Osteoporosis and osteosclerosis in sickle cell/beta-thalassemia: the role of the RANKL/osteoprotegerin axis

Bone mineral density (BMD) was evaluated in 52 patients with HbS/beta-thalassemia. Seventeen (32%) patients had osteopenia/osteoporosis and 30 (57%) had osteosclerosis. Bone resorption was diminished in patients with osteosclerosis and increased in those with osteopenia/osteoporosis. The sRANKL/osteoprotegerin ratio was elevated in the osteosclerotic group. Osteoporosis patients had mild renal impairment and their BMD correlated with osteoprotegerin, and bone resorption markers. Osteosclerosis patients had multiple infarctions in the studied bones that led to reduced osteoclast activity and increased BMD. In conclusion, HbS/beta-thalassemia patients may develop osteopenia/osteoporosis mainly due to marrow expansion or osteosclerosis because of ischemia after a vaso-occlusive crisis. The RANKL/ osteoprotegerin axis participates in these phenomena.     

Inspiration during the sleep stages without and after preceding exercise, as a factor supporting circulation of blood and the "resting procedure"

In a previous preliminary work we found a longer inspiration than expiration period during sleep, opposite to what normally happens during wakefulness. These results which derived from quite a few measurements, but only from two male subjects, were not categorized to sleep stages. In the present paper we have studied the heart rate/minute, the respiration rate/minute and also the duration of inspiration and expiration (respiration ratio), in six healthy subjects, four men and two women aged 23-42, in all four stages of sleep, the REM stage and in arousals. These parameters were studied in the same subjects twice, once after a resting pre-sleep period (sleep A) and another time after "exercise" before going to sleep (sleep B), in an attempt to trace any changes in the above parameters that could be related to the "resting procedure". "Exercise" before sleep B consisted of a heavy dinner taken after 21:30 h and some physical activity. Results were analyzed by the Wilcoxon non-parametric tests. The differences between sexes were analyzed by the Mann-Whitney, two independent samples, test and have shown the following: a) The heart rate and the respiration rate did not increase significantly in sleep B as compared to sleep A in most of the sleep stages and arousals. b) Respiration ratio did not change significantly between sleep A and sleep B. c) We have confirmed our previous finding that during sleep, the mean values of inspiration are longer than those of expiration and have also shown that the increase in the duration of inspiration as indicated by the respiration ratio, existed in all four stages of sleep, the REM and the arousal periods. d) Significantly higher heart rate and respiration rate and lower respiration ratio were observed in women as compared to men, throughout the study and especially during sleep B as compared to sleep A. This finding, although statistically acceptable, needs confirmation due to the small number of women studied. e) Statistical analysis by the Wilcoxon test of the accumulated means of all sleep A and B stages in heart rate, respiratory rate and respiration ratio were compared with the same findings during arousal periods and showed no significant difference except for stage 1 sleep B (P=0.002). f) The action of inspiration inducing a negative pressure in the thorax and altering the intra-abdominal pressure may be considered an "elastic" action supporting blood flow and contributing to the "resting procedure" during sleep. In conclusion: (a) The results a) and b) indicate that in the young subjects studied, the "exercise" they had before sleep B was not sufficient to significantly modify the above parameters. (b) The "arousal" period, according to the above findings, may be considered as part of the usual sleeping period. (c) Women as compared to men had higher heart rate and respiration rate and lower respiration ratio, especially in sleep B as compared to sleep A. This result needs confirmation. (d) We found increased duration of inspiration during sleep. As reminded above, inspiration has favorable hemodynamic action in the thorax, delivers oxygen to the heart and body tissues and exercises an elastic action to the abdominal vessels. Having all these in mind, inspiration may be considered as a factor supporting the circulation of blood and the "resting procedure" during sleep.     

Molecular genetics of “X-linked” sideroblastic anemia

We have studied three compound heterozygotes for Hb Lepore (“Pylos”)/HbS hemoglobin, a combination quite uncommon in the literature. It is of interest that while two of these cases are clinically similar to those thus far reported, the third one is free of symptoms and the diagnosis was put incidentally. This mild condition may be due to the high level of fetal hemoglobin produced. © 1995 Wiley-Liss, Inc.     

New insights into the pathophysiology and management of osteoporosis in patients with beta thalassaemia

Osteoporosis represents an important cause of morbidity in adult patients with thalassaemia major (TM). The pathogenesis of osteoporosis in TM is multifactorial, and includes bone marrow expansion, endocrine dysfunction and iron overload. Additional genetic factors, such as the COLIA 1 gene polymorphism, seem to play an important role in the development of low bone mass in these patients. However, the mechanisms through which these factors lead to bone loss have not been completely clarified. The diminished osteoblast function is accompanied by a comparable or even greater increase in osteoclast activity. The receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway has been recently recognized as the final, dominant mediator of osteoclast proliferation and activation. There is increased evidence that this pathway interferes in the pathogenesis of thalassaemia-induced osteoporosis. Currently, bisphosphonates that are potent inhibitors of osteoclast function have been used in TM patients with encouraging results. This review attempts to summarize all the novel data for the biology of bone damage in TM. It also describes the results of all major studies that have investigated the effects of different treatment modalities for TM-induced osteoporosis, their mode of action, and the future implications of their use.