This study is the first, to our knowledge, to compare the BMD changes between HD and nocturnal HD patients. Our results revealed that bone loss is reduced in nocturnal HD patients over 1 year, possibly conferring lower fracture risk in nocturnal HD. These findings are possibly explained by the lower phosphate levels, reduced calcium-phosphate product, and improved uremic clearance that occurs in nocturnal HD [12–14].
Hyperphosphatemia is a stimulus for parathyroid gland hyperplasia and consequently secondary hyperparathyroidism, causing high turnover bone disease [15, 16]. Several, but not all, reports have suggested an association between high circulating parathyroid hormone levels and increased fracture risk [5, 17]. Furthermore, a recent randomized control trial showed that there was a significant reduction in serum phosphate levels in nocturnal HD patients compared to those in conventional HD . We also observed statistically significant reductions in phosphate levels within the nocturnal HD group after 1 year and compared to our conventional HD group (Table 2). This reduction and even normalization of phosphate may explain the attenuated BMD loss that we observed after 1 year in the nocturnal HD patients.
Nocturnal HD is a novel dialytic modality that offers enhanced uremic clearance through an increase in dialysis frequency and duration. It is well known that larger molecules with increased charge require a longer time to achieve effective clearance due to the selectivity of the dialysis membrane and binding to other proteins. Growing evidence has suggested that phosphate plays an important role as a uremic toxin, possibly potentiating fracture risk . Therefore, it is conceivable that through improved clearance of uremic toxins in nocturnal HD, bone loss and potential fracture risk are reduced.
As it pertains to hyperparathyroidism, our study did not demonstrate any change in mean plasma PTH levels but still demonstrated a significant attenuation in BMD loss in the nocturnal HD cohort. Yuen et al.  demonstrated that nocturnal HD lowers parathyroid hormone levels significantly. Walsh and colleagues also showed a reduction in PTH levels in a recent randomized controlled trial but with no significant differences between nocturnal HD and conventional HD patients . The lack of differences in these results including ours may likely be due to dialysis vintage and that modest reductions in phosphate do not alter PTH levels given the progressive nature of moderate and severe secondary hyperparathyroidism. It also supports the belief that other mechanisms may be contributing to bone loss in these patients.
Our unadjusted univariate analysis showed no significant differences in the BMD loss over 1 year between the groups. However, when we adjusted for factors that could contribute to bone loss, conventional HD patients experienced a significantly greater decline in BMD than nocturnal HD patients at the femoral neck, total hip, and lumbar spine as assessed by DXA (Table 3). Although we found no significant differences between PTH levels, we included them in our multivariate analysis as a recent longitudinal study showed HD patients with low or high PTH had higher fracture risk .
This study has some limitations. Firstly, it was a retrospective convenience sample and as a result we could not match the nocturnal HD and conventional HD patients for certain confounding variables. We believe that the sampling method may have introduced biases since it was not an inception cohort and a convenience sample in that the study time began when patients had their first BMD scan. These could potentially both introduce biases with similar effects for both types of dialysis and not impacting overall findings.
To address this concern, we used linear regression models to adjust for factors that appear to influence bone fracture risk. We cannot guarantee, however, that our analysis completely adjusted for the effects of these and other potentially unidentified confounders such as physical activity. Additionally, the lack of information about medication administration in this study is a major limitation. Identifying differences in medication administration between the two groups would be important, particularly for agents that may influence BMD such as vitamin D, calcium, or non-calcium-based phosphate binders, cinacalcet, and bisphosphonates.
Despite the lack of differences in PTH values between the two groups, a clearer history and documentation in charts of previous parathyroidectomy surgery would have been useful and could be a potential confounder in our results.
Furthermore, there are likely to be inherent differences between the conventional HD and nocturnal HD populations that can only be corrected for in randomized control trials. For example, we show differences in age and diabetes between the groups representing another significant limitation in this study (Table 1). We did not adjust for diabetes in our multivariate analysis. Recent literature has shown that diabetes is often correlated with increased risk of fracture, but counterintuitively, it is usually characterized by normal or high BMD .
Although there were no notable differences in hypertension and vascular disease (Table 1), a more readily available and comprehensive past medical history would have provided useful insight in terms of any significant differences in comorbidities between the two groups.
Ethnicity was not accounted for nor documented in the retrospective data obtained for this study which may have been an additional confounder. A recent systematic review suggested that persons of African descent have higher BMD values at baseline . Although we adjusted for the differences in age between the two groups, it is important to highlight that BMD is well known to decrease with age . Additionally, due to the retrospective nature of this study and because standard clinical protocols only involved assessment of these three sites, we were not able to assess bone density at other relevant sites such as the radius. Recent data has shown that BMD at the radius is useful in predicting fracture risk in ESRD patients . Despite this, quantitative histomorphometry rather than BMD is the preferred method for assessing bone integrity in patients with renal disease .
Finally, this study was of short duration (1 year), and involved a small cohort, which in turn limited our statistical power. Consequently, our results may have not fully captured the effects of conventional or home nocturnal HD on bone physiology and strength over a longer period of time.