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PMID-11346808 – Teriparatide Fracture Prevention Trial (Neer 2001)

PMID-11346808 – Teriparatide Fracture Prevention Trial (Neer 2001)

Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001;344(19):1434-1441.

Quick Reference

Property Value
PMID 11346808
DOI 10.1056/NEJM200105103441904
Year 2001
Journal New England Journal of Medicine
Study Type RCT
Evidence Level I
Sample n=1637 postmenopausal women with prior vertebral fractures
Peptide(s) Studied Teriparatide

Key Findings

  • Daily subcutaneous teriparatide (20 mcg) reduced new vertebral fractures by 65% compared with placebo (RR 0.35; 95% CI 0.22-0.55)
  • The 40 mcg dose reduced vertebral fractures by 69% (RR 0.31; 95% CI 0.19-0.50)
  • Non-vertebral fragility fractures were reduced by 53% with the 20 mcg dose (RR 0.47; 95% CI 0.25-0.88)
  • Lumbar spine BMD increased by 9.7% (20 mcg) and 13.7% (40 mcg) vs placebo over median 21 months
  • Femoral neck BMD increased by 2.8% (20 mcg) and 5.1% (40 mcg)
  • This was the pivotal trial that led to FDA approval of teriparatide (Forteo) in 2002

Study Design

Randomized, double-blind, placebo-controlled trial. 1,637 postmenopausal women (mean age 69.5 years) with at least one prior vertebral fracture were randomized 1:1:1 to receive daily subcutaneous injections of 20 mcg teriparatide, 40 mcg teriparatide, or placebo. All participants received 1000 mg calcium and 400-1200 IU vitamin D. Primary endpoint was new vertebral fractures assessed by radiography. Median treatment duration was 21 months (trial stopped early due to unrelated osteosarcoma signal in Fischer 344 rats).

Limitations

  • Trial stopped early (median 21 months instead of planned 36 months) due to osteosarcoma finding in rodent toxicology studies at doses 3-60x the human exposure
  • All participants had prior vertebral fractures, limiting generalizability to lower-risk populations
  • Predominantly Caucasian population
  • Short treatment duration limits conclusions about long-term efficacy and safety
  • Hip fracture reduction did not reach statistical significance (likely underpowered)

Clinical Relevance

This landmark trial established teriparatide as the first anabolic agent for osteoporosis, demonstrating that intermittent PTH(1-34) stimulates bone formation rather than simply inhibiting resorption. The robust vertebral fracture reduction (65%) exceeded anything seen with bisphosphonates at the time, establishing a new paradigm: bone-building therapy for severe osteoporosis. The distinction between intermittent (anabolic) and continuous (catabolic) PTH exposure was confirmed clinically, with daily injections producing net bone formation through preferential stimulation of osteoblasts over osteoclasts.

Related

#research #RCT #teriparatide #evidence-level-I