Bone mineral density in men and children with haemophilia A and B: a systematic review and meta-analysis. 2014

S A Paschou, and P Anagnostis, and S Karras, and C Annweiler, and S Vakalopoulou, and V Garipidou, and D G Goulis
Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki Medical School, "Papageorgiou" General Hospital, Ring Road, 56403, Nea Efkarpia, Thessaloniki, Greece.

CONCLUSIONS Although haemophilia is not considered among the classic causes of secondary osteoporosis, the present meta-analysis provides strong evidence that men with haemophilia have a significant reduction in both lumbar spine and femoral bone mineral density, which appears to begin in childhood. BACKGROUND Haemophilia is not considered among the classic causes of secondary osteoporosis. The aim of this study was to systematically review the literature for case-control trials that have studied bone mass in males with haemophilia and to meta-analyze the best evidence available. METHODS Electronic databases MEDLINE, EMBASE and CENTRAL were systematically searched for case-control trials that have studied bone mass in men or boys with haemophilia. Standardized mean difference (SMD) for bone mineral density (BMD) in the lumbar spine was the main study outcome and SMD in femoral neck and total hip BMD the secondary ones. Patient and control characteristics, such as age, body mass index (BMI), level of physical activity and blood-borne infections were recorded as possible predictors of the main outcome. RESULTS Thirteen studies were included in the systematic review and ten in the main outcome meta-analysis. Men with haemophilia demonstrated reduced lumbar spine [random effects SMD [95 % confidence interval (CI)] = -0.56 (-0.84, -0.28), between-study heterogeneity (I (2)) = 51 %] and femoral neck BMD [random effects SMD (95 % CI) = -0.82 (-1.21, -0.44), I (2) = 63 %] compared with controls, which indicated a large and clinically significant association. Similar results were obtained for children [random effects SMD (95 % CI) = -0.92 (-1.77, -0.07), I (2) = 92 %]. No evidence of publication bias was detected. There was no evidence that age, BMI, level of physical activity or presence of blood-borne infections predicted lumbar spine BMD. CONCLUSIONS This meta-analysis shows that men with haemophilia present a significant reduction in both lumbar spine and hip BMD, which appears to begin in childhood.

UI MeSH Term Description Entries
D008159 Lumbar Vertebrae VERTEBRAE in the region of the lower BACK below the THORACIC VERTEBRAE and above the SACRAL VERTEBRAE. Vertebrae, Lumbar
D008297 Male Males
D010024 Osteoporosis Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis. Age-Related Osteoporosis,Bone Loss, Age-Related,Osteoporosis, Age-Related,Osteoporosis, Post-Traumatic,Osteoporosis, Senile,Senile Osteoporosis,Osteoporosis, Involutional,Age Related Osteoporosis,Age-Related Bone Loss,Age-Related Bone Losses,Age-Related Osteoporoses,Bone Loss, Age Related,Bone Losses, Age-Related,Osteoporoses,Osteoporoses, Age-Related,Osteoporoses, Senile,Osteoporosis, Age Related,Osteoporosis, Post Traumatic,Post-Traumatic Osteoporoses,Post-Traumatic Osteoporosis,Senile Osteoporoses
D002836 Hemophilia B A deficiency of blood coagulation factor IX inherited as an X-linked disorder. (Also known as Christmas Disease, after the first patient studied in detail, not the holy day.) Historical and clinical features resemble those in classic hemophilia (HEMOPHILIA A), but patients present with fewer symptoms. Severity of bleeding is usually similar in members of a single family. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma. Treatment is similar to that for hemophilia A. (From Cecil Textbook of Medicine, 19th ed, p1008) Christmas Disease,Factor IX Deficiency,Deficiency, Factor IX,F9 Deficiency,Haemophilia B,Hemophilia B Leyden,Hemophilia B(M),Plasma Thromboplastin Component Deficiency,Bs, Hemophilia,Deficiencies, F9,Deficiencies, Factor IX,Deficiency, F9,Disease, Christmas,F9 Deficiencies,Factor IX Deficiencies,Haemophilia Bs,Hemophilia Bs,Hemophilia Bs (M)
D005272 Femur Neck The constricted portion of the thigh bone between the femur head and the trochanters. Femoral Neck,Neck, Femoral,Neck, Femur
D006467 Hemophilia A The classic hemophilia resulting from a deficiency of factor VIII. It is an inherited disorder of blood coagulation characterized by a permanent tendency to hemorrhage. Factor VIII Deficiency,Hemophilia,Autosomal Hemophilia A,Classic Hemophilia,Deficiency, Factor VIII,Factor 8 Deficiency, Congenital,Factor VIII Deficiency, Congenital,Haemophilia,Hemophilia A, Congenital,Hemophilia, Classic,As, Autosomal Hemophilia,Autosomal Hemophilia As,Classic Hemophilias,Congenital Hemophilia A,Congenital Hemophilia As,Hemophilia A, Autosomal,Hemophilia As,Hemophilia As, Autosomal,Hemophilia As, Congenital,Hemophilias, Classic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012680 Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed) Specificity,Sensitivity,Specificity and Sensitivity
D015519 Bone Density The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS. Bone Mineral Content,Bone Mineral Density,Bone Densities,Bone Mineral Contents,Bone Mineral Densities,Density, Bone,Density, Bone Mineral
D015982 Bias Any deviation of results or inferences from the truth, or processes leading to such deviation. Bias can result from several sources: one-sided or systematic variations in measurement from the true value (systematic error); flaws in study design; deviation of inferences, interpretations, or analyses based on flawed data or data collection; etc. There is no sense of prejudice or subjectivity implied in the assessment of bias under these conditions. Aggregation Bias,Bias, Aggregation,Bias, Ecological,Bias, Statistical,Bias, Systematic,Ecological Bias,Outcome Measurement Errors,Statistical Bias,Systematic Bias,Bias, Epidemiologic,Biases,Biases, Ecological,Biases, Statistical,Ecological Biases,Ecological Fallacies,Ecological Fallacy,Epidemiologic Biases,Experimental Bias,Fallacies, Ecological,Fallacy, Ecological,Scientific Bias,Statistical Biases,Truncation Bias,Truncation Biases,Bias, Experimental,Bias, Scientific,Bias, Truncation,Biase, Epidemiologic,Biases, Epidemiologic,Biases, Truncation,Epidemiologic Biase,Error, Outcome Measurement,Errors, Outcome Measurement,Outcome Measurement Error

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