Determinants of Reduced Bone Mineral Density and Increased Bone Turnover after Kidney Transplantation: Cross-sectional Study

Similar documents
Long-term follow-up study on bone mineral density and fractures after simultaneous pancreas-kidney transplantation

Prevalence of Osteoporosis in Patients After Renal Transplantation: Results from a Single Center

Clinician s Guide to Prevention and Treatment of Osteoporosis

PART FOUR. Metabolism and Nutrition

Posttransplant Bone Disease. Budapest 2007

Ca, Mg metabolism, bone diseases. Tamás Kőszegi Pécs University, Department of Laboratory Medicine Pécs, Hungary

Bone and Mineral. Comprehensive Menu for the Management of Bone and Mineral Related Diseases

Chapter 5: Evaluation and treatment of kidney transplant bone disease Kidney International (2009) 76 (Suppl 113), S100 S110; doi: /ki.2009.

Bone Disease after Kidney Transplantation

Forteo (teriparatide) Prior Authorization Program Summary

Management of mineral and bone disorders in renal transplant recipients

Elecsys bone marker panel. Optimal patient management starts in the laboratory

Calcium Nephrolithiasis and Bone Health. Noah S. Schenkman, MD

The Skeletal Response to Aging: There s No Bones About It!

Comparison of the Humoral Markers of Bone Turnover and Bone Mineral Density in Patients on Haemodialysis and Continuous Ambulatory Peritoneal Dialysis

Correlation between Thyroid Function and Bone Mineral Density in Elderly People

Persistent post transplant hyperparathyroidism. Shiva Seyrafian IUMS-97/10/18-8/1/2019

Improvement of adynamic bone disease after renal transplantation

Southern Derbyshire Shared Care Pathology Guidelines. Primary Hyperparathyroidism

S.L. Ferrari*, L.P. Nicod**, J. Hamacher**, A. Spiliopoulos +, D.O. Slosman ++, T. Rochat**, J-P. Bonjour*, R. Rizzoli*

KIDNEY TRANSPLANTATION is the optimal

Prophylactic treatment for osteoporosis: Student EBM Presentation

Pharmacy Management Drug Policy

Bone Turnover Markers for the Diagnosis and Management of Osteoporosis and Diseases Associated with High Bone Turnover. Original Policy Date

Skeletal Manifestations

9/26/2016. The Impact of Dietary Protein on the Musculoskeletal System. Research in dietary protein, musculoskeletal health and calcium economy

Additional Research is Needed to Determine the Effects of Soy Protein on Calcium Binding and Absorption NDFS 435 3/26/2015. Dr.

Product: Denosumab (AMG 162) Clinical Study Report: month Primary Analysis Date: 21 November 2016 Page 1

INTRODUCTION. Original Article

Study of secondary causes of male osteoporosis

chapter 1 & 2009 KDIGO

Original Article Fasting Plasma Glucose Levels Are Related to Bone Mineral Density in Postmenopausal Women with Primary Hyperparathyroidism

Bone Mass Measurement BONE MASS MEASUREMENT HS-042. Policy Number: HS-042. Original Effective Date: 8/25/2008

Product: Cinacalcet HCl Observational Research Clinical Study Report: Date: 23 July 2012 Page Page 2 2 of of 1203

Osteoporosis. When we talk about osteoporosis, we have to be familiar with the constituents of bone and what it is formed of.

Index. B BMC. See Bone mineral content BMD. See Bone mineral density Bone anabolic impact, Bone mass acquisition

Page: 1 of 12. Bone Turnover Markers for Diagnosis and Management of Osteoporosis and Diseases Associated With High Bone Turnover

Breast Cancer and Bone Loss. One in seven women will develop breast cancer during a lifetime

Comparison of Alendronate and Pamidronate on Bone Loss in Kidney Transplant Patients for the First 6 Months of

Fragile Bones and how to recognise them. Rod Hughes Consultant physician and rheumatologist St Peter s hospital Chertsey

Annie WC Kung, Keith DK Luk, LW Chu, and Peter KY Chiu

A Case of Cushing Syndrome Diagnosed by Recurrent Pathologic Fractures in a Young Woman

COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) GUIDELINE ON THE EVALUATION OF NEW MEDICINAL PRODUCTS IN THE TREATMENT OF PRIMARY OSTEOPOROSIS

