llama tenacidad. La resistencia del cuerpo a la fractura es proporcional al stress que puede soportar sin separarse en fragmentos por deformación (no hay fractura sin deformación y sin stress previo). El stress máximo que un cuerpo puede soportar sin fracturarse resulta de una combinación de ambas propiedades: rigidez y tenacidad, cada una con distintos determinantes biológicos. Una o varias deformaciones del cuerpo pueden provocarle resquebrajaduras sin fracturarlo. La acumulación de resquebrajaduras determina la "fatiga" del material constitutivo del cuerpo, que reduce su rigidez, tenacidad y resistencia a la fractura para la próxima ocasión ("fragilidad por fatiga"). En el caso de los huesos, en general, los términos stress y fatiga tienen las connotaciones amplias referidas, respecto de todas las fracturas posibles. La fatiga predispone a fracturas a cargas bajas, que se denominan (correctamente) "fracturas por fatiga" y también (incorrectamente) "fracturas por stress", para distinguirlas de las que ocurren corrientemente, sin resquebrajaduras previas al trauma, que se denominan (incorrectamente) "fracturas por fragilidad, o por insuficiencia". En realidad, todas las fracturas se producen por stress y por fragilidad o insuficiencia (en conjunto); pero la distinción grosera entre fracturas "por fatiga, o por stress", por un lado, y "por fragilidad" o "por insuficiencia", por otro, aceptando las amplias connotaciones referidas antes, tiene valor en la práctica clínica. Este artículo intenta explicar esas particularidades biomecánicas y describir las distintas condiciones que predisponen a las fracturas "por fatiga o por stress" en la clínica, distinguiéndolas de las fracturas "por fragilidad o por insuficiencia" (manteniendo estas denominaciones) y detallando las características de interés directo para su diagnóstico y tratamiento. (AU)
The term "stress" expresses the force exerted by an external load on a solid body and the accompanying, opposed force (Newton's Law), expressed per unit of an imaginary area perpendicular to the loading direction. The internal loads generated this way deform (strain) proportionally the body's structure. The resistance of the body to strain expresses its stiffness. Critical strain magnitudes may induce micro-fractures (microdamage), the confluence of which may fracture the body. The body's resistance to separation into fragments determines its toughness. Hence, the body's resistance to fracture is proportional to the stress the body can support (or give back) while it is not fractured by the loadinduced strain (no stress, no strain -> no fracture). Therefore, the maximal stress the body can stand prior to fracture is determined by a combination of both, its stiffness and its toughness; and each of those properties is differently determined biologically. One or more deformations of the body may induce some microdamage but not a fracture. Microdamage accumulation determines the fatigue of the material constitutive of the body and reduces body's toughness, leading to a "fatigue-induced fragility". In case of bones, in general, both stress and fatigue have the referred, wide connotations, regarding any kind of fractures. In particular, bone fatigue predisposes to low-stress fractures, which are named (correctly) "fatigue fractures" and also misnamed "stress fractures", to distinguish them from the current fractures that occur without any excess of microdamage, that are named (wrongly) "fragility" or "insufficiency" fractures. In fact, all fractures result from all stress and fragility or insufficiency as a whole; however, the gross distinction between "fatigue or stress fractures", on one side, and "fragility or insufficiency fractures", on the other, accepting the wide connotations of the corresponding terminology, is relevant to clinical practice. This article aims to explain the above biomechanical features and describe the different instances that predispose to "fatigue or stress fractures" in clinical practice, as a different entity from "insufficiency or fragility fractures" (maintaining this nomenclature), and describe their relevant features to their diagnosis and therapy. (AU)
Assuntos
Humanos , Fenômenos Biomecânicos/fisiologia , Fraturas de Estresse/fisiopatologia , Osteogênese Imperfeita/etiologia , Osso e Ossos/fisiologia , Osso e Ossos/química , Fragilidade/fisiopatologia , Resistência à Flexão/fisiologiaRESUMO
