ABSTRACT
UNLABELLED: Triple A syndrome (alacrima, achalasia, adrenal failure, progressive neurodegenerative disease) is caused by mutations in the AAAS gene which encodes the protein alacrima achalasia adrenal insufficiency neurologic disorder (ALADIN). Our investigation suggests that low bone mineral density (BMD) for age/osteoporosis could be a common but overlooked symptom of unexplained etiology in this rare multisystemic disease. INTRODUCTION: The purpose of this study is to evaluate incidence and etiology of BMD for age/osteoporosis, a possibly overlooked symptom in triple A syndrome. METHODS: Dual-energy X-ray absorptiometry (DXA) of the femoral neck, total hip, lumbar spine, and radius, bone turnover markers, minerals, total alkaline phosphatase (ALP), 25-hydroxy vitamin D (25-OHD), 1,25-dihydroxy vitamin D (1,25-OH2D), intact parathyroid hormone (PTH), and adrenal androgens (dehydroepiandrosterone sulfate (DHEAS) and androstenedione) were measured in five male and four female patients. RESULTS: At time of diagnosis, low BMD for age was suspected on X-ray in seven of nine patients aged 2-11 years (not performed in two patients); normal levels of minerals and ALP were found in nine patients and low levels of adrenal androgens in eight patients (not measured in one patient). Reevaluation 5-35 years after introduction of 12 mg/m(2)/day hydrocortisone showed low BMD for age in two children, osteopenia in one, and osteoporosis in six adults. Normal levels of minerals, ALP, PTH, 1,25-OH2D, procollagen type 1, crosslaps, and osteocalcin were found in all patients. Low levels of adrenal androgens were found in all and 25OHD deficiency in six patients. Body mass index was <25 % for age and sex in eight of nine patients. CONCLUSION: Low BMD for age/osteoporosis in our patients probably is not a result of glucocorticoid therapy but could be the consequence of low level of adrenal androgens, neurological impairment causing physical inactivity, inadequate sun exposure, and protein malnutrition secondary to achalasia. Considering ubiquitous ALADIN expression, low BMD/osteoporosis may be a primary phenotypic feature of the disease. Besides optimizing glucocorticoid dose, physical activity, adequate sun exposure, appropriate nutrition, and vitamin D supplementation, therapy with DHEA should be considered.
Subject(s)
Adrenal Insufficiency/complications , Esophageal Achalasia/complications , Osteoporosis/etiology , Absorptiometry, Photon/methods , Adrenal Insufficiency/physiopathology , Androgens/blood , Bone Density/physiology , Child , Child, Preschool , Esophageal Achalasia/physiopathology , Female , Follow-Up Studies , Humans , Male , Osteoporosis/diagnosis , Osteoporosis/physiopathologyABSTRACT
Neurotrophic effects of the growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin on the central nervous system have become more apparent in the past decade. In this study, we measured serum and cerebrospinal fluid (CSF) concentrations of GH, IGF-1 and insulin in 35 patients with motor neuron disease (MND) [24 patients with definite amyotrophic lateral sclerosis (ALS) and 11 patients with progressive bulbar palsy] and in 40 healthy controls. Levels of serum concentrations of GH and IGF-1 did not significantly differ between the MND patient group and the healthy controls, while the level of insulin was significantly decreased (P = 0.0033) in the MND patient group. However, levels of all three examined parameters in CSF were significantly lower in the MND group than in the healthy controls with the statistical significance for IGF-1 and insulin of P < 0.001. This finding has not been reported previously, and further investigations into its association with ALS should establish whether it can be used as an early marker of the disease, or whether it merely represents a consequence of ALS development.
