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Relationship between serum beta 2-microglobulin, bone histology, and dialysis membranes in uraemic patients
1INSERM Unité 90, Hôpital Necker-Enfants Malades, Paris, France.
Background:
beta 2-Microglobulin (beta 2M) is the main constituent of osteoarticular amyloid deposits in haemodialysis patients. When dialysed with cellulosic (C) membrane such patients present a higher incidence of beta 2M-related amyloid arthropathy than with synthetic high-flux (SHF) membrane, and they have higher serum levels of beta 2M. This could favour beta 2M deposition as amyloid fibrils and/or modify bone and cartilage metabolism.
Methods:
We examined 56 uraemic patients dialysed in the same centre for 7.5 +/- 4.8 years (mean +/- SD). Based on bone histomorphometry criteria they were classified into either high-turnover bone disease (HTBD, 45 patients) or normal/low-turnover bone disease (N/LTBD, 11 patients). A subgroup of 30 patients had been dialysed with the same dialysis membrane for at least 18 months prior to study, 8 on C and 22 on SHF membrane.
Results:
Serum intact parathyroid hormone levels were not different between the two patient subgroups. In contrast, serum beta 2M levels were higher in patients on C than on SHF membrane: 59.8 +/- 14.1 versus 32.8 +/- 8.7 mg/l, and so were serum total alkaline phosphatase and osteocalcin levels: 323 +/- 167 versus 173 +/- 50 IU/l, and 656 +/- 395 versus 288 +/- 263 ng/ml respectively. The increase of these serum markers of bone formation was associated with a higher bone cell number: osteoblast surface, 21.7 +/- 5.1 versus 9.8 +/- 11%; osteoclast surface, 4.27 +/- 1.86 versus 1.96 +/- 1.34%; and osteoclast number/mm2, 2.85 +/- 1.26 versus 1.27 +/- 0.88 respectively. Serum beta 2M was positively correlated with serum osteocalcin (r = 0.58, P < 0.001), bone-specific alkaline phosphatase (bAP) (r = 0.46, P < 0.008), and free pyridinoline (PYD) (r = 0.62, P < 0.002), and negatively correlated, only for HTBD, with osteoid volume: r = -0.40, P < 0.006. Serum beta 2M was higher in patients with HTBD than N/LTBD:
Conclusion:
The bone metabolism of chronic haemodialysis patients may be influenced by dialysis membrane biocompatibility. Moreover, the association of high serum beta 2M with increased bone cell number and serum markers of bone turnover suggests that beta 2M is either another marker of bone cell activity or an activator of bone cells.