title: PINP as an aid for monitoring patients treated with teriparatide.
abstract: Biochemical markers of bone turnover may be useful aids for managing patients with osteoporosis. A 12-month, phase 3, multicenter trial of Japanese patients at high risk of fracture was conducted to assess the effects of teriparatide 20 μg/day on BMD, serum markers of bone turnover, and safety. Two-hundred and seven subjects (93% female; median age 70 years) were randomized in double-blind fashion 2:1 to teriparatide versus placebo. Bone turnover markers including procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (bone ALP) and type I collagen cross-linked C-telopeptide (CTX) were collected at baseline, 1, 3, 6, and 12 months. Lumbar spine, femoral neck, and total hip BMD were measured at baseline, 3, 6, and 12 months. Increases in PINP at 1 month correlated best with increases in lumbar spine BMD at 12 months (r=0.76; P<0.01). The proportions of patients with an increase from baseline in PINP >10 μg/L at 1, 3, and 6 months were 3%, 0%, and 2% in the placebo, and 93%, 87%, and 83% in the teriparatide group. The proportions of patients with an increase in PINP >10 μg/L at either 1 or 3 months were 3% in the placebo and 95% in the teriparatide group (P<0.001). The proportions of patients with a significant increase in lumbar spine BMD (increase from baseline ≥3%) at 12 months were 20% in the placebo and 94% in the teriparatide group. The proportions of patients with an increase in PINP >10 μg/L at 1 or 3 months and an increase in lumbar spine BMD ≥3% at 12 months was 0% of placebo group patients and 92% of teriparatide group patients (P<0.001). These data confirm a strong relationship between early change in PINP and later change in lumbar spine BMD during teriparatide therapy. Also, these results suggest that monitoring with PINP and lumbar spine BMD successfully identifies positive responses in most patients taking teriparatide and negative responses in most patients not taking teriparatide. PINP monitoring may be a useful aid in the management of patients with osteoporosis during teriparatide treatment.
authors.affiliation: Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Sannomiya Plaza Building, 7-1-5 Isogamidori, Kobe 651-0086, Japan. Tsujimoto_mika@lilly.com
authors.forename: Mika
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Peiqi
authors.initials: P
authors.lastname: Chen
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sowa
authors.forename: John H
authors.initials: JH
authors.lastname: Krege
mesh_terms: D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling; D004311:Double-Blind Method; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D008297:Male; D008991:Monitoring, Physiologic; D010024:Osteoporosis / Q000188:drug therapy*; D010919:Placebos; D019379:Teriparatide / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D010919:Placebos; D019379:Teriparatide