Este trabajo consta de dos secciones, que, en orden didáctico, exponen I. una actualización del conocimiento elemental actual sobre interrelaciones biomecánico-estructurales entre los huesos y su entorno mecánico, y II. unaaplicación de esos conceptos al análisis y a la interpretación de datos tomográficos de varios indicadores osteomusculares obtenidos de individuos que sobrellevan habitualmente distintas intensidades de actividad física. En la sección de actualización, se destaca que el desarrollo de los esqueletos está determinado, en todos los vertebrados, por factores morfogenéticos y epigenéticos, y que, de estos últimos, prácticamente sólo intervienenmoduladores mecánicos y endocrinometabólicos. Los moduladores mecánicos tienen efectos direccionales, y constituyen el input del mecanostato óseo, un sistema que regula la única propiedad ósea cibernéticamente controlada en todos los esqueletos: la rigidez estructural de cada hueso, con alta especificidad regional. Los moduladores endocrinometabólicostienen efectos sistémicos, no direccionales, que modulan la mayoría de las funciones y propiedades óseas, pero que no participan en la regulación retroalimentada de ninguna de ellas. Se añade una referencia técnica a la metodología de pQCT que fundamentasu aplicabilidad al análisis del estadoosteo-muscular humano de acuerdo conesas nuevas ideas. En la sección de aplicaciones clínicas, se presentanalgunos estudios tomográficos (pQCT)recientes de la tibia, efectuados en forma preliminar en varones y mujeres adultos, sanos, de hábitos sedentarios o crónicamente entrenados en carrera de larga distancia.(AU)
Assuntos
Humanos , Masculino , Feminino , Sistema Musculoesquelético , Atividade Motora , Fenômenos Biomecânicos , Biomarcadores Ambientais , Fenômenos Fisiológicos Musculoesqueléticos , Desenvolvimento Musculoesquelético , Esqueleto , Desenvolvimento ÓsseoRESUMO
Este trabajo consta de dos secciones, que, en orden didáctico, exponen I. una actualización del conocimiento elemental actual sobre interrelaciones biomecánico-estructurales entre los huesos y su entorno mecánico, y II. unaaplicación de esos conceptos al análisis y a la interpretación de datos tomográficos de varios indicadores osteomusculares obtenidos de individuos que sobrellevan habitualmente distintas intensidades de actividad física. En la sección de actualización, se destaca que el desarrollo de los esqueletos está determinado, en todos los vertebrados, por factores morfogenéticos y epigenéticos, y que, de estos últimos, prácticamente sólo intervienenmoduladores mecánicos y endocrinometabólicos. Los moduladores mecánicos tienen efectos direccionales, y constituyen el input del mecanostato óseo, un sistema que regula la única propiedad ósea cibernéticamente controlada en todos los esqueletos: la rigidez estructural de cada hueso, con alta especificidad regional. Los moduladores endocrinometabólicostienen efectos sistémicos, no direccionales, que modulan la mayoría de las funciones y propiedades óseas, pero que no participan en la regulación retroalimentada de ninguna de ellas. Se añade una referencia técnica a la metodología de pQCT que fundamentasu aplicabilidad al análisis del estadoosteo-muscular humano de acuerdo conesas nuevas ideas. En la sección de aplicaciones clínicas, se presentanalgunos estudios tomográficos (pQCT)recientes de la tibia, efectuados en forma preliminar en varones y mujeres adultos, sanos, de hábitos sedentarios o crónicamente entrenados en carrera de larga distancia.
Assuntos
Humanos , Masculino , Feminino , Biomarcadores Ambientais , Fenômenos Biomecânicos , Atividade Motora , Desenvolvimento Musculoesquelético , Fenômenos Fisiológicos Musculoesqueléticos , Sistema Musculoesquelético , Desenvolvimento Ósseo , EsqueletoRESUMO
PURPOSE: The purpose was to study the relationship between mechanical environment and bone structure by comparing the tibia in people with different physical activities. MATERIALS AND METHODS: Indicators of bone mass (bone mineral content), bone material "quality" (cortical volumetric mineral density (vBMD)), and diaphyseal design (endocortical and periosteal perimeters (EcPm and PoPm, respectively), cortical thickness (CtTh), circularity, and bending and torsion cross-sectional moments of inertia (CSMIs)) were determined in serial peripheral quantitative computed tomography scans taken at 5% steps of the tibia in 40 voluntary men and women age 25-40 yr who were either physically inactive or experienced distance runners (n = 10-12 per group). RESULTS: Bone mass and design indicators were higher in runner than in nonrunner men, with a variable effect size along the tibia. In the distal tibia, runners had enhanced bone mineral content and CtTh (resistance to compression), but EcPm, PoPm, circularity, and CSMI were unaffected. In the midshaft, CSMIs (resistance to bending/torsion) were enhanced in runners, whereas bone mass was unaffected. In the proximal third, effects were observed for CtTh, EcPm, and PoPm. In female runners, these benefits were restricted to CSMIs only. Cortical vBMD, naturally lower in men than in women, was reduced in runners of either sex. DISCUSSION: Results are coherent with previous findings in physically inactive people and with Frost's mechanostat theory. The observed group differences in cortical vBMD could reflect an increase in intracortical porosity (enhanced remodeling for damage repair), eventually compensated biomechanically by CSMI improvements. The sex specificity of exercise effects may suggest the interference by the endocrine environment. Results confirm that the mechanical environment is a strong determinant of regional tibia structure and suggest that the endocrine environment may reduce the effects of physical interventions on bone health in fertile women.
