In 1952, . Peterson and . Murray of Upjohn developed a process that used Rhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone.  The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US $6 per gram, falling to $ per gram by 1980. Percy Julian's research also aided progress in the field.  The exact nature of cortisone's anti-inflammatory action remained a mystery for years after, however, until the leukocyte adhesion cascade and the role of phospholipase A2 in the production of prostaglandins and leukotrienes was fully understood in the early 1980s.
In 2014, Dr. George Habib who has authored many studies trying to find out if, how, and when a cortisone injection into the knee has side-effects throughout the body, found that injection of the glucosteroid methylprednisolone acetate disrupted the hypothalamic-pituitary-adrenal axis in 25% of subject patients receiving the injection for knee osteoarthritis. These were patients who first failed to respond to nonsteroidal anti-inflammatory medications and physical therapy. The disruption was transient, lasting 2 – 4 weeks after the injection.
Using tritiated glycine (glycine 3H) as an indicator of amino acid incorporation in protein synthesis in cartilage matrices, Mankin and Conger injected hydrocortisone acetate into rabbit knees. Their data showed a rapid and profound decrease in glycine incorporation that appeared to depend on dosages. Maximum decline was seen six hours after the injection. 28 They did a similar experiment using glycine 14C as the radiotracer, which showed a definite decrease in the rate of protein synthesis within two hours of the injection. They noted that the rate of the inhibitory effect of intraarticular hydrocortisone on cartilage protein synthesis was about twice that of the observed rate for corticosteroids given by intramuscular route. 29 One year later, researchers injected hydrocortisone into normal rabbit knees and produced thinning of the cartilage, and the development of fissures and fibrillations in the articular cartilage. They also found multiple small white deposits within the substance of the articular cartilage, which were found to represent cystic areas of degeneration within the middle zone of the cartilage matrix. These effects were most marked in the animals which had the greatest number of injections. 30 Deleterious effects of cortisone were reported by some researchers who noted that the drug inhibited the synthesis and deposition of chondroitin sulfate in cartilage. 31-33