Relationship between Bone Metabolism and Plasma Cytokine Levels in Patients at Risk of Post-Transplantation Bone Disease after Bone Marrow Transplantation

Withold, Wolfgang; Wolf, Hans‐Heinrich; Kollbach, Sabine; Heyll, A.; Schneider, Wolfgang; Reinauer, H.

doi:10.1515/cclm.1996.34.4.295

Cited by 10 publications

(11 citation statements)

References 18 publications

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“…To our knowledge, there has been only one study observing the change in bone turnover markers and cytokines following BMT and the correlation between them. In the study by Withold et al [18] the enhancement of bone resorption after BMT was related to the increase in circulating IL-6. However, we did not observe a correlation between circulating IL-6 and bone resorption marker after BMT.…”

Section: Discussionmentioning

confidence: 92%

The Role of Cytokines in the Changes in Bone Turnover Following Bone Marrow Transplantation

Lee¹,

Kang²,

Oh³

et al. 2002

Osteoporosis International

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Osteoporosis is a common disease among patients undergoing transplantation and a loss of bone mass is usually detected after bone marrow transplantation (BMT), particularly during the immediate post-BMT period. Post-BMT bone loss is primarily related to gonadal dysfunction and immunosuppression. Cytokines, especially interleukin 6, play an important role in the pathogenesis of postmenopausal osteoporosis. However, the pathogenetic role of cytokines in post-BMT bone loss is unknown and data on the changes of cytokines in accordance with bone turnover markers are scarce. The aim of this study was to assess the relationship between bone turnover markers and cytokines, which are regularly sampled at peripheral blood and bone marrow before and after allogeneic BMT. This prospective study included two analyses. The first was a study of 46 BMT recipients (M/F 28/18), examining the relationship between bone turnover markers and serum cytokines that were measured before and at 1 week, 2 weeks, 3 weeks, 4 weeks and 3 months after BMT. Serum intact parathyroid hormone was measured before BMT and at 3 weeks after BMT and its relation to other cytokines and bone turnover markers was evaluated. The second analysis was a study of 14 (M/F 9/5) of 46 patients in whom bone marrow plasma cytokines [interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)] were measured at 3 weeks after BMT. The relationship between bone marrow plasma cytokines and bone turnover markers was studied because bone marrow is the microenvironment where the real changes in bone turnover occur. Serum type I collagen carboxyterminal telopeptide (ICTP), a bone resorption marker, increased progressively until 4 weeks (peak) after BMT and then decreased thereafter. Serum osteocalcin, a bone formation marker, decreased progressively until 3 weeks after BMT and then increased thereafter. Serum IL-6 increased until 2 weeks after BMT and declined thereafter. Serum TNF-alpha increased until 3 weeks after BMT and declined thereafter. There was a significant positive correlation between serum ICTP and bone marrow IL-6 levels at 3 weeks after BMT, when a marked change in bone metabolism occurs following BMT. However, a correlation between bone turnover markers and bone marrow TNF-alpha or peripheral blood cytokines was not found. At 3 months after BMT, there was a significant negative correlation between the mean daily steroid dose and the serum osteocalcin level (r = -0.43, p < 0.05). The correlation between the Mean daily steroid dose and serum ICTP was also significant (r = 0.41, p < 0.05). Our data suggest that the progressive increase in bone resorption during the immediate post-BMT period is related to both steroid dose and the increase in bone marrow IL-6, which is a potent stimulator of bone resorption in vivo.

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Section: Discussionmentioning

confidence: 92%

The Role of Cytokines in the Changes in Bone Turnover Following Bone Marrow Transplantation

Lee¹,

Kang²,

Oh³

et al. 2002

Osteoporosis International

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“…This study demonstrated that an increase in IL-6 and TNF-a levels during the early post-BMT period was related to the decreased lumbar BMD. 8 Withold et al 7 reported that there was a correlation between the increased bone resorption markers and the increased peripheral blood IL-6 levels after BMT. The above findings suggest that the changes in the bone-resorbing cytokines are possible causes for the post-BMT bone loss.…”

Section: Discussionmentioning

confidence: 99%

“…6 However, there are few reports on the relationship between changes in the bone metabolism and cytokine levels after a BMT. 7,8 In particular, there is no report on the effects of the drastically changing cytokine levels in the early post-BMT period on the long-term changes in the BMD after a BMT. It was previously reported that the bone marrow plasma IL-6 level, which reflects the real changes in the bone marrow microenvironment, was significantly related to the serum bone resorption markers after a BMT.…”

mentioning

confidence: 99%

Impact of circulating bone-resorbing cytokines on the subsequent bone loss following bone marrow transplantation

