Osaka Metropolitan University confirms effectiveness of parathyroid hormone in treating rotator cuff tears: Treatment suppresses fat infiltration and muscle atrophy

A research group led by Graduate Student Ryosuke Iio, Lecturer Tomoya Manaka, and Professor Hiroaki Nakamura of the Graduate School of Medicine at Osaka Metropolitan University demonstrated that the administration of parathyroid hormone (PTH) induces the browning of fibro-adipogenic progenitors (FAPs) to suppress fatty infiltration of rotator cuff muscles and progression of muscle atrophy associated with rotator cuff tears. These results were announced on October 31. Using rat models for rotator cuff rupture, the researchers compared PTH-treated and untreated groups. The researchers confirmed that fat infiltration was suppressed by approximately 70% and the muscle atrophy was suppressed by approximately 50% in the group administered PTH for 8 weeks as compared to the non-treated group. This is expected to provide a new treatment for rotator cuff tears. The results were published on October 31 in the international academic journal The American Journal of Sports Medicine.

A rotator cuff tear is a condition where the tendon connecting the humerus and shoulder blade becomes brittle, mainly due to aging, leading to shoulder pain, a limited range of motion, and muscle weakness. This condition is often confused with frozen shoulder. Rotator cuff tears occur in an estimated one in four people in Japan aged 50 years and over. As time passes after rupture, progression of the fat infiltration and muscle atrophy of the rotator cuff muscle cause decreased muscle quality and quantity.

The research group focused on the browning of FAPs in the treatment of fat infiltration and muscle atrophy. PTH is used for the treatment of osteoporosis and was selected for use to promote FAP browning. PTH was administered to the rat model of rotator cuff tear for 4－8 weeks, and progress was monitored.

At 8 weeks, the fat infiltration was suppressed by about 70% in the PTH group compared to the control group. Moreover, the muscle atrophy was suppressed by about 50% based on measurement of the wet weight of the supraspinatus muscle.

The results of culture experiments of FAPs from mice confirmed that PTH administration increased the expression levels of browning-related genes, suppressed lipid droplet accumulation, and promoted muscle differentiation.

The results also revealed that the vascular endothelial growth factor (VEGF), a factor secreted by beige adipocytes whose differentiation was induced by PTH, promoted muscle regeneration. The reversal of fat infiltration and muscle atrophy previously considered to be permanent may lead to new treatments.

Iio commented, "There is no established treatment for the reduction of muscle mass and quality in the rotator cuff muscles after progression of rotator cuff tear. The results of our study revealed that the administration of PTH can suppress fat infiltration and muscle atrophy. PTH may also be applied to muscle regeneration and, in the future, to treat locomotive syndrome and disuse syndrome (deterioration of physical ability and mental state in patients on prolonged bed rest). We hope that PHT will also lead to the treatment of these symptoms."