In patients with steroid-induced osteoporosis, the peptide drug teriparatide built more than twice as much bone and cut spinal fracture risk 10-fold compared to standard bisphosphonate therapy.
0.6% vs 6.1%New vertebral fracture rate in teriparatide vs. alendronate patients over 18 months — a 10-fold difference favoring the peptide therapy
What the researchers found
In a head-to-head comparison of 428 patients with glucocorticoid-induced osteoporosis, the peptide drug teriparatide increased lumbar spine bone density by 7.2% over 18 months, compared to 3.4% with the bisphosphonate alendronate (p<0.001). The difference was already significant by 6 months.
Most strikingly, teriparatide dramatically reduced new vertebral fractures: only 0.6% of teriparatide patients suffered a new vertebral fracture versus 6.1% of alendronate patients (p=0.004) — a 10-fold difference. Nonvertebral fracture rates were similar between groups. Teriparatide did cause more elevated calcium levels as a side effect.
Why it matters
Millions of people take glucocorticoids (like prednisone) for conditions such as rheumatoid arthritis, asthma, and autoimmune diseases, and bone loss is one of the most serious long-term side effects. This landmark NEJM trial showed that the peptide teriparatide doesn't just slow bone loss (like alendronate does) — it actively builds new bone, resulting in more than twice the bone density gain and a 10-fold reduction in spinal fractures. It changed how clinicians think about treating steroid-induced osteoporosis.
The numbers in context
n=428 · 18-month trial · Spine BMD: +7.2% vs +3.4% (p<0.001) · Vertebral fractures: 0.6% vs 6.1% (p=0.004) · Teriparatide 20 μg/day vs alendronate 10 mg/day
How the study worked
An 18-month randomized, double-blind, controlled trial enrolling 428 men and women (ages 22-89) with osteoporosis who had been taking glucocorticoids (≥5 mg prednisone equivalent daily) for at least 3 months. Patients were randomized 1:1 to receive either teriparatide (20 μg daily injection) or alendronate (10 mg daily oral). The primary outcome was change in lumbar spine bone mineral density, with secondary outcomes including hip BMD, bone turnover markers, and fracture incidence.
Who was studied
428 men and women (ages 22-89) with osteoporosis on long-term glucocorticoid therapy (≥3 months, ≥5 mg prednisone equivalent daily)
What this study cannot tell us
The trial lasted 18 months, so longer-term comparative outcomes are unknown. Nonvertebral fracture rates were not significantly different, possibly due to insufficient power for this endpoint. More teriparatide patients experienced elevated calcium. Teriparatide requires daily injections while alendronate is oral, affecting real-world adherence. The study was industry-sponsored (Eli Lilly, maker of teriparatide).
How to read the evidence
This is a large, randomized, double-blind controlled trial published in the New England Journal of Medicine — one of the highest standards of clinical evidence. The results are statistically significant with clear clinical relevance.
When this study was published
Published in 2007 in NEJM. This remains a landmark trial and is still widely cited in osteoporosis treatment guidelines. Teriparatide continues to be used clinically based in part on this evidence.
The bigger picture
This trial was pivotal in establishing that bone-building (anabolic) therapy is superior to bone-preserving (antiresorptive) therapy for steroid-induced osteoporosis. It helped shift clinical practice toward using teriparatide first in high-risk patients rather than as a last resort. The results also demonstrated that peptide-based therapies can address the root cause of bone loss — insufficient new bone formation — rather than just slowing breakdown.
Questions still open
- Would longer treatment beyond 18 months maintain or extend teriparatide's advantage, and what happens when treatment stops?
- Could newer peptide therapies like abaloparatide show even greater benefits in glucocorticoid-induced osteoporosis?
- Is the elevated calcium seen with teriparatide clinically significant in long-term use?
Common questions
Why do steroids cause bone loss?
How is teriparatide different from other osteoporosis drugs?
Read the original research
Teriparatide or alendronate in glucocorticoid-induced osteoporosis.
The New England journal of medicine, 357(20), 2028-39
Citation
Saag, Kenneth G; Shane, Elizabeth; Boonen, Steven; Marín, Fernando; Donley, David W; Taylor, Kathleen A; Dalsky, Gail P; Marcus, Robert. (2007). Teriparatide or alendronate in glucocorticoid-induced osteoporosis.. The New England journal of medicine, 357(20), 2028-39.