Chronic idiopathic neutropenia of adults is associated with decreased bonemineral density and alterations in bone turnover biochemical markers

The aim of this study was to assess bone mineral density (BMD) and biochemi cal indices of bone metabolism in patients with chronic idiopathic neutrope nia of adults (CINA) and define the relationships, if any, between these pa rameters and serum levels of interleukin-1 beta (IL-1 beta) and tumour necr osis factor-alpha (TNF-alpha), two cytokines normally involved in bone meta bolism. Femoral neck BMD, serum osteocalcin (OC), bone-specific alkaline ph osphatase (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 i n 45 CINA patients and 36 normal subjects. Patients were arbitrarily classi fied in two groups, A and B, as having mild (neutrophils 1700-2500/ mu l) o r 'pronounced' (neutrophils<1700/mu l) neutropenia, respectively. BMD value s were found significantly reduced in both groups of patients, compared to controls, and they strongly correlated with the number of circulating neutr ophils. Serum OC and urinary NTx were significantly increased in patients o f group B. Both serum OC and urinary NTx correlated inversely with the numb er of circulating neutrophils. Serum BAP and PICP and urine Dpd and CTx wer e within normal range. Serum IL-1 beta 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-1 bet a, inversely correlated with OC and NTx. These findings indicate that CINA patients have biochemical evidence of increased bone turnover which leads t o decreased BMD. The elevated serum IL-1 beta 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.