Table 1. Fracture risk reduction with bisphosphonate therapy in osteopenia.

BMD: bone mass density, CI: confidence interval, FLEX: fracture intervention trial long-term extension, FIT: fracture international trial, FOSIT: Fosamax international trial; HR: hazard ratio, OD: odds ratio, P: Pearson value, RH: relative hazard, RR: relative risk

Study	Drug of choice vs placebo	Duration of study	Subjects	Results (Drug of choice vs placebo)
Reid IR et al. [28]	5 mg intravenous zoledronate once a year.	18 months	Women of age 65 years or older with osteopenia (T score –1 to –2.5).	HR with zolendronic acid for fragility fractures was 0.63; P<0.001. HR with zolendronic acid for non-vertebral fracture was 0.66; P = 0.001. OR for non-vertebral fracture was 0.45; P = 0.002
Pols HA et al. [29] (FOSIT)	10 mg oral alendronate per day.	1 year	Postmenopausal women with BMD <2.	Non-vertebral fracture risk reduction was 47% in the treatment group; P = 0.021
Cummings SR et al. [30] (FIT)	5 mg oral alendronate per day for two years followed by 10 mg per day for the remaining period of the trial.	4.2 years	Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2.	No significant reduction in clinical fractures was noted in the alendronate group for the osteopenic population with RH, 1.08; 95% CI, 0.87-1.35. RR for vertebral fracture with alendronate therapy was 0.56; 95% CI, 0.39-0.80
Black DM et al. [31] (FLEX)	5 mg or 10 mg oral alendronate per day.	5 years	Postmenopausal women who had been randomized to alendronate in FIT, with a mean of 5 years of prior alendronate treatment.	RR for clinically recognized vertebral fractures in the treatment group was 0.45; 95% CI, 0.24-0.85. RR for non-vertebral fractures in the treatment group was 1.00; 95% CI, 0.76-1.32
Posthoc analysis by Siris ES et al. [32]	5 mg oral risedronate per day.	3 years	Postmenopausal women with osteopenia (T score -1.5 to -2.5) were included.	Incidence of cumulative non-vertebral fracture was 0.4%; 95% CI, 0.01-0.71; P = 0.022. Incidence of cumulative vertebral fracture was 1.8% in treatment group; 95% CI, 0.11-1.78; P = 0.249
Black DM et al. [31]	5mg oral alendronate per day for 2 years and then 10mg per day for another one year.	3 years	Women aged 55-81 years with low femoral-neck BMD and at least one existence vertebral fracture.	For vertebral fractures (morphometric) RR was 0.53; 95% Cl, 0.41-0.68. For vertebral fractures (clinical) RH was 0.45 ;95% Cl, 0.27-0.72. For non-vertebral fracture RH was 0.72; 95% Cl, 0.58-0.90
Lyles KW et al. [34]	5 mg intravenous zolendronic acid once a year.	5 years	Men and women 50 years of age or older who had surgical repair of a hip fracture sustained with minimal trauma within 90 days prior to participation in the trial.	The rates of developing new clinical fracture were 8.6% in the treatment group; P = 0.001. The rates of developing a new clinical vertebral fracture were 1.7% in the treatment group; P = 0.02. The rates of developing new non-vertebral fractures were 7.6% in the treatment group; P = 0.03
Chesnut CH et al. [35]	Oral ibandronate administered either daily (2.5 mg per day) or intermittently (20 mg every other day for 12 doses every 3 months).	3 years	Postmenopausal women with a BMD T score	Daily and intermittent dosing of oral ibandronate reduced the risk of new morphometric vertebral fractures by 62% (P = 0.0001) and 50% (P = 0.0006), respectively. Daily and intermittent dosing of oral ibandronate produced a significant RRR in clinical vertebral fractures (49% and 48% for daily and intermittent ibandronate dosing, respectively). The incidence of nonvertebral fractures was similar between the ibandronate and placebo groups after three years (9.1%, 8.9%, and 8.2% in the daily, intermittent, and placebo groups, respectively; the difference between arms not significant).