Pharmacy Management Drug Policy

Metabolic Bone Disease Related to Chronic Kidney Disease

Clinical Study Effect of Zoledronic Acid on Bone Mineral Density in Men with Prostate Cancer Receiving Gonadotropin-Releasing Hormone Analog

Bone Metabolism in Postmenopausal Women Influenced by the Metabolic Syndrome

Chapter 39: Exercise prescription in those with osteoporosis

Osteoporosis/Fracture Prevention

ORIGINAL INVESTIGATION

DXA When to order? How to interpret? Dr Nikhil Tandon Department of Endocrinology and Metabolism All India Institute of Medical Sciences New Delhi

Patients who have stage 5 chronic kidney disease (CKD)

Efficacy of risedronate in men with primary and secondary osteoporosis: results of a 1-year study

Interpreting DEXA Scan and. the New Fracture Risk. Assessment. Algorithm

CKD-MBD CKD mineral bone disorder

Page: 1 of 12. Bone Turnover Markers for Diagnosis and Management of Osteoporosis and Diseases Associated With High Bone Turnover

Bone strength is proportional to bone mass, measured with DXA. Bone turnover markers indicate the status of bone quality.

Osteoporosis. Overview

Diagnosis and Treatment of Osteoporosis. Department of Endocrinology and Metabolism Ajou University School of Medicine.

ORIGINAL INVESTIGATION. Effects of Hormone Replacement Therapy on Bone Mineral Density in Postmenopausal Women

Alendronate sodium in the management of osteoporosis

A Novel Murine Model Of Adynamic Bone Disease (ABD)

BMD: A Continuum of Risk WHO Bone Density Criteria

Pharmacy Management Drug Policy

Sponsor / Company: sanofi-aventis and Proctor & Gamble Drug substance(s): Risedronate (HMR4003)

Kobe University Repository : Kernel

NEW DEVELOPMENTS IN OSTEOPOROSIS: SCREENING, PREVENTION AND TREATMENT

Building Bone Density-Research Issues

Pathophysiology of Postmenopausal & Glucocorticoid Induced Osteoporosis. March 15, 2016 Bone ECHO Kate T Queen, MD

Hyperparathyroidism: Operative Considerations. Financial Disclosures: None. Hyperparathyroidism. Hyperparathyroidism 11/10/2012

DM and Osteoporosis. Why is it important?

Decreased bone area, bone mineral content, formative markers, and increased bone resorptive markers in endogenous Cushing s syndrome

Do We Do Too Many Parathyroidectomies in Dialysis? Sagar Nigwekar MD, MMSc Massachusetts General Hospital

OSTEOPOROSIS, OSTEOARTHRITIS AND MUSKOSKELETAL DISEASE: A CALL FOR ACTION

Use of DXA / Bone Density in the Care of Your Patients. Brenda Lee Holbert, M.D. Associate Professor Senior Staff Radiologist

Effects of Anti RANK ligand Denosumab on Beta Thalassemia induced osteoporosis

8/6/2018. Glucocorticoid induced osteoporosis: overlooked and undertreated? Disclosure. Objectives. Overview

BONE FLUORIDE IN PROXIMAL FEMUR FRACTURES

Osteoporosis. Current Trend in Osteoporosis Management for Elderly in HK- Medical Perspective. Old Definition of Osteoporosis

Osteoporosis. Treatment of a Silently Developing Disease

Glycaemic control and serum intact parathyroid hormone levels in diabetic patients on haemodialysis therapy

PART FOUR. Metabolism and Nutrition

Effects of Diabetes Mellitus, Age, and Duration of Dialysis on Parathormone in Chronic Hemodialysis Patients. Hamid Nasri 1, Soleiman Kheiri 2

Osteoporosis. Open Access. John A. Kanis. Diseases, University of Sheffield, UK

HRT and Risedronate Combined Anabolic and Antiresorptive Therapy

Guideline for the investigation and management of osteoporosis. for hospitals and General Practice

Journal of Hainan Medical University. Wei Li. 1. Introduction. 28 Journal of Hainan Medical University 2016; 22(21): 28-32

The Role of the Laboratory in Metabolic Bone Disease

nogg Guideline for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK

Download slides:

CKD Mineral and Bone Disorder Management in Kidney Transplant Recipients

Changes in serum osteocalcin levels in the follow-up of kidney transplantation

POLICY PRODUCT VARIATIONS DESCRIPTION/BACKGROUND RATIONALE DEFINITIONS BENEFIT VARIATIONS DISCLAIMER CODING INFORMATION REFERENCES POLICY HISTORY

Nutritional Aspects of Osteoporosis Care and Treatment Cynthia Smith, FNP-BC, RN, MSN, CCD Pars Osteoporosis Clinic, Belpre, Ohio

European Journal of Endocrinology (1997) ISSN

hypercalcemia of malignancy hyperparathyroidism PHPT the most common cause of hypercalcemia in the outpatient setting the second most common cause

OSTEOPOROSIS IN MEN. Nelson B. Watts, MD OSTEOPOROSIS AND BONE HEALTH SERVICES CINCINNATI, OHIO

Bone mineral density, collagen type 1 a 1 genotypes and bone turnover in premenopausal women with diabetes mellitus

Vol. 19, Bulletin No. 108 August-September 2012 Also in the Bulletin: Denosumab 120mg for Bone Metastases

Transcription:

398 41(4):396-400,2000 CLINICAL SCIENCES Determinants of Reduced Bone Mineral Density and Increased Bone Turnover after Kidney Transplantation: Cross-sectional Study Vesna Kušec, Ru ica Šmalcelj 1, Selma Cvijetiæ 2, Berislav Ro man 3, Franjo Škreb 3 Clinical Institute of Laboratory Diagnosis and 1 Dialysis Unit of the Department of Urology, Zagreb University Hospital Center; 2 Institute of Medical Research and Occupational Health; and 3 Department of Nuclear Medicine, Dubrava University Hospital, Zagreb, Croatia Aim. To analyze bone metabolism and the risk factors of bone loss in kidney transplant recipients. Methods. The bone mineral density (BMD) of the lumbar spine, femoral neck, and radius was determined by dual-energy X-ray absorptiometry in 52 patients 8 days to 228 months after kidney transplantation. Total and bone alkaline phosphatase (BAP), osteocalcin, procollagen, type I collagen telopeptide, collagen cross links, calcium, intact parathyroid hormone (ipth), and creatinine were measured in all patients. Results. The BMD of the spine and femoral neck was reduced in 57%, and of the radius in 72% of the patients. Reduced BMD was associated with significantly increased levels of ipth, osteocalcin, and procollagen. Dialysis duration negatively correlated with the radius BMD in all patients and the femoral neck BMD in women. No relationship between BMD and length of post-transplantation time, age, cumulative steroid dose, or serum creatinine level was established. All biochemical parameters negatively correlated with the spine BMD, but not with the BMD of the femoral neck and radius. The correlation between BAP and telopeptide and length of post-transplantation time was also negative. No difference in the incidence of osteopenia was found between genders. Conclusion. Osteopenia/osteoporosis and increased bone turnover were present in more than a half of the kidney transplant recipients. Reduced BMD was associated with enhanced bone remodeling, primarily mediated by PTH hypersecretion. The length of post-transplantation period, cumulative steroid dose, gender, and age could not be identified as risk factors of reduced BMD. Key words: absorptiometry; bone density; creatinine; gender role; kidney transplantation; osteocalcin; osteoporosis; parathyroid hormones; photon; transplantation, renal End-stage renal failure and long-term dialysis treatment are well-recognized risk factors of developing mineral metabolism disorder and skeletal impairment, i.e., renal osteodystrophy (1,2). Major contributors to the development of this complex disorder are increased parathyroid secretion and decreased calcitriol synthesis (2-5). Successful kidney transplantation corrects many of the disturbances in calcium and phosphorus metabolism, and restores the production of biologically active vitamin D. Nonetheless, bone disorder may persist from the pre-transplantation period and after the transplantation can be further aggravated by corticosteroids and immunosuppressants (6). Thus, osteopenia and increased fracture risk are among the major complications of renal and other organ transplantations (5,7-13). Experience in treatment of postmenopausal osteoporosis and steroidinduced osteoporosis with bisphosphonates, sodium fluoride, calcitonin, calcium, vitamin D, and combination regimens (14-17) has recently been employed in ameliorating post-transplantation osteopenia. Many studies have been conducted with the aim of better understanding of different factors influencing bone mass and mineral metabolism. So far, steroids, both genders, dialysis duration, age, and hyperparathyroidism (15,18,19) have been recognized as having the most adverse effects upon the skeleton. Follow-up studies reported short-term variations of biochemical markers of bone metabolism within the first two post-transplantation years (20). However, this follow-up period may have been too short, as a resolution of hyperparathyroidism can take many years (2) and high bone turnover rate is directly related to the