Assuntos
Densidade Óssea/fisiologia , Corrida/fisiologia , Tíbia/anatomia & histologia , Adulto , Atletas , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Comportamento Sedentário , Fatores Sexuais , Tíbia/fisiologiaRESUMO
En las últimas décadas, nuestro grupo de trabajo ha contribuido a desarrollar algunas de las nuevas ideas sobre las verdaderas características estructurales que definen la llamada ôcalidad óseaõ, y sus relaciones con sus determinantes genéticos y con la influencia de los entornos mecánico y sistémico que afectan a las células óseas.La moderna corriente es suficientementeimportante como para haber desviadoel interés de los sponsors internacionales de estudios clínicos controlados. El antiguo estudio densitométrico de masas mineralizadas, y el análisis bioquímico de indicadores del turnover óseo, ceden prioridad hoy al estudio de imágenes seccionales osteo-musculares con criterio biomecánico, y al análisis de las interacciones músculo-hueso. Este conocimiento configura ya una unidadconceptual suficientemente coherentecomo para ser divulgado en forma integrada, para uso del médico práctico. Pese a la obvia complejidad del marco teórico del tema en cuestión, los aspectos más relevantes de la nueva corriente de pensamiento para la correcta interpretación de la Osteología moderna pueden resumirse en 13 puntos críticos, cada uno de ellos defácil comprensión si se lo analiza por separado. A continuación se expone una secuencia didáctica de esos 13 puntos, que enumera y describe, para cada uno de ellos, una triada de aspectos fundamentales para su comprensióny asimilación a la nueva corriente, y deriva de ellos un mensaje práctico para su aplicación fisiopatológica, clínica, o terapéutica.
Assuntos
Humanos , Masculino , Feminino , Fenômenos Biomecânicos , Desenvolvimento Ósseo/genética , Fraturas Ósseas/genética , Fraturas Ósseas/metabolismo , Estruturas Genéticas , Osso e Ossos/fisiologia , Osso e Ossos/metabolismoRESUMO
OBJECTIVE: This study evaluated dual-energy x-ray absorptiometry-assessed whole-body bone-muscle relationship (bone mineral content/lean mass [BMC/LM]) as an indicator of its nonmechanical perturbations (ie, systemic) in pre- and postmenopausal women. A total of 3,205 women were studied, either healthy (no fracture [No Fx] groups, 1,035 premenopausal, 1,556 postmenopausal) or with recent fractures (Fx groups, 139 premenopausal, 475 postmenopausal) located at osteoporotic sites (hip, spine, long-bone metaphyses; Type II Fx, n = 386) or at other skeletal sites (Type I Fx, n = 228) to evaluate the impact of decreased muscle mass on fracture incidence before and after menopause. DESIGN: SD-scored graphs of BMC/LM proportionality were obtained from the No Fx groups as normal references. Based on the reference BMC versus LM curves obtained from their respective No Fx pre- and postmenopausal controls, BMC-LM SD scores were calculated for all women with fractures. RESULTS: BMC-LM SD scores in all premenopausal women with fractures and in Type I Fx postmenopausal women were similar to the reference. In contrast, SD scores in Type II Fx postmenopausal women were lower than the reference, especially in those with hip fractures. Except for Type II Fx postmenopausal women, all groups showed linear and similar BMC versus LM curves. Type II Fx postmenopausal women showed nonlinear relationships, with progressively decreasing BMC and BMC-LM SD scores as their LM decreased. CONCLUSIONS: Results suggest that both LM and BMC-LM SD scores can help to differentiate between systemic and mechanical (disuse-related) osteopenia/osteoporosis after menopause. Low LM values or BMC-LM SD scores seem to constitute additional fracture risk factors beyond those usually detected in premenopausal women or in women with other types of fractures. This application of dual-energy x-ray absorptiometry technology may lead to more effective diagnosis and treatment at low cost.
