Monitoring of Bone Metabolism after Bone Marrow Transplantation by Measuring Two Different Markers of Bone Turnover

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

doi:10.1515/cclm.1996.34.3.193

Cited by 15 publications

(11 citation statements)

References 15 publications

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“…20 It has been reported that it can even correlate with BMD in post-menopausal females. 21 The earlier study by Withold et al 22 of biochemical markers reflecting bone turnover is in agreement with our observations after BMT where BAP and BMD had an inverse correlation with BMD ( Figure 3). Type I collagen is the predominant protein (90%) in bone.…”

Section: Discussionsupporting

confidence: 92%

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Bone mineral density after allogeneic bone marrow transplantation

Kauppila

Irjala²,

Koskinen³

et al. 1999

Bone Marrow Transplant

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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...

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Section: Discussionsupporting

confidence: 92%

“…CsA therapy has been associated with decreased serum testosterone levels 30 and accelerated bone turnover. 22 One of our subjects had severe intestinal GVHD lasting for two years. As the result of malabsorption and long-term treatment with glucocorticoid and CsA she had the lowest BMD which improved (Z-score from −4 to −2.2 s.d.)…”

Section: Discussionmentioning

confidence: 92%

Bone mineral density after allogeneic bone marrow transplantation

Kauppila

Irjala²,

Koskinen³

et al. 1999

Bone Marrow Transplant

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“…ABMT is associated with an acute increase in bone turnover due to the high-dose chemotherapy, marrow reinfusion and G-CSF administration, but effects on long-term bone density are unknown. [3][4][5] The late effects of ABMT on BMD are primarily due to the hypogonadism induced by the alkylating agents and total body irradiation given pre-transplant. [6][7][8][9] The patient's underlying disease also contributes to reduced BMD.…”

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confidence: 99%

Decreased bone mineral density is common after autologous blood or marrow transplantation

Schimmer

Mah

Bordeleau

et al. 2001

Bone Marrow Transplant

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Summary:Survivors of autologous blood or marrow transplantation (ABMT) are predisposed to decreased bone mineral density (BMD), but data are lacking on the incidence and risk factors for this condition. Therefore, we measured BMD in 64 of 68 consecutive ABMT survivors (35 men and 29 women) attending the University of Toronto ABMT long-term follow-up clinic. Patients were evaluated a median of 4.2 years (range: 4.9 months-11.4 years) after ABMT. Median age at evaluation was 49.6 years (range: 23.5-68.2 years). At the L1-L4 vertebrae, 17 (26%) patients (eight men and nine women) had osteopenia and one male (2%) had osteoporosis. Mean BMD at L1-L4 did not differ from healthy young adults or age and sex matched controls. At the femoral neck, 30 patients (46%) (18 men and 12 women) had osteopenia and five (8%) (two men and three women) had osteoporosis. Mean BMD at the femoral neck was significantly lower than in healthy young adults and age-and sex-matched controls. By regression analysis, patients with decreased BMD were older than those with normal BMD (P = 0.02). Gender, body mass index, time from BMT to evaluation and presence of hypogonadism were not associated with decreased BMD. Treatment of decreased bone density was instituted and follow-up data were obtained 1 year after treatment in 22 of 39 patients with reduced BMD. Nineteen (86%) patients had stabilization or improvement of their bone density at follow-up. We conclude that, after ABMT, over half of the patients have evidence of osteopenia or osteoporosis. Men and women were equally affected. In our study, only older age at evaluation was predictive for loss of BMD. We recommend the measurement of BMD as an integral component to the follow-up of ABMT patients. Bone Marrow Transplantation (2001) As the number of long-term survivors of autologous blood or marrow transplantation (ABMT) increases, greater attention is turning to the late complications of this procedure. One such complication is decreased bone mineral densityosteopenia and osteoporosis. Osteopenia is a systemic condition characterized by reduced bone mass and increased susceptibility to bone fracture. Osteoporosis is a more severe reduction in bone mass and a greater susceptibility to bone fracture.In the short term, osteoporosis seems trivial compared with a diagnosis of cancer, but for those cured of their disease, decreased bone mineral density contributes to chronic morbidity and mortality in the form of bone fractures. For example, 50% of patients who sustain an osteoporosisrelated hip fracture require assistance with activities of daily living 1 and elderly patients who suffer an osteoporosis-related hip fracture have an increased 1-year mortality of 12-37%. 2 ABMT predisposes to decreased BMD through early and late acting mechanisms. ABMT is associated with an acute increase in bone turnover due to the high-dose chemotherapy, marrow reinfusion and G-CSF administration, but effects on long-term bone density are unknown. [3][4][5] The late effects of ABMT on BMD are primarily due to t...