399 increased secretion of parathyroid hormone. The cross-sectional studies on patients at different times after transplantation and/or dialysis offer grounds for assumptions on the dynamics of bone metabolism. Both longitudinal and cross-sectional studies on transplant recipients have shown advantages and disadvantages, which should be taken into account when evaluating the results. We analyzed bone metabolism in 52 kidney transplant recipients using dual-energy X-ray absorptiometry and biochemical markers of bone metabolism. The relevance of recognized risk factors was evaluated according to the bone status. Methods Patients Fifty-two patients (29 men, 23 women) with stable kidney graft function were included in this cross-sectional study. Average age (mean±sd) was 45.3±10.0 years, range 21-64 years. Twelve women had been in postmenopause for one year or more. Dialysis duration before transplantation was 62.6±49.7 months (range 2-216 months) and the length of post-transplantation period was 47.0±46.7 months (range 8 days to 228 months). No difference was found between men and women (t-test) in age, the length of post- -transplantation period, or duration of dialysis treatment. Mean serum creatinine at the time of the study was 124.3±31.9 mmol/l (range 68-199 mmol/l), which indicated a satisfactory graft function. For patients who had a rejection crisis, at least 3 months had lapsed before they were included in the study. Immunosuppressive therapy consisted of cyclosporine A, azathioprine, and prednisone in 37 patients, and of cyclosporine A and prednisone in 15 patients. Cumulative steroid dose was calculated and included in the statistical analysis (14,276±9,474 mg; range 470-34,962 mg). None of the patients received calcitriol or other treatment for osteopenia. Biochemical Measurements The serum for measuring biochemical parameters was obtained from the blood of the patients, after overnight fasting. If assays were not performed on the same day, serum was frozen (-20ºC), stored, and analyzed later. Markers of bone formation, i.e., products of osteoblast activity, such as bone alkaline phosphatase, osteocalcin, and procollagen (C-terminal propeptide type I procollagen) were measured, as well as telopeptide (C-terminal telopeptide type I collagen) and collagen cross-links (free deoxypyridinoline, free pyridinium cross-links), as products of the bone collagen breakdown. Serum levels of the following biochemical parameters were also determined (reference range): total calcium (2.14-2.53 mmol/l) by standard method, intact parathyroid hormone (ipth, 1-6 pmol/l) by IRMA kit (PTH intakt, IBL, Hamburg, Germany), total (<90 IU/L) and bone (<40 IU/L) alkaline phosphatase by kinetic method (Boehringer Mannheim, Mannheim, Germany), osteocalcin (<16 µg/l) by ELISA kit (Novocalcin, Metra Biosystems), procollagen (<76 µg/l) by ELISA (Prolagen C, Metra Biosystems), and telopeptide (<5 µg/l) by RIA kit (ICTP, Orion Diagnostica, Espoo, Finland). A sample of second morning void was used for the measurement of deoxypyridinoline (Pyrilinks-D; <9.5 nmol/mol creatinine) and pyridinium cross-links (Pyrilinks; <30 nmol/mol creatinine) by ELISA kits (Metra Biosystems). The full set of biochemical parameters was not available for each patient. Bone Mineral Density Bone mineral density was measured by dual-energy X-ray absorptiometry (Lunar DPX, Lunar Co., Madison, WI, USA) at the lumbar spine (L1-L4) and the femoral neck in all patients, and also at the distal third of the radius in 29 patients. It was not measured before kidney transplantation. For statistical analysis, bone mineral density (g/cm 2 )and T-scores (bone mineral density expressed as standard deviations of healthy young population) were used. Reduced bone mineral density was established if the T-score (standard deviation of bone mineral density values in the young normal European reference population supplied by the manufacturer) had been lower than -1, which was considered an indicator of osteopenia. Data Analysis The statistical analyses performed were descriptive statistics, correlation, t-test, and chi-square test, with p<0.05 as statistically significant. Results Bone mineral density in kidney transplant recipients was reduced (T-score lower than -1) in more than a half of the patients at all three analyzed sites (at the L1-L4 and femoral neck in 57%, and at the distal radius in 72% of patients). Femoral neck T-scores for both genders are presented in Figure 1. Descriptive statistics of the measured biochemical parameters in serum and the urine markers showed that intact parathyroid hormone (ipth), osteocalcin, and telopeptide levels were above the reference range in approximately 60% of the patients (Table 1). Other parameters were increased to a lesser extent. Analysis of biochemical parameters in patients with kidney transplant showed that patients with reduced bone mineral density had significantly higher ipth, osteocalcin, and procollagen than those with normal bone mineral density (Table 2). No difference between patients with reduced or normal bone mineral density was found with respect to age, post-transplantation period, dialysis duration, serum creatinine, or received cumulative dose of steroids. There was no correlation between the length of post-transplantation period and bone mineral density or T-scores at any of the three densitometry sites. Moreover, the number of patients with reduced bone mineral density was the same before and after 12 post-transplantation months, as shown by chi-square test (Table 3). This is in agreement with the result that showed the lack of correlation between bone mineral density and the length of post-transplantation period. Femoral neck T-score 2 1 0-1 -2-3 -4-5 -6-7 20 25 30 35 40 45 50 55 60 65 70 Age (years) Figure 1. Determinants of reduced bone mineral density and increased bone turnover after kidney transplantation. T-score for the femoral neck in men (black diamonds) and women (open circles) with kidney transplant according to age.

