title: Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial.
abstract: BACKGROUND
  Osteoporosis medications increase bone-mineral density (BMD) and lower but do not eliminate fracture risk. The combining of anabolic agents with bisphosphonates has not improved efficacy. We compared combined teriparatide and denosumab with both agents alone.
  
  
  METHODS
  From September, 2009, to January, 2011, we enrolled postmenopausal women with osteoporosis into this randomised, controlled trial. Patients were assigned in a 1:1:1 ratio to receive 20 μg teriparatide daily, 60 mg denosumab every 6 months, or both. BMD was measured at 0, 3, 6, and 12 months. Women who completed at least one study visit after baseline were assessed in a modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00926380.
  
  
  RESULTS
  94 (94%) of 100 eligible women completed at least one study visit after baseline. At 12 months, posterior-anterior lumbar spine BMD increased more in the combination group (9·1%, [SD 3·9]) than in the teriparatide (6·2% [4·6], p=0·0139) or denosumab (5·5% [3·3], p=0·0005) groups. Femoral-neck BMD also increased more in the combination group (4·2% [3·0]) than in the teriparatide (0·8% [4·1], p=0·0007) and denosumab (2·1% [3·8], p=0·0238) groups, as did total-hip BMD (combination, 4·9% [2·9]; teriparatide, 0·7% [2·7], p<0·0001; denosumab 2·5% [2·6], p=0·0011).
  
  
  CONCLUSIONS
  Combined teriparatide and denosumab increased BMD more than either agent alone and more than has been reported with approved therapies. Combination treatment might, therefore, be useful to treat patients at high risk of fracture.
  
  
  BACKGROUND
  Amgen, Eli Lilly, National Center for Research Resources.
authors.affiliation: Department of Medicine, Endocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Joy N
authors.initials: JN
authors.lastname: Tsai
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Uihlein
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.forename: Ruchit
authors.initials: R
authors.lastname: Kumbhani
authors.forename: Erica
authors.initials: E
authors.lastname: Siwila-Sackman
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: McKay
authors.forename: Sherri-Ann M
authors.initials: SA
authors.lastname: Burnett-Bowie
authors.forename: Robert M
authors.initials: RM
authors.lastname: Neer
authors.forename: Benjamin Z
authors.initials: BZ
authors.lastname: Leder
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000379:methods; D000069448:Denosumab; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy*; D019379:Teriparatide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004338:Drug Combinations; D019379:Teriparatide; D000069448:Denosumab