RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass

Effect of Denosumab on Falls, Muscle Strength, and Function in Community‐Dwelling Older Adults

“…Despite improvements in measures of physical performance with Dmab, the underlying biological mechanisms are unclear and require further investigation. A recent study found overexpression of receptor activator of nuclear factor kappa‐B ligand in mice resulted in impairments to muscle structure, including loss of strength and mass, which may be a possible mechanism by which Dmab acts …”

“…A recent study found overexpression of receptor activator of nuclear factor kappa-B ligand in mice resulted in impairments to muscle structure, including loss of strength and mass, which may be a possible mechanism by which Dmab acts. 5 Limitations include a lack of randomization between Dmab and ZOL groups, resulting in a skewed distribution of participants. Increasing the sample size in each group would increase the power and findings in the study.…”

“…However, potential mechanisms have not been elucidated . Recently, a study among 18 postmenopausal women found 3 years of Dmab prescription improved lean mass, muscle strength, and bone mineral density (BMD) . As such, we compared Dmab de novo to an established treatment (zoledronic acid [ZOL]) to examine changes in muscle strength, balance, and function of older adults at risk of falls and fractures.…”

Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism

“…As such, in addition to RANKLinducing osteoclast differentiation and osteoclast-derived osteoblastcoupling factors, the ability to make glucose available to differentiating osteoblasts may also be a key component of RANKLinduced energy coupling at a systemic level. Indeed, consistent with this hypothesis, Bonnet et al 57 recently demonstrated that transgenic mice overexpressing RANKL have systemic insulin resistance and reduced glucose uptake in non-skeletal tissues (muscle, brain), but increased glucose update in bone (femur). Although evident in the adult, as in our study, these effects of RANKL may be particularly important during rapid growth and development, when the energy needs of the skeleton are substantial.…”

Commentary on the effects of receptor activator of nuclear factor‐B ligand inhibition on bone mass and muscle strength

“…Furthermore, in human clinical studies, the falling rate was flattened; appendicular lean mass and handgrip were increased in patients receiving RANKL inhibitor. A recent publication investigating the effects of RANKL inhibitors found that they could improve muscle strength and insulin sensitivity in osteoporotic mice and humans. Accordingly, the RANK/RANKL/OPG system plays an important role not only in bone, but also in muscle metabolism.…”