The association between bone and renal function in healthy seniors is not well studied. In this cross-sectional and longitudinal study in 1713 older men and women, creatinine clearance was significantly associated with hip BMD. If confirmed, this may warrant adding mild to moderate renal dysfunction as an indication for osteoporosis screening. This study determined the cross-sectional and longitudinal association between measures of renal function and BMD, bone loss, and osteoporotic fracture in older adults. It determined which measure of renal function--creatinine clearance by the Cockcroft-Gault (CG) equation, estimated glomerular filtration rate by the Modification of Diet in Renal Disease (MDRD) equation, or serum creatinine--is most strongly associated with BMD and osteoporotic fracture. This was a cross-sectional and prospective study in older community-dwelling men and women. Between 1992 and 1995, 1713 participants (average age, 71.3 +/- 11.1 years) completed standardized questionnaires, physical examinations, laboratory testing, and bone densitometry; 1023 participants returned for a follow-up visit in 1997-1999, an average of 4.1 +/- 0.9 years later. Calculated renal function declined with age (p < 0.001). Renal function was categorized by Kidney Disease Outcomes Quality Initiative (K/DOQI) chronic kidney disease (CKD) stage. By the CG equation, at baseline, 5.5% of participants had stage 1 CKD (glomerular filtration rate > or = 90 ml/min/1.73 m(2)), 43.0% had stage 2 CKD (60-89 ml/min/1.73 m(2)), 48.8% had stage 3 CKD (30-59 ml/min/1.73 m(2)), and 2.7% had stages 4 and 5 CKD (<30 ml/min/1.73 m(2)). Using the MDRD equation, these percents were 7.0%, 61.7%, 30.9%, and 0.5%, respectively. In cross-sectional analyses, there was a significant linear association between creatinine clearance by CG or glomerular filtration rate by MDRD and hip BMD. In prospective analyses, there was an average annual bone loss of 0.6% and a significant association between baseline CG and 4-year hip bone loss. There was no association between baseline MDRD or serum creatinine and bone loss. At baseline, 180 of 1713 participants (11%) reported at least one clinical fracture of the hip, femur, forearm, or wrist; 79 (8%) reported new clinical fractures during follow-up. Baseline renal function by any measure was not significantly associated with prevalent or incident clinical fractures. Although renal function measured by both CG and MDRD was associated with BMD in cross-sectional analyses, only creatinine clearance by CG predicted 4-year bone loss. If confirmed, this should be the preferred method for assessing the association between renal function and BMD. Cross-sectional associations between renal function and BMD were strongest at higher CKD stage. None of the baseline renal function estimates was associated with prevalent or incident fractures, perhaps reflecting the multifactorial etiology of fractures beyond BMD. If further studies in the elderly confirm renal function as an important predictor of bone loss and fracture, this may warrant adding mild to moderate renal dysfunction as an indication for osteoporosis screening.