Several studies have explored the association between renal function and BMD [5-9, 13, 14]. However, the literatures are conflicting, and the relationship between renal function and the risk of osteoporosis in healthy older population is rare. In the current study, we examined the relationship of renal function with BMD and the risk of osteoporosis in 776 relatively healthy postmenopausal Chinese women. Our present study found that participants with worse renal function were associated with lower femoral neck and total hip BMD. However, after adjusting for age, menopausal duration and BMI, the decline in renal function was not associated with increased risk of osteoporosis as compared with normal renal function.
As for the relationship between renal function and BMD in the general population, the results are controversial. Kaji et al.  reported a positive relationship between eGFR, calculated using the Modification of Diet in Renal Disease (MDRD) equation for assessing renal function, and BMD in postmenopausal women. Similarly, a retrospective study of 1172 CKD outpatients also demonstrated an association between reduced BMD and impaired renal function (using the CKD-EPI equation) . Ensrud et al.  suggested that lower eGFR, calculated using CKD-EPI 2012 equation, was associated with increased risk of hip fracture in older community-dwelling men. However, Hsu et al.  demonstrated that a decline in renal function was not associated with decreased BMD. Malmgren et al.  also showed that the prevalence of osteoporosis did not differ with renal function. Our findings are consistent with the results of these studies. Although Spearman’s correlation analysis showed a positive relationship between eGFR and BMD values, this relationship was attenuated after adjustment for potential confounders. These discrepancies might be due to the differences in sex, site of BMD observation, the equations used for estimating eGFR, and the higher rate of normal population in subjects of the present study. With MDRD equations, the eGFR tends to be underestimated in people with normal renal function . It is more accurate to use CKD-EPI equations for assessing renal function in older population and healthy individuals, as compared with MDRD equations [30, 31].
In a study of 1,815,943 participants, the association was negative for eGFR and rates of fracture, but after adjusting for additional demographic variables and comorbidities, the relationship disappeared . Similar to their findings, our study showed that decreased eGFR was associated with reduced BMD; however, after adjustment for age, menopausal duration and BMI, we found no evidence to support the hypothesis that the decline in renal function is independently associated with osteoporosis risk. Why was reduced eGFR not associated with increased osteoporosis risk, in contrast to the excess osteoporosis risk observed in patients with end-stage renal disease (ESRD) ? In comparison to earlier study, we focused on relatively healthy postmenopausal Chinese women, so we excluded subjects with impaired renal function (eGFR < 60 ml/min/1.73m2). This may explain in part why our results differ from previous studies , which included 415 CKD outpatients with eGFR < 60 ml/min/1.732. In addition, we found that eGFR was associated with age and menopausal duration, both of which are known risk factors for osteoporosis [33, 34]. Thus, we assume that the association between eGFR and BMD can be explained by known confounding factors, such as age and menopausal duration.
Spearman’s correlation analysis of the data showed that BUN and SCr were not associated with BMD values. Despite its widespread use, BUN and SCr can be affected by many factors that are unrelated to eGFR. Therefore, they are much less sensitive for detection of renal function, particularly in the older population [35, 36]. Our findings are consistent with the previous study, which found no relationships between SCr and BUN with BMD .
In our study, only BMD at femoral neck and total hip but not lumbar spine were significantly lower in the eGFR < 90 ml/min/1.73 m2 group compared with the higher eGFR group (eGFR ≥ 90 ml/min/1.73m2). However, after stratification by age, eGFR did not correlate with BMD at all sites. Those with eGFR < 90 ml/min/1.73m2 were older compared with those with eGFR ³ 90 ml/min/1.73m2. These findings indicate that the association of lower BMD with lower eGFR was due in large part to age. Several reasons could partly explain the skeletal site-specificity differences. First, the overlying aortic calcifications make it difficult to measure BMD at lumbar spine in the elderly . Besides, present BMD does not reflect present bone metabolism alone, but rather integrates bone metabolism from the past to present. Finally, spine BMD remains approximately stable or increases over time, whereas BMD of the total hip and femoral neck declines at an increasing rate in elderly people [38, 39]. In the present study, we focus on relatively healthy subjects with eGFR ³ 60 ml/min/1.73m2. Thus, further studies are needed to explore the relationship between reduced renal function and BMD in CKD.
The present study has notable strengths including its relatively large sample size, focus on the healthy postmenopausal Chinese women, where data on this population are rare. No participant had taken a drug known to affect bone metabolism and renal function. Besides, important confounding factors were adjusted in the regression analysis. The present study has several potential limitations. Firstly, due to the observational study design, it is impossible to establish a causal relation between renal function and BMD. A longitudinal follow-up study is necessary to ascertain these relationships. Another limitation, which should be mentioned, is that we excluded subjects with impaired renal function (eGFR < 60ml/min/1.73m2). Thus, our findings might not be applicable to the entire population of Chinese postmenopausal women. In addition, this study included subjects with CKD stage 2 (defined an eGFR 60-90 ml/min/1.73m2) . Thirdly, the great majority of studies concluded that formulas based on serum cystatin C are superior to SCr-based eGFR [26, 40]. However, Keddis et al  showed that SCr-based CKD-EPI equation was preferred over cystatin C-based eGFR in kidney transplant recipients because they are less biased, more accurate. Moreover, the gold standard for detecting eGFR is inulin clearance, which is rarely done due to issues with inconvenience and time consuming for epidemiologic studies. Finally, urine protein or imaging examination, for example, is lacking for confirming impaired renal function.