Papadaki H A, Margioris A N, Miliaki M, Steriopoulos C, Valatas W, Eliopoulos G D
Department of Haematology, University Hospital of Heraklion, Crete, Greece.
Eur J Haematol. 1999 May;62(5):311-6. doi: 10.1111/j.1600-0609.1999.tb01908.x.
The aim of this study was to assess bone mineral density (BMD) and biochemical indices of bone metabolism in patients with chronic idiopathic neutropenia of adults (CINA) and define the relationships, if any, between these parameters and serum levels of interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha), two cytokines normally involved in bone metabolism. Femoral neck BMD, serum osteocalcin (OC), bone-specific alkaline phosphatase (BAP) and type I procollagen carboxy-terminal propeptide (PICP), as well as urine-free deoxypyridoline (Dpd) cross-links, N-telopeptide (NTx) and C-telopeptide (CTx) cross-links of type I of collagen were measured in 45 CINA patients and 36 normal subjects. Patients were arbitrarily classified in two groups, A and B, as having mild (neutrophils 1700-2500/microl) or 'pronounced' (neutrophils<1700/microl) neutropenia, respectively. BMD values were found significantly reduced in both groups of patients, compared to controls, and they strongly correlated with the number of circulating neutrophils. Serum OC and urinary NTx were significantly increased in patients of group B. Both serum OC and urinary NTx correlated inversely with the number of circulating neutrophils. Serum BAP and PICP and urine Dpd and CTx were within normal range. Serum IL-1beta and TNF-alpha were elevated in both groups of patients and correlated inversely with the number of circulating neutrophils and the values of BMD. In addition, TNF-alpha, but not IL-1beta, inversely correlated with OC and NTx. These findings indicate that CINA patients have biochemical evidence of increased bone turnover which leads to decreased BMD. The elevated serum IL-1beta and TNF-alpha concentrations, suggestive of an underlying chronic inflammatory process in these patients, may be part of a mechanism accelerating bone turnover which, if prolonged, causes lowering of BMD.
本研究旨在评估成年慢性特发性中性粒细胞减少症（CINA）患者的骨矿物质密度（BMD）和骨代谢生化指标，并确定这些参数与白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）血清水平之间的关系（若有），这两种细胞因子通常参与骨代谢。对45例CINA患者和36名正常受试者测量了股骨颈骨密度、血清骨钙素（OC）、骨特异性碱性磷酸酶（BAP）和I型前胶原羧基末端前肽（PICP），以及I型胶原的尿游离脱氧吡啶啉（Dpd）交联物、N-端肽（NTx）和C-端肽（CTx）交联物。患者被任意分为A、B两组，分别为轻度（中性粒细胞1700 - 2500/微升）或“明显”（中性粒细胞<1700/微升）中性粒细胞减少症。与对照组相比，两组患者的骨密度值均显著降低，且与循环中性粒细胞数量密切相关。B组患者血清OC和尿NTx显著升高。血清OC和尿NTx均与循环中性粒细胞数量呈负相关。血清BAP和PICP以及尿Dpd和CTx在正常范围内。两组患者血清IL-1β和TNF-α均升高，且与循环中性粒细胞数量和骨密度值呈负相关。此外，TNF-α而非IL-1β与OC和NTx呈负相关。这些发现表明，CINA患者有骨转换增加的生化证据，这导致骨密度降低。血清IL-1β和TNF-α浓度升高，提示这些患者存在潜在的慢性炎症过程，可能是加速骨转换机制的一部分，若持续时间延长，会导致骨密度降低。
