Influence of body weight on bone mass, architecture and turnover

Abstract

Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. While the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size.

Role of estrogen receptor signaling in skeletal response to leptin in female ob/ob mice

“…Bone balance is highly sensitive to changes in energy availability (Iwaniec and Turner 2016). Caloric restriction in adult rats, resulting in only 5% weight loss, had dramatic negative effects on bone metabolism, including reduced bone formation, increased osteoclast perimeter and reduced cancellous bone volume fraction (Turner and Iwaniec 2011).…”

Biomechanics, obesity, and osteoarthritis. The role of adipokines: When the levee breaks

“…Furthermore, extreme obesity is associated with impaired leptin signaling, which induced alterations in the subchondral bone without changing systemic inflammatory cytokine levels or OA incidence . Accordingly, leptin‐deficient (ob/ob) mice had reduced bone mass as well as altered bone microarchitecture (of note, axial and appendicular bones may be differentially affected) and consequently, modified bone biomechanical properties, with potential effect in bone fracture healing . Exogenous leptin administration can act through central nervous system or peripherally, inhibiting or enhancing bone formation, respectively.…”

Using three-point bending to evaluate tibia bone strength in ovariectomized young mice

“…An increase in tibial length will occur via endochondral ossification, in which, osteoclasts will facilitate the resorption of cartilage and osteoblasts will build the bone matrix. Osteoblasts will also deposit bone matrix along the periosteum [23]. After 2 weeks post-surgery (10 weeks of age), only the maximal load and stress withstood by the tibias was reduced in the ovariectomized mice.…”

“…Ovariectomization of the mice appears to negate this age effect. Iwaniec and Turner [23] have recently described that with growth, weight gain, and the subsequent increase in bone mass, there is an adaptive skeletal response that is induced by the mechanical strain on the skeletal system. This adaptive response, which is sometimes referred to as the mechanostat theory and is not well understood, provides some insight into our results, which demonstrate that an increase in age increases the maximum load, elasticity, stress, and stiffness of bone.…”