Table 1.

Characteristics of included studies

Study	Participants	Intervention	Outcomes	Methodological quality	Notes
Black et al17	1099 postmenopausal women from the US, originally with BMD ≤ 0.68 g/cm2, who received alendronate	Alendronate 5 mg/day (n = 329) or 10 mg/day (n = 333) vs placebo (n = 437) for 5 years	Change in BMD at hip and other sites Changes in bone turnover markers Fracture incidencea Outcomes measured at 5-year follow-up	AS adequately generated AC not clear Blinding: patients, physicians, data collectors, and outcome assessors Incomplete data adequately addressed No selective outcome reporting, or other threats to validity	Funded by Merck and Co. (makers of alendronate, the study drug) Merck involved with study design, editorial input, and approval of final manuscript Not all participants had “osteoporosis” by WHO definition, inclusion criterion was BMD ≤ 0.68 g/cm2
	5 mg/day for 2 years and then 10 mg/day for a total mean duration of therapy of 5 years’ treatment during the Fracture Intervention Trial
Bone et al19	804 postmenopausal women from multiple countries with BMD T-scores <–2.5 underwent initial randomization; 247 included in the year 8–10 extension study (used for this review)	Alendronate 5 mg/day (n = 78) vs 10 mg/day (n = 86) for 10 yrs vs 20 mg/day for 2 years then 5 mg/day for 3 years then placebo for 5 years (n = 83)	Change in BMD at lumbar spine and other sites Changes in bone turnover markers Morphometric and clinical vertebral fracture incidenceb Height change Safety Outcomes measured at either 2- or 5-year follow-up	AS and AC not clear “Double blinded”, also data assessors blinded Incomplete data not adequately addressed All outcomes not fully reported No other threats to validity	Funded by Merck Research Laboratories (makers of alendronate, the study drug) First author with honorariums and grant support from Merck
Miller et al18	97 postmenopausal women from the US with a history of fragility fracture completed 7 years of follow-up with at least 5 years of etidronate therapy	Continued cyclical etidronate (n = 51) vs placebo (n = 46) (subgroups of larger extension study)	Change in BMD at lumbar spine and other sites Morphometric vertebral fracture incidence Safety Outcomes measured at 2-year follow-up	AS adequately generated AC not clear “Double blinded” Incomplete data not adequately addressed All outcomes not fully reported No other threats to validity	Funded by Procter and Gamble Pharmaceuticals (makers of etidronate, the study drug)

Notes:

^aFracture incidence was considered an exploratory outcome;

^bFracture incidence collected as safety endpoint, no formal analysis planned. No attempt made to exclude trauma-related fractures.

Abbreviations: AC, allocation concealment; AS, allocation sequence; BMD, bone mineral density; WHO, World Health Organization.