Teriparatide for idiopathic osteoporosis in premenopausal women: a pilot study

CONTEXT: Premenopausal women with idiopathic osteoporosis (IOP) have abnormal cortical and trabecular bone microarchitecture. OBJECTIVE: The purpose of this study was to test the hypotheses that teriparatide increases bone mineral density (BMD) and bone formation and improves trabecular microarchitecture and stiffness in women with IOP. DESIGN: This was an open-label pilot study. SETTING: The setting was a tertiary care referral center. PATIENTS: Participants were 21 premenopausal women with unexplained fragility fractures or low BMD. INTERVENTION: Teriparatide was administered at 20 μg daily for 18 to 24 months. MAIN OUTCOME MEASURES: The primary endpoint was within-subject percent change in lumbar spine BMD. Secondary endpoints included percent change in hip and forearm BMD, transiliac biopsy parameters (trabecular bone volume, microarchitecture, stiffness, and adipocytes), serum N-terminal propeptide of procollagen type 1 (P1NP), and C-telopeptide. RESULTS: BMD increased at the spine (10.8 ± 8.3% [SD]), total hip (6.2 ± 5.6%), and femoral neck (7.6 ± 3.4%) (all P < .001). Serum P1NP doubled by 1 month, peaked at 6 months, and returned to baseline by 18 to 24 months. Transiliac biopsies demonstrated significant increases in cortical width and porosity and trabecular bone volume and number increased, mirrored by a 71% increase in trabecular bone stiffness (P < .02-.001). Adipocyte area, perimeter, and volume/marrow volume decreased, with no change in adipocyte number. Four women had no increase in BMD and a blunted, delayed increase in serum P1NP. Nonresponders had markedly lower baseline bone formation rate (0.002 ± 0.001 vs 0.011 ± 0.006 mm²/mm/y; P < .001) and higher serum IGF-1 (208 ± 54 vs 157± 44 ng/mL; P = .03). CONCLUSIONS: Teriparatide was associated with increased spine and hip BMD and improved trabecular microarchitecture and stiffness at the iliac crest in the majority of women with IOP.