A Histological and Immunohistochemical Approach to Understanding Sarcopenia

Sarcopenia is a condition characterized by muscle fiber atrophy that can lead to issues with balance and gait as well as falls and fractures. A study presented as a poster abstract at the recent World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases in Milan, Italy (March 26–29, 2015), aimed to clarify the histological and immunohistochemical underpinnings of this condition in aging patients.

Eleonora Piccirilli, MD, Department of Orthopaedics and Traumatology, PTV Foundation, Rome, Italy, and colleagues assessed 102 individuals who underwent a total hip arthroplasty (THA), 54 individuals with osteoporosis (OP)-related hip fracture, and 48 individuals with osteoarthritis (OA), assessed using the Kellgren-Lawrence grading scale (a measure of OA  severity) and the Harris Hip Score (a measure of hip function).

Each patient underwent biopsy of the vastus lateralis (the muscle located on the lateral side of the thigh that makes up the largest portion of the quadriceps formoris group) as well as dual-energy X-ray absorptiometry (DXA) scans. The researchers counted and measured patients’ muscle fibers and performed morphometric analysis on serial transverse cryostat sections. The sections were also analyzed for immunohistochemical markers of muscle atrophy.

“We quantified cytokines (TGF-β [transforming growth factor beta], BMP [bone morphogenetic protein], myostatin) and cell markers (CD 56),” the authors wrote in the poster. “By statistical analysis we correlated the fiber atrophy with BMD [bone mineral density] in the OP group and Harris Hip Score in the OA group.”

Piccirilli and colleagues detected higher levels of atrophy—particularly involving type II muscle fibers—in the OP group; this was associated with lower BMD values. In the OA group, atrophy was less prevalent, was homogeneous between the different fibers, and was not affected by Harris Hip Score values.

The authors reported positive correlations of BMP-2 concentrations with BMD values in the OP group and with the severity of OA in the OA group. Additionally, high levels of TGF-β and myostatin were associated with a greater degree of muscle atrophy.

“We can assume that there is a mutual influence between sarcopenia and degree of OP, which could be an opening to therapeutic perspectives,” the authors concluded.

They hypothesized that myostatin and TGF-β inhibitor use may lead to an improvement in sarcopenic, OA, and OP treatment frameworks.

“Finally, the use of BMP-2 may promote bone and cartilage repair mechanisms, improving the values of BMD, OP, and OA,” they wrote.