400 Table 1. Descriptive statistics of biochemical parameters in 52 kidney transplant recipients Variable (unit) Number of patients Mean ±SD % increase a Intact parathyroid 48 12.8±16.7 61 hormone (pmol/l) Total alkaline 47 78.8±45.8 22 phosphatase (IU/L) Bone alkaline 42 33.8±30.7 25 phosphatase (IU/L) Osteocalcin (µg/l) 34 23.7±17.9 61 Procollagen (µg/l) 43 110.6±40.0 5 Telopeptide (µg/l) 26 9.3±9.0 60 Deoxypyridinoline 27 6.6±4.2 11 (nmol/mol creatinine) Pyridinium cross-links 27 32.7±24.7 33 (nmol/mol creatinine) Total calcium (mmol/l) 51 2.5±0.2 25 a Percent of patients whose findings were above the reference range. Table 2. Biochemical parameters (mean±sd) in kidney transplant recipients with normal and reduced bone mineral density (BMD) Finding in patients with Biochemical parameter normal BMD reduced BMD (T>-1) a (T<-1) p Intact PTH 7.2±6.3 (21) b 17.2±20.7 (27) 0.039 Osteocalcin 16.5±9.9 (18) 31.9±21.5 (16) 0.010 Procollagen 89.9±22.7 (18) 125.6±43.3 (25) 0.002 a Standard deviation of bone mineral density values in the young and healthy European reference population. b Number of patients. Table 3. Number (%) of kidney transplant patients with reduced bone mineral density (T-score <-1) for the three measured sites in the post-transplantation periods less and more than 12 months Incidence of reduced bone mineral Measured site density at post-transplantation time <12 months >12 months p a L1-L4 7/11 (64) 21/40 (50) 0.758 Femoral neck 8/11 (73) 20/40 (50) 0.439 Radius 5/5 (100) 15/24 (63) 0.269 a Chi-square test. There was a significant negative correlation between the dialysis duration and the radius bone mineral density and T-score in all patients (r=-0.58, p<0.01, n=29, and r=-0.56, p<0.01, n=29, respectively), but only in women the dialysis duration correlated with the femoral neck bone mineral density (r=-0.44, p<0.05, n=23). There was no statistically significant correlation between bone mineral density and age, cumulative steroid dose, or serum creatinine. Correlations between biochemical parameters and bone mineral density were found negative (Table 4). All parameters were statistically significant for the L1-L4 site, but not for the femoral neck and the radius site. Correlations were statistically significant and negative between post-transplantation period and both bone alkaline phosphatase (r=-0.39, p<0.01, n=41) and telopeptide (r=-0.39, p<0.05, n=25). Theexpecteddifferenceinbonemineraldensity between genders, as tested by t-test, was statistically significant at all three sites (Table 5). But, as no overall difference in T-scores existed, women did not have significantly lower T-scores. However, the effect of the menopause was observed. Half of the women were postmenopausal and had significantly lower bone mineral density and T-score at the L1-L4 and the femoral neck than premenopausal women (Table 6). There was no difference in the radius bone mineral density and T-score. Discussion In this study, reduced bone mineral density was found in more than half of the patients, i.e., in 57% at the spine and the femoral neck, and in 72% at the distal radius. Our results are in agreement with other reports that also stressed the cortical bone loss in the radius as a predominant one (4,8,21,22). Parry et al (25) reported higher incidence of osteopenia/osteoporosis in the femoral neck, which contains more cortical bone than the spine. Excess of PTH, which often occurs during dialysis treatment of chronic kidney failure and in a considerable number of patients after kidney transplantation, is responsible for this salient cortical bone loss (3,4,19). Bone turnover was increased in 60% of patients included in this study, as assessed indirectly by biochemical markers of bone metabolism: intact parathyroid hormone, osteocalcin, and telopeptide. These three parameters are indicators of bone tissue activity (remodeling, formation, and resorption) and an evidence of high bone turnover rates. Increased levels of osteocalcin were also reported in 45% of pancreas-kidney transplant recipients, in whom they again correlated with ipth (8). In our previous study on bone markers in kidney transplant recipients, we reported positive relationships between ipth and biochemical markers of bone formation and resorption (24,25). Patients with reduced bone mineral density had significantly higher levels of ipth, osteocalcin, and procollagen when compared with those with normal bone mineral density. Other factors, such as age, the length of post-transplantation period, dialysis duration, serum creatinine, or the cumulative dose of received steroids, were ruled out as possible causes. Also, the lower the bone mineral density, the more active was bone remodeling. This calls attention to a subgroup of kidney transplant recipients who lose bone at high rate and are at particular risk of fracture (19). Parathyroid hormone most probably played a significant role in the accelerated bone loss (19,21),

