Year: 2013
Type: dissertation
Study design: Observational Study
Abstract: Osteoporosis is the most common metabolic bone disease characterized by low bone mass and altered material properties.Compromised bone strength predisposes the individual to fractures.Dual-energy X-ray absorptiometry (DXA) is commonly used to measure bone mineral density (BMD).However, BMD accounts for only 60% of bone strength, i.e., changes in bone quality as well as density may increase the fracture risk.This study aimed to characterize bone quality in different cohorts of patients using bone histomorphometry, microcomputed tomography (micro-CT), and Fourier transform infrared spectroscopic imaging (FTIRI).Iliac crest biopsies were collected from different cohorts: i) patients with osteoporosis (OP, n=15) or renal osteodystrophy (ROD, n=11) or healthy controls (n=10), ii) patients with atypical femoral fractures (AFFs, n=4), ii) children with suspected primary osteoporosis (n=24), and iv) children after solid organ transplantation (n=19).Bone histomorphometry was performed to examine bone remodeling and turnover, micro-CT to study bone microarchitecture, and FTIRI to study bone composition.The results were correlated with fracture history, clinical characteristics, densitometry, and biochemistry when appropriate.The reproducibility of bone histomorphometry and the agreement between bone histomorphometry and micro-CT were studied.Further, the incidence of AFFs was investigated within our hospital catchment area.Repeated measurements for structural bone parameters revealed linear correlation coefficients (ρ) of 0.87-0.92(CV 8.3-27.2%)for histomorphometry and of 0.66-0.94(CV 4.4-23.4%)for micro-CT.There were no significant differences in reproducibilities in the samples obtained from the different study groups (OP, ROD, healthy controls).When comparing the techniques, cancellous bone volume (BV/TV), trabecular thickness, and trabecular number displayed moderate correlations (ρ=0.39-0.62,p<0.05), and the agreement for BV/TV was highest in OP samples.The incidence of AFFs among patients receiving biphosphonates was 0.61 fractures/1000 patients per year within the catchment area of Kuopio University Hospital, compared to 0.0067/1000 per year among untreated subjects.Histomorphometry in 4 patients revealed a low cancellous bone volume.Bone formation and resorption parameters were found to be low.Based on FTIRI, a high phosphate-toamide I ratio and a high collagen maturity were detected in comparison with normal samples.Children with vertebral fracture (n=14) were examined, in 36% of cases low cancellous bone volume (BV/TV <-1.0 SD) was detected by histomorphometry, and in 64% of the children the bone turnover rate was abnormal.Children with vertebral fractures had lower a carbonate-to-phosphate ratio, higher collagen maturity, and a narrower collagen distribution (p<0.05)than children without vertebral fracture.In children after solid organ transplantation (n=19), 21% had sustained peripheral fractures and 58% had suffered vertebral compression fractures.Histomorphometric analyses showed low cancellous bone volume (<-1.0SD) in six children (32%) and decreased trabecular thickness in 14 children (74%).Seven children (37%) had a high bone turnover and six children (32 %) had low turnover.VI There was moderate agreement between bone histomorphometry and micro-CT using clinical bone samples.The reproducibility was not affected by the health status of bone.The overall incidence of AFFs was low.The poor fracture resistance in some patients on longterm bisphosphonate-therapy could be explained by low bone formation, and changes in bone composition.Further, changes in bone composition were found among fracture-prone children who had sustained vertebral fracture.The changes in these children might contribute to their greater propensity to sustain vertebral fractures.A great heterogeneity in the histological findings was found in children after organ transplantation, and the results were unpredictable if only non-invasive methods were available.The observed changes in bone quality rather than the actual loss of cancellous bone, might explain the increased fracture risk in pediatric solid organ transplant recipients.Based on the present results, histomorphometry is needed in clinical practice to study remodeling balance in bone, with the other potential methods available to study bone quality being complementary.
Author: Inari S Tamminen
Language: English
Subfield: Orthopedics and Sports Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3094968253