Effect of osteoporosis treatment on mortality: a meta-analysis.
BACKGROUND
Fragility fractures cause significant morbidity and mortality. Effective osteoporosis treatment can reduce fracture incidence, but it is not known whether it reduces mortality.


OBJECTIVE
The aim of the study was to determine whether effective osteoporosis treatment reduces mortality.


METHODS
We searched Medline and the Cochrane Central Register of Trials prior to September 2008, as well as 2000-2008 American Society for Bone and Mineral Research conference abstracts.


METHODS
Eligible studies were randomized placebo-controlled trials of approved doses of medications with proven efficacy in preventing both vertebral and nonvertebral fractures, in which the study duration was longer than 12 months and there were more than 10 deaths. Trials of estrogen and selective estrogen receptor modulators were specifically excluded.


METHODS
Data were extracted from the text of the retrieved articles, published meta-analyses, or the Food and Drug Administration web site.


RESULTS
Eight eligible studies of four agents (risedronate, strontium ranelate, zoledronic acid, and denosumab) were included in the primary analysis. During two alendronate studies, the treatment dose changed, and those studies were only included in secondary analyses. In the primary analysis, treatment was associated with an 11% reduction in mortality (relative risk, 0.89; 95% confidence interval, 0.80-0.99; P = 0.036). In the secondary analysis, the results were similar (relative risk, 0.90; 95% confidence interval, 0.81-1.0; P = 0.044). Mortality reduction was not related to age or incidence of hip or nonvertebral fracture, but was greatest in trials conducted in populations with higher mortality rates.


CONCLUSIONS
Treatments for osteoporosis with established vertebral and nonvertebral fracture efficacy reduce mortality in older, frailer individuals with osteoporosis who are at high risk of fracture.
Bolland
Mark J
MJ
Osteoporosis Research Group, Department of Medicine, University of Auckland, Private Bag 92 019, Auckland, New Zealand. m.bolland@auckland.ac.nz
Grey
Andrew B
AB
Gamble
Greg D
GD
Reid
Ian R
IR
D000367:Age Factors; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use; D012968:Etidronic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D050723:Fractures, Bone / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000627:therapeutic use; D010024:Osteoporosis / Q000188:drug therapy* / Q000401:mortality*; D053245:RANK Ligand / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000068296:Risedronic Acid; D013876:Thiophenes / Q000627:therapeutic use; D016896:Treatment Outcome; D000077211:Zoledronic Acid
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009942:Organometallic Compounds; D053245:RANK Ligand; D013876:Thiophenes; C081587:strontium ranelate; D000069448:Denosumab; D000077211:Zoledronic Acid; D000068296:Risedronic Acid; D012968:Etidronic Acid