Subject(s)
Growth Hormone/cerebrospinal fluid , Insulin-Like Growth Factor I/cerebrospinal fluid , Insulin/cerebrospinal fluid , Motor Neuron Disease/blood , Motor Neuron Disease/cerebrospinal fluid , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Growth Hormone/blood , Humans , Insulin/blood , ROC Curve , Reference Values , Sensitivity and SpecificityABSTRACT
The CYP21A2 mutations that are in linkage disequilibrium with particular HLA-A, -B, -DRB1 alleles/haplotypes, cause deficiency of the 21-hydroxylase enzyme (21-OHD) and account for the majority of congenital adrenal hyperplasia (CAH) cases. The aim of this study was to investigate those associations with the p.V282L mutation linked to the non-classical (NC) form of CAH among Croatians. The study included parents of patients with the NC form of CAH, positive for the p.V282L mutation (N = 55) and cadaveric donor samples (N = 231). All subjects were HLA-A, -B, and -DRB1 typed and tested for the presence of the p.V282L mutation. Among parents of patients, 92.73% of subjects were positive for the B*14:02 allele and almost half of them carried the HLA-A*33:01-B*14:02-DRB1*01:02 haplotype. Among cadaveric samples 77 out of 96 subjects positive for the B*14:02 allele had the p.V282L mutation. Among them, 37 were positive for the HLA-A*33:01-B*14:02-DRB1*01:02 haplotype, 23 had the HLA-A*33:01-B*14:02-DRB1*03:01 haplotype, 8 had the B*14:02-DRB1*01:02 combination and 5 were carrying the HLA-A*68:02-B*14:02-DRB1*13:03 haplotype. Only 4 of these subjects were positive for the B*14:02 allele. HLA-B*14:02 was the only single allele with association that reached statistically significant P value (RR = 12.00; P = 0.0024). Haplotypes B*14:02-DRB1*01:02 (P < 0.001) and HLA-A*68:02-B*14:02-DRB1*13:03 (P < 0.001) as well as HLA-A*33:01-B*14:02-DRB1*01:02 and HLA-A*33:01-B*14:02-DRB1*03:01 showed high relative risks (RR = 45.00, RR = 41.63 and RR = 36.96, respectively). Our data support the previously documented association of the HLA-A*33:01-B*14:02-DRB1*01:02 haplotype with the p.V282L mutation, but also point out a high frequency of the p.V282L mutation among Croatians with HLA-A*33:01-B*14:02-DRB1*03:01 and HLA-A*68:02-B*14:02-DRB1*13:03 haplotypes.
Subject(s)
Adrenal Hyperplasia, Congenital/genetics , Alleles , HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-DRB1 Chains/genetics , Mutation , Steroid 21-Hydroxylase/genetics , Adrenal Hyperplasia, Congenital/epidemiology , Adrenal Hyperplasia, Congenital/immunology , Adrenal Hyperplasia, Congenital/pathology , Adult , Amino Acid Substitution , Croatia/epidemiology , Female , Gene Frequency , Genetic Predisposition to Disease , HLA-A Antigens/immunology , HLA-B Antigens/immunology , HLA-DRB1 Chains/immunology , Haplotypes , Histocompatibility Testing , Humans , Linkage Disequilibrium , Male , Steroid 21-Hydroxylase/immunologyABSTRACT
Estrogen is essential for the development and maintenance of optimal bone mass in women and men, and acts through activation of estrogen receptors (ER). We have examined the pathways of estrogen action on the skeleton by seeking to localize the "classical" estrogen receptor, ER alpha, to particular cells to test the hypotheses that 1) estrogen directly influences growth plate chondrocytes; and 2) estrogen has a principal action on bone tissue via osteoblasts. ER alpha messenger ribonucleic acid (mRNA) was localized by in situ hybridization in human specimens from five males (11-15 yr old), two females (9 and 11 yr old), and three growing rabbits. In all of the human material examined, ER alpha mRNA was consistently identified in chondrocytes. In all of the rabbit tissue studied, ER alpha mRNA was localized in chondrocytes of the growth plate and the subarticular epiphyseal growth center. ER alpha mRNA signals were readily observed in both active osteoblasts and lining cells on trabecular surfaces of all samples. No clear evidence of positive staining was detectable in osteoclasts or osteocytes in either species. The distribution of ER alpha mRNA coincided with immunolocalization of the ER protein in the human specimens. These data suggest a direct action of estrogen on growth plate chondrocytes that may affect longitudinal growth and subsequent fusion of the growth plate and also on osteoblasts to affect bone formation at trabecular sites.
