We read with great interest the article by Ureña et al. [1] on the relation between fracture risk in haemodialysis patients and bone mineral density (BMD) at various sites. We would like to make the following comments and ask a few questions.
We are puzzled by the fact that the mid-radius-BMD, which is the only site to show a dramatic decrease in Z-score (2.8) in relation to cortical bone loss, high parathyroid hormone (PTH) and bone remodelling markers, is paradoxically not predictive of total fracture and rib fractures whereas mid-radius-BMD compared with lumbar-BMD had been shown by Yamaguchi et al. [2] to be better predictive of all fractures, and equally predictive of vertebral fractures. In contrast, total body BMD, which was also negatively related to PTH but not to resorption markers and which mean is normal, is predictive of both total fracture and rib fracture. We wonder why the authors have focused their attention specifically on rib fractures and not adopted the more classical approach of studying fracture risk, by distinguishing axial and appendicular skeleton. Indeed the risk of fracture with secondary hyperparathyroidism is greater at the appendicular skeleton in relation to a marked cortical bone loss whereas aluminium-induced osteopenia associated with low bone turnover increases more the risk of axial skeleton fractures [3]. Therefore, we would like to know whether the authors have found a lower mid-radius-BMD in the 13 patients with fractures of the appendicular skeleton when compared with patients without fracture.
Regarding the rib fractures, we wonder whether serum aluminium was considered as a risk factor as in the total population its range is 0.104.0 µmol/l, i.e. probably quite high in a significant proportion of the population (normal <0.30) in spite of the fact that aluminium phosphate binder had probably been discontinued many years ago.
Since duration on dialysis had such a critical role, with a risk increase of 4.7 at 5 years and of 6.4 at 10 years, we would like to know: (i) what was the serum aluminium of the patients with rib fractures compared with those without fracture before and after 5 or 10 years and (ii) in which year aluminium phosphate binders were definitively excluded from the centre.
Regarding the patients with vertebral fractures, their lumbar spine BMD Z-score is not reported: was it not decreased as that of the mid-radius?
We are quite impressed by the high prevalence of patients with severe hyperparathyroidism as 50% of the population had an iPTH >469 pg/ml, which may account for the very low mean Z-score at 2.8 at the mid-radius. These high PTH levels may be explained by the low levels of P25 OH vitamin D 10.6±6.7 ng/ml and by the low daily dose of CaCO3 (0.53 g/day, i.e. 2001200 mg of elemental calcium), whereas 1aOH vitamin D derivatives were given only in 35% of the patients. Indeed in a comparable population in terms of age [duration of dialysis, dialysate calcium concentration but with a still more parsimonious use of 1aOHD3 (17%)] only 30% of our population had an iPTH >220 pg/ml with increased bone alkaline phosphatase, and their mean mid-radius Z-score was normal (0.5). However, in our patients the dose of CaCO3 was higher (8 g/day) as well as the mean P25 OH vitamin D (25±ng/ml). The fact that Ureña et al. find no correlation between P25 OH vitamin D or P1,25 (OH)2 D and Z-score at any site and in particular at the mid-radius site is therefore curious. It may be related to the small dispersion of the values, as in their patient the P25 OH vitamin D was 10.6±6.7 ng/ml. It would be interesting to know whether they have found any correlation between PTH and vitamin D levels and at which season (or seasons) of the year the biochemical evaluation of their patients was performed.
Regarding the direct correlation of leptin with total body and lumbar spine BMD, as well as with BMI and fat mass, we suggest that to better understand its direct role in bone mineral mass, the correlation of leptin with BMD should be adjusted to BMI and/or fat mass, because of the role of mechanical stress in BMD of the axial skeleton and femur. This had been done in our work, which in addition had taken into account the elevation of leptin in relation to the presumed level of saturation of its transporter across the bloodbrain barrier. This allowed us to show a significant positive correlation between mid-radius and ultradistal radius only for the leptin values above this threshold (>20 ng/ml). Below this level there was no correlation that is consistant with the association in Ureña patients with rib fractures between very low leptin level and very low BMDZ score, regardless of the site (from 1.237 at femoral risk to 3.046 at the mid radius. It would be interesting for Ureña et al. look at their data and see whether on a larger basis (70 to 33) they confirm our observations.
Conflict of interest statement. None declared.
1 Nephrology Department of Amiens CHU2 Nephrology Department of Creil Centre Hospitalier France Email: fournier.albert{at}chu.amiens.fr
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