Saag and colleagues undertook trial comparing teriparatide and alendronate in patients with GIO. All patients also received 1000 mg of calcium carbonate and 800 IU of vitamin D. The primary outcome was change in bone density at the LS.
Patients had a history of sustained GC therapy and a T-score at the LS or total hip of either -2.0 or less or -1.0 or less plus at least one fragility fracture while receiving GCs.
Four hundred twenty-eight patients were randomized, and 75% were being treated for rheumatologic disorders (almost half with RA). The median daily prednisone dose was 7.6 mg and the median duration of therapy was 1.3 years. Almost 70% had prevalent fragility fractures and the mean baseline LS T-score was -2.5.
At 18 months, patients in the teriparatide group had a significantly greater increase in mean bone mineral density (BMD) at the LS than those in the alendronate group. Similarly, at the total hip, the teriparatide group’s increase in BMD from baseline (3.8±0.6%) was significantly greater than the alendronate group (2.4±0.6%, p=0.005).
Ten patients in the alendronate group (n=165) had new radiographic vertebral fractures while only one in the teriparatide group (n=171) did (p=0.004). Markers of bone formation and resorption both showed increases in the teriparatide group and decreases in the alendronate group.
There were no significant differences in the overall incidence of adverse events between the two groups, although more patients treated with teriparatide had one or more serum calcium values greater than 10.5; there were no instances of sustained elevation.
I think this paper should encourage rheumatologists to be more aggressive in evaluating patients on sustained GCs and considering the various therapeutic options. For many individuals on GCs who are at relatively low risk for immediate GIO or fracture—such as younger individuals starting GCs, individuals with only mildly or moderately low BMD, or those with relatively mild osteoporosis—I’ll undoubtedly continue to use oral bisphosphonates.
However, this study’s patient population, which clearly was at high risk for fracture (over two-thirds had prevalent GC-induced fractures at baseline), benefited significantly from teriparatide compared with alendronate. Less than 5% of the patients in this study had PMR and the mean age of the patients was 57. It seems likely that for patient populations which are enriched in PMR, GCA, and other diseases in older individuals, benefits of teriparatide might be even more striking.
At least two practical issues could limit the use of teriparatide: daily injections and cost. In particular, when Fosamax becomes available generically in 2008 and cost is reduced, resistance from payers to use of teriparitide can be expected. Cost-effectiveness analyses may be necessary to demonstrate the magnitude of fracture risk needed to justify teriparatide use. In the meantime, this study should reinforce the value of performing routine fracture assessments on postmenopausal women and men over age 60 who are on chronic GCs in order to help identify patients at particularly high risk.
References
- ACR Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. Arthritis Rheum. 2001;44:1496-1503.
- Jilka RL, Weinstein RS, Bellido T, et al. Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest. 1999;104:439-446.
