Bone biopsy specimens were obtained from 23 patients, 12 in the zoledronic acid group and 11 in the risedronate group. 30 Qualitative assessment showed normal bone architecture and quality without mineralization defects. Apparent reductions in activation frequency and remodeling rates were seen when compared with the histomorphometric results in the zoledronic acid postmenopausal osteoporosis population. 31 The long-term consequences of this degree of suppression of bone remodeling in the glucocorticoid-treated patients are unknown.
The overall safety and tolerability of zoledronic acid in the glucocorticoid-induced osteoporosis population was similar to that in the postmenopausal osteoporosis clinical trial. 29,31 Adverse reactions reported in at least 2% of patients that were either not reported in the postmenopausal osteoporosis trial or were reported more frequently in the glucocorticoid-induced trial included the following: abdominal pain, musculoskeletal pain, nausea, and dyspepsia. The incidence of serious adverse events was similar in the zoledronic acid and the active control groups. In the zoledronic acid group, 2.2% of the patients withdrew from the study due to adverse events vs 1.4% in the active control group.
Teriparatide, a parathyroid hormone drug
Teriparatide (Forteo) consists of a fragment of the human parathyroid hormone molecule. It is given once daily by subcutaneous injection. It was also approved for treating glucocorticoid-induced osteoporosis after the current guidelines were written.
Teriparatide was compared with alendronate in a randomized, double-blind trial in patients with glucocorticoid-induced osteoporosis. 32 Entry criteria were treatment with at least 5 mg of prednisone per day for at least 3 months before screening and a T score of −2.0 or less in the lumbar spine, total hip, or femoral neck, or −1.0 or less plus one or more fragility fractures.
Eighty-three men and 345 women ages 21 or older were enrolled and randomized to receive injectable teriparatide 20 μg per day plus oral placebo or oral alendronate 10 mg per day plus injectable placebo. All of them also received calcium 1,000 mg per day and vitamin D 800 IU per day.
At 18 months, the bone mineral density had increased significantly more in the teriparatide group than in the alendronate group in the lumbar spine ( P < .001) and in the total hip ( P < .01). As expected, markers of bone turnover were suppressed in the alendronate group but were increased in the teriparatide group.
New vertebral fractures were found on radiography in 10 of 165 patients in the alendronate group vs 1 of 171 patients in the teriparatide group ( P = .004). Clinical vertebral fractures occurred in 3 of 165 patients treated with alendronate but in none of the teriparatide-treated patients ( P = .07). Nonvertebral fractures occurred in 8 of 214 patients treated with alendronate and 12 of 214 patients treated with teriparatide ( P = .362). Three of 214 patients treated with alendronate suffered nonvertebral fragility fractures, compared with 5 of 214 patients treated with teriparatide ( P = .455).
Denosumab, an antibody to RANK ligand
Denosumab (Prolia) is a fully human monoclonal antibody to RANK ligand. (Recall that glucocorticoids are associated with increases in RANK ligand and decreases in osteoprotegerin.) Denosumab is given subcutaneously in a dosage of 60 mg every 6 months. It was recently approved for the treatment of postmenopausal osteoporosis.