Assuntos
Composição Corporal , Peso Corporal , Fraturas Ósseas/epidemiologia , Osteoporose Pós-Menopausa/epidemiologia , Absorciometria de Fóton , Idoso , Argentina/epidemiologia , Densidade Óssea , Causalidade , Comorbidade , Feminino , Fraturas Ósseas/diagnóstico , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/diagnóstico , Valor Preditivo dos Testes , Valores de Referência , Fatores de Risco , Saúde da MulherRESUMO
Correlations between dual-energy X-ray absorptiometry (DXA)-assessed bone mineral content and lean mass (BMC-LM curves), and between BMC/LM ratio and age ([BMC/LM]-age curves), were analyzed in the whole body (WB), the upper limbs (ULs) and the lower limbs (LLs) of 3,063 healthy Hispanic adults. Groups of 472 men aged 25-87 years, 1,035 premenopausal (pre-MP) women aged 27-54 years, and 1,556 post-menopausal (post-MP) women aged 48-93 years were studied with a GE-Lunar DPX-Plus device. BMC-LM curves confirmed previous observations that BMC and LM masses always correlate linearly, with similar slopes within each region, but differing in intercepts according to gender and hormonal status. Multiple regression tests showed little or no independent interaction of body weight or height with those relationships. [BMC/LM]-age curves were flat in men but showed the positive influence of estrogens throughout the age range in women. Z-scored graphs of all the corresponding relationships were compiled, showing the confidence intervals for means +/-1, +/-2, and +/-3 SDs of the data (+/-1, +/-2, +/-3 z-scores) along BMC-LM and [BMC/LM]-age curves. These charts are proposed as references for assessing how well bone mass (as assessed by BMC) and muscle mass (assumed proportional to LM) follow the natural anthropometric/biomechanical proportionality in Hispanic men and women within the age range studied, employing similar devices. Charts for LLs, showing the lowest variance amongst the studied correlations and approaching the origin as an exclusive feature, could provide the most accurate reference curves. Differences between data from ULs and LLs may provide information about any eventual interaction of body-weight bearing with the general results. The proposed analysis may provide useful information for approaching a differential diagnosis between disuse-related and other types of osteopenias employing only DXA.
Assuntos
Absorciometria de Fóton/métodos , Composição Corporal/fisiologia , Densidade Óssea/fisiologia , Menopausa/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braço , Colômbia/epidemiologia , Feminino , Humanos , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Pós-Menopausa/fisiologia , Pré-Menopausa/fisiologia , Valores de Referência , Estudos RetrospectivosRESUMO
In this article, we summarize the results of six different tomographic/biomechanical rat studies involving hypophysectomy (Hx), ovariectomy, treatment with rhGH, olpadronate, alendronate, and toxic doses of aluminum and the development of a genetic diabetes in the eSS strain. All these conditions induced some interesting and rarely reported effects on postyield bone strength. These effects were generally related neither to the degree of mineralization or the elastic modulus of the bone tissue nor to the preyield behavior of the bones. In two particular cases (Hx, eSS), the elastic modulus of bone tissue varied independently of its degree of mineralization. These results suggest the involvement of some microstructural factor(s) of bone tissue resistance to crack progression (a postyield feature of bone behavior), rather than to crack initiation (the yield-determining factor) in the corresponding mechanism. Changes in collagen or crystal structure may play that role. These changes are relevant to the mechanism of fracture production during plastic deformation, a feature of bone strength that might be independent from mineralization. Therefore, these changes might help to explain some effects of novel treatments on bone strength unrelated to bone mineralization. This questions the belief that the remaining bone mass in metabolic osteopenias is biologically and mechanically normal.
