title: Evaluation of Bone Mineral Density and Bone Biomarkers in Patients With Type 2 Diabetes Treated With Canagliflozin.
abstract: BACKGROUND
  Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM).
  
  
  OBJECTIVE
  Our objective is to describe the effects of canagliflozin on bone mineral density (BMD) and bone biomarkers in patients with T2DM.
  
  
  METHODS
  This was a randomized study, consisting of a 26-week, double-blind, placebo-controlled period and a 78-week, double-blind, placebo-controlled extension.
  
  
  METHODS
  This study was undertaken in 90 centers in 17 countries.
  
  
  METHODS
  Patients were aged 55-80 years (N = 716) and whose T2DM was inadequately controlled on a stable antihyperglycemic regimen.
  
  
  METHODS
  Canagliflozin 100 or 300 mg or placebo were administered once daily.
  
  
  METHODS
  BMD was assessed using dual-energy x-ray absorptiometry at weeks 26, 52, and 104. Bone strength was assessed using quantitative computed tomography and finite element analysis at week 52. Serum collagen type 1 β-carboxy-telopeptide, osteocalcin, and estradiol were assessed at weeks 26 and 52.
  
  
  RESULTS
  Canagliflozin doses of 100 and 300 mg were associated with a decrease in total hip BMD over 104 weeks, (placebo-subtracted changes: -0.9% and -1.2%, respectively), but not at other sites measured (femoral neck, lumbar spine, or distal forearm). No meaningful changes in bone strength were observed. At week 52, canagliflozin was associated with an increase in collagen type 1 β-carboxy-telopeptide that was significantly correlated with a reduction in body weight, an increase in osteocalcin, and, in women, a decrease in estradiol.
  
  
  CONCLUSIONS
  In older patients with T2DM, canagliflozin showed small but significant reductions in total hip BMD and increases in bone formation and resorption biomarkers, due at least in part to weight loss.
authors.affiliation: Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; Mercy Health Osteoporosis and Bone Health Services (N.B.W.), Cincinnati, Ohio 45236; Janssen Research & Development, LLC (K.U., A.F., D.S., N.R.), Raritan, New Jersey 08869; and Janssen Research & Development, LLC (D.P.), San Diego, California 92121.
authors.forename: John P
authors.initials: JP
authors.lastname: Bilezikian
authors.affiliation: Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; Mercy Health Osteoporosis and Bone Health Services (N.B.W.), Cincinnati, Ohio 45236; Janssen Research & Development, LLC (K.U., A.F., D.S., N.R.), Raritan, New Jersey 08869; and Janssen Research & Development, LLC (D.P.), San Diego, California 92121.
authors.forename: Nelson B
authors.initials: NB
authors.lastname: Watts
authors.affiliation: Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; Mercy Health Osteoporosis and Bone Health Services (N.B.W.), Cincinnati, Ohio 45236; Janssen Research & Development, LLC (K.U., A.F., D.S., N.R.), Raritan, New Jersey 08869; and Janssen Research & Development, LLC (D.P.), San Diego, California 92121.
authors.forename: Keith
authors.initials: K
authors.lastname: Usiskin
authors.affiliation: Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; Mercy Health Osteoporosis and Bone Health Services (N.B.W.), Cincinnati, Ohio 45236; Janssen Research & Development, LLC (K.U., A.F., D.S., N.R.), Raritan, New Jersey 08869; and Janssen Research & Development, LLC (D.P.), San Diego, California 92121.
authors.forename: David
authors.initials: D
authors.lastname: Polidori
authors.affiliation: Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; Mercy Health Osteoporosis and Bone Health Services (N.B.W.), Cincinnati, Ohio 45236; Janssen Research & Development, LLC (K.U., A.F., D.S., N.R.), Raritan, New Jersey 08869; and Janssen Research & Development, LLC (D.P.), San Diego, California 92121.
authors.forename: Albert
authors.initials: A
authors.lastname: Fung
authors.affiliation: Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; Mercy Health Osteoporosis and Bone Health Services (N.B.W.), Cincinnati, Ohio 45236; Janssen Research & Development, LLC (K.U., A.F., D.S., N.R.), Raritan, New Jersey 08869; and Janssen Research & Development, LLC (D.P.), San Diego, California 92121.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sullivan
authors.affiliation: Division of Endocrinology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032; Mercy Health Osteoporosis and Bone Health Services (N.B.W.), Cincinnati, Ohio 45236; Janssen Research & Development, LLC (K.U., A.F., D.S., N.R.), Raritan, New Jersey 08869; and Janssen Research & Development, LLC (D.P.), San Diego, California 92121.
authors.forename: Norm
authors.initials: N
authors.lastname: Rosenthal
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D001835:Body Weight; D015519:Bone Density; D000068896:Canagliflozin / Q000009:adverse effects* / Q000627:therapeutic use*; D024042:Collagen Type I / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D007004:Hypoglycemic Agents; D000068896:Canagliflozin