401 Table 4. Correlations between the bone mineral density (spine, femoral neck, and radius) and biochemical parameters in kidney transplant recipients a Variable L1-L4 Femoral neck Radius r p n r p n r p n Intact parathyroid hormone -0.34 0.013 48-0.30 0.016 48-0.45 0.023 25 Total alkaline phosphatase -0.30 0.037 50-0.30 0.037 50 Bone alkaline phosphatase -0.32 0.037 42-0.32 0.037 42-0.48 0.015 24 Osteocalcin -0.40 0.019 34 Procollagen -0.40 0.009 43 Telopeptide -0.42 0.030 26 Deoxypyridinoline -0.41 0.031 27-0.46 0.013 27 Pyridinium cross-links -0.44 0.021 27-0.45 0.019 27 Total calcium -0.32 0.021 51 a Only statistically significant correlations between pairs of variables are presented. Table 5. Bone mineral density (BDM) and corresponding T-scores for the spine, femoral neck, and radius in men and women with a functional kidney graft (mean±sd, t-test) a Measured site Men p Women L1-L4 BMD 1.06±0.20 0.024 0.93±0.19 L1-L4 T-score -0.99±1.15 0.103-1.64±1.86 Femoral neck BMD 0.92±0.15 0.001 0.76±0.19 Femoral neck T-score -0.92±1.56 0.126-1.66±1.58 Radius BMD 0.66±0.08 0.012 0.56±0.09 Radius T-score -1.80±1.02 0.921-1.76±1.65 a Men n=29 for femoral and L1-L4 values, n=19 for radius values; women n=23 for femoral and L1-L4 values, n=10 for radius values. Table 6. Bone mineral density and T-scores (mean±sd) in premenopausal (n=11) and postmenopausal (n=12) women with a functional kidney graft (t-test) Measured Findings in site premenopause p postmenopause L1-L 41.02±0.17 0.025 0.84±0.17 L1-L4 T-score -0.94±1.80 0.036-2.31±1.00 Femoral neck 0.86±0.17 0.019 0.67±0.17 Femoral neck T-score -0.71±1.62 0.018-2.49±1.60 since its level was increased in the osteopenic/osteoporotic patients and negatively correlated with bone density at all three bone sites. Carlini et al (26) also reported on an inverse relationship between parathyroid hormone level and the spinal bone mineral density. The fact that all measured biochemical parameters were negatively correlated with the spinal bone mineral density, only some of them with the femoral neck bone mineral density, and ipth and bone alkaline phosphatase with the radius, indicated that the observed bone mineral density variance in the skeletal parts containing more trabecular bone was better accounted for by biochemical parameters, i.e., the increased bone turnover. This means that factors other than parathyroid hormone influenced the bone turnover and bone mineral density. The cumulative steroid dose could not be identified as one of them in this particular study group, as was also shown by Smets (8) for kidney-pancreas transplantation patients. Despite ample evidence that bone loss continues after transplantation, most rapidly in the first post-transplant year and thereafter it slows down (4,12,13), the decline in bone mineral density over post-transplantation time could not be proven by all investigators (8). We found no change in bone mineral density, T-scores, or incidence of reduced bone mineral density over post-transplantation time. This could have been a consequence and one of the drawbacks of a cross-sectional study, but employing T-scores and frequencies of osteopenia/osteoporosis in the analysis might have partly counteracted this if there had been a genuine trend of deterioration of bone mineral density over post-transplantation time. Slowing down of the bone turnover rate after transplantation was indicated by negative correlations of bone alkaline phosphatase and telopeptide over post-transplantation time. Return of ipth to normal levels or healing of renal osteodystrophy was reported to take many months, even years (4 and more) (2,15,26). Normalization of parathyroid secretion and, consequently, of bone remodeling could be responsible for prevention of further deterioration of the bone density (bone mineral density and T-scores) over time post-transplantation. Among factors influencing the skeletal status is the duration of dialysis treatment prior to transplantation (10,25). Its deleterious effect was associated with the radius bone mineral density and T-score in both genders and the femoral neck bone mineral density in women only. It can be assumed that the dialysis factor comprises the function of time, i.e., duration of chronic kidney failure, and parathyroid hypersecretion with its consequences upon bone tissue. Women had lower bone mineral density than men at all the three measured sites but were not more affected by bone loss, since the genders did not differ regarding T-scores. Julian et al (12) found no difference between men and women in bone loss at the spine and radius site, but Nisbeth et al (9) reported more fractures in women. In contrast, Cueto-Manzano et al (10) reported that male gender