Subject(s)
Bone and Bones/chemistry , Receptors, Estrogen/analysis , Adolescent , Animals , Child , Estrogen Receptor alpha , Female , Humans , Immunohistochemistry , In Situ Hybridization , Male , Rabbits , Species SpecificityABSTRACT
Androgens have important effects on the human skeleton, and deficiency has been associated with bone loss in both males and females. The skeletal actions of androgens may be mediated directly via the androgen receptor (AR) or indirectly via the estrogen receptor after aromatization to estrogens. The presence of androgen receptors has been demonstrated in bone cells and chondrocytes in vitro, but their presence in human bone in situ has not been reported. In order to provide further evidence for a direct action of androgens on bone via androgen receptors, we have used specific monoclonal antibodies to investigate the expression of human AR in normal developing and osteophytic bone of both sexes. In the growth plates from the developing bone, androgen receptors were predominantly expressed in hypertrophic chondrocytes and in osteoblasts at sites of bone formation. They were also observed in osteocytes in the bone, and in mononuclear cells and endothelial cells of blood vessels within the bone marrow. In the osteophytes, androgen receptors were widely distributed at sites of endochondral ossification in proliferating, mature, and hypertrophic chondrocytes and at sites of bone remodeling in osteoblasts. They were also expressed in osteocytes and mononuclear cells within the bone marrow. The pattern and number of cells expressing the receptor was similar in both sexes. Our results show for the first time the presence and distribution of androgen receptors in normal developing human and osteophytic bone in situ and further provide evidence for a direct action of androgens on bone and cartilage cells.
Subject(s)
Bone and Bones/metabolism , Receptors, Androgen/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adolescent , Bone Development/physiology , Bone Remodeling/physiology , Bone and Bones/cytology , Child , Female , Growth Plate/cytology , Growth Plate/metabolism , Humans , Male , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Tissue DistributionABSTRACT
Glucocorticoids have well-documented effects on the skeleton, although their mechanism of action is still poorly understood. The actions of glucocorticoids on bone cells are mediated, in part, directly via specific receptors. The presence of these receptors has been demonstrated in both rodent and human osteoblastic cells in vitro, but their presence in human bone in vivo has not been reported. In this study, we have used specific affinity purified polyclonal antibodies to the functional glucocorticoid receptor alpha (GRalpha) to investigate its expression in both developing and adult human bone using sections of neonatal rib, calvarial, and vertebral bones, tibial growth plates from adolescents, and iliac crest biopsies from adults who were to undergo liver transplantation. In the tibial growth plates, GRalpha was predominantly expressed in the hypertrophic chondrocytes within the cartilage. In the primary spongiosa, the receptor was highly expressed by osteoblasts at sites of bone modeling. Within the bone marrow, receptors were also detected in mononuclear cells and in endothelial cells of blood vessels. In the neonatal rib and vertebrae, GRalpha was widely distributed at sites of endochondral bone formation in resting, proliferating, mature, and hypertrophic chondrocytes. They were also highly expressed in osteoblasts at sites of bone modeling. At sites of intramembranous ossification in neonatal calvarial bone and rib periosteum, GRa was widely expressed in cells within the fibrous tissue and in osteoblasts at both the bone-forming surface and at modeling sites. In the iliac crests from adults, GRalpha was predominantly expressed in osteocytes. The receptors were not detected in osteoclasts. Our results show for the first time the presence of the functional GRalpha in human bone in situ and suggest that the actions of glucocorticoids on bone may be mediated, in part, directly via the GR at different stages of life. The absence of receptor expression in osteoclasts also suggests that the effects of glucocorticoids on bone resorption may be mediated indirectly.
Subject(s)
Bone and Bones/metabolism , Receptors, Glucocorticoid/metabolism , Adolescent , Adult , Bone Remodeling , Cartilage/cytology , Cartilage/metabolism , Child , Chondrocytes/metabolism , Female , Growth Plate/cytology , Growth Plate/metabolism , Humans , Ilium/metabolism , Infant, Newborn , Male , Osteoblasts/metabolism , Protein Isoforms/metabolism , Ribs/metabolism , Spine/metabolism , Tibia/metabolism , Tissue DistributionABSTRACT
Impairment of bone remodelling due to chronic renal failure persists even after successful kidney transplantation. Bone turnover was assessed in 22 kidney transplant recipients by measurement of serum bone markers: total (tALP) and bone alkaline phosphatase (bALP), osteocalcin (OC), procollagen I C-terminal propeptide (PICP), collagen I C-terminal telopeptide (ICTP), and iPTH. The patients were on dialysis 56.6 +/- 43.1 months before transplantation (mean +/- SD) and 34.2 +/- 23.0 months had elapsed after transplantation. The bone markers were within the reference range in 23% of patients for iPTH, 73% for tALP and 82% for bALP, 41% for OC, 73% for PICP and 50% for ICTP. A positive correlation was found between dialysis duration and ICTP, and iPTH and bone formation markers (OC, bALP). The obtained results indicate that bone turnover was increased after kidney transplantation, with prevailing bone resorption, which seems to be influenced by dialysis duration.
