Glucocorticoids Promote Osteoclast Survival
Glucocorticoids Promote Osteoclast Survival
The purpose of this study is to determine the difference in response to bisphosphonate
 therapy in patients receiving excess glucocorticoids compared to patients with postmenopausal
 or male osteoporosis. Bisphosphonates are approved by the FDA for the treatment of
 postmenopausal women and osteoporotic men who are at high risk of fracture and in men and
 women with excess glucocorticoid administration.
Aminobisphosphonates are extensively used to prevent fractures in patients with osteoporosis
 (1-6). Treatment with these drugs leads to decreases in bone resorption and biochemical
 markers of bone turnover and progressive increases in bone mineral density (BMD). The
 increase in BMD in response to bisphosphonate therapy in glucocorticoid-treated patients is,
 however, less than half that measured in women and men with osteoporosis unrelated to
 glucocorticoid drugs even though the patients with osteoporosis are usually older. The goal
 of this objective is to determine the contribution of increased osteoclast survival to the
 diminished response to bisphosphonate therapy in patients receiving excess glucocorticoids
 compared to patients with osteoporosis.

 1. Liberman U, Weiss SR, Broll J, et al. Effect of oral alendronate on bone mineral density
 and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med
 1995;333:1437-1443.

 2. Bone HG, Downs RW, Tucci JR, et al. Dose-response relationships for alendronate
 treatment in osteoporotic elderly women. J Clin Endocrinol Metab 1997;82:265-274.

 3. McClung M, Clemmesen B, Daifotis A, et al. Alendronate prevents postmenopausal bone loss
 in women without osteoporosis. Ann Intern Med 1998;128:253-261.

 4. Recker RR, Weinstein RS, Chestnut CH III, et al. Histomorphometric evaluation of daily
 and intermittent oral ibandronate in women with postmenopausal osteoporosis: results
 from the BONE study. Osteoporosis Int 2004;15:231-237.

 5. Saag KG, Emkey R, Schnitzer TJ, et al. Alendronate for the prevention and treatment of
 glucocorticoid-induced osteoporosis. Glucocorticoid-Induced Osteoporosis Intervention
 Study Group. N Engl J Med 1998;339:292-299.

 6. Orwoll E, Ettinger M, Weiss S, et al. Alendronate for the treatment of osteoporosis in
 men. N Engl J Med 2000;343:604-610.
Inclusion Criteria:

 1. 18 years old or greater

 2. agree to at least one bone biopsy

 3. agree to BMD, blood and urine tests

 4. receiving at least 10 mg/day of prednisone for at least three months

 5. either be a candidate for alendronate or be taking alendronate (70 mg/week for at
 least three months)

 Exclusion Criteria:

 1. any metabolic bone disorder such as Paget's disease, renal osteodystrophy, parathyroid
 disease or osteomalacia

 2. obesity enough to make a biopsy difficult

 3. concurrent use of any tetracycline

 4. hypercalcemia

 5. kidney stones in the last two years

 6. home O2

 7. gastric surgery, stapling or bypass

 8. inflammatory bowel disease

 9. untreated thyroid disease

 10. organ transplants

 11. malabsorption

 12. anticoagulation

 13. current infection

 14. serious illness

 15. allergy to Demerol, Valium, iodine, tetracycline, tape

 16. use of anticonvulsant drugs, heparin, Forteo, calcitonin or high-dose fluoride within
 the past six months