Assuntos
Densidade Óssea/fisiologia , Calcificação Fisiológica/fisiologia , Animais , Doenças Ósseas Metabólicas/fisiopatologia , Feminino , Fraturas Ósseas/fisiopatologia , Humanos , Ratos , Ratos Sprague-Dawley , Estresse Mecânico , Resistência à Tração/fisiologiaRESUMO
This report summarizes some preliminary absorptiometric (DXA, QCT/pQCT) studies from our laboratory, supporting the following assumptions. 1. In Homo sapiens at all ages, natural proportionality between DXA-assessed bone mineral mass (bone mineral content, BMC) and muscle mass (lean mass, LM) of the whole body or limbs is specific for ethnicity, gender, and reproductive status, but not for body weight, height, or body mass index. 2. This proportionality is sensitive to many kinds of endocrine-metabolic perturbations. 3. Percentilized or Z-scored charts of the BMC/LM correlations as determined in large samples of healthy individuals can provide a diagnostic reference for evaluating proportionality in different conditions. 4. Employing exclusively DXA, this methodology can be applied to discriminate between "disuse-related" and "metabolic" osteopenias based on the finding of normal or low BMC/LM percentiles or Z-scores respectively, with important therapeutic and monitoring implications.
Assuntos
Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Osteoporose/diagnóstico por imagem , Absorciometria de Fóton , Osso e Ossos/patologia , Feminino , Humanos , Masculino , Músculo Esquelético/patologia , Tamanho do Órgão , Osteoporose/patologiaRESUMO
To study the musculoskeletal effects of hypophysectomy (Hx) and a partial replacement treatment with recombinant human growth hormone (rhGH) in rats, we determined the stiffness (elastic modulus, E) and volumetric BMD (vBMD) of cortical bone; the periosteal and endosteal perimeters, area and bending moment of inertia (xCSMI) of the cross sections, and the structural stiffness and pre- and post-yield strength of the femur diaphyses by pQCT and mechanical tests, and the gastrocnemius weight of rats that were either intact (n = 9) or Hx at 15 days of age (20). The latter were otherwise untreated (Hx controls, 4) or given 0.4 (8) or 2.0 (8) IU kg(-1) day(-1), s.c., of rhGH for 45 days starting 15 days after surgery. Hx delayed musculoskeletal development (gastrocnemius weight, bone geometric properties), thus affecting the diaphyseal stiffness and strength. It also reduced the cortical vBMD through an undefined mechanism, and increased the elastic modulus of cortical bone. The Hx also affected the correlation between bone geometric and material properties (xCSMI vs. E), suggesting an antianabolic interaction with the biomechanical control of bone modeling in response to strains caused by mechanical usage. As a result, Hx reduced the stiffness, post-yield, and ultimate strength of the diaphyses. These effects should reflect changes in bone tissue microstructure, perhaps associated with crack generation and progress, but unrelated to bone mineral mass. They are compatible with the induction of a delay in collagen turnover with associated increases in fibers' diameter and crystals' size that may have resulted from the suppression of some other hormones, such as thyroid, prolactin, or other hormones regulated by ACTH. The above doses of rhGH significantly but incompletely prevented the negative Hx effects on bone and muscle development (bone geometric properties, muscle mass). However, rhGH treatment failed to prevent the demineralizing and stiffening effect of Hx on bone tissue and the unusual effects on the post-yield strength (less clearly related to muscle development than the former). Consequently, rhGH treatment tended to preserve the natural relationship between muscle function and bone geometry but not bone strength. The effects of larger rhGH doses and the interaction of other hormones with the described effects remain to be investigated. Nevertheless, these findings would deserve special attention because they challenge the prevailing view that in endocrine-metabolic bone-weakening diseases the bone matrix always has a normal composition.