402 was among the strongest predictive factors for low bone mass. Menopause also showed an adverse influence upon the female skeleton, with lower bone mineral density and T-scores for the spine and the femoral neck in postmenopausal women. In conclusion, the length of post-transplantation period, cumulative steriod dose, gender, and age could not be identified as risk factors for reduced bone mineral density in kidney transplant recipients. But the lower bone mineral density was associated with enhanced bone remodeling, primarily mediated by PTH hypersecretion. References 1 Hruska KA, Teitelbaum SL. Renal osteodystrophy. N Engl J Med 1995;333:166-73. 2 Parfitt AM. The hyperparathyroidism of chronic renal failure: a disorder of growth. Kidney Int 1997; 52:3-9. 3 Messa P, Sindici C, Cannella G, Miotti V, Risaliti A, Gropuzzo M, et al. Persistent secondary hyperparathyroidism after renal transplantation. Kidney Int 1998;54:1704-13. 4 Setterberg L, Sandberg J, Elinder CG, Nordenstrom J. Bone demineralisation after renal transplantation: contribution of secondary hyperparathyroidism manifested by hypercalcaemia. Nephrol Dial Transplant 1996;11:1825-8. 5 Parfitt AM. A structural approach to renal bone disease. J Bone Miner Res 1998;13:1213-20. 6 Massari PU. Disorders of bone and mineral metabolism after renal transplantation. Kidney Int 1997; 52:1412-21. 7 Coen G. Fracturing osteoporosis after kidney transplantation what are the options? Nephrol Dial Transplant 1996;11:567-9. 8 Smets YF, van der Pijl JW, de Fijter JW, Ringers J, Lemkes HH, Hamdy NA. Low bone mass and high incidence of fractures after successful simultaneous pancreas-kidney transplantation. Nephrol Dial Transplant 1998;13:1250-5. 9 Nisbeth U, Lindh E, Ljunghall S, Backman U, Fellstrom B. Increased fracture rate in diabetes mellitus and females after renal transplantation. Transplantation 1999;67:1218-22. 10 Cueto-Manzano AM, Konel S, Hutchison AJ, Crowley V, France MW, Freemont AJ, et al. Bone loss in long-term renal transplantation: histopathology and densitometry analysis. Kidney Int 1999;55: 2021-9. 11 Ramsey-Goldman R, Dunn JE, Dunlop DD, Stuart FP, Abecassis MM, Kaufman DB, et al. Increased risk of fracture in patients receiving solid organ transplants. J Bone Miner Res 1999;14:456-63. 12 Julian BA, Laskow DA, Dubowsky J, Dubowsky EV, Curtis JJ, Quarles LD. Rapid loss of vertebral mineral density after renal transplantation. N Engl J Med 1991;3225:544-50. 13 Horber FE, Casez JP, Steiger U, Czerniak A, Montandon A, Jaeger P. Changes in bone mass early after kidney transplantation. J Bone Miner Res 1994; 9:1-9. 