Novel Anabolic Therapy for Osteoporosis Using IGFs.

PAPPA-A Transiliac Bone Biopsy

Normal

PAPPA-A Transiliac Bone Biopsy

HCAO

The ability to stimulate new bone formation and increase bone mass in patients with osteoporosis is an important goal. Patients with a rare syndrome of hepatitis C-associated osteosclerosis (HCAO), who develop marked increases in bone mass as adults, first provided clues for an innovative approach using the IGF system. The IGFs are important skeletal growth factors, and our detailed analysis of the IGF system in patients with HCAO indicated a unique increase in an IGF-II precursor molecule and IGFBP-2. Subsequent studies in cultured human bones demonstrated preferential binding of the IGF-II/IGFBP-2 complex to bone matrix and stimulation of osteoblast proliferation. Animal studies showed increases in bone mineral density following short-term IGF-II/IGFBP-2 administration. This project is continuing with the pre-clinical analyses of this novel anabolic approach to the treatment of osteoporosis.