Assuntos
Envelhecimento/fisiologia , Fêmur/efeitos dos fármacos , Hormônio do Crescimento Humano/farmacologia , Hipofisectomia , Animais , Calcificação Fisiológica/efeitos dos fármacos , Feminino , Fêmur/anatomia & histologia , Fêmur/crescimento & desenvolvimento , Hormônio do Crescimento Humano/genética , Músculos/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Nuevos desarrollos en osteología están ejerciendo impacto sobre la interpretación de algunos aspectos nutricionales de la fisiopatología, el diagnóstico y el tratamiento de todas las enfermedades que reducen la masa o la resistencia esquelética. En general, esos conceptos se refieren principalmente a 1. los diferentes niveles de complejidad biológica de las estructuras esqueléticas;2. los verdaderos determinantes de las propiedades biomecánicas del hueso y de los huesos;3. la forma como los huesos se autoensamblan;4. el control biológico de la eficiencia biomecánica de la estructura ósea;5. los efectos del entorno mecánico sobre la expresión de los determinantes genéticos de las características estructurales óseas, y 6. la interferencia de factores sistémicos (no-direccionales), endocrino-metabólicos, sobre el control biomecánico de la rigidez y la resistencia óseas. Este trabajo ofrece una visión general de esas cuestiones, focalizada en los fundamentos necesarios para interpretar el papel de la nutrición en la fisiología y fisiopatología óseas, y las interferencias nutricionales con los correspondientes mecanismos.
Assuntos
Osso e Ossos , Ciências da Nutrição , Fenômenos Biomecânicos , Doenças Ósseas Metabólicas , OsteoporoseRESUMO
The current (metabolic) conception of bone-weakening diseases regards bone strength as determined by a systemically-controlled "mineralized mass" which grows until it reaches a peak and then is lost at individually-specific rates. This concept disregards bone biomechanics. Skeletons are structures, it reaches of which depends on the stiffness and the spatial distribution rather than the volume of the calcified material. Rather than allowing a systemic regulation of their "mass" as a way to optimize their strength, bones autocontrol their stiffness by orienting bone formation and destruction as locally determined by the directional sensing, by osteocytes, of the strains caused by mechanical usage (gravity, muscle contractions). Bone mass and strength are just side products of that control. Endocrine-metabolic systems modulate non-directionally the work of bone cells as required for achieving a mineral equilibrium, despite the biomechanical controls, and can determine osteopenias and osteoporoses. Osteoporoses are not "intense osteopenias" (as per the current WHO's conception) but "osteopenic bone fragilities" (as recently stated by the NIH). The diagnosis of osteopenia is an anthropometric problem that can be solved densitometrically; but that of bone fragility is a biomechanical matter that requires evaluation of bone material's stiffness and distribution by other means ("resistometry"). For therapeutic purposes, osteopenias and osteoporoses should be also evaluated according to the relationship between bone mass or strength and muscle mass or strength in order to distinguish between "mechanical" (disuse) and "metabolic" etiologies (intrinsic bone lesion, or systemic disequilibrium), in which the bone/muscle proportionality tends to remain normal or to deteriorate, respectively.
Assuntos
Antropometria , Doenças Ósseas Metabólicas/diagnóstico , Fenômenos Biomecânicos , Humanos , Osteoporose/diagnósticoRESUMO
The current (metabolic) conception of bone-weakening diseases regards bone strength as determined by a systemically-controlled [quot ]mineralized mass[quot ] which grows until it reaches a peak and then is lost at individually-specific rates. This concept disregards bone biomechanics. Skeletons are structures, it reaches of which depends on the stiffness and the spatial distribution rather than the volume of the calcified material. Rather than allowing a systemic regulation of their [quot ]mass[quot ] as a way to optimize their strength, bones autocontrol their stiffness by orienting bone formation and destruction as locally determined by the directional sensing, by osteocytes, of the strains caused by mechanical usage (gravity, muscle contractions). Bone mass and strength are just side products of that control. Endocrine-metabolic systems modulate non-directionally the work of bone cells as required for achieving a mineral equilibrium, despite the biomechanical controls, and can determine osteopenias and osteoporoses. Osteoporoses are not [quot ]intense osteopenias[quot ] (as per the current WHOs conception) but [quot ]osteopenic bone fragilities[quot ] (as recently stated by the NIH). The diagnosis of osteopenia is an anthropometric problem that can be solved densitometrically; but that of bone fragility is a biomechanical matter that requires evaluation of bone materials stiffness and distribution by other means ([quot ]resistometry[quot ]). For therapeutic purposes, osteopenias and osteoporoses should be also evaluated according to the relationship between bone mass or strength and muscle mass or strength in order to distinguish between [quot ]mechanical[quot ] (disuse) and [quot ]metabolic[quot ] etiologies (intrinsic bone lesion, or systemic disequilibrium), in which the bone/muscle proportionality tends to remain normal or to deteriorate, respectively.
