Monitoring of osteoblast activity with an immunoradiometric assay for determination of bone alkaline phosphatase mass concentration in patients receiving renal transplants

Withold, Wolfgang; Degenhardt, Stefan; Castelli, Daniela; Heins, M.; Grabensee, B

doi:10.1016/0009-8981(94)90041-8

Cited by 23 publications

(8 citation statements)

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“…The suppressive effect on osteoblast function reported (15) was only transient, and normal values of bone alkaline phosphatase were regained after 3 months; alterations of cytokine secretion are most strongly pronounced immediately after bone marrow transplantation. In contrast, in patients receiving renal transplants, an activating effect of cyclosporin A upon osteoblast activity (detected by determination of bone turnover markers) can be found 3 months at the earliest after transplantation (12). Due to the cross-sectional character of our study and the much longer follow-up period we were therefore not able to detect the slight suppressive effects on bone formation shown by Carlson et al (15).…”

Section: Discussioncontrasting

confidence: 57%

“…In patients under immunosuppressive therapy with cyclosporin A a comparable increase of serum (bone) alkaline phosphatase activities was observed after renal transplantation (12)(13)(14). (a) The follow-up period of Carlson's study was only 3 months following bone marrow transplantation whereas in the present communication the mean time since transplantation was 335 days.…”

Section: Discussionsupporting

confidence: 55%

“…This indicates that bone alkaline phosphatase concentrations are more sensitive than the other two measurable quantities in the detection of disturbances of bone metabolism (12). Therefore in patients following bone marrow transplantation, bone alkaline phosphatase in particular may be a useful marker substance for detection of increased bone turnover.…”

Section: Discussionmentioning

confidence: 96%

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

Withold¹,

Wolf²,

Kollbach³

et al. 1996

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Bone marrow transplant recipients may be at increased risk of osteoporosis. In a cross-sectional study we therefore measured two biochemical markers of bone turnover, bone alkaline phosphatase and the C-terminal propeptide of type I procollagen, in 22 serum samples from 9 patients before ailogeneic bone marrow transplantation and 85 serum samples from 14 patients after ailogeneic bone marrow transplantation.Following ailogeneic bone marrow transplantation, female (but not male) patients showed elevated serum bone alkaline phosphatase values (p < 0.05). After bone marrow transplantation both female and male patients were characterized by elevated serum concentrations of the C-terminal propeptide (p < 0.01). Both the duration of cyclosporin A therapy (p < 0.05) and the time since transplantation (p < 0.01) were independent predictors of serum bone alkaline phosphatase values, whereas the duration of cyclosporin A therapy was the only independent predictor of C-terminal propeptide serum concentrations (p < 0.01). There was a correlation between bone alkaline phosphatase serum concentrations and C-terminal propeptide values in serum (p < 0.0001).These findings indicate an accelerated bone turnover in patients following bone marrow transplantation due to the stimulation of osteoblasts by cyclosporin A. In addition, oestrogen deficiency after total body irradiation may accelerate bone mass loss in female patients.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 96%

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

Withold¹,

Wolf²,

Kollbach³

et al. 1996

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“…19 In renal transplant patients it has risen following transplantation and is considered as a marker of osteoblast activation. 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).…”

Section: Discussionmentioning

confidence: 99%

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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“…In patients receiving renal transplants, 17% of sera which were characterized by a total alkaline phosphatase activity in the upper half of the reference range showed increased bone alkaline phosphatase mass concentrations (22). The same applies to patients after bone marrow transplantation and those with prostate cancer suffering from bone metastases (23).…”

Section: Diagnostic Validity As Compared With Total Alkaline Phosphatmentioning

confidence: 91%

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1996

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A review is given summarizing the present knowledge of bone turnover markers with special emphasis on biological, preanalytical and technical criteria in the proper judgement of efficacy and limitations of the methods employed. The marker substances may be either measures of bone formation or bone resorption.Markers of bone formation are bone alkaline phosphatase, osteocalcin and the carboxyl-terminal propeptide of procollagen type I. Bone alkaline phosphatase has proved to be superior to total alkaline phosphatase activity with respect to diagnostic sensitivity and specificity. Immunochemical techniques for measuring bone alkaline phosphatase show a cross-reactivity of 14-20% with liver alkaline phosphatase. However, this does not compromise the clinical usefulness of these assays except for patients with severe liver diseases. Osteocalcin is strictly bone-specific but shows numerous disadvantages with respect to apparent instability and discordant results as obtained by different methods; however, in certain diagnostic situations (corticosteroid-induced osteopenia, absence of destroyed bone architecture) osteocalcin may serve as a sensitive bone turnover marker. The carboxyl-terminal propeptide of procollagen type I generally shows low discriminating power in the diagnosis of bone diseases.The urinary excretion of pyridinium 'cross-links' has been carefully evaluated so far with respect to analytical performance and clinical usefulness. This marker may be a substitute for 4-hydroxyproline measurements as the method of choice for assessment of bone resorption. There are other degradation products from the telopeptide regions of bone-derived collagen type I which are excreted into the urine (N-telopeptides, CrossLaps™)\ these analytes are promising tools in the assessment of bone resorption but require further evaluation, in particular with respect to their extraskeletal clearance and putative origin outside bone. Moreover, their clinical usefulness may vary depending on the patient group examined. In contrast, the serum concentration of the cross-linked telopeptide region of collagen type I seems to lack both diagnostic specificity and sensitivity in the majority of patient groups. Tartrate-resistant acid phosphatase (as determined by the presently available methods) cannot be recommended as a routine tool for assessment of bone resorption.Brought to you by | University of Arizona Authenticated Download Date | 7/8/15 5:47 AM

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Monitoring of osteoblast activity with an immunoradiometric assay for determination of bone alkaline phosphatase mass concentration in patients receiving renal transplants

Cited by 23 publications

References 9 publications

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

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

Bone mineral density after allogeneic bone marrow transplantation

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