title: Effect of Teriparatide on Bone Formation in the Human Femoral Neck.
abstract: Teriparatide (TPTD) improves bone mass and microstructure resulting in reduced risk of vertebral and nonvertebral fractures. However, hip bone mineral density improvements are modest and there are no data confirming that TPTD reduces hip fracture risk. To study the effects of TPTD on the proximal femur, we performed a double-blind trial of TPTD vs placebo (PBO) in patients with osteoarthritis from whom femoral neck (FN) samples were obtained at total hip replacement (THR) surgery.
  
  
  
  Participants were randomly assigned to receive TPTD or PBO for an average of 40 days before THR. Double tetracycline labeling was initiated 21 days prior to THR to allow histomorphometric assessment of bone formation. During the THR, an intact sample of the FN was procured, fixed, and sectioned transversely. Serum levels of bone turnover markers were measured at baseline and during the THR. Standard histomorphometric parameters were measured and calculated on four bone envelopes (cancellous, endocortical, intracortical, and periosteal). The primary outcome measure was bone formation rate/bone surface (BFR/BS).
  
  
  
  Forty individuals were enrolled (25 women, mean age, 71.5 ± 8.0 y and 15 men, mean age, 68.9 ± 7.7 y). In cancellous and endocortical envelopes, BFR/BS was 100% higher in the TPTD vs PBO group (P < .05). Bone turnover markers measured at the time of THR correlated with BFR/BS.
  
  
  
  TPTD stimulates bone formation rapidly in cancellous and endocortical envelopes of the FN. Our findings provide a mechanistic basis for TPTD-mediated improvement in FN bone mass and ultimately hip strength. This study is the first demonstration of the effect of any osteoporosis medication on osteoblast activity in the human proximal femur.
authors.affiliation: Regional Bone Center, Helen Hayes Hospital (F.C., D.W.D., J.W.N., H.Z., M.Z., C.R., R.L.), West Haverstraw, New York 10993; Department of Medicine (F.C., R.L.), Department of Pathology (D.W.D.), and Department of Epidemiology (J.W.N.), Columbia University, New York, New York 10032; and Department of Orthopedics (Y.H., M.B.), Hospital for Special Surgery, New York, New York 10021.
authors.forename: Felicia
authors.initials: F
authors.lastname: Cosman
authors.affiliation: Regional Bone Center, Helen Hayes Hospital (F.C., D.W.D., J.W.N., H.Z., M.Z., C.R., R.L.), West Haverstraw, New York 10993; Department of Medicine (F.C., R.L.), Department of Pathology (D.W.D.), and Department of Epidemiology (J.W.N.), Columbia University, New York, New York 10032; and Department of Orthopedics (Y.H., M.B.), Hospital for Special Surgery, New York, New York 10021.
authors.forename: David W
authors.initials: DW
authors.lastname: Dempster
authors.affiliation: Regional Bone Center, Helen Hayes Hospital (F.C., D.W.D., J.W.N., H.Z., M.Z., C.R., R.L.), West Haverstraw, New York 10993; Department of Medicine (F.C., R.L.), Department of Pathology (D.W.D.), and Department of Epidemiology (J.W.N.), Columbia University, New York, New York 10032; and Department of Orthopedics (Y.H., M.B.), Hospital for Special Surgery, New York, New York 10021.
authors.forename: Jeri W
authors.initials: JW
authors.lastname: Nieves
authors.affiliation: Regional Bone Center, Helen Hayes Hospital (F.C., D.W.D., J.W.N., H.Z., M.Z., C.R., R.L.), West Haverstraw, New York 10993; Department of Medicine (F.C., R.L.), Department of Pathology (D.W.D.), and Department of Epidemiology (J.W.N.), Columbia University, New York, New York 10032; and Department of Orthopedics (Y.H., M.B.), Hospital for Special Surgery, New York, New York 10021.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Regional Bone Center, Helen Hayes Hospital (F.C., D.W.D., J.W.N., H.Z., M.Z., C.R., R.L.), West Haverstraw, New York 10993; Department of Medicine (F.C., R.L.), Department of Pathology (D.W.D.), and Department of Epidemiology (J.W.N.), Columbia University, New York, New York 10032; and Department of Orthopedics (Y.H., M.B.), Hospital for Special Surgery, New York, New York 10021.
authors.forename: Marsha
authors.initials: M
authors.lastname: Zion
authors.affiliation: Regional Bone Center, Helen Hayes Hospital (F.C., D.W.D., J.W.N., H.Z., M.Z., C.R., R.L.), West Haverstraw, New York 10993; Department of Medicine (F.C., R.L.), Department of Pathology (D.W.D.), and Department of Epidemiology (J.W.N.), Columbia University, New York, New York 10032; and Department of Orthopedics (Y.H., M.B.), Hospital for Special Surgery, New York, New York 10021.
authors.forename: Catherine
authors.initials: C
authors.lastname: Roimisher
authors.affiliation: Regional Bone Center, Helen Hayes Hospital (F.C., D.W.D., J.W.N., H.Z., M.Z., C.R., R.L.), West Haverstraw, New York 10993; Department of Medicine (F.C., R.L.), Department of Pathology (D.W.D.), and Department of Epidemiology (J.W.N.), Columbia University, New York, New York 10032; and Department of Orthopedics (Y.H., M.B.), Hospital for Special Surgery, New York, New York 10021.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Houle
authors.affiliation: Regional Bone Center, Helen Hayes Hospital (F.C., D.W.D., J.W.N., H.Z., M.Z., C.R., R.L.), West Haverstraw, New York 10993; Department of Medicine (F.C., R.L.), Department of Pathology (D.W.D.), and Department of Epidemiology (J.W.N.), Columbia University, New York, New York 10032; and Department of Orthopedics (Y.H., M.B.), Hospital for Special Surgery, New York, New York 10021.
authors.forename: Robert
authors.initials: R
authors.lastname: Lindsay
authors.affiliation: Regional Bone Center, Helen Hayes Hospital (F.C., D.W.D., J.W.N., H.Z., M.Z., C.R., R.L.), West Haverstraw, New York 10993; Department of Medicine (F.C., R.L.), Department of Pathology (D.W.D.), and Department of Epidemiology (J.W.N.), Columbia University, New York, New York 10032; and Department of Orthopedics (Y.H., M.B.), Hospital for Special Surgery, New York, New York 10021.
authors.forename: Mathias
authors.initials: M
authors.lastname: Bostrom
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005272:Femur Neck / Q000187:drug effects*; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D019379:Teriparatide / Q000494:pharmacology*
chemical_list: D050071:Bone Density Conservation Agents; D019379:Teriparatide