title: Safety of daily teriparatide treatment: a post hoc analysis of a Phase III study to investigate the possible association of teriparatide treatment with calcium homeostasis in patients with serum procollagen type I N-terminal propeptide elevation.
abstract: OBJECTIVE
  Serum procollagen type I N-terminal propeptide (PINP), a representative marker of bone anabolic action, is strongly related to bone mineral density during teriparatide therapy. This post hoc study analyzed data from a Phase III study (ClinicalTrials.gov identifier NCT00433160) to determine if there was an association between serum PINP elevation and serum calcium concentration or calcium metabolism-related disorders.
  
  
  METHODS
  Japanese subjects with osteoporosis at high risk of fracture were randomized 2:1 to teriparatide 20 μg/day (n=137) or placebo (n=70) for a 12-month double-blind treatment period, followed by 12 months of open-label teriparatide treatment of all subjects.
  
  
  METHODS
  Serum PINP levels were measured at baseline, and after 1, 3, 6, 12, 18, and 24 months of treatment. Serum calcium levels were measured at baseline, and after 1, 3, 6, 9, 12, 15, 18, 21, and 24 months of treatment.
  
  
  RESULTS
  Serum PINP increased from baseline to 1 month of treatment and then remained high through 24 months. Twenty-eight of 195 subjects experienced PINP elevations >200 μg/L during teriparatide treatment. Serum calcium concentration in both the teriparatide and placebo groups remained within the normal range. There was no clinically relevant difference in serum calcium concentration between subjects with PINP >200 μg/L and subjects with PINP ≤200 μg/L. Two subjects experienced hypercalcemia and recovered without altering teriparatide treatment. Adverse events possibly related to calcium metabolism disorders included periarthritis calcarea (one subject) and chondrocalcinosis pyrophosphate (two subjects), but neither was accompanied with a significant increase in PINP or serum calcium concentration.
  
  
  CONCLUSIONS
  Although the moderate size of this study prevented statistical analysis of any potential association between calcium metabolism-related disorders and elevated PINP, this analysis suggests that there was no association between serum PINP elevation during daily teriparatide treatment and serum calcium concentration or calcium metabolism-related disorders in Japanese subjects.
authors.affiliation: Medical Science, Lilly Research Laboratories, Medicines Development Unit Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Asia Pacific Statistical Science-Japan, Science and Regulatory Affairs, LRL MDU-Japan, Eli Lilly Japan K.K, Kobe, Hyogo, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Tsujimoto
authors.affiliation: Medical Science, Lilly Research Laboratories, Medicines Development Unit Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sowa
mesh_terms: D000368:Aged; D015415:Biomarkers; D015992:Body Mass Index; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002118:Calcium / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy*; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D019379:Teriparatide / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D019379:Teriparatide; D002118:Calcium
keywords: bone metabolism markers; hypercalcemia; osteoporosis; procollagen type I N-terminal propeptide; teriparatide