title: Assessing the Effects of Teriparatide Treatment on Bone Mineral Density, Bone Microarchitecture, and Bone Strength.
abstract: BACKGROUND
  To gain insight into how teriparatide affects various bone health parameters, we assessed the effects of teriparatide treatment with use of standard DXA (dual x-ray absorptiometry) technology and two newer technologies, high-resolution MRI (magnetic resonance imaging) and finite element analysis of quantitative CT (computed tomography) scans.
  
  
  METHODS
  In this phase-4, open-label study, postmenopausal women with severe osteoporosis received 20 μg/day of teriparatide. Assessments included (1) changes in areal BMD (bone mineral density) (in g/cm2) at the radius, spine, and hip on DXA, (2) changes in volumetric BMD (in mg/cm3) at the spine and hip on quantitative CT scans, (3) changes in bone microarchitecture at the radius on high-resolution MRI, (4) estimated changes in spine and hip strength according to finite element analysis of quantitative CT scans, (5) changes in bone turnover markers in serum, and (6) safety.
  
  
  RESULTS
  Thirty-five subjects were enrolled; thirty completed eighteen months and twenty-five completed an optional six-month extension. No significant changes were observed for the primary outcome, high-resolution MRI at the distal aspect of the radius. At month eighteen, the least-squares mean percentage change from baseline in total volumetric BMD at the spine was 10.05% (95% confidence interval [CI], 6.83% to 13.26%; p < 0.001), and estimated spine strength increased 17.43% (95% CI, 12.09% to 22.76%; p < 0.001). Total volumetric BMD at the hip increased 2.22% (95% CI, 0.37% to 4.06%; p = 0.021), and estimated hip strength increased 2.54% (95% CI, 0.06% to 5.01%; p = 0.045). Areal BMD increased at the lumbar spine and femoral neck, was unchanged for the total hip and at the distalmost aspect of the radius, and decreased at a point one-third of the distance between the wrist and elbow. Bone turnover markers increased at months three, six, and twenty-four (all p < 0.05). No unexpected adverse events were observed.
  
  
  CONCLUSIONS
  High-resolution MRI failed to identify changes in bone microarchitecture at the distal aspect of the radius, a non-weight-bearing site that may not be suitable for assessing effects of an osteoanabolic agent. Teriparatide increased areal BMD at the spine and femoral neck and volumetric BMD at the spine and hip. Estimated vertebral and femoral strength also increased. These findings and increases in bone turnover markers through month twenty-four are consistent with the known osteoanabolic effect of teriparatide.
  
  
  METHODS
  Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Toledo, 3000 Arlington Avenue, Toledo, OH 43614. E-mail address: mkleerekoper@yahoo.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Kleerekoper
authors.affiliation: Osteoporosis Treatment and Prevention Center, University of Pittsburgh, 3459 Fifth Avenue, 4th Floor, Pittsburgh, PA 15213.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Greenspan
authors.affiliation: New Mexico Clinical Research & Osteoporosis Center, 300 Oak Street N.E., Albuquerque, NM 87106.
authors.forename: E Michael
authors.initials: EM
authors.lastname: Lewiecki
authors.affiliation: Colorado Center for Bone Research, University of Colorado Health Sciences Center, 3190 South Wadsworth Boulevard, Lakewood, CO 80227.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Miller
authors.affiliation: University of British Columbia, 150-943 West Broadway, Vancouver, BC V5Z 4E1, Canada.
authors.forename: David L
authors.initials: DL
authors.lastname: Kendler
authors.affiliation: Catalina Pointe Rheumatology, 7520 North Oracle Road, Suite 100, Tucson, AZ 85724.
authors.forename: Michael
authors.initials: M
authors.lastname: Maricic
authors.affiliation: Departments of Mechanical Engineering and Bioengineering, 6175 Etcheverry Hall, MC 1740, University of California, Berkeley, CA 94720-1740.
authors.forename: Tony M
authors.initials: TM
authors.lastname: Keaveny
authors.affiliation: O.N. Diagnostics, 2150 Shattuck Avenue, Suite 610, Berkeley, CA 94704.
authors.forename: David L
authors.initials: DL
authors.lastname: Kopperdahl
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Ruff
authors.affiliation: Novartis Pharmaceuticals Corporation, One Health Plaza East, East Hanover, NJ 07936.
authors.forename: Xiaohai
authors.initials: X
authors.lastname: Wan
authors.affiliation: Eli Lilly Canada Inc., 3650 Danforth Avenue, Toronto, ON M1N 2E8, Canada.
authors.forename: Boris
authors.initials: B
authors.lastname: Janos
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
authors.forename: Kelly
authors.initials: K
authors.lastname: Krohn
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002170:Canada; D005260:Female; D020342:Finite Element Analysis; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D019379:Teriparatide / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome; D014481:United States
chemical_list: D050071:Bone Density Conservation Agents; D019379:Teriparatide