Effects of teriparatide versus alendronate for treating glucocorticoid‐induced osteoporosis: Thirty‐six–month results of a randomized, double‐blind, controlled trial

Abstract

Objective. To compare the bone anabolic drug teriparatide (20 g/day) with the antiresorptive drug alendronate (10 mg/day) for treating glucocorticoidinduced osteoporosis (OP).Methods. This was a 36-month, randomized, double-blind, controlled trial in 428 subjects with OP (ages 22-89 years) who had received >5 mg/day of prednisone equivalent for >3 months preceding screening. Measures included changes in lumbar spine and hip bone mineral density (BMD), changes in bone biomarkers, fracture incidence, and safety.Results. Increases in BMD from baseline were significantly greater in the teriparatide group than in the alendronate group, and at 36 months were 11.0% versus 5.3% for lumbar spine, 5.2% versus 2.7% for total hip, and 6.3% versus 3.4% for femoral neck (P < 0.001 for all). In the teriparatide group, median percent increases from baseline in N-terminal type I procollagen propeptide (PINP) and osteocalcin (OC) levels were significant from 1 to 36 months (P < 0.01), and increases in levels of C-terminal telopeptide of type I collagen (CTX) were significant from 1 to 6 months (P < 0.01). In the alendronate group, median percent decreases in PINP, OC, and CTX were significant by 6 months and remained below baseline through 36 months (P < 0.001). Fewer subjects had vertebral fractures in the teriparatide group than in the alendronate group (3 [1.7%] of 173 versus 13 [7.7%] of 169; P ‫؍‬ 0.007), with most occurring during the first 18 months. There was no significant difference between groups in the incidence of nonvertebral fractures (16 [7.5%] of 214 subjects taking teriparatide versus 15 [7.0%] of 214 subjects taking alendronate; P ‫؍‬ 0.843). More subjects in the teriparatide group (21%) versus the alendronate group (7%) had elevated predose serum calcium concentrations (P < 0.001).Conclusion. Our findings indicate that subjects with glucocorticoid-induced OP treated with teriparatide for 36 months had greater increases in BMD and fewer new vertebral fractures than subjects treated with alendronate.Glucocorticoids are beneficial for treating chronic inflammatory conditions, such as rheumatoid ClinicalTrials.gov identifier: NCT00051558.

Safety of osteoanabolic therapy: A decade of experience

“…(2,3,55) In the clinical trials with teriparatide and PTH(1-84), no increase in nonosseous cancers was found. (20,26,29,31) However, because many tissues and solid tumors could express the PTH/PTHrP receptor, it has been suggested that patients with a history of cancers in the past 5 years avoid PTH therapy. (75) There may be wisdom in this recommendation for those whose malignancies harbor osteoblastic potential, such as breast and prostate cancer.…”

“…(20) Similar results were reported in other clinical trials, which also showed little or no incidence of hypercalcemia within 24 hours after teriparatide injection. (26,28,29,79,80) In a post hoc analysis, Miller and colleagues (81) showed a significantly higher incidence of hypercalcemia in patients with moderate renal impairment (glomerular filtration rate [GFR] 30-49 mL/min).…”

“…(28) In the follow-up 18-month extension trial, significant differences in BMD and fracture risk between the two groups were maintained. (29) PTH (1-84) Full-length, native PTH [PTH ] has also shown efficacy in postmenopausal osteoporosis and is approved for use in Europe. Hodsman and colleagues (30) conducted the first randomized, placebo-controlled trial that compared 50, 75, or 100 mg PTH(1-84) daily with placebo over 12 months.…”

“…(20,26,29,31) The cumulative number of patients in these trials and observational studies amounts to more than 16,000 and up to 3 years of continuous treatment. (67) The postapproval experience with teriparatide and PTH(1-84) has given us additional information.…”

Guidelines for the diagnosis, prevention and management of osteoporosis

“…Teriparatide: in a 36-month study that compared teriparatide versus alendronate in patients treated with glucocorticoids, teriparatide was more effective than alendronate in improving BMD (primary endpoint) and incidence of vertebral fractures (secondary endpoint) (38). For this reason, treatment with teriparatide is considered as a first line option for patients with glucocorticoid-induced osteoporosis and at least one previous fracture (secondary prevention) in the recent revision of the Italian AIFA Note 79.…”