Subject(s)
Bone Remodeling/physiology , Chronic Kidney Disease-Mineral and Bone Disorder/enzymology , Kidney Failure, Chronic/surgery , Kidney Transplantation/physiology , Adult , Alkaline Phosphatase/blood , Chronic Kidney Disease-Mineral and Bone Disorder/diagnosis , Collagen/blood , Collagen Type I , Female , Follow-Up Studies , Humans , Kidney Failure, Chronic/enzymology , Kidney Function Tests , Male , Middle Aged , Osteocalcin/blood , Parathyroid Hormone/blood , Peptide Fragments/blood , Peptides/blood , Procollagen/blood , Renal DialysisABSTRACT
The purpose of our study was to evaluate the effects of orally administered combined sequential estradiol (2 mg 17 beta estradiol) with progestin (1 mg norethisteron acetate) daily during ( +/- SD) 15.34 +/- 13.89 months on bone markers in perimenopausal cigarette smoking women. The control group consisted of cigarette smoking perimenopausal women without hormone replacement therapy (HRT). The following biochemical bone markers were analyzed in hormone replacement users (N = 35) and non-users (N = 28): serum total calcium (Ca), total alkaline phosphatase (ALP), procollagen I C-terminal propeptide (PICP), cros-linked carboxyterminal collagen I telopeptide (ICTP) and osteocalcin (OC). When we compared the results of bone markers in the cigarette smoking current users and non cigarette smoking non-users, we found statistically significant lower levels of bone formation markers, ALP and OC, and lower level of bone resorption marker; ICTP in users than in non-users. In perimenopausal cigarette smoking women on HRT lower levels of new biological markers reflected less intensive bone remodelling and probable decrease in bone loss than in non-users. These results indicate that the measurement of biological bone markers are useful to identify risk women for osteoporosis who may have special benefit from the treatment with hormone replacement therapy, even when they smoke.
Subject(s)
Biomarkers/blood , Estrogen Replacement Therapy , Osteoporosis, Postmenopausal/diagnosis , Smoking/adverse effects , Alkaline Phosphatase/blood , Calcium/blood , Collagen/analysis , Collagen Type I , Estradiol/administration & dosage , Female , Humans , Middle Aged , Norethindrone/administration & dosage , Norethindrone/analogs & derivatives , Norethindrone Acetate , Osteocalcin/blood , Osteoporosis, Postmenopausal/prevention & control , Peptide Fragments/blood , Peptides/analysis , Procollagen/bloodABSTRACT
Osteocalcin concentrations were measured in 40 healthy males and 60 healthy females aged 21-90 years by a commercial RIA kit. No significant difference between sexes was found for osteocalcin, and a negative and exponential regression with age existed only for females. In comparison to reference values of other investigators, higher osteocalcin concentrations were observed and considered consequential to sample selection and wide age range. Validity of the established reference range (1-18 ng/mL) was confirmed by measuring osteocalcin in patients with different bone metabolism disorders.
Subject(s)
Osteocalcin/blood , Adult , Aged , Aged, 80 and over , Croatia , Female , Humans , Male , Middle Aged , Reference ValuesABSTRACT
Biochemical changes related to skeletal turnover in puberty were investigated in a sample of 67 girls aged 8-14 years. The following biochemical parameters were measured in serum: total calcium, phosphate, magnesium, total alkaline phosphatase, osteocalcin, and calcium and hydroxyproline in the second morning urine. Thirty-five premenarchal girls (8-11 years) had significantly lower serum calcium, and higher alkaline phosphatase and phosphate than those menstruating regularly (N = 32, 12-14 years). A statistically significant negative correlation of serum parameters and age was found for phosphate and alkaline phosphatase in all subjects, and for calcium and magnesium only in the premenarchal girls. These results indicated the more intensive processes of skeletal metabolism occurring in prepubertal age and early puberty to reflect in basic biochemical parameters of calcium and bone metabolism. Analysis of correlation between biochemical parameters showed alkaline phosphatase and phosphate to correlate positively with hydroxyproline excretion and negatively with urinary calcium in all subjects. In the subjects after menarche, osteocalcin correlated with alkaline phosphatase and phosphate. Thus, biochemical parameters indirectly reflected physiologic changes occurring with bone turnover in puberty. Variations in bone turnover during puberty, including a more pronounced bone formation during prepubertal or early stages, can be indirectly observed through biochemical parameters related to calcium and bone metabolism. Investigations of skeletal growth and puberty would benefit from specific markers of bone remodeling and "basic" biochemical parameters, as it might disclose subtle metabolic relationships.
