Teriparatide, the first anabolic agent for treatment of osteogenesis imperfecta improves bone mineral density at the hip and spine: a randomized, blinded, placebo-controlled trial. SC. Sreenath Nagamani1, J. Shapiro2, S. Veith3, Y. Wang3, J. Lapidus3, JL. Reeder3, TM. Keaveny4, D. Lee4, MA. Mullins1, B. Lee1,5, ES. Orwoll3 1) Baylor College of Medicine, Houston, TX, USA; 2) Kennedy Krieger Institute, Baltimore, MD, USA; 3) Oregon Health & Science University, Portland, OR, USA; 4) ON Diagnostics, Berkeley, CA, USA; 5) Howard Hughes Medical Institute, Houston, TX, USA.

   Osteogenesis Imperfecta (OI) refers to a group of disorders that are characterized by bone fragility and recurrent fractures. Therapy for OI is presently limited to bisphosphonates and there have been few controlled studies for treatment of OI. As mutations in OI alter the bone matrix, affect osteoblast function and bone remodeling, treatment with anabolic bone agents may be useful to increase bone mass and strength. In the largest placebo-controlled trial in adults with OI, and the first trial of anabolic therapy in this disease, we evaluated the effects of teriparatide treatment. We performed a randomized, double-blind, placebo-controlled trial of teriparatide in 77 adults with OI (33 men, 44 women). The mean age of subjects was 41 years (range 18-75). Fifty-one had OI type I, 14 had OI type III, and 12 had OI type IV. Subjects were treated for 18 months with either teriparatide (20g/day) or placebo. Baseline and 6-monthly measures of bone mineral density (BMD), i.e. DXA scans and vertebral QCT scans were obtained. Self-reported fractures at any site were recorded. Serum P1NP and urine NTX levels increased (135+14% and 64+10%, respectively) with teriparatide therapy but remained stable in the placebo group suggesting increased bone remodeling with therapy. Total hip areal BMD (2.5+1.3 % vs. -3.4+1.1; p< 0.001) and spine BMD (6.0+1.2 % vs. 0.9+1.2 %; p< 0.05) increased significantly more in the teriparatide treated than in the placebo group. Volumetric spine BMD increased in those receiving teriparatide therapy (18+6%) but declined in those receiving placebo (-5.0+6%; p< 0.05). The estimated vertebral strength as assessed by finite element analysis increased 14% in the teriparatide group and decreased 2.5% in the placebo group (p= 0.001). The BMD increase was robust in patients with OI type 1 whereas there was no significant increase in those with OI types III and IV. The study could not definitively assess the effects on fracture outcomes as it was not adequately powered to detect a change in fracture rates. There was no statistically significant difference in fractures (RR 0.8; CI 0.42-1.55). There were no drug-related serious adverse events. Our study proves that anabolic therapy with teriparatide in adults with OI is well-tolerated and increases BMD at the hip and the spine, particularly in those with OI type I. Teriparatide could be a potential therapy for OI though further studies would be needed to assess its effects on fracture rates.