title: Chronic idiopathic neutropenia of adults is associated with decreased bone mineral density and alterations in bone turnover biochemical markers.
abstract: 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.
authors.affiliation: Department of Haematology, University Hospital of Heraklion, Crete, Greece.
authors.forename: H A
authors.initials: HA
authors.lastname: Papadaki
authors.forename: A N
authors.initials: AN
authors.lastname: Margioris
authors.forename: M
authors.initials: M
authors.lastname: Miliaki
authors.forename: C
authors.initials: C
authors.lastname: Steriopoulos
authors.forename: W
authors.initials: W
authors.lastname: Valatas
authors.forename: G D
authors.initials: GD
authors.lastname: Eliopoulos
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D015519:Bone Density; D016723:Bone Remodeling; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000097:blood / Q000503:physiopathology*; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D007375:Interleukin-1; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D014409:Tumor Necrosis Factor-alpha; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D003094:Collagen