RESUMO
The current (metabolic) conception of bone-weakening diseases regards bone strength as determined by a systemically-controlled "mineralized mass" which grows until it reaches a peak and then is lost at individually-specific rates. This concept disregards bone biomechanics. Skeletons are structures, it reaches of which depends on the stiffness and the spatial distribution rather than the volume of the calcified material. Rather than allowing a systemic regulation of their "mass" as a way to optimize their strength, bones autocontrol their stiffness by orienting bone formation and destruction as locally determined by the directional sensing, by osteocytes, of the strains caused by mechanical usage (gravity, muscle contractions). Bone mass and strength are just side products of that control. Endocrine-metabolic systems modulate non-directionally the work of bone cells as required for achieving a mineral equilibrium, despite the biomechanical controls, and can determine osteopenias and osteoporoses. Osteoporoses are not "intense osteopenias" (as per the current WHOs conception) but "osteopenic bone fragilities" (as recently stated by the NIH). The diagnosis of osteopenia is an anthropometric problem that can be solved densitometrically; but that of bone fragility is a biomechanical matter that requires evaluation of bone materials stiffness and distribution by other means ("resistometry"). For therapeutic purposes, osteopenias and osteoporoses should be also evaluated according to the relationship between bone mass or strength and muscle mass or strength in order to distinguish between "mechanical" (disuse) and "metabolic" etiologies (intrinsic bone lesion, or systemic disequilibrium), in which the bone/muscle proportionality tends to remain normal or to deteriorate, respectively.(AU)
Assuntos
Humanos , RESEARCH SUPPORT, NON-U.S. GOVT , Doenças Ósseas Metabólicas/diagnóstico , Antropometria , Osteoporose/diagnóstico , Fenômenos BiomecânicosRESUMO
The current (metabolic) conception of bone-weakening diseases regards bone strength as determined by a systemically-controlled "mineralized mass" which grows until it reaches a peak and then is lost at individually-specific rates. This concept disregards bone biomechanics. Skeletons are structures, it reaches of which depends on the stiffness and the spatial distribution rather than the volume of the calcified material. Rather than allowing a systemic regulation of their "mass" as a way to optimize their strength, bones autocontrol their stiffness by orienting bone formation and destruction as locally determined by the directional sensing, by osteocytes, of the strains caused by mechanical usage (gravity, muscle contractions). Bone mass and strength are just side products of that control. Endocrine-metabolic systems modulate non-directionally the work of bone cells as required for achieving a mineral equilibrium, despite the biomechanical controls, and can determine osteopenias and osteoporoses. Osteoporoses are not "intense osteopenias" (as per the current WHO's conception) but "osteopenic bone fragilities" (as recently stated by the NIH). The diagnosis of osteopenia is an anthropometric problem that can be solved densitometrically; but that of bone fragility is a biomechanical matter that requires evaluation of bone material's stiffness and distribution by other means ("resistometry"). For therapeutic purposes, osteopenias and osteoporoses should be also evaluated according to the relationship between bone mass or strength and muscle mass or strength in order to distinguish between "mechanical" (disuse) and "metabolic" etiologies (intrinsic bone lesion, or systemic disequilibrium), in which the bone/muscle proportionality tends to remain normal or to deteriorate, respectively.
