Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy

J Clin Endocrinol Metab. 2005 Jul;90(7):3970-7. doi: 10.1210/jc.2003-1703. Epub 2005 Apr 19.

Abstract

Context: Biochemical markers of bone turnover may reflect bone structure during anabolic treatment.

Objective: The objective was to evaluate associations between changes in biochemical markers and structural and dynamic bone parameters during teriparatide treatment.

Design: This study was a randomized, multicenter, double-blind, placebo-controlled fracture prevention trial, with 20-month median treatment duration for biopsy subset.

Setting: The trial was conducted at 11 clinical study sites.

Patients: Sixty-one postmenopausal women with osteoporosis who had paired transiliac biopsy specimens participated in the study.

Interventions: Once-daily sc injections of either placebo or teriparatide (20 or 40 microg) were administered.

Main outcome measures: The study measured: 1) serum and urinary biochemical markers of bone formation [bone alkaline phosphatase and procollagen I C-terminal propeptide (PICP)] and resorption (N-telopeptide and deoxypyridinoline); and 2) structural and dynamic analyses of bone biopsies, including two-dimensional (2D) histomorphometry and three-dimensional (3D) micro-computed tomography evaluations measured at baseline (n = 57) and 12 (n = 21) or 22 (n = 36) months.

Results: U-N-telopeptide/creatinine and serum-PICP correlated with bone structure and dynamic indices at baseline, respectively. Changes in bone alkaline phosphatase at 1 month correlated with changes at 22 months in 2D wall thickness (r = 0.73; P = 0.001), trabecular bone volume (trabecular bone volume per total volume, BV/TV) (r = 0.58; P < 0.05), marrow star volume (r = -0.51; P = 0.05); 3D trabecular thickness (r = 0.49; P < 0.05), and BV/TV (r = 0.54; P < 0.05). Changes in PICP at 1 month correlated with changes in wall thickness (r = 0.60; P = 0.01), and 2D BV/TV (r = 0.51; P < 0.05) at 22 months. Changes in markers at 6 or 12 months were not associated with changes in structural or dynamic parameters.

Conclusions: Early (1-month) changes in biochemical markers of bone formation, but not resorption, correlated with improvements in bone structure after 22 months of teriparatide therapy.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alkaline Phosphatase / blood
  • Amino Acids / urine
  • Bone and Bones / drug effects*
  • Collagen / urine
  • Collagen Type I
  • Female
  • Humans
  • Middle Aged
  • Osteogenesis / drug effects*
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / metabolism
  • Peptide Fragments / blood
  • Peptides / urine
  • Procollagen / blood
  • Teriparatide / therapeutic use*

Substances

  • Amino Acids
  • Collagen Type I
  • Peptide Fragments
  • Peptides
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • procollagen type I carboxy terminal peptide
  • Teriparatide
  • deoxypyridinoline
  • Collagen
  • Alkaline Phosphatase