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“…After 3 months, there is recovery of bone formation markers and elevated turnover persists during the latter half of the year [226,231,236,237,240,241]. After autologous BMT, rates of FN bone loss are lower, about 4%, but the losses persist for as long as 2 years.…”

Section: Bone Marrow Transplantationmentioning

confidence: 99%

Osteoporosis in Organ Transplant Patients

Stein

Shane

2013

Osteoporosis

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As transplantation osteoporosis results from alterations in the bone remodeling system, a review of normal bone remodeling is helpful to understanding the pathogenesis of this disease. The bone remodeling cycle is an orderly progression of events in which old, microdamaged bone is replaced by new, mechanically stronger bone. The complete remodeling cycle at each remodeling site requires approximately 3-6 months. Bone remodeling occurs by two main processes, resorption [1] followed by formation [2], which take place on both cancellous and cortical bone surfaces. Resorption begins with activation of macrophage precursors to form osteoclasts, giant multinucleated cells that excavate a cavity on the bone surface. Osteoclasts express receptors for receptor activator of receptor activator of nuclear factor-kappaB ligand (RANKL), which is produced by osteoblasts and osteocytes, and for calcitonin, prostaglandins (PGs), calcium, and vitronectin (integrin α 1 β 3 ). Approximately 0.05 mm 3 of bone tissue is resorbed by each osteoclast, leaving small resorption pits on the bone surface called Howship's lacunae in a process that takes approximately 2-3 weeks. A brief rest period called the reversal phase follows. Next, local mesenchymal bone marrow stem cells differentiate into osteoblasts that are attracted to the empty resorption pits where they accumulate as clusters of plump cuboidal cells along the bone surface. Osteoblasts produce the collagenous and noncollagenous proteins that constitute the matrix of the newly formed bone and are responsible for mineralization of the matrix or osteoid after a period of maturation that lasts approximately 20 days. Osteoblasts express receptors for several hormones (thyroid and parathyroid hormones, estrogens, vitamin D 3 ), cell adhesion molecules (integrins), and cytokines. RANKL, receptor activator of nuclear factor-kappaB (RANK), and osteoprotegerin (OPG) are three members of the tumor necrosis factor (TNF) ligand and receptor-signaling family that are final mediators of bone resorption [3,4]. RANKL is expressed in osteoblasts, osteocytes, and bone marrow stromal cells. When sufficient concentrations of macrophage colony stimulating factor (M-CSF) are present, RANKL binds to RANK, which is expressed on the surface of osteoclast lineage cells. This binding results in rapid differentiation of osteoclast precursors in bone marrow to mature osteoclasts, increased osteoclast activity, and reduced apoptosis of mature osteoclasts. RANKL is neutralized by binding to OPG, which is secreted by cells of the osteoblast lineage. Competitive binding of RANKL to either RANK or OPG regulates bone remodeling by increasing (RANK) or decreasing (OPG) osteoclastogenesis. Immunosuppressants exert their effects on bone remodeling by interacting with the RANK/RANKL/ OPG system [5].In healthy adults, declines in bone mass as a result of remodeling imbalance occur, but are small. When bone remodeling becomes "uncoupled," such that the rate of resorption exceeds the rate of formation, bone loss will occur...

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Monitoring of Bone Metabolism after Bone Marrow Transplantation by Measuring Two Different Markers of Bone Turnover

Cited by 15 publications

References 15 publications

Bone mineral density after allogeneic bone marrow transplantation

Bone mineral density after allogeneic bone marrow transplantation

Decreased bone mineral density is common after autologous blood or marrow transplantation

Osteoporosis in Organ Transplant Patients

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