Lee

Baek

Rhee

et al. 2004

Bone Marrow Transplant

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Summary:Cytokines including IL-6 and TNF-a play an important role in the pathogenesis of postmenopausal osteoporosis. However, the relationship between changes in the cytokine levels and subsequent bone loss in patients undergoing a bone marrow transplantation (BMT) is unclear. A total of 46 patients undergoing an allogeneic BMT were prospectively investigated. The bone turnover markers and the serum cytokines were measured before BMT and serially after BMT. Bone mineral density (BMD) was measured before and 1 year after BMT. At 1 year after BMT, the lumbar spine BMD had decreased by 4.8%, and the total proximal femoral BMD had decreased by 12.3%. The serum IL-6 and TNF-a levels increased until 2 and 3 weeks after BMT, respectively. The lumbar BMD was significantly decreased as the serum IL-6 and TNF-a levels increased by post-BMT 3 weeks. The lumbar BMD decreased significantly as the cumulative prednisolone and cyclosporine dose increased. Patients with GVHD Xgrade II had higher lumbar bone loss than patients with GVHD ograde I. In conclusion, immunosuppressants, GVHD occurrence and increase in bone-resorbing cytokines in the early post-BMT period were associated with later bone loss after BMT. Further studies are needed to elucidate the precise mechanism. Bone marrow transplantation (BMT) is an established method for treating various hematological diseases. As the number of long-term survivors increased due to the improved prognosis after BMT, the number of endocrine complications has also increased. Endocrine complications brought about after a BMT include hypogonadism, thyroid dysfunction, hypopituitarism, diabetes and osteoporosis. A significant bone loss occurs during the first year after a BMT with up to a 5-10% decrease in the bone mineral density (BMD) in the lumbar spine and proximal femur. The post-BMT bone loss is mainly related to the immunosuppressants and the gonadal dysfunctions secondary to myeloablative therapy and/or total body irradiation (TBI). [1][2][3][4][5] The rapid impairment in bone formation and the increase in bone resorption, as mirrored by the biochemical markers, might play a role in bone loss, particularly during the early post-BMT period. 1 The pathogenic role of the cytokines is well known in the development of postmenopausal osteoporosis and other forms of secondary osteoporosis. Interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-a) are known to increase bone resorption by stimulating osteoclasts. 6 However, there are few reports on the relationship between changes in the bone metabolism and cytokine levels after a BMT. 7,8 In particular, there is no report on the effects of the drastically changing cytokine levels in the early post-BMT period on the long-term changes in the BMD after a BMT. It was previously reported that the bone marrow plasma IL-6 level, which reflects the real changes in the bone marrow microenvironment, was significantly related to the serum bone resorption markers after a BMT. 8 This study measured the serum IL-6, TNF-a and bone ...

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“…Possible factors implicated include physical inactivity, nutritional deficiencies, secondary hypogonadism induced by the preparatory regimen, direct toxicity to the bone microenvironment by high-dose chemoradiotherapy (Hamanishi et al, 1994;Withold et al, 1996;Banfi et al, 2001) and, lastly, the influence of the malignancy (e.g. myeloma) itself.…”

Section: Discussionmentioning

confidence: 99%

“…The pathogenesis of bone loss after SCT is not completely understood (Weilbaecher, 2000). Several factors have been implicated, including low bone mass prior to transplant, secondary hyperparathyroidism due to vitamin D deficiency, immobilization, graft-versus-host disease (GVHD) and its treatment (Katz & Epstein, 1992;Laan et al, 1993;Carlson et al, 1994;Weinstein et al, 1998), malignancy-related mechanisms, ovarian insufficiency in women, and altered cellular or cytokine-mediated bone marrow function (Hamanishi et al, 1994;Withold et al, 1996;Banfi et al, 2001).…”

mentioning

confidence: 99%

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long‐term follow‐up of a prospective study

Gandhi¹,

Lekamwasam

Inman³

et al. 2003

Br J Haematol

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Summary. Reduced bone mineral density (BMD) has been reported following allogeneic stem cell transplantation (alloSCT) but the effects of autologous SCT (autoSCT) are less well characterized. We performed a prospective study of BMD changes and its determinants in 44 SCT recipients (38 auto and six allo; 30 peripheral blood SCT and 14 bone marrow transplantation). Serial measurements of BMD at the lumbar spine and femoral neck were performed at baseline and at 3, 6, 12 and 24 months, and spinal radiographs were performed at baseline and 12 months. Mean baseline BMD values at the femoral neck and spine were within normal limits. At 3 months, there was a significant decline of BMD at the femoral neck (P ¼ 0AE011) and a nonsignificant trend towards reduction at the spine. BMD loss persisted for up to 2 years at the femoral neck (P ¼ 0AE005), but values returned to baseline at the spine. Reflecting the rapid initial decline in BMD, bone-specific alkaline phosphatase (a serum marker of bone formation) showed a significant initial decline at 1 month but had recovered to pretransplant levels by 3 months. No new fractures were detected at 1 year post transplant. Sex, diagnosis, use of total body irradiation, stem cell source and type of graft (auto versus allo) did not significantly predict BMD change over the first 12 months. In conclusion, significant and persistent bone loss at the femoral neck was demonstrated in this group of patients following stem cell transplantation. The implications of these findings for future fracture risk require further study.

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Relationship between Bone Metabolism and Plasma Cytokine Levels in Patients at Risk of Post-Transplantation Bone Disease after Bone Marrow Transplantation

Cited by 10 publications

References 18 publications

The Role of Cytokines in the Changes in Bone Turnover Following Bone Marrow Transplantation

The Role of Cytokines in the Changes in Bone Turnover Following Bone Marrow Transplantation

Impact of circulating bone-resorbing cytokines on the subsequent bone loss following bone marrow transplantation

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long‐term follow‐up of a prospective study

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