Wilkinson J Mark, Jackson Brendan, Eastell Richard
Bone Metabolism Group, Division of Clinical Sciences (North), University of Sheffield, Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK.
Calcif Tissue Int. 2003 Oct;73(4):326-31. doi: 10.1007/s00223-002-2154-7. Epub 2003 Jul 24.
Periprosthetic bone loss is an important factor that limits implant survival after total hip arthroplasty (THA). In a randomized trial we previously reported that pamidronate therapy prevented periprosthetic bone loss and decreased urinary excretion of N-telopeptide collagen cross-links over the first 6 months after THA, but had no apparent effect on free deoxypyridinoline excretion (J Bone Miner Res 2001; 16:556-564). In this study we investigated this discrepant observation that pamidronate reduced conjugated cross-link excretion but had no effect on free cross-links. Free and total deoxypyridinoline (DPD) were assayed by reverse-phase high-performance liquid chromatography (HPLC) and by immunosorbent assay (ELISA) at preoperative baseline and at week 6 after surgery in 46 subjects who had taken part in the trial. Randomly selected, 22 subjects received a single 90 mg intravenous infusion of pamidronate and 24 received placebo. Acute rises in free and total DPD occurred in both study groups at week 6 (P < 0.05). Total DPD excretion was lower in the pamidronate group than in the placebo group when measured by both HPLC and ELISA (P < 0.05). No difference in free DPD was found between groups. A rise in the ratio of free to total DPD occurred in the pamidronate group at week 6 (P = 0.03), but not in the placebo group. Pamidronate treatment suppresses excretion of total DPD. This is consistent with the effect of pamidronate on other turnover markers and periprosthetic bone loss after THA. Urinary-free DPD is a poor marker of response to treatment as the ratio of free-to-total cross-links is affected by amino-bisphosphonate therapy.
假体周围骨丢失是限制全髋关节置换术（THA）后植入物存活的重要因素。在一项随机试验中，我们之前报道过，帕米膦酸盐治疗可预防假体周围骨丢失，并在THA后的前6个月减少N-端肽胶原交联物的尿排泄，但对游离脱氧吡啶啉排泄无明显影响（《骨与矿物质研究杂志》2001年；16:556 - 564）。在本研究中，我们调查了这一矛盾的观察结果，即帕米膦酸盐可减少结合交联物排泄，但对游离交联物无影响。在参与该试验的46名受试者中，于术前基线和术后第6周通过反相高效液相色谱法（HPLC）和免疫吸附测定法（ELISA）检测游离和总脱氧吡啶啉（DPD）。随机选择，22名受试者接受单次90 mg帕米膦酸盐静脉输注，24名接受安慰剂。两个研究组在第6周时游离和总DPD均出现急性升高（P < 0.05）。通过HPLC和ELISA测量时，帕米膦酸盐组的总DPD排泄均低于安慰剂组（P < 0.05）。两组间游离DPD无差异。帕米膦酸盐组在第6周时游离与总DPD的比值升高（P = 0.03），而安慰剂组未升高。帕米膦酸盐治疗可抑制总DPD的排泄。这与帕米膦酸盐对THA后其他周转标志物和假体周围骨丢失的作用一致。由于游离与总交联物的比值受氨基双膦酸盐治疗影响，尿游离DPD不是治疗反应的良好标志物。
