Bone mineral density after allogeneic bone marrow transplantation

Abstract

Summary:Bone turnover markers and bone mineral density (BMD) were studied in 25 adult patients (14 females, 11 males) who had undergone allogeneic bone marrow transplantation (BMT). The interval from BMT to the first examination was at least 1 year (mean 3, range 1-10). Mean age of the patients at the time of first evaluation was 42 (range 19-54) years. Blood samples and urine collections for evaluation of biochemical factors reflecting skeletal turnover were performed together with the first BMD measurement. BMD was measured from the lumbar vertebrae (L2 to L4) with computed tomography and results were expressed as Z-scores. At the time of the first measurement five patients (20%) had Z-scores Ͻ−2.5 s.d. and 12 patients (48%) between −1 and −2.5 s.d. In 12 patients BMD assessments were repeated and it seemed that reduction in BMD had mostly occurred during and shortly after BMT and remained the same during follow-up. The cross-linked carboxyterminal telopeptide of type I collagen (ICTP) correlated negatively with BMD (r = −0.45, P = 0.045) as did bone-specific alkaline phosphatase (BAP; r = −0.64, P = 0.002). No correlation between BMD and time interval from diagnosis to BMT, conditioning regimen, corticosteroid use or hospital stay during transplantation was found. In conclusion, bone disease is common after BMT. Our findings demonstrate an increased collagen and bone turnover and a high risk of osteoporosis. BMD measurements must be repeated regularly and collagen markers such as ICTP and BAP can be beneficial in estimating the activity of bone disease. Keywords: allogeneic bone marrow transplantation; ICTP; bone-specific alkaline phosphatase; bone mineral density; osteoporosis Transplant recipients are at risk of osteoporosis. Muchmore et al 1 reported low mean density of vertebral bone in heart transplant patients. Bone loss takes place mostly during the initial year after transplantation. 2 Rapid loss of vertebral mineral density has also been reported after renal transplantation, with most of the loss occurring within the first 6 months. after. Bone loss was related to number of hospital days but not to any other factor.Patients after allogeneic BMT are also exposed to numerous factors that can affect bone mineral metabolism: induction and consolidation therapies, bed rest, 5,6 conditioning regimen for BMT, steroids, 7 CsA therapy 8,9 and GVHD. 10 In female patients disturbance of gonadal function causes chronic estrogen deficiency 11 with an increased risk for osteoporosis. Carlson et al 12 studied the effect of myeloablative therapy on bone metabolism during the first 3 months after transplantation and found significant changes in serum markers of bone metabolism, which implied a net loss of bone over the study period. In 1997 Keilholz et al 13 reported normal BMDs after ABMT with a median interval of 5 years from autografting.The purpose of the present study was to evaluate the occurrence of bone disease after BMT by measuring BMD and biochemical markers of bone metabolism. Patients and methodsWe exami...

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

“…However, in our study, we did not find this association, which is consistent with the findings from two other studies. 11, 13 The relatively low proportion of patients receiving glucocorticoids may explain the absence of an association between O/O and Acute GvHD grade II-IV treatment and glucocorticoid-containing GvHD prophylaxis regimens were combined as an indicator of glucocorticoid exposure: none ¼ not exposed to glucocorticoid from either source; either ¼ exposed to glucocorticoids from either GVHD treatment or prophylaxis; both ¼ exposed to glucocorticoids during both prophylaxis and treatment of GVHD.…”

“…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.…”

High-dose chemotherapy shows a dose-dependent toxicity to bone marrow osteoprogenitors

“…3,13 Several authors have studied the effects of bone marrow transplant (BMT) conditioning regimens on bone marrow stroma hemopoietic supporting function, 14 -21 showing that the microenvironment is heavily and permanently damaged. Conversely, various groups have reported a decrease in BMD in post-BMT patients, [22][23][24][25][26][27][28][29][30] mainly after allogeneic transplants and with conditioning regimens including total-body irradiation (TBI), but the role of osteoprogenitor damage was not investigated.…”

Conséquences endocriniennes, osseuses et métaboliques des greffes de cellules souches hématopoïétiques allogéniques chez l’adulte

“…41 Des études plus anciennes montraient une fréquence d'ostéoporose à 1 an post-greffe entre 7 et 20 %, et une baisse de la DMO (densité minérale osseuse) dans 39 à 53 % des cas. 26,42,43 A notre connaissance, aucune étude ne s'est intéressée à l'impact métabolique des patients allogreffés à l'âge adulte.…”