title: Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor.
  
  
  OBJECTIVE
  To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture.
  
  
  METHODS
  The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll.
  
  
  METHODS
  Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 μg (n = 824); or open-label teriparatide, 20 μg (n = 818) for 18 months.
  
  
  METHODS
  Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants.
  
  
  RESULTS
  Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text].
  
  
  CONCLUSIONS
  Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01343004.
authors.affiliation: Colorado Center for Bone Research, Lakewood.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Miller
authors.affiliation: Radius Health, Waltham, Massachusetts.
authors.forename: Gary
authors.initials: G
authors.lastname: Hattersley
authors.affiliation: Nordic Bioscience, Copenhagen, Denmark.
authors.forename: Bente Juel
authors.initials: BJ
authors.lastname: Riis
authors.affiliation: Radius Health, Waltham, Massachusetts.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Williams
authors.affiliation: Center for Health & Medical Research, Hong Kong, People's Republic of China.
authors.forename: Edith
authors.initials: E
authors.lastname: Lau
authors.affiliation: Center for Clinical and Basic Research, Rio de Janeiro, Brazil.
authors.forename: Luis Augusto
authors.initials: LA
authors.lastname: Russo
authors.affiliation: Center for Clinical and Basic Research, Vejle, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Alexandersen
authors.affiliation: Centro Paulista de Investigação Clinica; São Paulo, Brazil.
authors.forename: Cristiano A F
authors.initials: CA
authors.lastname: Zerbini
authors.affiliation: Radius Health, Waltham, Massachusetts.
authors.forename: Ming-yi
authors.initials: MY
authors.lastname: Hu
authors.affiliation: Radius Health, Waltham, Massachusetts.
authors.forename: Alan G
authors.initials: AG
authors.lastname: Harris
authors.affiliation: Radius Health, Waltham, Massachusetts.
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: Fitzpatrick
authors.affiliation: Clinical Research Center, Helen Hayes Hospital, West Haverstraw, New York.
authors.forename: Felicia
authors.initials: F
authors.lastname: Cosman
authors.affiliation: Nordic Bioscience, Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000502:physiology; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced; D007279:Injections, Subcutaneous; D008159:Lumbar Vertebrae / Q000293:injuries* / Q000503:physiopathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal; D058866:Osteoporotic Fractures / Q000517:prevention & control*; D044162:Parathyroid Hormone-Related Protein / Q000009:adverse effects / Q000627:therapeutic use*; D010384:Pelvic Bones / Q000187:drug effects / Q000502:physiology; D010919:Placebos / Q000627:therapeutic use; D017698:Postmenopause; D011859:Radiography; D016103:Spinal Fractures / Q000517:prevention & control*; D019379:Teriparatide / Q000009:adverse effects / Q000627:therapeutic use; D013904:Thoracic Vertebrae / Q000293:injuries*
chemical_list: D050071:Bone Density Conservation Agents; D044162:Parathyroid Hormone-Related Protein; D010919:Placebos; D019379:Teriparatide; C000596789:abaloparatide