IN A NUTSHELL

Fatty muscles: The negative effects of ectopic fat on bone health and physical function in older adults

The term “sarcopenia” was first proposed in the late 1980’s to describe the age-related loss of skeletal muscle mass. It was initially assumed that muscle atrophy in ageing was the primary cause of functional decline, but subsequent research demonstrated that this was not the case. In fact, muscle loss per se explains a relatively small amount of the age-related loss of muscle strength, and it is clear that functional decline is predominantly explained by neuromuscular changes. This knowledge has led to an increased focus on “muscle quality”; the micro- and macroscopic changes in muscle structure during ageing that contribute to decreased force production per unit of muscle mass.

Ageing muscle is infiltrated by increasing amounts of adipose tissue. This ectopic fat compartment is called inter- and intramuscular adipose tissue (IMAT) and in the lower-limbs, IMAT increases by up to 50% over just five years in adults aged in their seventies. IMAT is associated with increased secretion of inflammatory cytokines, insulin resistance and cardiovascular disease in older adults. Perhaps unsurprisingly given the non-contractile nature of this tissue, IMAT is also associated with poorer muscle strength and physical performance. Moreover, low skeletal muscle density assessed by CT, which is indicative of higher amounts of IMAT, has been independently associated with increased risk of hip fractures in older adults (https://www.ncbi.nlm.nih.gov/pubmed/20422623). However, no previous study has determined with the mechanism of this effect is increased risk of falls, poorer bone health, or both.

In our study published in Bone, we utilised data from the Healthy Ageing Initiative to study the link between IMAT, bone health and falls in older adults. Ourpopulation-based study included2,214 community-dwelling 70-year-olds residing in Umeå, Sweden. At baseline, all participants underwent dual-energy X-ray absorptiometry for assessment of areal bone mineral density (aBMD) at the hip and lumbar spine, and peripheral quantitative computed tomography for assessment of volumetric bone mineral density (vBMD) and trabecular and cortical bone architecture at the distal and proximal tibia and radius. The proximal tibia scan was also utilised to assess mid-calf skeletal muscle density. This represents a simple, non-invasive and low-radiation method for estimating lower-limb IMAT.  

We foundthat higher mid-calf muscle density (indicating lower IMAT) was not associated with total hip aBMD, and, unexpectedly, was associated with poorer lumbar spine aBMD after adjustment for potential confounders. The only association observed at the radius was a positive association with proximal cortical vBMD, while at the distal tibia, muscle density was positively associated with total and trabecular vBMD. The most consistent associations however were observed at the proximal tibia (the same site at which muscle density was quantified); mid-calf muscle density was positively associated with all of total and cortical vBMD, cortical thickness, cortical area and stress-strain index.Interestingly, muscle density was also negatively associated with proximal tibia total bone area. We proposed that the association of greater IMAT with greater bone area, but poorer bone density, is consistent with the concept of periosteal apposition in response to bone loss.

Following baseline appointments, all participants wore an accelerometer for objective monitoring of physical activity over one week. At six- and 12-months following baseline, participants were contacted by telephone and to record falls. We observedthatthere were relatively few fallers in this population (14%), likely owing to their relatively good health and also the definition of falls applied (only falls resulting in coming to rest on the ground were included). Nevertheless, for each standard deviation decrease in mid-calf muscle density (indicating an increase in IMAT), the likelihood of having more than one fall over 12 months was increased by 61%.Sedentary time and light intensity activity were not associated with mid-calf muscle density, but higher amounts of moderate and vigorous intensity physical activity were independently associated with bettermuscle density.

While further studies are required to confirm these associations, particularly prospective studies to determine causation in relationships between muscle density and bone health, we concluded that IMAT may have localised negative effects on bone density and structure in older adults. This, in combination with increased risk for falls, may explain the previously described association of IMAT with osteoporotic fractures. These findings suggest that improving muscle quality may be an effective target for reducing fracture risk in older adults. However, given that independent associations were only observed for moderate and vigorous physical activity in our study, we believe that interventions focused only on reducing sedentary time and/or promoting light intensity activities will be ineffective for reducing IMAT.

These findings are described in the article entitled “Mid-calf skeletal muscle density and its associations with physical activity, bone health and incident 12-month falls in older adults: The Healthy Ageing Initiative” published in Bone. This work was conducted by David Scott, Lachlan McMillan and Peter Ebeling from Monash University, Melbourne, Australia in collaboration with Jonas Johansson, Anna Nordstrom and Peter Nordstom from Umeå University, Umeå, Sweden. The Healthy Ageing Initiative was funded by the Swedish Research Council.

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David Scott

David Scott, PhD
NHMRC Career Development Fellow at Monash University, Melbourne, Australia