Reduction of Bone Mass in Women after Bone Marrow Transplantation

110

Summary:Transplantation of solid organs including heart, kidney, and liver is associated with rapid bone loss and increased rate of fracture; data on bone marrow transplantation recipients (BMT) are scarce. The purpose of the present study was to examine the magnitude, timing, and mechanism of bone loss following allogeneic BMT, and to study whether bone loss can be prevented by calcium with or without calcitonin. Sixty-nine patients undergoing allogeneic BMT for malignant blood diseases were enrolled into the study. Forty-four (22 women, 22 men) completed 6 months, and 36 patients 1 year follow-up. They were randomized to receive either no additional treatment (n ‫؍‬ 22), or oral calcium 1 g twice daily for 12 months (n ‫؍‬ 12) or the same dose of calcium plus intranasal calcitonin 400 IU/day for the first month and then 200 IU/day for 11 months (n ‫؍‬ 10). Bone mineral density (BMD) at the lumbar spine and three femoral sites (femoral neck, trochanter, Ward's triangle) was measured by dual-energy X-ray absorptiometry (DXA). Bone turnover rate was followed with markers of bone formation and resorption (serum bone-specific alkaline phosphatase (B-ALP), type I procollagen carboxyterminal (PICP) and aminoterminal propeptide (PINP), serum type I collagen carboxyterminal telopeptide (ICTP)). Serum testosterone was assayed in men. Calcium with or without calcitonin had no effect on bone loss or bone markers; consequently the three study groups were combined. During the first 6 post-transplant months BMD decreased by 5.7% in the lumbar spine and by 6.9% to 8.7% in the three femoral sites (P Ͻ 0.0001 for all); no significant further decline occured between 6 and 12 months. Four out of 25 assessable patients experienced vertebral compression fractures. Markers of bone formation reduced: B-ALP by 20% at 3 weeks (P ‫؍‬ 0.027), PICP by 40% (P Ͻ 0.0001) and PINP by 63% at 6 weeks (P Ͻ 0.0001), with a return to baseline by 6 months. The marker of bone resorption, serum ICTP was above normal throughout the whole observation period, with a peak at 6 weeks (77% above baseline, P Ͻ 0.0001). In male patients serum testosterone decreased reaching a nadir (57% below baseline) at 6 weeks (P ‫؍‬ 0.0003). In conclusion, significant bone loss occurs after BMT. It results from imbalance between reduced bone formation and increased bone resorption; hypogonadism may be a contributing factor in men. Bone loss can not be prevented by calcium with or without calcitonin.

Section: Discussionmentioning

confidence: 77%

mentioning

confidence: 99%

A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin

Välimäki

Kinnunen

Volin

et al. 1999

110

“…30 The administration of steroids to treat GVHD and GVHD itself may be another possible explanation for the decreased osteoblastic activity following a BMT. 9 A previous study observed a negative correlation between the serum osteocalcin level and the mean daily dose of steroids that were administered during the 3 months after a BMT. 8 This study also observed a significant correlation between the cumulative steroid dose and bone loss in the lumbar and proximal femoral bones during the first year after a BMT.…”

Section: Discussionmentioning

confidence: 94%

“…It was previously reported that bone disease is one of the complications of a BMT. 1,5 According to Castaneda et al, 9 33 and 18% of BMT recipients had osteopenia and osteoporosis in the lumbar spine when examined 33.6 months after BMT. The main causes of bone loss following a BMT include the use of immunosuppressants and hypogonadism induced by TBI or chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

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

Lee

Baek

Rhee

et al. 2004

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 ...

“…6 It has been described after hematopoietic stem cell transplantation (SCT) as well, with the majority of cases reported in alloSCT recipients. [7][8][9][11][12][13][14][15][16][17][18][19][20][21][22][24][25][26][27][28][29][30][31][32][33][34][35] AlloSCT-associated BMD loss is usually described in the first 6-12 months after the transplantation, but varies widely from 40 days 17 to 4-6 years after the transplantation, 30,31,34 and in some instances can persist for 10-12 years. 26,28 Baseline BMD pre-SCT is usually within the normal limits; [15][16][17]24,[27][28][29][30]33 the few exceptions noting high O/O prevalence pre-SCT are probably due to the underlying diseases or intensive chemotherapy prior to the transplantation.…”

Section: Introductionmentioning

confidence: 99%

High prevalence of early-onset osteopenia/osteoporosis after allogeneic stem cell transplantation and improvement after bisphosphonate therapy

Yao

McCarthy

Dunford

et al. 2007

Osteopenia/osteoporosis (O/O) has been associated with allogeneic stem cell transplantation (alloSCT). We retrospectively reviewed 102 patients undergoing a first alloSCT from 2000 to 2005 at our center to evaluate the prevalence of O/O p6 and 46 months post-alloSCT. Fifty-six patients did not have a dual energy X-ray absorptiometry (DXA) scan following alloSCT. Approximately half (n ¼ 13/27) of those with a first DXA scan p6 months post-alloSCT had O/O and a similar rate (n ¼ 9/19) was seen in those with a first DXA scan 46 months. There were no significant differences in patient characteristics between the normal and O/O groups. The dual femur (DF) appeared to be more vulnerable to alloSCTinduced bone mineral density (BMD) loss than the lumbar spine (LS), regardless of screening time. O/O patients were treated with bisphosphonates and 41% had a repeat DXA scan post-treatment. No patient developed jaw osteonecrosis and significant BMD improvement was seen at the LS (mean BMD, 1.03 ± 0.13 vs 1.08 ± 0.12, P ¼ 0.004) but not the DF (mean BMD, 0.84±0.06 vs 0.85 ± 0.08, P ¼ 0.29), indicating BMD loss at the DF is more resistant than the LS to antiresorptive therapy. Our results demonstrate that O/O is an early and late complication post-alloSCT and bisphosphonate treatment reverses BMD loss at the LS.