Muscle loss and bone loss: Master and slave?

Abstract

Among the ever-growing list of benefits associated with physical activity, bone and muscle health remain near the top. Exercise improves muscle strength, and simultaneously enhances bone architecture and fracture resistance. The strong association between these two parameters has been explored in greater detail in recent years, to begin to understand the extent to which muscle might play a governing role in bone adaptation. This role has practical implications, for if muscle does govern bone, then physical activity exercises should be targeted to primarily maximize muscle strength, and the bone will follow. Despite early claims of a cause-effect relation, based on anecdotal evidence, individual case studies, or orthopaedic experience, experimental data directly addressing this issue have been scarce.[1] Perhaps the lack of progress in this arena can be linked to a paucity of suitable animal models. With the exception of tail suspension studies, which have their own limitations (e.g., fluid shift), it has been difficult to experimentally (and non-surgically) reduce and subsequently restore muscle function without directly affecting the adjacent bone.More recently, development of the Botox reversible muscle-paralysis model of disuse [2] has circumvented many of these concerns, and has ushered in the potential to more directly address some cause-effect questions regarding the regulatory role of muscle forces on bone properties. Moreover, the recent generation of high resolution in vivo μCT technology has permitted the opportunity to track small changes in bone and muscle size noninvasively over long periods of time, i.e., through muscle paralysis and subsequent recovery. In this issue of Bone, two independent groups report the results of several elegant Botox-induced muscle paralysis experiments in mice, which monitor longitudinal changes noninvasively in muscle size and bone mass over a 12-16 wk post-paralysis period. [3,4] These two studies highlight some interesting, novel, and remarkably consistent findings that address the role of muscle size/ function on bone mass and architecture.

Site-Specific Variance in Radius and Tibia Bone Strength as Determined by Muscle Size and Body Mass

“…6 Observational evidence of factors that determine bone mass and strength will facilitate the development of RCTs and tailored therapies for upper-extremity bones. Since bone mass and strength adapt to loading, 7-10 and muscular forces produce the greatest natural loads on the skeleton, 7,[11][12][13][14][15][16][17] interventions aimed at enhancing muscle strength and size may also have the potential to enhance bone strength. Muscle mass and strength are positively associated with bone mass and strength, but the role of muscle in predicting bone strength independently from other measures of body size is less clear.…”

Follistatin-like 3 is a mediator of exercise-driven bone formation and strengthening

“…FSTL3 gene deletion results in loss of mechanosensitivity, bone mechanical strength and exercise driven bone formation, paralleled by loss of SOST regulation. Interestingly, exercise regulates bone and muscle structure and strength simultaneously in an integrated manner (52). FSTL3 is also shown to regulate muscle mass by neutralizing myostatin, an inhibitor of muscle growth that is downregulated by exercise (40, 51).…”

The effect of diabetic neuropathy on foot bones: a systematic review and meta‐analysis

“…Autonomic neuropathy is proposed to reduce bone strength via a reduction in sympathetic vascular tone and bone hyperaemia . Motor neuropathy may reduce the muscular load on bone that influences remodelling .…”

“…It is known that a major factor involved in maintenance of bone mass is mechanical load, which is in part made up of muscular force applied by actively contracting muscles . Diabetic peripheral neuropathy frequently involves the intrinsic foot muscles .…”