Cortical bone loss at the tibia in postmenopausal women with osteoporosis is associated with incident non-vertebral fractures: results of a randomized controlled ancillary study of HORIZON.
BACKGROUND
In postmenopausal women, yearly intravenous zoledronate (ZOL) compared to placebo (PLB) significantly increased bone mineral density (BMD) at lumbar spine (LS), femoral neck (FN), and total hip (TH) and decreased fracture risk. The effects of ZOL on BMD at the tibial epiphysis (T-EPI) and diaphysis (T-DIA) are unknown.


METHODS
A randomized controlled ancillary study of the HORIZON trial was conducted at the Department of Osteoporosis of the University Hospital of Berne, Switzerland. Women with ≥1 follow-up DXA measurement who had received ≥1 dose of either ZOL (n=55) or PLB (n=55) were included. BMD was measured at LS, FN, TH, T-EPI, and T-DIA at baseline, 6, 12, 24, and 36 months. Morphometric vertebral fractures were assessed. Incident clinical fractures were recorded as adverse events.


RESULTS
Baseline characteristics were comparable with those in HORIZON and between groups. After 36 months, BMD was significantly higher in women treated with ZOL vs. PLB at LS, FN, TH, and T-EPI (+7.6%, +3.7%, +5.6%, and +5.5%, respectively, p<0.01 for all) but not T-DIA (+1.1%). The number of patients with ≥1 incident non-vertebral or morphometric fracture did not differ between groups (9 ZOL/11 PLB). Mean changes in BMD did not differ between groups with and without incident fracture, except that women with an incident non-vertebral fracture had significantly higher bone loss at predominantly cortical T-DIA (p=0.005).


CONCLUSIONS
ZOL was significantly superior to PLB at T-EPI but not at T-DIA. Women with an incident non-vertebral fracture experienced bone loss at T-DIA.
Department of Osteoporosis, Inselspital, Berne University Hospital and University of Berne, Switzerland.
A W
AW
Popp
Department of Osteoporosis, Inselspital, Berne University Hospital and University of Berne, Switzerland.
H
H
Buffat
Department of Osteoporosis, Inselspital, Berne University Hospital and University of Berne, Switzerland.
A
A
Cavelti
AO Research Institute Davos, Biomedical Services, Davos, Switzerland.
M
M
Windolf
Department of Osteoporosis, Inselspital, Berne University Hospital and University of Berne, Switzerland.
R
R
Perrelet
Department of Osteoporosis, Inselspital, Berne University Hospital and University of Berne, Switzerland.
C
C
Senn
Department of Osteoporosis, Inselspital, Berne University Hospital and University of Berne, Switzerland. Electronic address: kurt.lippuner@insel.ch.
K
K
Lippuner
D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D015994:Incidence; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D013977:Tibia / Q000378:metabolism*; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
Fracture risk; Post-dose symptoms; Postmenopausal osteoporosis; Tibial BMD; Zoledronate