Excessive production of cortisol by the body or chronic use of corticosteroids (CS) for treatment of disease causes accelerated bone loss and in about 30% of patients it causes osteoporosis related fractures. The first fractures usually occur in the vertebrae.

Corticosteroid-induced osteoporosis (CIO) results from multiple effects on calcium and bone metabolism. CS inhibits the absorption of calcium from the intestine and increase the loss of calcium in the urine. These events, in turn, cause calcium to be mobilized from bone to maintain a normal blood calcium level. The production of estrogen in women and testosterone in men is inhibited by CS. Deficiency of these gonadal hormones causes increased breakdown of bone. At the same time that bone is being broken down, CS impairs the ability of the bone forming cells (osteoblasts) to lay down new bone.

As a result of all of these effects, CS causes the most rapid rate of bone loss observed in patients. Steroid-induced osteoporosis is similar to postmenopausal osteoporosis but the bone loss associated with steroids is much more rapid, and the bone appears to be more fragile than in patients with postmenopausal osteoporosis.

Osteonecrosis is different than osteoporosis in that it can occur without significant bone loss, and can occur very soon after steroid levels become elevated. Osteonecrosis means death of bone. This problem most frequently occurs in the hip, the shoulder, or the distal thigh bone. It is thought that the bone dies because CS causes a significant increase in the amount of fat in the center of the bone, in the bone marrow. This increase in fat in a closed space which cannot expand causes pressure on the small, thin, blood vessels which nourish the bone. This causes the bone to die due to lack of blood supply. Sometimes the bone will heal if the patient just doesn’t bare weight on the bone for several weeks. At other times, joint replacement is required.

All patients requiring treatment with steroids such as prednisone, or patients with excessive production of cortisol due to an ACTH producing pituitary tumor or adrenal tumor should have their bone density measured in the spine and hip using dual energy x-ray. This will tell you how much bone you have lost, will help determine how aggressive treatment should be to prevent bone loss, and will allow future assessment of response to treatment. The amount of calcium that is being lost in the urine should be measured, and if high, efforts made to reduce the loss. If there is any reason to suspect that the patient has vitamin D deficiency, the serum level of 25-hydroxy vitamin D should be measured. Estradiol levels should be measured in women and testosterone levels in men.

Patients with elevated cortisol levels or taking CS should limit the sodium in their diet to no more than 3 grams (3000 milligrams) daily. They should eat a well balanced diet and consume about 1500 mg of calcium a day (if their urine calcium is not elevated). Exercise is important and it would be helpful to walk for 30 minutes daily. If the patient has trouble getting up out of a chair without using their arms or difficulty climbing stairs, they should be instructed in exercises which specifically strengthen the quadriceps and pelvic girdle muscles since these particular muscle groups are weakened by steroids. Women who are postmenopausal or premenopausal women whose estradiol levels are low should be given hormone replacement if they do not have other contraindications. Likewise, men with low testosterone should be give replacement therapy if it is not contraindicated.

Hormone replacement, the bisphos-phonate drugs Fosamax and Didronel, and calcitonin have all been shown to prevent steroid-induced bone loss. The response to these drugs is very similar to that seen in women with postmenopausal osteoporosis.

In most instances a considerable amount of bone is regained when the cortisol levels return to normal or the administration of steroids is stopped. In patients requiring replacement doses of cortisol, it is important to keep the dose as low as possible but adequate to maintain normal levels.

Steroid-induced osteoporosis is a preventable and treatable disease. We need to be more diligent in recognizing it.

Author: Dr. Barbara Lukert MD (Fall, 1998)

Editor’s Note: Dr. Barbara Lukert is a Professor of Medicine, Endocrinology, Metabolism and Genetics and Director of the Hiatt Osteoporosis Center at the University of Kansas Medical Center in Kansas City, Kansas. Dr. Lukert has been involved with the study and treatment of osteoporosis for many years.