14 Arlen DJ, Adachi JD. Are bisphosphonates useful in the management of corticosteroid induced osteoporosis in transplant patients? J Nephrol 1999;12:5-8. 15 Brown JH. Pre-transplant management: cardiovascular disease and bone disease. Nephrol Dial Transplant 1995;10 Suppl 1:14-19. 16 Grotz WH, Rump LC, Niessen A, Schmidt-Gayk H, Reichelt A, Kriste G, et al. Treatment of osteopenia and osteoporosis after kidney transplantation. Transplantation 1998;66:1004-8. 17 Jehle PM, Jehle DR, Mohan S, Keller F. Renal osteodystrophy: new insights in pathophysiology and treatment modalities with special emphasis on the insulin-like growth factor system. Nephron 1998;79: 249-64. 18 Reid IR. Glucocorticoid effects on bone. J Clin Endocrinol Metab 1998;83:1860-1. 19 Grotz WH, Mundinger FA, Rasenack J, Speidel L, Olschewski M, Exner VM, et al. Bone loss after kidney transplantation: a longitudinal study in 115 graft recipients. Nephrol Dial Transplant 1995; 10:2096-100. 20 Reinhardt W, Bartelworth H, Jockenhovel F, Schmidt-Gayk H, Witzke O, Wagner K, et al. Sequential changes of biochemical bone parameters after kidney transplantation. Nephrol Dial Transplant 1998; 13:436-42. 21 Grotz WH, Mundinger FA, Gugel B, Exner VM, Kirste G, Schollmeyer PJ. Bone mineral density after kidney transplantation. A cross-sectional study in 190 graft recipients up to 20 years after transplantation. Transplantation 1995;59:982-56. 22 Duan Y, De Luca V, Seeman E. Parathyroid hormone deficiency and excess: similar effects on trabecular bone but differing effects on cortical bone. J Clin Endocrinol Metab 1999;84:718-22. 23 Parry RG, Jackson J, Stevens JM, Higgins B, Altmann P. Long-term bone densitometry post-renal transplantation in patients treated with either cyclosporin or prednisolone [letter]. Nephrol Dial Transplant 1998;13:531-2. 24 Kušec V, Šmalcelj R, Glavaš-Boras S, Slavièek J. Disorder of bone metabolism after kidney transplantation assessment by bone markers. Period biol 2000; 102:55-8. 25 Šmalcelj, Kušec V, Z Puretiæ, Z Marekoviæ. Biochemical parameters of bone turnover in kidney transplant recipients. Wiener Klinische Wochenschrift 1998;110/9:326-30. 26 Carlini RG, Rojas E, Arminio A, Weisinger JR, Bellorin-Font E. What are the bone lesions in patients with more than four years of a functioning renal transplant? Nephrol Dial Transplant 1998;13 Suppl 3:103-4. Received: May 18, 2000 Accepted: August 25, 2000 Correspondence to: Vesna Kušec Clinical Institute of Laboratory Diagnosis Zagreb University Hospital Center Kišpatiæeva 12 10 000 Zagreb, Croatia rkusec@rudjer.irb.hr