Subject(s)
Bone Remodeling , Bone and Bones/metabolism , Calcium/metabolism , Puberty/metabolism , Adolescent , Alkaline Phosphatase/blood , Child , Female , Humans , Phosphates/bloodABSTRACT
The aim of this paper was to present and describe standardized terminology used in histologic and histomorphometric analysis of bone tissue. Bone tissue is characterized by specific activities which are the result of cell function throughout life. Histologic analysis of bone tissue specimen provides an insight in the features and quality of cellular activities. Histomorphometry is direct measurement and calculation of many parameters which permits quantification of characteristics and dynamics of particular bone tissue function. This method may be applied in diagnostics and monitoring of therapy effects in different metabolic bone disorders.
Subject(s)
Bone and Bones/anatomy & histology , Terminology as Topic , Bone and Bones/pathology , Histology , Humans , Pathology, ClinicalABSTRACT
A 41-year old female patient with metabolic bone disease is presented. The disease was caused by malabsorption which developed as a result of gluten induced enteropathy. The diagnosis was confirmed by histological finding of the small intestine mucosa and bones. Following gluten-free diet, calcitriol and calcium tablets, the patient started to move independently and the bone mineralisation improved.
Subject(s)
Celiac Disease/complications , Osteomalacia/etiology , Adult , Biopsy , Bone and Bones/pathology , Celiac Disease/diagnosis , Female , Fractures, Spontaneous/diagnostic imaging , Fractures, Spontaneous/etiology , Humans , Intestinal Mucosa/pathology , Osteomalacia/diagnosis , RadiographyABSTRACT
The results of measurement of bone mass in three areas (lumbar spine, femoral neck and radius) where osteoporotic fractures most commonly occur are presented. The sample of 103 women was divided into three groups: premenopausal, early menopausal (up to 5 years of menopause) and late menopausal (more than 5 years of menopause). Both menopausal groups were additionally divided in two subgroups regarding the previous fractures. A statistically significant difference (p < 0.01) was found between bone mineral density (lumbar spine, femoral neck) and bone mineral content (radius) among all the groups. No difference was established for bone mass between postmenopausal women with and without fractures (> 0.05) by using the Kruskal-Wallis analysis of variance. A significant negative correlation (p < 0.01) was found between bone mass in all three tested regions on one side vs age of women as well as the period of menopause on the other. These results indicate that bone mass is significantly decreased in postmenopausal women. Therefore, the authors recommend densitometry to be employed in all postmenopausal women.
Subject(s)
Aging/metabolism , Bone Density , Menopause/metabolism , Adult , Croatia , Female , Fractures, Bone/complications , Humans , Middle Aged , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/diagnosis , Urban HealthSubject(s)
Calcifediol/blood , Adolescent , Adult , Female , Humans , Male , Middle Aged , Reference Values , SeasonsABSTRACT
The aim of this study was to investigate the relationship between interleukin 6 (IL-6), transforming growth factor (TGF)-beta 1, IL-6 soluble receptors, and biochemical parameters of bone turnover after kidney transplantation. Of 64 patients enrolled in the study, 19 received the kidney transplant 2 to 12 months before the study, and 45 within the previous 15 to 175 months. We measured IL-6, TGF-beta 1, intact parathyroid hormone (PTH) bone alkaline phosphatase (BALP), osteocalcin (OC), and procollagen type I propeptide (P1CP) concentrations in the serum, and deoxypyridinoline crosslinks (DPD) in the urine of the patients. In 16 patients in the first posttransplantation year, the concentrations of IL-6 (P = 0.02), TGF-beta 1 (P = 0.01), BALP (P = 0.0002), OC (P = 0.001), and DPD (P = 0.01) were significantly higher than in patients with longer posttranslation period. Statistically significant negative correlation was found between post-transplantation time and IL-6 (P = 0.04), BALP (P = 0.003), OC (P = 0.0009), P1CP (P = 0.03), and DPD (P = 0.01) concentrations. Repeated measurements of the investigated parameters in the first post-transplantation year showed a significant decrease only in TGF-beta I level. In all patients, IL-6 correlated positively with PTH (P = 0.0009) and DPD (P = 0.03), and IL-6 soluble receptor (IL-6 sR) with DPD (P = 0.03). A decrease in IL-6 and TGF-beta 1 concentrations that paralleled the decrease in bone turnover markers in the posttransplantation period indicated that IL-6 and TGF-beta 1 were probably involved in the bone turnover after kidney transplantation.