Assuntos
Humanos , Antropometria , Doenças Ósseas Metabólicas , Fenômenos Biomecânicos , OsteoporoseRESUMO
La calidad mecánica de cualquier hueso está determinada por la rigidez (micro-arquitectura, grado de calcificación, microfracturas) y distribución espacial (macro-arquitectura) de su material cortical (en cualquier hueso) y trabecular (sólo en cuerpos vertebrales), resultantes de una combinación de modelación y remodelación óseas. Estos procesos están regulados direccionalmente por el "mecanostato" óseo, sistema retroalimentado cuyo estímulo proviene del uso mecánico regional del esqueleto, y cuyo punto de referencia está permanentemente modulado (no regulado) en forma sistémica por el entorno endocrino-metabólico. Todos los tratamientos medicamentosos en uso para las osteopatías, fragilizantes, incluyendo los bisfosfonatos actúan únicamente modificando no-direccionalmente este último factor. Por eso, sus resultados dependen del grado de estimulación del mecanostato por el uso, y sólo pueden estimarse determinando parßmetros de calidad material y de eficiencia arquitectónica ósea. Los bisfosfonatos mejoran la eficiencia mecánica ósea por inhibir la remodelación (que usualmente arroja balances negativos de masa) afectando, en algún grado (menor para los productos de más cercana generación), la mineralización del material rígido. En nuestro medio contamos con tres productos con efectos biomecánicos óseos positivos demostrados: pamidronato, olpadronato y alendronato. En animales intactos, los tres mejoran la macro-arquitectura ósea a cualquier dosis, aunque el pamidronato deteriora la mineralización del material a dosis muy altas. En animales ooforectomizados o inmovilizados, los tres protegen contra la repercusión biomecánica negativa de la osteopenia impidiendo el deterioro de la calidad del material y sin alterar el diseño arquitectónico óseo. También potencian o prolongan los efectos anabólicos óseos de la hPTH. Sus ventajas terapéuticas se fundan en que ninguno de los tres perturba el accionar del mecanostato, dejando intactos los mecanismos regulatorios de la eficiencia mecánica de la estructura ósea por el uso mecánico, o incluso potenciándolos sistémicamente (efecto anti-catabólico). Esta característica explica que sus efectos dependan mucho del uso mecánico del esqueleto en las regiones que se desea mejorar. Está aun por definirse si una inhibición demasiado intensa o prolongada de la remodelación por los bisfosfonatos pudiera deteriorar o no la reparación de microfracturas que la misma provee, con consecuencias biomecánicas potencialmente...
Assuntos
Humanos , Animais , Ratos , Osso e Ossos/efeitos dos fármacos , Doenças Ósseas Metabólicas/tratamento farmacológico , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Fenômenos Biomecânicos , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Relação Dose-Resposta a DrogaRESUMO
Los bisfosfonatos regulan el recambio óseo por inhibición de la reabsorción óssea osteoclástica. Sus características farmacodinémicas y farmacocinéticas les confieren un particular perfil fármaco-toxicológico, determinado en gran parte por su alto grado de especialidad escasa o nula distribución en tejidos blandos, fuerte afinidad por tejidos calcificados. Los estudios de toxicología preclínica, cuyo objetivo principal es localizar el o los órganos blanco de toxicidad y estimar el margen de seguridad de un "candidato a agente terapéutico" en animales de experimentación, permiten extraer conclusiones generales que, en el caso de los bisfosfonatos, se avalan con resultados propios y obtenidos en la literatura. Se consideran distintos integrantes de este grupo farmacológico: Alendronato, Clodronato, Etidronato, Olpadronato, Pamidronato. En general, deben administrarse dosis muy altas de bisfosfonatos para la observación, en grado e incidencia variable, de efectos tóxicos extraesqueléticos: reacción local, hipocalcemia- y sus consecuencias sobre el sistema cardiovascular y la posibilidad de tetania-, afectación de las estructuras dentarias y disfunción renal. La mayoría de estos efectos pueden atribuirse a la escasa solubilidad en fluídos biológicos, a la formación de complejos con el ión calcio, a su potente efecto inhibitorio de la reabsorción ósea endógena o inducida y a su principal vía de excreción. Otros efectos tóxicos (oculares, pulmonares, hepáticos), pueden relacionarse con excesivas dosis reiteradas. Si se considera la cantidad total de Olpadronato administrada a distintas especies animales en estudios toxicológicos y en modelos experimentales farmacodinámicos (osteopenias por deprivación estrogénica e inmovilización, hipercalcemia inducida por retinoides), se puede estimar un margen de seguridad de 200-300:1 entre las dosis "tóxicas" y "farmacológicas". Si las dosis tóxicas en animales se relacionan con las máximas propuestas para humanos, la relación asciende a 300 - 1000:1 dependiendo de la patología y la vía de administración consideradas. Con respecto a su efecto óseo, los datos experimentales con los nuevos bisfosfonatos sugieren un marcado alejamiento entre dosis activas farmacológicamente y aquellas que producen defectos en la mineralización ósea. La exagerada inhibición del remodelamiento óseo, producto del empleo de altas dosis en animales normales, es la natural consecuencia del efecto farmacológico de este tipo de compuestos. ...