Relationship between changes in BMD and nonvertebral fracture incidence associated with risedronate: reduction in risk of nonvertebral fracture is not related to change in BMD.
Whether greater treatment-related changes in BMD result in greater decreases in fracture risk is controversial. We analyzed the relationship between BMD change and nonvertebral fracture risk in postmenopausal osteoporotic women from the risedronate fracture program. Change in BMD did not influence the magnitude of risedronate's effect on nonvertebral fractures; the incidence of nonvertebral fractures was equally low in treated patients whose BMD increased or decreased.


BACKGROUND
In untreated patients, low BMD correlates with increased fracture risk. Whether greater increases in BMD induced by anti-osteoporosis drugs are related to greater decreases in vertebral fracture risk is controversial, and little has been written about the relationship between change in BMD and nonvertebral fracture risk. We analyzed the relationship between BMD change and nonvertebral fracture incidence using individual patient data from postmenopausal osteoporotic women receiving antiresorptive treatment with risedronate.


METHODS
This posthoc analysis combined data from three pivotal risedronate fracture endpoint trials. Women received risedronate 2.5 or 5 mg (n = 2,561) or placebo (n = 1,418) daily for up to 3 years. BMD and nonvertebral fractures confirmed by radiograph (hip, wrist, pelvis, humerus, clavicle, and leg) were assessed periodically over 3 years.


RESULTS
The incidence of nonvertebral fractures in risedronate-treated patients was not different between patients whose spine BMD decreased (7.8%) and those whose spine BMD increased (6.4%; hazard ratio to subgroup of patients who lost BMD [HR], 0.79; 95% CI, 0.50, 1.25) or between those whose femoral neck BMD decreased (7.6%) and those whose femoral neck BMD increased (7.5%; HR, 0.93; 95% CI, 0.68, 1.28). The changes in lumbar spine and femoral neck BMD explained only 12% (95% CI, 2%, 21%; p = 0.014) and 7% (95% CI, 2%, 13%; p = 0.005), respectively, of risedronate's nonvertebral fracture efficacy.


CONCLUSIONS
For patients treated with risedronate, changes in BMD as measured by DXA do not predict the degree of reduction in nonvertebral fractures.
Watts
Nelson B
NB
University of Cincinnati Bone Health and Osteoporosis Center, Ohio, USA. nelson.watts@uc.edu
Geusens
Piet
P
Barton
Ian P
IP
Felsenberg
Dieter
D
D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005272:Femur Neck / Q000737:chemistry; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D008159:Lumbar Vertebrae / Q000737:chemistry; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D000068296:Risedronic Acid; D018570:Risk Assessment
D050071:Bone Density Conservation Agents; D000068296:Risedronic Acid; D012968:Etidronic Acid