Subject(s)
Biomarkers/analysis , Bone Resorption/blood , Bone and Bones/metabolism , Interleukin-6/blood , Kidney Transplantation , Transforming Growth Factor beta/blood , Adolescent , Adult , Aged , Amino Acids/urine , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Postoperative Period , Transforming Growth Factor beta1ABSTRACT
Granulocyte/macrophage (GM), mixed colony and erythroid burst forming unit assays were performed in 9 post-transplant erythrocytosis (PTE) patients, 18 non-PTE kidney transplant recipients and 12 healthy volunteers. The number of GM precursors was lower in PTE patients than in normal subjects. This indicates that hematopoietic stem cell potential is not altered in PTE.
Subject(s)
Hematopoietic Stem Cells/cytology , Kidney Transplantation , Polycythemia/blood , Adult , Aged , Hematopoietic Stem Cells/physiology , Humans , Kidney Transplantation/adverse effects , Middle Aged , Polycythemia/pathology , Polycythemia/physiopathologyABSTRACT
AIM: Investigation of biochemical markers of bone metabolism in postmenopausal women with respect to hormone replacement therapy and smoking as a risk factor for osteoporosis. METHODS: Cross-sectional study of 107 healthy women receiving hormone replacement therapy (24 smokers) and 50 postmenopausal women (20 smokers) who served as a control group. The following biochemical parameters were analyzed in the serum: total calcium, inorganic phosphate, total alkaline phosphatase, procollagen I C-terminal propeptide (PICP), and cross-linked carboxyterminal collagen I telopeptide (ICTP). The effect of hormone replacement therapy and smoking on biochemical parameters was assessed by a two-way ANOVA. RESULTS: Significantly lower values of total calcium, inorganic phosphate, alkaline phosphatase, and ICTP in women on hormone replacement therapy compared to the control group indicated a higher rate of bone remodeling in the untreated postmenopause. In women smokers versus non-smokers, significantly lower values of only ICTP were found. Both hormone replacement therapy and smoking affected total calcium and phosphate levels, with the lowest values in non-smoking women on hormone replacement therapy and the highest in non-smoking control women. CONCLUSION: Reduction of bone turnover by hormone replacement therapy in menopause was indicated by lower values of biochemical parameters and collagen-related bone markers. Hormone replacement therapy is the prevalent factor affecting biochemical parameters, and probably conceals the possible effect of smoking.
Subject(s)
Bone and Bones/metabolism , Estrogen Replacement Therapy , Postmenopause/metabolism , Smoking/adverse effects , Cross-Sectional Studies , Female , Humans , Middle Aged , Osteoporosis, Postmenopausal/etiology , Osteoporosis, Postmenopausal/metabolism , Osteoporosis, Postmenopausal/prevention & control , Risk FactorsABSTRACT
We studied 18 adult male New Zealand rabbits with a critical right-sided ulnar defect of 15 mm. In six animals the defect was grafted with homologous compressed cancellous bone, in six animals with homologous compressed cancellous bone including 300 micro g bone morphogenetic protein (BMP)-7 and in six animals with homologous compressed cancellous bone including 0.5 ml autologous bone marrow. The defect was studied using radiographs every second week for 10 weeks. At the conclusion of the experiment the animals were killed and the defect studied by histology and histomorphometry. In all animals treated with the addition of autologous bone marrow and in five of six animals treated with the addition of BMP-7, the defect healed. There was no union in animals treated with homologous compressed cancellous bone without additive. The histological picture of the regenerated area was similar in the two experimental groups. Woven bone contained small marrow spaces with fibrous tissue and capillaries. The osteoid seams were on average greater in animals that received autologous bone marrow as compared to animals that received BMP-7.
Subject(s)
Bone Marrow Transplantation , Bone Morphogenetic Proteins/pharmacology , Bone Transplantation , Ulna/injuries , Wound Healing/drug effects , Animals , Bone Remodeling , Male , Rabbits , Radiography , Statistics, Nonparametric , Transplantation, Autologous , Transplantation, Homologous , Ulna/diagnostic imaging , Ulna/surgeryABSTRACT
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.