title: Randomized trial of alendronate plus vitamin D3 versus standard care in osteoporotic postmenopausal women with vitamin D insufficiency.
abstract: Vitamin D insufficiency is common in patients with osteoporosis. We conducted a randomized trial comparing alendronate 70 mg combined with vitamin D(3) 5,600 IU in a single tablet (ALN/D5600, n = 257) with standard care chosen by the patients' personal physicians (n = 258) in patients with postmenopausal osteoporosis (BMD T score ≤2.5 or ≤1.5 and a prior fragility fracture) who had vitamin D insufficiency (serum 25[OH]D values 8-20 ng/ml) and who were at risk of falls. Virtually all patients randomized to standard care received bisphosphonate therapy, and in approximately 70% of cases this was combined with vitamin D supplements. However, only 24% took ≥800 IU/day of supplemental vitamin D. At 6 months the proportion of patients with vitamin D insufficiency was 8.6% in the ALN/D5600 group compared with 31.0% in the standard care group (P < 0.001). Those in the ALN/D5600 group also had a greater reduction in urinary NTX/creatinine ratio (-57% vs. -46%, P < 0.001) and bone-specific alkaline phosphatase (-47% vs. -40%, P < 0.001). In the ALN/5600 group, by 12 months the increase in BMD was greater at the lumbar spine (4.9% vs. 3.9%, P = 0.047) and the total hip (2.2% vs. 1.4%, P = 0.035), significantly fewer patients were vitamin D-insufficient (11.3% vs. 36.9%, P < 0.001), and bone turnover marker (BTM) results were similar to those at 6 months. There was no difference between groups in those who experienced falls or fractures, and adverse events were similar. Based on the finding that ALN/D5600 was more effective than standard care at correcting vitamin D insufficiency, increasing BMD, and reducing BTMs in this patient group, greater attention needs to be directed toward optimizing the treatment of osteoporosis and correcting vitamin D deficiency in postmenopausal women.
authors.affiliation: Rheumatic Diseases Unit, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, UK. stuart.ralston@ed.ac.uk
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
authors.forename: Neil
authors.initials: N
authors.lastname: Binkley
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Kiel
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Reginster
authors.forename: Christian
authors.initials: C
authors.lastname: Roux
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rosenberg
authors.forename: Arthur
authors.initials: A
authors.lastname: Santora
mesh_terms: D000058:Accidental Falls / Q000706:statistics & numerical data; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000008:administration & dosage* / Q000009:adverse effects; D000465:Algorithms; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy*; D017698:Postmenopause / Q000187:drug effects / Q000502:physiology; D059039:Standard of Care; D014808:Vitamin D Deficiency / Q000150:complications / Q000188:drug therapy*
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D004338:Drug Combinations; D002762:Cholecalciferol; D019386:Alendronate