Differential features of muscle fiber atrophy in osteoporosis and osteoarthritis

Abstract

We demonstrated that osteoporosis is associated with a preferential type II muscle fiber atrophy, which correlates with bone mineral density and reduced levels of Akt, a major regulator of muscle mass. In osteoarthritis, muscle atrophy is of lower extent and related to disease duration and severity.

Introduction: Osteoarthritis (OA) and osteoporosis (OP) are associated with loss of muscle bulk and power. In these diseases, morphological studies on muscle tissue are lacking, and the underlying mechanisms of muscle atrophy are not known. The aim of our study was to evaluate the OP- or OA-related muscle atrophy and its correlation with severity of disease. Muscle levels of Akt protein, a component of IGF-1/PI3K/Akt pathway, the main regulator of muscle mass, have been determined.

Methods: We performed muscle biopsy in 15 women with OP and in 15 women with OA (age range, 60-85 years). Muscle fibers were counted, measured, and classified by ATPase reaction. By statistical analysis, fiber-type atrophy was correlated with bone mineral density (BMD) in the OP group and with Harris Hip Score (HHS) and disease duration in the OA group. Akt protein levels were evaluated by Western blot analysis.

Results: Our findings revealed in OP a preferential type II fiber atrophy that inversely correlated with patients' BMD. In OA, muscle atrophy was of lower extent, homogeneous among fiber types and related to disease duration and HHS. Moreover, in OP muscle, the Akt level was significantly reduced as compared to OA muscles.

Conclusions: This study shows that in OP, there is a preferential and diffuse type II fiber atrophy, proportional to the degree of bone loss, whereas in OA, muscle atrophy is connected to the functional impairment caused by the disease. A reduction of Akt seems to be one of the mechanisms involved in OP-related muscle atrophy.

Fig. 1

Analysis of muscle fiber atrophy. a In osteoporosis, vastus lateralis muscle biopsy reacted for ATPase pH 4.2 shows a preferential type II muscle fiber (light fibers) atrophy. b Mega-histogram comparing fiber diameter distribution in OP and OA. Type II fibers in the OP group have a higher degree of deviation from the normal distribution toward the atrophic range. c Linear regression graph showing in OP an inverse correlation between type II fiber atrophy and BMD

Fig. 2

Akt is decreased in OP muscle fibers. Representative immunoblot and densitometric analysis show that in OP muscle, Akt is reduced 2.5-fold as compared to OA. The actin bands indicate protein loading in each sample