title: Increased bone resorption is implicated in the pathogenesis of bone loss in hemophiliacs: correlations with hemophilic arthropathy and HIV infection.
abstract: Osteoporosis has been recently recognized as a severe comorbidity factor in hemophilia. However, its pathogenesis is still obscure. We evaluated the incidence of osteoporosis in 90 hemophilia patients and investigated possible correlations with clinical and laboratory data. Out of the 90 patients, 80 (89%) had severe hemophilia, and 35 (38.9%) were human immunodeficiency virus (HIV)-positive. Hemophilic arthropahty was assessed using World Federation of Hemophilia clinical score and Petterson radiological score. Bone mineral density of the lumbar spine (LS) and femoral neck (FN) were measured using dual-energy X-ray absortiometry. Bone turnover was evaluated by the measurement of: (1) bone resorption markers [N-terminal cross-linking telopeptide of collagen type I (NTX), C-terminal cross-linking telopeptide of collagen type I (CTX), and tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)], (2) bone formation markers [bone-alkaline phosphatase (bALP) and osteocalcin], and (3) osteoclast stimulators (receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, and tumor necrosis factor-alpha). Osteopenia or osteoporosis was observed in 86% and 65% of the patients in FN and LS, respectively. Osteoporosis was more common among HIV-positive patients in both FN (65.3% vs 41.6%; p = 0.007) and LS (17.86% vs 5.41%, p = 0.004). The severity of osteoporosis in FN correlated with the patients' total clinical and radiological score (p = 0.001). Hemophilia patients showed increased osteoclastic activity (significant increase of TRACP-5b, NTX, and CTX), which was not accompanied by a comparable increased bone formation (reduced osteocalcin and borderline increase of bALP). In multivariate analysis, HIV infection (p = 0.05) and total clinical score (p = 0.001) were independent risk factors for osteoporosis development. We conclude that there is a high prevalence of osteoporosis among hemophiliacs, which is related to the severity of arthropathy and is enhanced by HIV infection. We report for the first time a high bone resorption that seems not to be balanced by a comparable bone formation.
authors.affiliation: 2nd Blood Transfusion Center and Hemophilia Center, "Laiko" General Hospital, Athens, Greece.
authors.forename: Olga
authors.initials: O
authors.lastname: Katsarou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.forename: Pantelis
authors.initials: P
authors.lastname: Chatzismalis
authors.forename: Stefanos
authors.initials: S
authors.lastname: Provelengios
authors.forename: Theophanis
authors.initials: T
authors.lastname: Adraktas
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Hadjidakis
authors.forename: Anna
authors.initials: A
authors.lastname: Kouramba
authors.forename: Anastasia
authors.initials: A
authors.lastname: Karafoulidou
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density / Q000502:physiology; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000503:physiopathology; D006467:Hemophilia A / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011859:Radiography; D055815:Young Adult