This study prospectively investigated the changes of the serum levels of the sex steroids, IL-7, soluble receptor activator of nuclear factor κB ligand (sRANKL) and osteoprotegerin (OPG) in bone marrow transplantation (BMT) recipients. This study also examined whether the changes of these cytokine levels and sex steroids actually influence bone turnover and post-BMT bone loss by correlation analysis. Data were analyzed from 39 patients (33.6 ± 6.4 years, 19 men and 20 women) who had DXA performed before BMT and at 1 year after BMT. The bone turnover markers, sex steroids and the cytokine levels were measured before BMT and serially after BMT.
The mean bone loss in the lumbar spine and the total proximal femur was 5.9% (P < 0.01) and 11.3% (P < 0.01), respectively. During the immediate post-BMT period, bone formation decreased, whereas the bone resorption increased. For the female recipients, the estradiol levels declined at 1 week after BMT, and they did not recover to the basal levels. For the male recipients, the testosterone levels decreased at 1 week and then it increased to its baseline level. The IL-7 levels reached their maximum at 1 week and then declined to baseline level by 3 months. The serum sRANKL, OPG levels and the sRANKL/OPG ratio showed their peak at post-BMT 3 weeks.
The mean daily dose of steroid was associated with suppressed bone formation, enhanced bone resorption and increased sRANKL levels. The IL-7 levels were also noted to be either positively correlated with the levels of ICTP or they were negatively correlated with the levels of osteocalcin at 1 and 3 weeks after BMT. Bone loss at the lumbar spine and the proximal femur was influenced by the decreased sex steroids and increased IL-7 levels. During the observation period, the IL-7 levels showed positive correlations with the sRANKL levels and the sRANKL/OPG ratio. For the female patients, the serum IL-7 levels were negatively associated with the estradiol levels at 1 and 3 weeks after BMT.
All these findings suggest that IL-7 plays an important role for post-BMT bone loss, and this possibly happens via the RANKL pathway. These data also suggest that the up-regulation of IL-7 during the early post-BMT period may result from a deficiency of estrogen. 相似文献
Introduction: The purpose of this study was to compare age-related differences in osteoprotegerin (OPG) in relationship with BMD and the serum bone markers osteocalcin (OC), collagen crosslinks (CTX), and tartrate-resistant acid phosphatase 5b (TRACP-5b). Methods: Data were derived from a cross-sectional study on bone health in a random sample of community-dwelling adults aged 30 to 85 years in the Reykjavik area in Iceland. All subjects had whole body, hip, and lumbar spine BMD measured (by DXA), gave blood samples, and answered a thorough questionnaire on medications and medical history. We assessed relationships using the Spearman correlation coefficient, partial correlation, and multivariable linear regression. Men and women were analyzed separately. Results: Of 2,310 subjects invited over 2 years, 1,630 participated. After excluding individuals with diseases and medications affecting bone metabolism, 517 women (age 56.1 ± 16.9 years) and 491 men (age 58.7 ± 14.9 years) remained for analysis. OPG increased steadily with age in both genders without a gender difference. In women, BMD at all sites declined steadily after age 50. In men, BMD remained relatively stable until age 70, after which it declined significantly. After controlling for age, BMI, and other confounding variables, OPG showed only a borderline positive relationship with whole body BMD in men (P=0.10), but the relationship was nonsignificant in women. In multivariable models, OPG was inversely related to TRACP-5b (P=0.002) and positively with OC (P=0.007), the OC/TRACP-5b (P=0.001) and OC/CTX (P=0.02) ratios in women. Among men, multivariable models showed a positive association between OPG and OC (P=0.05) and OC/TRACP-5b (P<0.009). Conclusions: We conclude that serum OPG levels are associated with a profile of bone turnover markers favoring bone formation, suggesting that OPG may be protective against age-related bone loss. Longitudinal studies are needed to address that issue. 相似文献
Rheumatoid arthritis (RA) is characterized by inflammation and proliferation of synovial tissue, leading to degradation of
articular cartilage and bone with functional impairment as a result. It has recently become clear that early suppression of
synovial inflammation is essential in preventing progressive joint destruction, although inflammation and destruction are
in part uncoupled. New insights into the role of matrix metalloproteinases (MMPs), aggrecanase, granzyme B, receptor activator
of nuclear factor κB (RANK)–receptor activator of nuclear factor κB ligand (RANKL) interaction, and other factors involved
in joint destruction may lead to the development of novel therapies aimed at specific inhibition of cartilage and bone degradation.
Correspondence to:P.P. Tak 相似文献
Background Sleep-disordered breathing (SDB) is known to occur frequently in and may predict worsening progression of patients with congestive heart failure (CHF). SDB is also known to play an important role in the development of idiopathic pulmonary arterial hyperten?sion (PAH) via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin (OPG) and endothelial progenitor cells (EPCs). The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAH. Methods EPCs were isolated, cultured, and quantified from CHF patients with SDB (n = 52), or without SDB (n = 68). OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP) from each group was analyzed and correlated with EPCs and the mean pulmonary artery pressure (mPAP) measured by right heart catheterization. Results A significant decrease in circulating EPCs (29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/× 200 field; P < 0.05) was found in CHF patients with SDB compared to those without SDB. Both OPG (789.83 ± 89.38 vs. 551.29 ± 42.12 pg/mL; P < 0.05) and NT-proBNP (5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P < 0.05) were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP (50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P < 0.05). EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour (RDI, r = –0.45, P = 0.037) and blood level of OPG (r = –0.53, P = 0.011). Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RDI. Conclusions SDB due to hypoxemia from decompensated CHF is associated with (1) OPG elevation, (2) EPC depletion, and (3) mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF. 相似文献