Results from a randomized, open-label, active comparator, phase 3 controlled study demonstrate that a recombinant human parathyroid hormone analog significantly increased lumbar spine volumetric bone mineral density compared with a bisphosphonate in men with glucocorticoid-induced osteoporosis.
According to the literature, teriparatide (Forteo, Eli Lilly and Company) is administered in a multi-dose prefilled delivery pen containing 28 daily doses of 20 mcg.
For this study, an 18-month open-label, randomized controlled trial was conducted in four European countries. The trial included men who had taken glucocorticoids for more than 3 months and had an areal BMD T-score of less than –1.5 (standard deviation), according to researchers. They were randomly assigned teriparatide 20 mcg per day (n=45) or risedronate 35 mg per week (n=47) and 1 g calcium and 1,200 IU vitamin D daily.
Data indicate that teriparatide and risedronate significantly increased lumbar spine volumetric BMD, with greater increases observed in patients assigned to teriparatide (mean change from baseline: 16.3% vs. 3.8%; P=.004) at 18 months.
“Though we often think of osteoporosis as a women’s disease, men can get it too. In fact, approximately 2 million American men have osteoporosis,” Claus-C. Glüer, PhD, professor of medical physics in the department of diagnostic radiology at the University Medical Center Schleswig-Holstein in Germany, said in a press release. “These study results can help health care professionals better determine which treatment may be best suited for individual male patients with glucocorticoid-induced osteoporosis.”
Of the secondary outcome data, Glüer and colleagues reported statistically significant increases in estimated vertebral strength in both groups (teriparatide: 26% to 34% vs. risedronate: 4.2% to 6.7%; P<.005) after 18 months.
Moreover, they wrote that adverse events were similar between groups, with five patients (10.6%) developing new fractures in the risedronate group, whereas zero displayed new fractures in the teriparatide group.
Disclosure: Glüer has received honoraria and research support from Eli Lilly & Company. See the study for a full list of disclosures.
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Glucocortocoids directly impair osteoblast function and bone formation, and fractures in patients on glucocortocoids are more of impairment in bone quality rather than impairment in BMD. It has previously been shown in comparator trials of teriparatide 20-mcg per day vs. alendronate 70-mg per week that teriparatide increases bone formation by quantitative bone histomorphometry, whereas alendronate, like all anti-resorptive agents, is associated with a decrease in bone formation and that the improvement in bone microstructure parameters mediated by teriparatide is highly correlated to the improvement in BMD.
The current manuscript by Glüer and colleagues studied the effects of teriparatide 20-mcg administered subcutaneously once daily vs. oral risedronate 35-mg once weekly using a wider variety of newer radiological techniques to measure bone strength including finite element analysis and microstructure of L1-L3 by high resolution quantitative computerized tomography, as well as BMD by both QCT and a DXA. Teriparatide was associated with significantly greater improvements in BMD, microstructure and bone strength than risedronate, though there were improvements in these parameters with risedronate as well.
These data suggest that for treatment-naïve patients receiving chronic glucocortiocids that teriparatide may be considered a first-line therapy due to its unique mechanism of action to directly counter the negative effects that glucocorticoids have on osteoblast and osteocyte function. Additionally, prior treatment with oral bisphosphonates delays the anabolic effect of teriparatide.
The Glüer data clearly show that a very important surrogate of bone strength is improved to a greater degree by the anabolic agent teriparatide than an anti-resorptive agent in glucocorticoids-exposed subjects. Surrogates of bone strength are evolving to replace fractures as efficacy endpoints due to the strength of the surrogate markers and especially the prohibitive costs of head-to-head fracture trials, especially with agents that both have beneficial effects in glucocorticoid-induced osteoporosis (teriparatide and bisphosphonates). The Glüer data, however, do strongly suggest that teriparatide should be considered as first-line therapy in glucocorticoid-induced bone disease.
- Paul D. Miller, MD
- Distinguished Clinical Professor of Medicine
University of Colorado Health Sciences Center
Medical Director
Colorado Center for Bone Research
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